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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.
Nanoscale characterization (TEM on FIB-SEM-prepared foils) was undertaken on feldspars undergoing transformation from early post-magmatic (deuteric) to hydrothermal stages in granites hosting the Olympic Dam Cu-U-Au-Ag deposit, and from the Cu-Au skarn at Hillside within the same iron-oxide copper-gold (IOCG) province, South Australia. These include complex perthitic textures, anomalously Ba-, Fe-, or REE-rich compositions, and REE-flourocarbonate + molybdenite assemblages which pseudomorph pre-existing feldspars. Epitaxial orientations between cryptoperthite (magmatic), patch perthite (dueteric) and replacive albite (hydrothermal) within vein perthite support interface-mediated reactions between pre-existing alkali-feldspars and pervading fluid, irrespective of micro-scale crystal morphology. Such observations are consistent with a coupled dissolution-reprecipitation reaction mechanism, which assists in grain-scale element remobilization via the generation of transient interconnected microporosity. Micro-scale aggregates of hydrothermal hyalophane (Ba-rich K-feldspar), crystallizing within previously albitized areas of andesine, reveal a complex assemblage of calc-silicate, As-bearing fluorapatite and Fe oxides along reaction boundaries in the enclosing albite-sericite assemblage typical of deuteric alteration. Such inclusions are good REE repositories and their presence supports REE remobilization at the grain-scale during early hydrothermal alteration. Iron-metasomatism is recognized by nanoscale maghemite inclusions within ‘red-stained’ orthoclase, as well as by hematite in REE-fluorocarbonates, which reflect broader-scale zonation patterns typical for IOCG systems. Potassium-feldspar from the contact between alkali-granite and skarn at Hillside is characterized by 100–1000 ppm REE, attributable to pervasive nanoscale inclusions of calc-silicates, concentrated along microfractures, or pore-attached. Feldspar replacement by REE-fluorcarbonates at Olympic Dam and nanoscale calc-silicate inclusions in feldspar at Hillside are both strong evidence for the role of feldspars in concentrating REE during intense metasomatism. Differences in mineralogical expression are due to the availability of associated elements. Lattice-scale intergrowths of assemblages indicative of Fe-metasomatism, REE-enrichment and sulfide deposition at Olympic Dam are evidence for a spatial and temporal relationship between these processes.
Do minority voters respond to co-racial or co-ethnic candidates? That is does the increased chance of substantive representation translate into increased participation? Here, we focus on this question among African American voters. While much of the empirical literature on this question has produced conflicting answers, recent studies suggest that minority candidates can significantly increase minority turnout. We argue that past work on this topic does not adequately account for the fact that minority voters in places with minority candidates may systematically differ in their level of participation than minority voters in places without minority candidates. In this study we address the weaknesses of previous research designs and offer a new design that exploits the redistricting process to gain additional leverage over this question. We find little evidence that African American voter turnout increases when voters are moved to African American candidates. We find some evidence that white voters, however, tend to vote at lower rates when they are represented by African American candidates.
Little is known about the association of cortical Aβ with depression and anxiety among cognitively normal (CN) elderly persons.
We conducted a cross-sectional study derived from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota; involving CN persons aged ≥ 60 years that underwent PiB-PET scans and completed Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). Cognitive diagnosis was made by an expert consensus panel. Participants were classified as having abnormal (≥1.4; PiB+) or normal PiB-PET (<1.4; PiB−) using a global cortical to cerebellar ratio. Multi-variable logistic regression analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (95% CI) after adjusting for age and sex.
Of 1,038 CN participants (53.1% males), 379 were PiB+. Each one point symptom increase in the BDI (OR = 1.03; 1.00–1.06) and BAI (OR = 1.04; 1.01–1.08) was associated with increased odds of PiB-PET+. The number of participants with BDI > 13 (clinical depression) was greater in the PiB-PET+ than PiB-PET- group but the difference was not significant (OR = 1.42; 0.83–2.43). Similarly, the number of participants with BAI > 10 (clinical anxiety) was greater in the PiB-PET+ than PiB-PET− group but the difference was not significant (OR = 1.77; 0.97–3.22).
As expected, depression and anxiety levels were low in this community-dwelling sample, which likely reduced our statistical power. However, we observed an informative albeit weak association between increased BDI and BAI scores and elevated cortical amyloid deposition. This observation needs to be tested in a longitudinal cohort study.
A dearth of population-based epidemiological research examines neuropsychiatric symptom (NPS) in sub-clinical populations across the spectrum from normal aging to mild cognitive impairment (MCI). The construct of mild behavioral impairment (MBI) describes the emergence of sustained and impactful NPS in advance of or in combination with MCI. This is the first epidemiological study to operationalize the recently published diagnostic criteria for MBI and determine prevalence estimates across the spectrum from cognitively normal to MCI.
MBI was assessed in 1,377 older (age range 72–79 years; 52% male; MCI ;= 133; cognitively normal, but-at-risk = 397; cognitively healthy = 847). MBI was assessed in accordance with the ISTAART-AA diagnostic criteria for MBI using the neuropsychiatric inventory.
34.1% of participants met the criteria for MBI. High prevalence of MBI across the cognitive spectrum was reported (48.9% vs. 43.1% vs. 27.6%). Irrespective of level of cognitive impairment, impulse dyscontrol (33.8% vs. 28.7% vs. 17.2%) and decreased motivation (32.3% vs. 26.2% vs. 16.3%) were the most frequently met MBI domains. MBI was more prevalent in men (χ2 = 4.98, p = 0.026), especially the domains of decreased motivation and impulse dyscontrol.
This study presents the first population-based prevalence estimates for MBI using the recently published ISTAART-AA diagnostic criteria. Findings indicate relatively high prevalence of MBI in pre-dementia clinical states and amongst cognitively healthy older adults. Findings were gender-specific, with MBI affecting more men than women. Knowing the estimates of these symptoms in the population is essential for understanding and differentiating the very early development of clinical disorders.
Affective and emotional symptoms such as depression, anxiety, euphoria, and irritability are common neuropsychiatric symptoms (NPS) in pre-dementia and cognitively normal older adults. They comprise a domain of Mild Behavioral Impairment (MBI), which describes their emergence in later life as an at-risk state for cognitive decline and dementia, and as a potential manifestation of prodromal dementia. This selective scoping review explores the epidemiology and neurobiological links between affective and emotional symptoms, and incident cognitive decline, focusing on recent literature in this expanding field of research.
Existing literature in prodromal and dementia states was reviewed, focusing on epidemiology, and neurobiology. Search terms included: “mild cognitive impairment,” “dementia,” “prodromal dementia,” “preclinical dementia,” “Alzheimer's,” “depression,” “dysphoria,” “mania,” “euphoria,” “bipolar disorder,” and “irritability.”
Affective and emotional dysregulation are common in preclinical and prodromal dementia syndromes, often being harbingers of neurodegenerative change and progressive cognitive decline. Nosological constraints in distinguishing between pre-existing psychiatric symptomatology and later life acquired NPS limit historical data utility, but emerging research emphasizes the importance of addressing time frames between symptom onset and cognitive decline, and age of symptom onset.
Affective symptoms are of prognostic utility, but interventions to prevent dementia syndromes are limited. Trials need to assess interventions targeting known dementia pathology, toward novel pathology, as well as using psychiatric medications. Research focusing explicitly on later life onset symptomatology will improve our understanding of the neurobiology of NPS and neurodegeneration, enrich the study sample, and inform observational and clinical trial design for prevention and treatment strategies.
Mild behavioral impairment (MBI) describes later life acquired, sustained neuropsychiatric symptoms (NPS) in cognitively normal individuals or those with mild cognitive impairment (MCI), as an at-risk state for incident cognitive decline and dementia. We developed an operational definition of MBI and tested whether the presence of MBI was related to caregiver burden in patients with subjective cognitive decline (SCD) or MCI assessed at a memory clinic.
MBI was assessed in 282 consecutive memory clinic patients with SCD (n = 119) or MCI (n = 163) in accordance with the International Society to Advance Alzheimer's Research and Treatment – Alzheimer's Association (ISTAART–AA) research diagnostic criteria. We operationalized a definition of MBI using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Caregiver burden was assessed using the Zarit caregiver burden scale. Generalized linear regression was used to model the effect of MBI domains on caregiver burden.
While MBI was more prevalent in MCI (85.3%) than in SCD (76.5%), this difference was not statistically significant (p = 0.06). Prevalence estimates across MBI domains were affective dysregulation (77.8%); impulse control (64.4%); decreased motivation (51.7%); social inappropriateness (27.8%); and abnormal perception or thought content (8.7%). Affective dysregulation (p = 0.03) and decreased motivation (p=0.01) were more prevalent in MCI than SCD patients. Caregiver burden was 3.35 times higher when MBI was present after controlling for age, education, sex, and MCI (p < 0.0001).
MBI was common in memory clinic patients without dementia and was associated with greater caregiver burden. These data show that MBI is a common and clinically relevant syndrome.
Objectives: The Priorities and Evaluation Committee (PEC) funding recommendations for new cancer drugs in British Columbia, Canada have been based on both clinical and economic evidence. The British Columbia Ministry of Health makes funding decisions. We assessed the association between cost-effectiveness of cancer drugs considered from 1998 to 2008 and the subsequent funding decisions.
Methods: All proposals submitted to the PEC between 1998 and 2008 were reviewed, and the association between cost-effectiveness and funding decisions was examined by (i) using logistic regression to test the hypothesis that interventions with higher incremental cost-effectiveness ratios (ICERs) have a lower probability of receiving a positive funding decision and (ii) using parametric and nonparametric tests to determine if a statistically significant difference exists between the mean cost-effectiveness of funded versus not funded proposals. A sub-analysis was conducted to determine if the findings varied across different outcome measures.
Results: Of the 149 proposals reviewed, 78 reported cost-effectiveness using various outcome measures. In the proposals that used life-years gained as the outcome (n = 22), a statistically significant difference of nearly $115,000 was observed between the mean ICERs for funded proposals ($42,006) and for unfunded proposals ($156,967). An odds ratio indicating higher ICERs have a lower probability of being funded was also found to be statistically significant (p < .05).
Conclusions: Economic evidence appears to play a role in British Columbia cancer funding decisions from 1998 to 2008; other decision-making criteria may also have an important role in recommendations and subsequent funding decisions.
High-resolution seismic reflection (HRSR) data acquired over the Pesotum Bedrock Valley in central Illinois, USA, helped construct the seismic stratigraphy of a valley fill and the overlying sediments. Integrating these data with drilling and borehole geophysics allowed us to develop a seismo-stratigraphic classification for sediments on undulating and folded bedrock. Seven seismo-stratigraphic units that overlie the bedrock surface were characterized. Seismic units A and B include glacial sediments of multiple Pleistocene glaciations above the Pesotum Bedrock Valley, which completely mask the feature. Seismic units C–F, the valley fill, primarily include tills and glacial lake sediment deposited during the earliest Pleistocene glaciations and preglacial alluvium and colluvium that is draped over in situ weathered bedrock. The preservation of conformable-lying glacial and preglacial deposits and paucity of sand and gravel in the buried valley strongly indicate that little or no incision by glacial meltwaters has occurred. These observations contrast markedly with interpretations from buried valleys elsewhere in North America and northern Europe where valley fills contain significant deposits of sand and gravel in tunnel valleys. The HRSR data assisted the characterization and analysis of heterogeneous sedimentary sequences over a buried valley where existing subsurface information was limited. The extent of Pleistocene-age glacial lakes is inferred from the lateral continuity of silt and clay units.
To investigate the differential associations between sensory loss and neuropsychiatric symptoms among older adults with and without diagnosed neurocognitive disorder.
The sample comprised 1,393 adults (52.3% men) aged between 72 and 79 years from a community-based cohort study. There were 213 cases of mild and 64 cases of major neurocognitive disorders. The main outcome was number of informant reported symptoms on the Neuropsychiatric Inventory (NPI). Sensory loss was defined by visual acuity worse the 0.3 logMAR (6/12 or 20/40) and self-reported hearing problems.
Clinically relevant NPI symptoms were reported in 182 (13.1%) participants, but no individual symptom occurred in more than 5% of the total sample. Among participants diagnosed with a major neurocognitive disorder, those with any sensory loss had over three times (95%CI: 1.72–11.78) greater rates of NPI symptoms than those with unimpaired levels of sensory functioning. There were no differences in the number of neuropsychiatric symptoms by type of sensory loss, and no additional risk associated with a dual sensory loss compared to a single sensory loss. There was no evidence of an association between sensory loss and number of neuropsychiatric symptoms among cognitively healthy adults.
The extent to which this association is the result of underlying neuropathology, unmet need, or interpersonal factors is unclear. These findings have significant implications for dementia care settings, including hospitals and respite care, as patients with sensory loss are at increased risk of neuropsychiatric symptoms and may require additional psychosocial support. Interventions to manage sensory loss and reduce the impact of sensory limitations on neuropsychiatric symptoms are needed.
Voting is a fundamental part of any democratic society. But survey-based measures of voting are problematic because a substantial proportion of nonvoters report that they voted. This over-reporting has consequences for our understanding of voting as well as the behaviors and attitudes associated with voting. Relying on the “bogus pipeline” approach, we investigate whether altering the wording of the turnout question can cause respondents to provide more accurate responses. We attempt to reduce over-reporting simply by changing the wording of the vote question by highlighting to the respondent that: (1) we can in fact find out, via public records, whether or not they voted; and (2) we (survey administrators) know some people who say they voted did not. We examine these questions through a survey on US voting-age citizens after the 2010 midterm elections, in which we ask them about voting in those elections. Our evidence shows that the question noting we would check the records improved the accuracy of the reports by reducing the over-reporting of turnout.
Traditional breeding has been used to develop grain sorghum germplasm that is tolerant to acetolactate synthase (ALS)-inhibiting herbicides (Inzen Technology, DuPont). Inzen sorghum carries a double mutation in the ALS gene (Val560Ile and Trp574Leu), which confers high level of tolerance to ALS-inhibiting herbicides. Overreliance on ALS-inhibiting herbicides for weed control during the 1990s resulted in the evolution of ALS inhibitor–resistant shattercane populations in Nebraska. According to a survey conducted in 2013, ALS inhibitor–resistant weedy Sorghum populations persist in Nebraska. The objectives of this research were to determine whether the ALS mutations present in Inzen sorghum were present in the ALS inhibitor–resistant shattercane and johnsongrass populations detected in Nebraska and northern Kansas, and whether these populations evolved ALS resistance independently. Primers specific to the Val560 and Trp574 region of the ALS gene were used to screen the populations with PCR. The Trp574Leu mutation was present in one ALS inhibitor–resistant johnsongrass population. The Val560Ile was detected in three ALS inhibitor–resistant shattercane, one susceptible shattercane, one ALS inhibitor–resistant johnsongrass, and one susceptible johnsongrass population. Moreover, Val560Ile was present in resistant and/or susceptible individuals within johnsongrass and shattercane populations that were segregating for ALS resistance, indicating that by itself the Val560Ile mutation does not confer resistance to ALS-inhibiting herbicides. None of the populations presented both mutations simultaneously, as does Inzen sorghum. A shattercane population containing the Ser653Thr mutation was also detected. This research indicates that the ALS mutations present in Inzen sorghum already exist individually in weedy sorghum populations. Moreover, our results present strong evidence that ALS resistance in these populations evolved independently. Thus, widespread overreliance on ALS-inhibiting herbicides prior to adoption of glyphosate-tolerant crops in the 1990s exerted sufficient selective pressure on shattercane and johnsongrass populations for resistance to evolve multiple times in the Midwest. Finally, a survey of the 5′ portion of the ALS gene in more diverse wild and weedy Sorghum species was hampered by limited coverage in genomic resequencing surveys, suggesting that refined PCR-based methods will be needed to assess SNP variation in this gene region, which includes the Ala122, Pro197, and Ala205 codons known to confer ALS resistance in other species.
This study aimed to measure changes in disease-specific quality of life in children following tonsillectomy or adenotonsillectomy.
A multicentre prospective cohort study was performed involving seven ENT departments in England. A total of 276 children entered the study over a 2-month period: 107 underwent tonsillectomy and 128 adenotonsillectomy. Forty-one children referred with throat problems initially managed by watchful waiting were also recruited. The follow-up period was 12 months. Outcome measures were the T14, parental impressions of their child's quality of life and the number of days absent from school.
One-year follow-up data were obtained from 150 patients (52 per cent). The mean baseline T14 score in the non-surgical group was significantly lower (T14 = 23) than in the tonsillectomy group (T14 = 31) or the adenotonsillectomy group (T14 = 35; p < 0.001). There was a significant improvement in the T14 scores of responders in all groups at follow up. The effect size was 1.3 standard deviations (SD) for the non-surgical group, 2.1 SD for the tonsillectomy group and 1.9 SD for the adenotonsillectomy group. Between-group differences did not reach statistical significance. A third of children in the non-surgical group underwent surgery during the follow-up period.
Children who underwent surgical intervention achieved a significant improvement in disease-specific quality of life. Less severely affected children were managed conservatively and also improved over 12 months, but 1 in 3 crossed over to surgical intervention.