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Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
The Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) are the most frequently used observer-rated and self-report scales of depression, respectively. It is important to know what a given total score or a change score from baseline on one scale means in relation to the other scale.
We obtained individual participant data from the randomised controlled trials of psychological and pharmacological treatments for major depressive disorders. We then identified corresponding scores of the HAMD and the BDI (369 patients from seven trials) or the BDI-II (683 patients from another seven trials) using the equipercentile linking method.
The HAMD total scores of 10, 20 and 30 corresponded approximately with the BDI scores of 10, 27 and 42 or with the BDI-II scores of 13, 32 and 50. The HAMD change scores of −20 and −10 with the BDI of −29 and −15 and with the BDI-II of −35 and −16.
The results can help clinicians interpret the HAMD or BDI scores of their patients in a more versatile manner and also help clinicians and researchers evaluate such scores reported in the literature or the database, when scores on only one of these scales are provided. We present a conversion table for future research.
Patients with chronic obstructive pulmonary disease (COPD) who experience acute exacerbations usually require treatment with oral steroids or antibiotics, depending on the etiology of the exacerbation. Current management is based on clinician's assessment and judgement, which lacks diagnostic accuracy and results in overtreatment. A test to guide these decisions in primary care is in development. We developed an early decision model to evaluate the cost-effectiveness of this treatment stratification test in the primary care setting in the United Kingdom.
A combined decision tree and Markov model was developed of COPD progression and the exacerbation care pathway. Sensitivity analysis was carried out to guide technology development and inform evidence generation requirements.
The base case test strategy cost GBP 423 (USD 542) less and resulted in a health gain of 0.15 quality-adjusted life-years per patient compared with not testing. Testing reduced antibiotic prescriptions by 30 percent, potentially lowering the risk of antimicrobial resistance developing. In sensitivity analysis, the result depended on the clinical effects of treating patients according to the test result, as opposed to treating according to clinical judgement alone, for which there is limited evidence. The results were less sensitive to the accuracy of the test.
Testing may be cost-saving in primary care, but this requires robust evidence on whether test-guided treatment is effective. High quality evidence on the clinical utility of testing is required for early modeling of diagnostic tests generally.
Deficits in frontal lobe perfusion have been demonstrated in late-life depression; however, studies to date have generally involved small numbers, used neuroimaging rather than bedside testing and have not controlled for important covariates.
We aimed to examine the association between depressive symptoms and frontal lobe perfusion during standing, in a large cohort of community-dwelling older people.
Participants aged ≥50 years underwent continuous measurement of orthostatic blood pressure by finometry, and frontal lobe perfusion by near-infrared spectroscopy. Depressive symptoms were assessed by the eight-item Centre for Epidemiological Studies Depression Scale. Real-time frontal lobe cerebral oxygenation was measured by the Portalite System, detecting changes in frontal lobe perfusion and reporting a tissue saturation index score.
Almost 8% (209 out of 2616) had clinically significant depressive symptoms. Multilevel models demonstrated a significantly lower tissue saturation index in participants with depressive symptoms at both 60 and 90 s post-stand, with coefficients of −0.43 (95% CI −0.63 to −0.22) and −0.37 (95% CI −0.57 to −0.16), respectively. Controlling for relevant covariates did not significantly attenuate these associations. After addition of systolic blood pressure this association was no longer significant, suggesting lower blood pressure may modify this relationship.
This study demonstrates that lower frontal lobe perfusion, related to lower values of baseline systolic blood pressure, is associated with clinically significant depressive symptoms in a cohort of community-dwelling older people. Given the recognised longitudinal association between lower blood pressure and depression in older people, this may represent a potential therapeutic target for prevention of incident depression.
Immune globulin (IG) is a publicly funded blood product with high utilization rates and rapidly rising costs. Inappropriate use of IG, particularly in dose and treatment duration, is observed in about 10 percent of cases, and the national guidelines for IG treatment are outdated. To develop a utilization management policy for IG, the Alberta, Manitoba and Saskatchewan Ministries of Health collaborated with health technology assessment (HTA) researchers and clinicians to develop evidence-based guideline recommendations for IG treatment to inform an authorization policy for IG utilization in the provinces.
A multidisciplinary committee comprising HTA researchers and 22 physicians from seven medical specialties adapted recommendations from 43 “seed” guidelines into one locally contextualized IG guideline. HTA methods and rapid review products were used extensively to update gaps in the evidence base. The guideline recommendation document was used to develop a provincial IG utilization management policy. The challenges of achieving a methodologically rigorous guideline development process will be discussed.
The guideline contained over 60 recommendations for IG use in different medical specialties. The health ministries used the guideline recommendations to develop an IG authorization policy. The clinician-sanctioned review criteria were used to construct a conditional reimbursement system for generating outcome data from controlled off-label IG use for conditions where evidence gaps existed, and were built into policies for benchmarking compliance.
Three provinces successfully collaborated to develop an IG utilization management policy. The unique approach involved a credible and transparent process that incorporated key review elements for compliance benchmarking and reimbursement, promoted clinician buy-in, and created a cadre of clinical champions willing to assist in policy development and implementation. The proactive, rather than retroactive, incorporation of clinician-sanctioned benchmarking and review criteria into policy will help bridge the know-do gap and foster a stronger, more direct link between health policy and evidence.
To assess trends of mortality attributable to child and maternal undernutrition (CMU), overweight/obesity and dietary risks of non-communicable diseases (NCD) in sub-Saharan Africa (SSA) using data from the Global Burden of Disease (GBD) Study 2015.
For each risk factor, a systematic review of data was used to compute the exposure level and the effect size. A Bayesian hierarchical meta-regression analysis was used to estimate the exposure level of the risk factors by age, sex, geography and year. The burden of all-cause mortality attributable to CMU, fourteen dietary risk factors (eight diets, five nutrients and fibre intake) and overweight/obesity was estimated.
All age groups and both sexes.
In 2015, CMU, overweight/obesity and dietary risks of NCD accounted for 826204 (95 % uncertainty interval (UI) 737346, 923789), 266768 (95 % UI 189051, 353096) and 558578 (95 % UI 453433, 680197) deaths, respectively, representing 10·3 % (95 % UI 9·1, 11·6 %), 3·3 % (95 % UI 2·4, 4·4 %) and 7·0 % (95 % UI 5·8, 8·3 %) of all-cause mortality. While the age-standardized proportion of all-cause mortality accounted for by CMU decreased by 55·2 % between 1990 and 2015 in SSA, it increased by 63·3 and 17·2 % for overweight/obesity and dietary risks of NCD, respectively.
The increasing burden of diet- and obesity-related diseases and the reduction of mortality attributable to CMU indicate that SSA is undergoing a rapid nutritional transition. To tackle the impact in SSA, interventions and international development agendas should also target dietary risks associated with NCD and overweight/obesity.
Conservation resources are limited, yet an increasing number of species are under threat. Assessing species for their conservation needs is, therefore, a vital first step in identifying and prioritizing species for both ex situ and in situ conservation actions. Using a transparent, logical and objective method, the Conservation Needs Assessment process developed by Amphibian Ark uses current knowledge of species in the wild to determine those with the most pressing conservation needs, and provides a foundation for the development of holistic conservation action plans that combine in situ and ex situ actions as appropriate. These assessments allow us to maximize the impact of limited conservation resources by identifying which measures could best serve those species requiring help. The Conservation Needs Assessment complements the IUCN Red List assessment, and together they provide a more holistic guide to conservation priorities and actions. Conservation Needs Assessments generate national prioritized lists of species recommended for conservation action. These can subsequently be used to assist in the development of species recovery plans and national action plans, or to inform national conservation priorities better. Additional tools that will evaluate the recommendations for ex situ rescues, to determine the best candidates for conservation breeding programmes, are currently under development.
UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors.
An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders.
An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders.
157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Declaration of interest
G.B. received grants from the National Institute for Health Research during the study; and support from Illumina Ltd. and the European Commission outside the submitted work. B.C. received grants from the Scottish Executive Chief Scientist Office and from The Dr Mortimer and Theresa Sackler Foundation during the study. C.S. received grants from the Medical Research Council and Wellcome Trust during the study, and is the Chief Scientist for UK Biobank. M.H. received grants from the Innovative Medicines Initiative via the RADAR-CNS programme and personal fees as an expert witness outside the submitted work.
Mental disorders in children and adolescents have an impact on educational attainment.
To examine the temporal association between attainment in education and subsequent diagnosis of depression or self-harm in the teenage years.
General practitioner, hospital and education records of young people in Wales between 1999 and 2014 were linked and analysed using Cox regression.
Linked records were available for 652 903 young people and of these 33 498 (5.1%) developed depression and 15 946 (2.4%) self-harmed after the age of 12 but before the age of 20. Young people who developed depression over the study period were more likely to have achieved key stage 1 (age 7 years) but not key stage 2 (age 11) (hazard ratio (HR) = 0.79, 95% CI 0.74–0.84) milestones, indicating that they were declining in academic attainment during primary school. Conversely, those who self-harmed were achieving as well as those who did not self-harm in primary school, but showed a severe decline in their attainment during secondary school (HR = 0.72, 95% CI 0.68–0.78).
Long-term declining educational attainment in primary and secondary school was associated with development of depression in the teenage years. Self-harm was associated with declining educational attainment during secondary school only. Incorporating information on academic decline with other known risk factors for depression/self-harm (for example stressful life events, parental mental health problems) may improve risk profiling methods.
Although hospital emergency preparedness efforts have been recognized as important, there has been growing pressure on cost containment, as well as consolidation within the US health care system. There is little data looking at what health care emergency preparedness functions have been, could be, or should be centrally coordinated at a system level.
We developed a questionnaire for academic health systems and asked about program funding, resources provided, governance, and activities. The questionnaire also queried managers’ opinions regarding the appropriate role for the system-level resources in emergency response, as well as about what is most helpful at the system-level supporting preparedness.
Fifty-two of 97 systems (54%) responded. The most frequently occurring system-wide activities included: creating trainings or exercise templates (75%), promoting preparedness for employees in the system (75%), providing access to specific subject matter experts (73%), and developing specific plans for individual member entities within their system (73%). The top resources provided included a common mass notification system (71%), arranging for centralized contracts for goods and services (71%), and providing subject matter expertise (69%).
Currently, there is wide variation in the resources, capabilities, and programs used to support and coordinate system-level emergency preparedness among academic health systems. (Disaster Med Public Health Preparedness. 2018;12:574–577)
Once-daily dosing with dasotraline, a novel dopamine and norepinephrine reuptake inhibitor, achieves stable plasma concentrations over 24 hours. This phase 3 study evaluated the efficacy and safety of dasotraline in children with attention deficithyperactivity disorder (ADHD) throughout the day, in a laboratory classroom setting (NCT02734693).
Children (6–12 years) meeting DSM-5 criteria for ADHD were randomized to 2 weeks of dasotraline or placebo (dosed daily at home at approximately 8 PM). Following an abbreviated practice day, laboratory classroom evaluations took place at baseline and on Day 15. The primary endpoint was mean change from baseline at Day 15 in ADHD symptoms, as measured by the Swanson, Kotkin, Agler, M-Flynn, and Pelham Combined Score (SKAMP-CS), obtained from the average of 7 assessments collected across the 12-hour laboratory classroom day (12–24 hours post-dose). Secondary endpoints included SKAMP scores obtained throughout the day at individual timepoints from 8 AM through 8 PM (12–24 hours post-dose), and measures of safety and tolerability.
The ITT population comprised 112 patients. Mean age was 9.5 years, 68.8% were male; 92% completed the study. Dasotraline 4 mg/day significantly improved mean SKAMP-CS versus placebo (p<0.0001, effect size 0.85) with significant effects persisting throughout the day. Mean SKAMP subscores improved significantly versus placebo (Attention p<0.0001, effect size 0.81; Deportment p<0.001, effect size 0.70). Treatment-emergent adverse events were generally mild or moderate in severity; most frequent (with dasotraline 4 mg/day; placebo) included: insomnia (19.6%; 3.6%, all terms combined), decreased appetite (10.7%; 3.6%), headache (10.7%; 8.9%), affect lability (8.9%; 7.1%), irritability (5.4%; 3.6%), postural orthostatic tachycardia syndrome (5.4%; 0%), and perceptual disturbances (5.4%; 0%).
In this 2-week, randomized, double-blind, laboratory classroom study in children with ADHD, once-daily dasotraline significantly improved ADHD symptoms (including deportment and attention), compared with placebo, and demonstrated sustained efficacyup to 24 hours post-dose. The most common adverse events were insomnia, decreased appetite, and headache.
Late life depression (LLD) confers significant morbidity and mortality but is well recognized that it often goes undetected or untreated. The objective of this study is to quantify the burden of untreated depression and death ideation (DI) at a population level.
Cross-sectional study ascertaining the prevalence of, and factors associated with, untreated depression and DI.
This study, embedded within the Irish Longitudinal Study on Ageing, involves over 7,000 community-dwelling people aged ≥50 years.
Depression was defined as Centre for Epidemiological Studies Depression scale ≥16 indicating current clinically relevant depressive symptoms or Composite International Diagnostic Interview indicative of major depressive episode within the last year. Participants not prescribed antidepressants/antipsychotics were defined as untreated. To define DI, participants were asked “In the last month, have you felt like you would rather be dead?”
In total, 12% (839/7,055) met criteria for depression with 29% (241/839) on pharmacological therapy. Those with untreated depression were less likely to endorse symptoms of persistent low mood or worthlessness, but there was no difference in age or general practitioner (GP) visits compared to those on treatment. Over 3% (223/7,055) of participants had DI and less than one-third had visited their GP within the last year.
This study demonstrates that two-thirds of depressed older people are not prescribed antidepressant/antipsychotic therapy. It is important to raise awareness of depression among older people and healthcare professionals, with particular focus on the fact that LLD is not an inevitable consequence of ageing and effective treatment is available.
Limbic white matter pathways link emotion, cognition, and behavior and are potentially malleable to the influences of traumatic events throughout development. However, the impact of interactions between childhood and later life trauma on limbic white matter pathways has yet to be examined. Here, we examined whether childhood maltreatment moderated the effect of combat exposure on diffusion tensor imaging measures within a sample of military veterans (N = 28). We examined five limbic tracts of interest: two components of the cingulum (cingulum, cingulate gyrus, and cingulum hippocampus [CGH]), the uncinate fasciculus, the fornix/stria terminalis, and the anterior limb of the internal capsule. Using effect sizes, clinically meaningful moderator effects were found only within the CGH. Greater combat exposure was associated with decreased CGH fractional anisotropy (overall structural integrity) and increased CGH radial diffusivity (perpendicular water diffusivity) among individuals with more severe childhood maltreatment. Our findings provide preliminary evidence of the moderating effect of childhood maltreatment on the relationship between combat exposure and CGH structural integrity. These differences in CGH structural integrity could have maladaptive implications for emotion and memory, as well as provide a potential mechanism by which childhood maltreatment induces vulnerability to later life trauma exposure.