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People with bipolar disorder (BD) often show inaccurate subjective ratings of their objective cognitive function. However, it is unclear what information individuals use to formulate their subjective ratings. This study evaluated whether people with BD are likely using information about their crystallized cognitive abilities (which involve an accumulated store of verbal knowledge and skills and are typically preserved in BD) or their fluid cognitive abilities (which involve the capacity for new learning and information processing in novel situations and are typically impaired in BD) to formulate their subjective cognitive ratings.
Method:
Eighty participants diagnosed with BD and 55 control volunteers were administered cognitive tests assessing crystallized and fluid cognitive abilities. Subjective cognitive functioning was assessed with the Cognitive Failures Questionnaire (CFQ), daily functioning was rated using the Multidimensional Scale of Independent Functioning (MSIF) and the Global Assessment of Functioning Scale (GAF), and quality of life was assessed with the Quality of Life in Bipolar Disorder scale (QoL.BD).
Results:
The BD group exhibited considerably elevated subjective cognitive complaints relative to controls. Among participants with BD, CFQ scores were associated with fluid cognitive abilities including measures of memory and executive function, but not to crystallized abilities. After controlling for objective cognition and depression, higher cognitive complaints predicted poorer psychosocial outcomes.
Conclusions:
Cognitive self-reports in BD may represent a metacognitive difficulty whereby cognitive self-appraisals are distorted by a person’s focus on their cognitive weaknesses rather than strengths. Moreover, negative cognitive self-assessments are associated with poorer daily functioning and diminished quality of life.
The question of how science can become a lever in achieving the Sustainable Development Goals permeates most recent sustainability research. Wide-ranging literature calling for a transformative approach has emerged in recent years. This ‘transformative turn’ is fueled by publications from fields such as sustainability science, social-ecological research, conservation science, sustainability transitions, or sustainability governance studies. However, there is a lack of a shared understanding specifically of what is meant for research to be transformative in this developing discourse around doing science differently to tackle sustainability problems. We aim to advance transformative research for sustainability. We define transformative research and outline six of its characteristics: (1) interventional nature and a theory of change focus; (2) collaborative modes of knowledge production, experimentation and learning; (3) systems thinking literacy and contextualization; (4) reflexivity, normative and inner dimensions; (5) local agency, decolonization, and reshaping power; (6) new quality criteria and rethinking impact. We highlight three tensions between transformative research and traditional paradigms of academic research: (1) process- and output-orientation; (2) accountability toward society and toward science; (3) methodologies rooted in scientific traditions and post-normal methodologies. We conclude with future directions on how academia could reconcile these tensions to support and promote transformative research.
Non-technical summary
Dominant ways of doing research are not enough to achieve the UN Sustainable Development Goals. The typical response of science to dealing with the current local and global sustainability crises is to produce and accumulate more knowledge. Transformative research seeks to couple knowledge production with co-creating change. This paper defines the transformative way of doing research to pro-actively support society's fight against pressing societal and environmental problems. We present six characteristics of transformative research. We reflect on the challenges related to implementing these characteristics in scientific practice and on how academia can play its part.
Social media summary
Sustainability transformation needs to be reflected in science, but what makes sustainability research transformative?
Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic.
Methods
By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions.
Results
A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021.
Conclusions
Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.
Identifying neuroimaging biomarkers of antidepressant response may help guide treatment decisions and advance precision medicine.
Aims
To examine the relationship between anhedonia and functional neurocircuitry in key reward processing brain regions in people with major depressive disorder receiving aripiprazole adjunct therapy with escitalopram.
Method
Data were collected as part of the CAN-BIND-1 study. Participants experiencing a current major depressive episode received escitalopram for 8 weeks; escitalopram non-responders received adjunct aripiprazole for an additional 8 weeks. Functional magnetic resonance imaging (on weeks 0 and 8) and clinical assessment of anhedonia (on weeks 0, 8 and 16) were completed. Seed-based correlational analysis was employed to examine the relationship between baseline resting-state functional connectivity (rsFC), using the nucleus accumbens (NAc) and anterior cingulate cortex (ACC) as key regions of interest, and change in anhedonia severity after adjunct aripiprazole.
Results
Anhedonia severity significantly improved after treatment with adjunct aripiprazole.
There was a positive correlation between anhedonia improvement and rsFC between the ACC and posterior cingulate cortex, ACC and posterior praecuneus, and NAc and posterior praecuneus. There was a negative correlation between anhedonia improvement and rsFC between the ACC and anterior praecuneus and NAc and anterior praecuneus.
Conclusions
Eight weeks of aripiprazole, adjunct to escitalopram, was associated with improved anhedonia symptoms. Changes in functional connectivity between key reward regions were associated with anhedonia improvement, suggesting aripiprazole may be an effective treatment for individuals experiencing reward-related deficits. Future studies are required to replicate our findings and explore their generalisability, using other agents with partial dopamine (D2) agonism and/or serotonin (5-HT2A) antagonism.
Despite replicated cross-sectional evidence of aberrant levels of peripheral inflammatory markers in individuals with major depressive disorder (MDD), there is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies.
Objectives
To assess associations between plasma levels of pro-inflammatory markers and treatment response to escitalopram and adjunctive aripiprazole in adults with MDD.
Methods
In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10– 20 mg daily for 8 weeks. Responders continued on escitalopram while non-responders received adjunctive aripiprazole 2–10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers – C-reactive protein, Interleukin (IL)-1β, IL-6, IL-17, Interferon gamma (IFN)-Γ, Tumour Necrosis Factor (TNF)-α, and Chemokine C–C motif ligand-2 (CCL-2) - measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyses to assess associations between inflammatory markers and treatment response.
Results
Pre-treatment levels of IFN-Γ and CCL-2 were significantly higher in escitalopram non-responders compared to responders. Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16.
Conclusions
Pre-treatment levels of IFN-Γ and CCL-2 were predictive of response to escitalopram. Increasing levels of these pro-inflammatory markers may predict non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.
OBJECTIVES/GOALS: Particulate matter (PM) and metabolic syndrome (MetSyn) increase risk of World Trade Center-Lung Injury (WTC-LI). Mediterranean-type diets have also been found to improve lung function. Fire Department of New York 1st-responders with a high PM exposure at WTC and MetSyn may have improved lung function after a Mediterranean dietary intervention. METHODS/STUDY POPULATION: Food Intake REstriction for Health OUtcome Support and Education (FIREHOUSE) randomized clinical trial (RCT) assessed our hypothesis that a low-calorie Mediterranean (LoCalMed) intervention targeting clinically relevant disease modifiers will improve metabolic risk, subclinical indicators of cardiopulmonary disease, quality of life, and lung function in firefighters with WTC-LI. Primary-outcome targeted a LoCalMed loss of BMI(≥1kg/m2). Secondary-outcomes included lung function, quality of life, and cardiovascular health. Male firefighters with WTC-LI and a BMI>27kg/m2 were randomized to: 1. LoCalMed (n=46); or 2. Usual Care (UC; n=43). Clinicaltrials.gov:NCT03581006. RESULTS/ANTICIPATED RESULTS: LoCalMed’s estimated efficacy on BMI reduction crossed the pre-specified significance boundary on interim analysis compared to UC. In addition, improvements were observed in secondary-outcomes of lung health (FEV1 and FVC), inflammation (WBC), vascular disease (DBP), quality of life (SF-36, health perception) and dietary habits (less cholesterol, carbohydrates, fats, and sweets and increased protein) in the LoCalMed arm. DISCUSSION/SIGNIFICANCE: LoCalMed significantly decreased BMI and alleviated adverse health outcomes in our WTC-exposed first responders. A fully powered RCT is required to determine if this approach is efficacious for the treatment of WTC-associated pulmonary disease, as well as LoCalMed’s generalizability to PM associated disease.
This study quantifies the effect of fertilizer and irrigation management on water use efficiency (WUE), crop growth and crop yield in sub-humid to semi-arid conditions of Limpopo Province, South Africa. An approach of coupling a cropping system model (DSSAT) with an agro-hydrological model (SWAT) was developed and applied to simulate crop yield at the field and catchment scale. Simulation results indicated that the application of fertilizer has a greater positive effect on maize yield than irrigation. WUE ranged from 0.10–0.57 kg/m3 (rainfed) to 0.84–1.39 kg/m3 (irrigated) and was positively correlated with fertilizer application rate. The combined application of the variants with deficit irrigation and fertilizer rate (120:60 kg N:P/ha) for maize turned out to be the best option, giving the highest WUE and increasing average yield by up to 5.7 t/ha compared to no fertilization and rainfed cultivation (1.3 t/ha). The simulated results at the catchment scale showed the considerable spatial variability of maize yield across agricultural fields with different soils, slopes and climate conditions. The average annual simulated maize yield across the catchment corresponding to the highest WUE ranged from 4.0 to 7.0 t/ha. The yield gaps ranged from 3.0 to 6.0 t/ha under deficit irrigation combined with 120N:60P kg/ha and ranged from 0.2 to 1.5 t/ha when only applying deficit irrigation but no fertilizer. This information can support regional decision makers to find appropriate interventions that aim at improving crop yield and WUE for catchments/regions.
In many locations around the world, shell radiocarbon dates underpin archaeological research. The dating of shell brings the chronological relationship between the sample and target event (e.g., hunting and food preparation) into congruence, while shells are valuable geochemical proxies for understanding past climate dynamics and environments. However, this information can be lost as the shell, composites of biopolymers and carbonate minerals (mostly calcite and or aragonite), undergo diagenetic alteration. While studies into Pleistocene-age carbonates are common in the radiocarbon literature, there has been little research into the impact of alteration on Holocene-age shells used to interpret recent societal developments. The limits of our understanding of these diagenetic changes became evident when dating Placuna placenta (naturally calcitic) and Tegillarca granosa (naturally aragonitic) shells from the site of Thach Lac in Vietnam. These shells returned ages significantly younger than associated charcoal and terrestrial bone at the site, but standard tests for secondary recrystallization (XRD and staining techniques) did not indicate any alteration. Further investigation revealed that cryptic recrystallization (i.e., of the same crystal structure) had occurred in both the calcite and aragonite shells. This finding suggests recrystallization may have an undetected impact on some shell radiocarbon dates.
For older adults, feeling subjectively younger is associated with improvements in cognition, subjective well-being and depressive symptoms. Positive psychiatry is the field that focuses on patient strengths and the promotion of positive outcomes, rather than just mitigation of illness. Younger subjective age may be a useful measure of successful aging, but little is known about how subjective age is associated with positive psychosocial characteristics.
Objectives
Our objective is to characterize how subjective age is related validated positive psychosocial measures, with the goal of better understanding the determinants of successful aging.
Methods
The Successful Aging Evaluation (SAGE) longitudinal study recruited over 1,300 community-dwelling residents of San Diego County, CA, from age 21 to over 100. A single-item question asked “How old/young do you feel?” We used spearman correlations to assess the relationship between subjective age and validated positive psychosocial scales such as the Self-Rated Successful Aging, Life Orientation Test, Personal Mastery Scale, Connor-Davidson Resilience Scale, Satisfaction with Life Scale, Adult Hope Scale, and Social Support Index.
Results
Mean chronological age was 65.5, and mean subjective age was 53.6. Mean age discrepancy was 11.5 years. Younger subjective age was positively associated with most of the positive psychosocial characteristics measured, including self-rated successful aging, optimism, personal mastery, resilience, curiosity, hope, and social support.
Conclusions
There is a growing movement within psychiatry to understand the positive characteristics that lead to successful aging. This is one of the first studies demonstrating younger age identities are associated with positive psychosocial characteristics and successful aging.
Prediction of treatment outcomes is a key step in improving the treatment of major depressive disorder (MDD). The Canadian Biomarker Integration Network in Depression (CAN-BIND) aims to predict antidepressant treatment outcomes through analyses of clinical assessment, neuroimaging, and blood biomarkers.
Methods
In the CAN-BIND-1 dataset of 192 adults with MDD and outcomes of treatment with escitalopram, we applied machine learning models in a nested cross-validation framework. Across 210 analyses, we examined combinations of predictive variables from three modalities, measured at baseline and after 2 weeks of treatment, and five machine learning methods with and without feature selection. To optimize the predictors-to-observations ratio, we followed a tiered approach with 134 and 1152 variables in tier 1 and tier 2 respectively.
Results
A combination of baseline tier 1 clinical, neuroimaging, and molecular variables predicted response with a mean balanced accuracy of 0.57 (best model mean 0.62) compared to 0.54 (best model mean 0.61) in single modality models. Adding week 2 predictors improved the prediction of response to a mean balanced accuracy of 0.59 (best model mean 0.66). Adding tier 2 features did not improve prediction.
Conclusions
A combination of clinical, neuroimaging, and molecular data improves the prediction of treatment outcomes over single modality measurement. The addition of measurements from the early stages of treatment adds precision. Present results are limited by lack of external validation. To achieve clinically meaningful prediction, the multimodal measurement should be scaled up to larger samples and the robustness of prediction tested in an external validation dataset.
This study aimed to evaluate the effect of an extended voluntary waiting period (VWP) on SCC, SCC elevations and clinical mastitis incidence during the complete lactation and the first 6 weeks of the next lactation. Holstein-Friesian dairy cows (N = 154) were blocked for parity, expected milk yield, calving season and breeding value for persistency and were randomly distributed across 3 VWP (50, 125, or 200 d: VWP-50, VWP-125, VWP-200). Cows were monitored from calving until 6 weeks into the next lactation, or until culling. An elevation of SCC in milk was defined as SCC in milk ≥200 000 cells/ml after two previous weeks with SCC < 200 000 cells/ml. Over the complete lactation, extending the VWP did not affect SCC elevations and the occurrence of clinical mastitis per lactation or per cow per year. There was no clear effect of VWP length on SCC in the complete lactation, except that multiparous cows in VWP-125 had a higher SCC compared with multiparous cows in VWP-50. Dry-off antibiotic usage per cow per year was lower in VWP-200 compared with VWP-50 for multiparous cows. In the first 6 weeks of the next lactation, cows in VWP-200 had a higher SCC compared with cows in VWP-50, with no effect of VWP on the number of elevations of SCC or the occurrence of clinical mastitis. Extending the VWP may therefore be used to reduce the frequency of transition periods and the associated use of dry-cow antibiotics, with limited impact on udder health, and a similar occurrence of SCC elevations and clinical mastitis per year.
To describe the evolution of respiratory antibiotic prescribing during the coronavirus disease 2019 (COVID-19) pandemic across 3 large hospitals that maintained antimicrobial stewardship services throughout the pandemic.
Design:
Retrospective interrupted time-series analysis.
Setting:
A multicenter study was conducted including medical and intensive care units (ICUs) from 3 hospitals within a Canadian epicenter for COVID-19.
Methods:
Interrupted time-series analysis was used to analyze rates of respiratory antibiotic utilization measured in days of therapy per 1,000 patient days (DOT/1,000 PD) in medical units and ICUs. Each of the first 3 waves of the pandemic were compared to the baseline.
Results:
Within the medical units, use of respiratory antibiotics increased during the first wave of the pandemic (rate ratio [RR], 1.76; 95% CI, 1.38–2.25) but returned to the baseline in waves 2 and 3 despite more COVID-19 admissions. In ICU, the use of respiratory antibiotics increased in wave 1 (RR, 1.30; 95% CI, 1.16–1.46) and wave 2 of the pandemic (RR, 1.21; 95% CI, 1.11–1.33) and returned to the baseline in the third wave, which had the most COVID-19 admissions.
Conclusions:
After an initial surge in respiratory antibiotic prescribing, we observed the normalization of prescribing trends at 3 large hospitals throughout the COVID-19 pandemic. This trend may have been due to the timely generation of new research and guidelines developed with frontline clinicians, allowing for the active application of new research to clinical practice.
The aim of this study was to characterize the type and extent of virtual care use among infectious disease specialists in Canada, with a focus on the clinical factors that influence the decision to provide virtual versus in-person care.
Methods:
Infectious disease physicians practicing in Canada were invited to complete a survey regarding their experiences with virtual care. The survey included 14 vignettes depicting new outpatient and post–hospital-discharge referrals. Participants were asked to select which (if any) virtual care modalities they would feel comfortable using and to specify a reason if they did not feel comfortable providing care virtually. Machine learning and natural language processing techniques were used to identify themes.
Results:
In total, 57 infectious disease physicians completed the survey. Respondents reported devoting 36.5% (SD, 18.4%) of their infectious disease practice to outpatient care, with 44.2% (SD, 23.2%) of it being delivered virtually. Respondents were more comfortable providing virtual care to post–hospital-discharge referrals who had been seen by an infectious disease physician compared to new outpatient referrals. When respondents were not comfortable with using any virtual care modality, the following common themes emerged: the need for physical examination, the importance of establishing a therapeutic relationship, the need for additional in-person tests or diagnostics, and patient counselling.
Conclusion:
This study provides a glimpse into the current state of virtual care use in Canada and some of the major themes that affect decision making for virtual versus in-person care.
Background: Phase 3 PREEMPT established safety and efficacy of 155-195U onabotulinumtoxinA in adults with chronic migraine (CM). This analysis of the PREDICT study (NCT02502123) evaluates real-world effectiveness and safety of 155U, 156-195U and 195U-onabotulinumtoxinA in CM. Methods: Patients received onabotulinumtoxinA approximately every 12-weeks (≤7 treatment cycles [Tx]) per Canadian product monograph). Primary endpoint was mean change from baseline in Migraine-Specific Quality of Life (MSQ) at Tx4. Headache days, physician and patient satisfaction were evaluated. Analysis stratified safety population (≥1 onabotulinumtoxin A dose) into 3 groups (155U,156-195U,195U) by dose received on ≥3 of the first 4 Tx. Results: 184 patients received ≥1 onabotulinumtoxin A dose (155U, n=68; 156-195U, n=156; 195U, n=13 on ≥3 Tx). Headache days decreased over time compared to baseline (Tx4: -7.1[6.7] 155U; -6.5[6.7] 156-195U; -11.2[6.4] 195U). Physicians rated most patients as improved, and majority of patients were satisfied at final visit (80.8% 155U; 83.6% 156-195U; 90% 195U). Treatment-emergent adverse events (TEAEs) were reported in 18/68(26.5%) patients in 155U-group, 41/65(63.1%) in 156-195U-group and 10/13(76.9%) in 195U-group; treatment-related TEAEs were 9(13.2%), 10(15.4%) and 3(23.1%) respectively; serious TEAEs were 0, 3(4.6%) and 1(7.7%), none treatment-related. Conclusions: Long-term treatment with 155U, 156-195U, and 195U-onabotulinumtoxinA in PREDICT was safe and effective CM treatment. No new safety signals were identified.
Background: Poorly-defined cases (PDCs) of focal epilepsy are cases with no/subtle MRI abnormalities or have abnormalities extending beyond the lesion visible on MRI. Here, we evaluated the utility of Arterial Spin Labeling (ASL) MRI perfusion in PDCs of pediatric focal epilepsy. Methods: ASL MRI was obtained in 25 consecutive children presenting with poorly-defined focal epilepsy (20 MRI- positive, 5 MRI-negative). Qualitative visual inspection and quantitative analysis with asymmetry and Z-score maps were used to detect perfusion abnormalities. ASL results were compared to the hypothesized epileptogenic zone (EZ) derived from other clinical/imaging data and the resection zone in patients with Engel I/II outcome and >18 month follow-up. Results: Qualitative analysis revealed perfusion abnormalities in 17/25 total cases (68%), 17/20 MRI-positive cases (85%) and none of the MRI-negative cases. Quantitative analysis confirmed all cases with abnormalities on qualitative analysis, but found 1 additional true-positive and 4 false-positives. Concordance with the surgically-proven EZ was found in 10/11 cases qualitatively (sensitivity=91%, specificity=50%), and 11/11 cases quantitatively (sensitivity=100%, specificity=23%). Conclusions: ASL perfusion may support the hypothesized EZ, but has limited localization benefit in MRI-negative cases. Nevertheless, owing to its non-invasiveness and ease of acquisition, ASL could be a useful addition to the pre-surgical MRI evaluation of pediatric focal epilepsy.
Background: PET imaging of [11C]ABP688 shows reduced hippocampal mGluR5 availability in mesial temporal lobe epilepsy (MTLE) patients, however the relation with post-surgical outcomes is unclear. Here, we tested whether [11C]ABP688 binding in hippocampal subfields vulnerable to glutamate excitotoxicity is related to post-surgical outcome. Methods: [11C]ABP688-PET was obtained from 31 unilateral MTLE patients and 30 controls. Hippocampal subfields were automatically segmented into 1) CA1-3, 2) CA4/dentate gyrus (DG), 3) Subiculum and manually corrected. Partial volume corrected [11C]ABP688 non-displaceable binding potential (BPND) was calculated in the subfields and compared between seizure-free and non-seizure-free patients. Results: [11C]ABP688 BPND was significantly reduced in ipsilateral CA1-3 & CA4/DG (p<0.001) compared to controls. No difference was seen in Subiculum. Ipsilateral CA1-3 [11C]ABP688 BPND was lower in seizure-free (p=0.012; Engel Ia, n=13) vs non-seizure- free (Engel Ic-III, n=10) patients, and this effect was independent of subfield volume. In a subset of patients with [18F]FDG-PET, CA1-3 [11C]ABP688 BPND was significantly lower in seizure-free patients (p=0.03), while no difference was found for [18F]FDG uptake. Conclusions: Reduced CA1-3 mGluR5 availability was associated with post-surgical seizure-freedom independent of atrophy and hypometabolism. Thus, [11C]ABP688-PET may offer a potential biomarker for surgical outcomes and may be particularly relevant for pre-surgical workup in MRI- and [18F]FDG-negative MTLE patients.
To examine the association between adherence to plant-based diets and mortality.
Design:
Prospective study. We calculated a plant-based diet index (PDI) by assigning positive scores to plant foods and reverse scores to animal foods. We also created a healthful PDI (hPDI) and an unhealthful PDI (uPDI) by further separating the healthy plant foods from less-healthy plant foods.
Setting:
The VA Million Veteran Program.
Participants:
315 919 men and women aged 19–104 years who completed a FFQ at the baseline.
Results:
We documented 31 136 deaths during the follow-up. A higher PDI was significantly associated with lower total mortality (hazard ratio (HR) comparing extreme deciles = 0·75, 95 % CI: 0·71, 0·79, Ptrend < 0·001]. We observed an inverse association between hPDI and total mortality (HR comparing extreme deciles = 0·64, 95 % CI: 0·61, 0·68, Ptrend < 0·001), whereas uPDI was positively associated with total mortality (HR comparing extreme deciles = 1·41, 95 % CI: 1·33, 1·49, Ptrend < 0·001). Similar significant associations of PDI, hPDI and uPDI were also observed for CVD and cancer mortality. The associations between the PDI and total mortality were consistent among African and European American participants, and participants free from CVD and cancer and those who were diagnosed with major chronic disease at baseline.
Conclusions:
A greater adherence to a plant-based diet was associated with substantially lower total mortality in this large population of veterans. These findings support recommending plant-rich dietary patterns for the prevention of major chronic diseases.
Major depressive disorder (MDD) is the leading cause of disability worldwide. Patients with MDD have high rates of comorbidity with mental and physical conditions, one of which is chronic pain. Chronic pain conditions themselves are also associated with significant disability, and the large number of patients with MDD who have chronic pain drives high levels of disability and compounds healthcare burden. The management of depression in patients who also have chronic pain can be particularly challenging due to underlying mechanisms that are common to both conditions, and because many patients with these conditions are already taking multiple medications. For these reasons, healthcare providers may be reluctant to treat such patients. The Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines provide evidence-based recommendations for the management of MDD and comorbid psychiatric and medical conditions such as anxiety, substance use disorder, and cardiovascular disease; however, comorbid chronic pain is not addressed. In this article, we provide an overview of the pathophysiological and clinical overlap between depression and chronic pain and review evidence-based pharmacological recommendations in current treatment guidelines for MDD and for chronic pain. Based on clinical experience with MDD patients with comorbid pain, we recommend rapidly and aggressively treating depression according to CANMAT treatment guidelines, using antidepressant medications with analgesic properties, while addressing pain with first-line pharmacotherapy as treatment for depression is optimized. We review options for treating pain symptoms that remain after response to antidepressant treatment is achieved.
Background: PET imaging of [11C]ABP688 shows reduced hippocampal mGluR5 availability in mesial temporal lobe epilepsy (MTLE) patients, however the relation with post-surgical outcomes is unclear. Here, we tested whether [11C]ABP688 binding in hippocampal subfields vulnerable to glutamate excitotoxicity is related to post-surgical outcome. Methods: [11C]ABP688-PET was obtained from 31 unilateral MTLE patients and 30 controls. Hippocampal subfields were automatically segmented into 1) CA1-3, 2) CA4/dentate gyrus (DG), and 3) Subiculum and manually corrected. Partial volume corrected [11C]ABP688 non-displaceable binding potential (BPND) was calculated in the subfields and compared between seizure-free and non-seizure-free patients. Results: [11C]ABP688 BPND was significantly reduced in ipsilateral CA1-3 & CA4/DG (p<0.001) compared to controls. No difference was seen in Subiculum. Ipsilateral CA1-3 [11C]ABP688 BPND was lower in seizure-free (p=0.012; Engel Ia, n=13) vs non-seizure-free (Engel Ic-III, n=10) patients, and this effect was independent of subfield volume. In a subset of patients with [18F]FDG-PET, CA1-3 [11C]ABP688 BPND was significantly lower in seizure-free patients (p=0.03), while no difference was found for [18F]FDG uptake. Conclusions: Reduced CA1-3 mGluR5 availability was associated with post-surgical seizure-freedom independent of atrophy and hypometabolism. Thus, [11C]ABP688-PET may offer a potential biomarker for surgical outcomes and may be particularly relevant for pre-surgical workup in MRI- and [18F]FDG-negative MTLE patients.
Background: Poorly-defined cases (PDCs) of focal epilepsy are cases with no/subtle MRI abnormalities or have abnormalities extending beyond the lesion visible on MRI. Here, we evaluated the utility of Arterial Spin Labeling (ASL) MRI perfusion in PDCs of pediatric focal epilepsy. Methods: ASL MRI was obtained in 25 consecutive children presenting with poorly-defined focal epilepsy (20 MRI- positive, 5 MRI-negative). Qualitative visual inspection and quantitative analysis with asymmetry and Z-score maps were used to detect perfusion abnormalities. ASL results were compared to the hypothesized epileptogenic zone (EZ) derived from other clinical/imaging data and the resection zone in patients with Engel I/II outcome and >18 month follow-up. Results: Qualitative analysis revealed perfusion abnormalities in 17/25 total cases (68%), 17/20 MRI-positive cases (85%) and none of the MRI-negative cases. Quantitative analysis confirmed all cases with abnormalities on qualitative analysis, but found 1 additional true-positive and 4 false-positives. Concordance with the surgically-proven EZ was found in 10/11 cases qualitatively (sensitivity=91%, specificity=50%), and 11/11 cases quantitatively (sensitivity=100%, specificity=23%). Conclusions: ASL perfusion may support the hypothesized EZ, but has limited localization benefit in MRI-negative cases. Nevertheless, owing to its non-invasiveness and ease of acquisition, ASL could be a useful addition to the pre-surgical MRI evaluation of pediatric focal epilepsy.