You've Got E-Mail: A Pilot Study Examining the Feasibility and Impact of a Group-Based Technology-Training Intervention Among Older Adults Living in Residential Care.

Older adults living in residential care often experience challenges in sustaining meaningful social relationships, which can result in compromised health and well-being. Online social networking has the potential to mitigate this problem, but few studies have investigated its implementation and its effectiveness in maintaining or enhancing well-being. This pilot study used a cluster-randomized pre-post design to examine the feasibility of implementing a 12-week group-based technology-training intervention for older adults (n = 48) living in residential care by exploring how cognitive health, mental health, and confidence in technology were impacted. Analysis of variance revealed significant increases in life satisfaction, positive attitudes toward computer use, and self-perceived competence among participants who received the intervention, but increased depressive symptoms for the control group. These findings suggest that, despite challenges in implementing the intervention in residential care, group-based technology training may enhance confidence among older adults while maintaining or enhancing mental health.

Say you'll be there: Associations between observed verbal responses, friendship quality, and perceptions of support in young adult friendships.

Friendships are a primary source of social support during young adulthood; however, little is known about the factors associated with young adults feeling greater support during interactions with friends. We examined how micro-level verbal responses and macro-level judgments of friendship quality were associated with perceptions of support following an interaction between friends. Same-gender friend dyads (N = 132; 66.2% female; 18-24 years, M age = 19.63) took turns speaking about a problem, then participants rated their perceptions of support given and received following the task. We coded each participant's verbal responses while in the listening role. Actor Partner Interdependence Models (APIMs) revealed significant partner effects for negative engagement responses, such that greater negative engagement responses were linked with the partner perceiving poorer support both given and received. Models revealed significant actor effects for supportive responses, such that greater supportive responses predicted the actor perceiving better support both given and received. Additionally, models revealed significant actor effects of friendship quality predicting actors' perceiving better support both given and received. Finally, exploratory models revealed minimal interactions between a few types of verbal responses and positive friendship quality. Taken together, results suggest that (a) negative verbal responding styles may be more meaningfully associated with partners' perceptions of support in the moment than are supportive behaviours, whereas (b) supportive verbal responding styles may be more meaningfully associated with actors' perceptions of support in the moment, and (c) actors' judgments of friendship quality are strongly associated with their overall perceptions of support, and a critical factor to consider in future research.

Lipid emulsion therapy during management of the critically-ill poisoned patient: a prospective cohort study.

BACKGROUND: Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity. METHODS: We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration. RESULTS: We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis (P = 0.89) or polynomial model (P = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration. CONCLUSION: Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.

Optimization of non-endorectal prostate MR image quality using PI-QUAL: A multidisciplinary team approach.

PURPOSE: To evaluate the utility of the PI-QUAL score in assessing protocol changes aimed to improve image quality from a non-endorectal coil prostate MR imaging protocol during a 9-month quality improvement (QI) project and to quantify the inter-reader agreement of PI-QUAL scores between radiologists, technologists, and physicists. METHODS: This retrospective study audited 1,012 multiparametric prostate MRI examinations as part of a national QI project according to the PI-QUAL standard. PI-QUAL scores were used to inform MR protocol changes. Following the project, 4 radiologists, 2 technologists, and 1 medical physicist collectively audited an additional set of 150 examinations to identify statistical improvements in image quality using the two-tailed Wilcoxon rank sum test. The improvements due to individual protocol changes were assessed among subsets of the 1,012 examinations which compared examinations occurring before and after the isolated protocol change. Inter-reader variability was assessed using the percent majority agreement and the average standard deviation of PI-QUAL scores between evaluators. RESULTS: During this QI project, PI-QUAL scores improved from 3.67 ± 0.75 to 4.16 ± 0.59 (p < 0.01) after implementing a series of protocol changes. Among a subset of 451 cases, we found that adopting R/L rather than A/P phase encoding reduced distortion in diffusion-weighted imaging (DW) from 21.6% (41/190 A/P phase encoded cases) to 11.5% (30/261 R/L phase encoded cases) (p < 0.01). Similarly, in the same 451 cases, adopting R/L phase encoding in T2WI reduced breathing motion artifacts from 34.6% (94/272 A/P phase encoding cases) to 12.8% (23/179 R/L phase encoding cases) (p < 0.01). DWI wraparound artifact was mitigated by employing a full-pelvis shim and enabling the abdomen shim option. The occurrence of low signal-to-noise ratio was reduced from 19.4% (19/98 cases without a weight-based threshold) to 6.3% (10/160) by instituting a weight-based threshold for using an endorectal coil (p < 0.01). The percent majority agreement was similar between radiologists, technologists and physicists, and all evaluators combined (72%, 77%, and 67%, respectively). CONCLUSIONS: PI-QUAL can evaluate image quality changes resulting from protocol optimizations at both the exam- and series-levels. With training, radiologists, technologists, and physicists can perform PI-QUAL scoring with similar performance. Broadening the scope of the quality improvement team can result in meaningful and lasting change.

Variations in signal-to-noise characteristics of tissue-equivalent attenuators for mammographic automatic exposure control system performance evaluation.

PURPOSE: This work investigates the impact of tissue-equivalent attenuator choice on measured signal-to-noise ratio (SNR) for automatic exposure control (AEC) performance evaluation in digital mammography. It also investigates how the SNR changes for each material when used to evaluate AEC performance across different mammography systems. METHODS: AEC performance was evaluated for four mammography systems using seven attenuator sets at two thicknesses (4 and 8 cm). All systems were evaluated in 2D imaging mode, and one system was evaluated in digital breast tomosynthesis (DBT) mode. The methodology followed the 2018 ACR digital mammography quality control (DMQC) manual. Each system-attenuator-thickness combination was evaluated using For Processing images in ImageJ with standard ROI size and location. The closest annual physicist testing results were used to explore the impact of varying measured AEC performance on image quality. RESULTS: The measured SNR varied by 44%-54% within each system across all attenuators at 4 cm thickness in 2D mode. The variation appeared to be largely due to changes in measured noise, with variations of 46%-67% within each system across all attenuators at 4 cm thickness in 2D mode. Two systems had failing SNR levels for two of the materials using the minimum SNR criterion specified in the ACR DMQC manual. Similar trends were seen in DBT mode and at 8 cm thickness. Within each material, there was 115%-131% variation at 4 cm and 82%-114% variation at 8 cm in the measured SNR across the four imaging systems. Variation in SNR did not correlate with system operating level based on visual image quality and average glandular dose (AGD). CONCLUSION: Choice of tissue-equivalent attenuator for AEC performance evaluation affects measured SNR values. Depending on the material, the difference may be enough to result in failure following the longitudinal and absolute thresholds specified in the ACR DMQC manual.

Comparative-effectiveness research of COVID-19 treatment: a rapid scoping review.

OBJECTIVES: The COVID-19 pandemic has stimulated growing research on treatment options. We aim to provide an overview of the characteristics of studies evaluating COVID-19 treatment. DESIGN: Rapid scoping review DATA SOURCES: Medline, Embase and biorxiv/medrxiv from inception to 15 May 2021. SETTING: Hospital and community care. PARTICIPANTS: COVID-19 patients of all ages. INTERVENTIONS: COVID-19 treatment. RESULTS: The literature search identified 616 relevant primary studies of which 188 were randomised controlled trials and 299 relevant evidence syntheses. The studies and evidence syntheses were conducted in 51 and 39 countries, respectively.Most studies enrolled patients admitted to acute care hospitals (84%), included on average 169 participants, with an average age of 60 years, study duration of 28 days, number of effect outcomes of four and number of harm outcomes of one. The most common primary outcome was death (32%).The included studies evaluated 214 treatment options. The most common treatments were tocilizumab (11%), hydroxychloroquine (9%) and convalescent plasma (7%). The most common therapeutic categories were non-steroidal immunosuppressants (18%), steroids (15%) and antivirals (14%). The most common therapeutic categories involving multiple drugs were antimalarials/antibiotics (16%), steroids/non-steroidal immunosuppressants (9%) and antimalarials/antivirals/antivirals (7%). The most common treatments evaluated in systematic reviews were hydroxychloroquine (11%), remdesivir (8%), tocilizumab (7%) and steroids (7%).The evaluated treatment was in favour 50% and 36% of the evaluations, according to the conclusion of the authors of primary studies and evidence syntheses, respectively. CONCLUSIONS: This rapid scoping review characterised a growing body of comparative-effectiveness primary studies and evidence syntheses. The results suggest future studies should focus on children, elderly ≥65 years of age, patients with mild symptoms, outpatient treatment, multimechanism therapies, harms and active comparators. The results also suggest that future living evidence synthesis and network meta-analysis would provide additional information for decision-makers on managing COVID-19.

Proton density water fraction as a reproducible MR-based measurement of breast density.

PURPOSE: To introduce proton density water fraction (PDWF) as a confounder-corrected (CC) MR-based biomarker of mammographic breast density, a known risk factor for breast cancer. METHODS: Chemical shift encoded (CSE) MR images were acquired using a low flip angle to provide proton density contrast from multiple echo times. Fat and water images, corrected for known biases, were produced by a six-echo CC CSE-MRI algorithm. Fibroglandular tissue (FGT) volume was calculated from whole-breast segmented PDWF maps at 1.5T and 3T. The method was evaluated in (1) a physical fat-water phantom and (2) normal volunteers. Results from two- and three-echo CSE-MRI methods were included for comparison. RESULTS: Six-echo CC-CSE-MRI produced unbiased estimates of the total water volume in the phantom (mean bias 3.3%) and was reproducible across protocol changes (repeatability coefficient [RC] = 14.8 cm3 and 13.97 cm3 at 1.5T and 3.0T, respectively) and field strengths (RC = 51.7 cm3 ) in volunteers, while the two- and three-echo CSE-MRI approaches produced biased results in phantoms (mean bias 30.7% and 10.4%) that was less reproducible across field strengths in volunteers (RC = 82.3 cm3 and 126.3 cm3 ). Significant differences in measured FGT volume were found between the six-echo CC-CSE-MRI and the two- and three-echo CSE-MRI approaches (p = 0.002 and p = 0.001, respectively). CONCLUSION: The use of six-echo CC-CSE-MRI to create unbiased PDWF maps that reproducibly quantify FGT in the breast is demonstrated. Further studies are needed to correlate this quantitative MR biomarker for breast density with mammography and overall risk for breast cancer.

Anti-vascular endothelial growth factor therapy for age-related macular degeneration: a systematic review and network meta-analysis.

BACKGROUND: The comparative safety and efficacy between anti-vascular endothelial growth factor agents (anti-VEGFs) and between combined therapies for patients with neovascular age-related macular degeneration (nAMD) is unclear. We conducted a systematic review to examine the comparative safety and efficacy anti-VEGFs for adults with nAMD. METHODS: Studies were identified through MEDLINE, EMBASE, and Cochrane CENTRAL (inception to June 3, 2019), grey literature, and scanning reference lists. Two reviewers independently screened citations and full-text articles to identify randomized controlled trials (RCTs), extracted data, and appraised risk of bias. Pairwise random-effects meta-analysis and Bayesian network meta-analysis (NMA) were conducted. The primary outcomes were the proportion of patients experiencing moderate vision gain (≥ 15 letters on the Early Treatment Diabetic Retinopathy Study chart) and the proportion of patients experiencing moderate vision loss (≤ 15 letters). RESULTS: After screening 3647 citations and 485 potentially relevant full-text articles, 92 RCTs with 24,717 patients were included. NMA (34 RCTs, 8809 patients, 12 treatments) showed small differences among anti-VEGFs in improving the proportion of patients with moderate vision gain, with the largest for conbercept versus broluczumab (OR 0.15, 95% CrI: 0.05-0.56), conbercept versus ranibizumab (OR 0.17, 95% CrI: 0.05-0.59), conbercept versus aflibercept (OR 0.19, 95% CrI: 0.06-0.65), and conbercept versus bevacizumab (OR 0.2, 95% CrI: 0.06-0.69). In NMA (36 RCTs, 9081 patients, 13 treatments) for the proportion of patients with moderate vision loss, small differences were observed among anti-VEGFs, with the largest being for conbercept versus aflibercept (OR 0.24, 95% CrI: 0-4.29), conbercept versus brolucizumab (OR 0.24, 95% CrI: 0-4.71), conbercept versus bevacizumab (OR 0.26, 95% CrI: 0-4.65), and conbercept versus ranibizumab (OR 0.27, 95% CrI: 0-4.67). CONCLUSION: The only observed differences were that ranibizumab, bevacizumab, aflibercept, and brolucizumab were statistically superior to conbercept in terms of the proportion of patients with nAMD who experienced moderate vision gain. However, this finding is based on indirect evidence through one small trial comparing conbercept with placebo. This does not account for drug-specific differences when assessing anatomic and functional treatment efficacy in variable dosing regimens. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42015022041.

Permafrost carbon feedbacks threaten global climate goals.

Rapid Arctic warming has intensified northern wildfires and is thawing carbon-rich permafrost. Carbon emissions from permafrost thaw and Arctic wildfires, which are not fully accounted for in global emissions budgets, will greatly reduce the amount of greenhouse gases that humans can emit to remain below 1.5 °C or 2 °C. The Paris Agreement provides ongoing opportunities to increase ambition to reduce society's greenhouse gas emissions, which will also reduce emissions from thawing permafrost. In December 2020, more than 70 countries announced more ambitious nationally determined contributions as part of their Paris Agreement commitments; however, the carbon budgets that informed these commitments were incomplete, as they do not fully account for Arctic feedbacks. There is an urgent need to incorporate the latest science on carbon emissions from permafrost thaw and northern wildfires into international consideration of how much more aggressively societal emissions must be reduced to address the global climate crisis.

Hyperpolarized 13C Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic Potential.

This study uses dynamic hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopic imaging (MRSI) to estimate differences in glycolytic metabolism between highly metastatic (4T1, n = 7) and metastatically dormant (4T07, n = 7) murine breast cancer models. The apparent conversion rate of pyruvate-to-lactate (kPL) and lactate-to-pyruvate area-under-the-curve ratio (AUCL/P) were estimated from the metabolite images and compared with biochemical metabolic measures and immunohistochemistry (IHC). A non-significant trend of increasing kPL (p = 0.17) and AUCL/P (p = 0.11) from 4T07 to 4T1 tumors was observed. No significant differences in tumor IHC lactate dehydrogenase-A (LDHA), monocarboxylate transporter-1 (MCT1), cluster of differentiation 31 (CD31), and hypoxia inducible factor-α (HIF-1α), tumor lactate-dehydrogenase (LDH) activity, or blood lactate or glucose levels were found between the two tumor lines. However, AUCL/P was significantly correlated with tumor LDH activity (ρspearman = 0.621, p = 0.027) and blood glucose levels (ρspearman = -0.474, p = 0.042). kPL displayed a similar, non-significant trend for LDH activity (ρspearman = 0.480, p = 0.114) and blood glucose levels (ρspearman = -0.414, p = 0.088). Neither kPL nor AUCL/P were significantly correlated with blood lactate levels or tumor LDHA or MCT1. The significant positive correlation between AUCL/P and tumor LDH activity indicates the potential of AUCL/P as a biomarker of glycolytic metabolism in breast cancer models. However, the lack of a significant difference between in vivo tumor metabolism for the two models suggest similar pyruvate-to-lactate conversion despite differing metastatic potential.

Peer Information and Substance Use Decision Making in Street-Involved Youth.

In the context of adolescent substance use, peers are a primary source of both influence and information. Substance-related peer information sharing is a relatively understudied phenomenon, particularly in street-involved youth. We recruited 84 youth from a community drop-in center to complete a survey assessing substance use and peer influence on drug use. A subset of youth completed a semi-structured interview assessing factors related to peer information sharing around drug use. Results showed that peer influence was highly relevant to drug use patterns in street-involved youth. Trust in the person supplying information, personal and peer experience, and salience of information played important roles in youths' assessments of drug-related information exchanged with peers. Implications for improving community information dissemination strategies are discussed.

Oxycodone, Hydromorphone, and the Risk of Suicide: A Retrospective Population-Based Case-Control Study.

INTRODUCTION: Opioids have been increasingly associated with suicide, but whether they are independent contributors is unclear. Oxycodone and hydromorphone are commonly prescribed high-potency opioids that can differentially affect mood. OBJECTIVE: The objective of this study was to explore whether oxycodone and hydromorphone are differentially associated with suicide. METHODS: We conducted a retrospective population-based case-control study in Ontario, Canada, from 1992 to 2014. Using coronial data, we defined case subjects as individuals who died by suicide involving an opioid overdose. Each of these was matched with up to four controls who died of accidental opioid overdose. We ascertained exposure to oxycodone, hydromorphone, and other opioids from postmortem toxicology testing. We used odds ratios and 95% confidence intervals to examine whether opioid-related suicide was disproportionately associated with oxycodone relative to hydromorphone. RESULTS: We identified 438 suicides and 1212 accidental deaths, each of which involved either oxycodone or hydromorphone but not both. The median age at death was 49 years and 51% were men. After adjusting for a history of self-harm, psychiatric illness, and exposure to other opioids, we found that oxycodone was more strongly associated with suicide than hydromorphone (adjusted odds ratio 1.59; 95% confidence interval 1.20-2.11). In a secondary analysis, we observed a trend of similar magnitude in which combined exposure to oxycodone and hydromorphone was more strongly associated with suicide than hydromorphone alone (adjusted odds ratio 1.68; 95% confidence interval 0.92-3.09). CONCLUSIONS: While preliminary, these findings support the possibility that some high-potency opioids might independently influence the risk of suicide in susceptible individuals.

Measuring the link between cardiac mechanical function and metabolism during hyperpolarized 13C-pyruvate magnetic resonance experiments.

PURPOSE: The goal of this study was to develop a methodology to investigate the relationship between contractile function and hyperpolarized (HP) [1-13C]pyruvate metabolism in a small animal model. To achieve sufficient signal from HP 13C compounds, HP 13C MRS/MRSI has required relatively large infusion volumes relative to the total blood volume in small animal models, which may affect cardiac function. METHODS: Eight female Sprague Dawley rats were imaged on a 4.7T scanner with a dual tuned 1H/13C volume coil. ECG and respiratory gated k-t spiral MRSI and an IDEAL based reconstruction to determine [1-13C]pyruvate metabolism in the myocardium. This was coupled with 1H cine MRI to determine ventricular volumes and mechanical function pre- and post-infusion of [1-13C]pyruvate. For comparison to the [1-13C]pyruvate experiments, three female Sprague Dawley rats were imaged with 1H cine MRI to determine myocardial function pre- and post-saline infusion. RESULTS: We demonstrated significant changes in cardiac contractile function between pre- and post-infusion of [1-13C]pyruvate. Specifically, there was an increase in end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF). Additionally, the ventricular vascular coupling ratio (VVCR) showed an improvement after [1-13C]pyruvate infusion, indicating increased systolic performance due to an increased arterial load. There was a moderate to strong relationship between the downstream metabolic conversion of pyruvate to bicarbonate and a strong relationship between the conversion of pyruvate to lactate and the cardiac mechanical function response. CONCLUSION: The infusion of [1-13C]pyruvate resulted in demonstrable increases in contractile function which was related to pyruvate conversion to bicarbonate and lactate. The combined effects of the infusion volume and inotropic effects of pyruvate metabolism likely explains the augmentation in myocardial mechanical function seen in these experiments. Given the relationship between pyruvate metabolism and contractile function observed in this study, this methodological approach may be utilized to better understand cardiac metabolic and functional remodeling in heart disease.

Does left ventricular hypertrophy by electrocardiogram predict adverse outcomes in pregnancies with chronic hypertension?

Objectives: The American College of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy recommends assessing left ventricular function with echocardiogram or electrocardiogram (ECG) in women with severe hypertension of long duration. We aim to compare the rates of superimposed preeclampsia (SIP) and other obstetrical outcomes in pregnancies with chronic hypertension (CHTN) and left ventricular hypertrophy (LVH) by ECG criteria with mothers without LVH.Study design: After IRB approval, we performed a retrospective chart review from January 2015 to December 2016. Singleton pregnancies with CHTN who carried the pregnancy beyond 20 weeks and planned to deliver at our institution were included for analysis. Patients with insufficient data, multiple gestations, and those with systemic lupus erythematosus were excluded from this study. Rates of SIP and other obstetrical outcomes were compared among those with LVH and those without LVH. Univariate parametric and nonparametric statistical models were applied as appropriate. Associations were considered statistically significant at an alpha level of 0.05.Results: We included 218 pregnancies. Nineteen (8.7%) had LVH. The rate of SIP was higher in pregnancies with LVH than in those without it (68 versus 41%; OR = 3.01; 95% CI 1.1-8.5; p = .022). The birthweight was lower in the LVH group (2432 g [2120-2990] versus 2870 g [2430-3440]; p = .016). Other obstetrical outcomes were not significantly different between those patients with LVH and those without.Conclusions: LVH by ECG criteria may be associated with higher rates of SIP and with lower birthweight in pregnancies with CHTN. ECG may be a cost-effective tool to identify patients with CHTN at risk of adverse outcomes. Larger trials are necessary to corroborate our findings.

Improved reconstruction stability for chemical shift encoded hyperpolarized 13 C magnetic resonance spectroscopic imaging using k-t spiral acquisitions.

PURPOSE: A multiecho, field of view (FOV)-oversampled k-t spiral acquisition and direct iterative decomposition of water and fat with echo asymmetry and least-squares estimation reconstruction is demonstrated to improve the stability of hyperpolarized 13 C magnetic resonance spectroscopic imaging (MRSI) in the presence of signal ambiguities attributed to low-SNR (signal-to-noise-ratio) species, local uncertainties in metabolite peaks, and echo-to-echo signal inconsistencies. THEORY: k-t spiral acquisitions redistribute readout points to be more densely spaced radially in k-space by acquiring an FOV and matrix that are oversampled by η. These more densely spaced spiral turns constitute effective intraspiral echoes and can supplement conventional interspiral echoes to improve spectral separation and reduce spectral cross-talk to better resolve 13 C-labeled species for spectroscopic imaging. METHODS: Digital simulations and imaging phantom experiments were performed for a range of interspiral echo spacings and η using multiecho, k-t spiral acquisitions. Image spectral cross-talk artifacts were evaluated both qualitatively and quantitatively as the percent error in measured metabolite ratios. In vivo murine experiments evaluated the feasibility of multiecho, k-t spiral [1-13 C]pyruvate MRSI to reduce spectral cross-talk for 3 scenarios of different expected reconstruction stability. RESULTS: Digital simulations and imaging phantom experiments both demonstrated reduced or comparable image spectral cross-talk and percent errors in measured metabolite ratios with increasing η and better choices of echo spacings. In vivo images displayed markedly reduced spectral cross-talk in lactate images acquired with η = 7 versus η = 1. CONCLUSION: The precision of hyperpolarized 13 C metabolic imaging and quantification in the presence of low-SNR species, local uncertainties in metabolite resonances, and echo-to-echo signal inconsistencies can be improved with the use of FOV-oversampled k-t spiral acquisitions.

Trends of intentional drug overdose among youth: a population-based cohort study.

Background: Intentional overdose is the commonest form of self-harm in adolescents globally. We explored temporal trends in intentional overdose among youth.Methods: Using multiple linked healthcare databases, we conducted a population-based cohort study in Ontario, Canada, from 2002 to 2015. We included all patients aged 8 to 19 years who presented to an emergency department (ED) or were hospitalized for intentional overdose, stratifying by age and agent(s) consumed. We determined the annual rate of intentional overdose over time. For context, we contrasted these data against the annual rate of select unintentional injuries (laceration of face or scalp, upper extremity fracture, and accidental burn) in the same group over the same period.Results: We identified 31,419 unique intentional overdose events in youth, with a striking U-shaped trend apparent over the study period. From 2002 to 2010, hospital presentations for intentional overdose gradually declined. However, from 2010 to 2015, ED visits increased by 75% and hospital admissions doubled. The sharpest increases were observed in adolescents aged 14 to 17 years, and the most commonly implicated substances were acetaminophen, antidepressants and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Over the study period, intentional overdoses involving antidepressants nearly doubled and those involving acetaminophen increased by 50%. In contrast, we observed steady and sustained declines in rates of hospital care for unintentional injuries in the same population over the same period.Conclusions: Since 2010, intentional overdoses have increased among youth, while other forms of unintentional injury have continued to decline. Further research is needed to understand the reasons for the unexpected rise in intentional overdose in adolescents, and strategies developed to mitigate this phenomenon.

Depression and ADHD-Related Risk for Substance Use in Adolescence and Early Adulthood: Concurrent and Prospective Associations in the MTA.

Childhood attention-deficit/hyperactivity disorder (ADHD) is prospectively linked to substance use and disorder. Depression emerging in adolescence is an understudied risk factor that may explain some of this risk. In the present study, we considered mediating and moderating roles of adolescent depression in explaining this association by using longitudinal data from the prospective 16-year follow-up of the Multimodal Treatment Study of ADHD (MTA). Participants were 547 children diagnosed with DSM-IV ADHD Combined Type, and 258 age- and sex-matched comparison children. In adolescence, depressive symptoms did not exacerbate effects of childhood ADHD on any substance use. For both groups, time-varying and average depressive symptoms were associated with more frequent use of all substances. Prospectively, we found no evidence of depression mediation to adult substance use. However, adolescent depression moderated the association between childhood ADHD and adult marijuana use. Although adults without ADHD histories used marijuana more frequently if they had elevated depressive symptoms in adolescence, marijuana use by adults with ADHD histories was independent of their adolescent depression. In adulthood, depression diagnoses and ADHD persistence continued to operate as independent, additive correlates of substance use risk. Our findings suggest a circumscribed role for depression in substance use risk that adds to, but does not alter or explain, ADHD-related risk.

Anti-vascular endothelial growth factor treatment for retinal conditions: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the comparative effectiveness and safety of intravitreal bevacizumab, ranibizumab and aflibercept for patients with choroidal neovascular age-related macular degeneration (cn-AMD), diabetic macular oedema (DMO), macular oedema due to retinal vein occlusion (RVO-MO) and myopic choroidal neovascularisation (m-CNV). DESIGN: Systematic review and random-effects meta-analysis. METHODS: Multiple databases were searched from inception to 17 August 2017. Eligible head-to-head randomised controlled trials (RCTs) comparing the (anti-VEGF) drugs in adult patients aged ≥18 years with the retinal conditions of interest. Two reviewers independently screened studies, extracted data and assessed risk of bias. RESULTS: 19 RCTs involving 7459 patients with cn-AMD (n=12), DMO (n=3), RVO-MO (n=2) and m-CNV (n=2) were included. Vision gain was not significantly different in patients with cn-AMD, DMO, RVO-MO and m-CNV treated with bevacizumab versus ranibizumab. Similarly, vision gain was not significantly different between cn-AMD patients treated with aflibercept versus ranibizumab. Patients with DMO treated with aflibercept experienced significantly higher vision gain at 12 months than patients receiving ranibizumab or bevacizumab; however, this difference was not significant at 24 months. Rates of systemic serious harms were similar across anti-VEGF agents. Posthoc analyses revealed that an as-needed treatment regimen (6-9 injections per year) was associated with a mortality increase of 1.8% (risk ratio: 2.0 [1.2 to 3.5], 2 RCTs, 1795 patients) compared with monthly treatment in cn-AMD patients. CONCLUSIONS: Intravitreal bevacizumab was a reasonable alternative to ranibizumab and aflibercept in patients with cn-AMD, DMO, RVO-MO and m-CNV. The only exception was for patients with DME and low visual acuity (<69 early treatment diabetic retinopathy study [ETDRS] letters), where treatment with aflibercept was associated with significantly higher vision gain (≥15 ETDRS letters) than bevacizumab or ranibizumab at 12 months; but the significant effects were not maintained at 24 months. The choice of anti-VEGF drugs may depend on the specific retinal condition, baseline visual acuity and treatment regimen. PROSPERO REGISTRATION NUMBER: CRD42015022041.

A novel bioreactor for combined magnetic resonance spectroscopy and optical imaging of metabolism in 3D cell cultures.

PURPOSE: Fluorescence lifetime imaging microscopy (FLIM) of endogenous fluorescent metabolites permits the measurement of cellular metabolism in cell, tissue and animal models. In parallel, magnetic resonance spectroscopy (MRS) of dynamic nuclear (hyper)polarized (DNP) 13 C-pyruvate enables measurement of metabolism at larger in vivo scales. Presented here are the design and initial application of a bioreactor that connects these 2 metabolic imaging modalities in vitro, using 3D cell cultures. METHODS: The model fitting for FLIM data analysis and the theory behind a model for the diffusion of pyruvate into a collagen gel are detailed. The device is MRI-compatible, including an optical window, a temperature control system and an injection port for the introduction of contrast agents. Three-dimensional printing, computer numerical control machining and laser cutting were used to fabricate custom parts. RESULTS: Performance of the bioreactor is demonstrated for 4 T1 murine breast cancer cells under glucose deprivation. Mean nicotinamide adenine dinucleotide (NADH) fluorescence lifetimes were 10% longer and hyperpolarized 13 C lactate:pyruvate (Lac:Pyr) ratios were 60% lower for glucose-deprived 4 T1 cells compared to 4 T1 cells in normal medium. Looking at the individual components of the NADH fluorescent lifetime, τ1 (free NADH) showed no significant change, while τ2 (bound NADH) showed a significant increase, suggesting that the increase in mean lifetime was due to a change in bound NADH. CONCLUSION: A novel bioreactor that is compatible with, and can exploit the benefits of, both FLIM and 13 C MRS in 3D cell cultures for studies of cell metabolism has been designed and applied.

Second-generation anti-depressants and risk of new-onset seizures in the elderly.

BACKGROUND: Anti-depressants are among the most widely-prescribed medications. It is unknown whether the risk of seizure during therapeutic use differs by drug. We ranked the seizure risk of popular anti-depressants. METHODS: We conducted a population-based case-control study between April 2002 and March 2015 in Ontario, Canada. Cases were Ontario residents aged ≥65 years hospitalized for a first-ever seizure within 60 d of filling a prescription for one of nine second-generation anti-depressants, each dispensed more than 1 million times (range: 1,196,810 [fluvoxamine] to 19,849,930 [citalopram]) during the study period. For each case, we identified up to four seizure-free controls receiving a similar anti-depressant, and matched on age, sex, date and a pre-defined seizure-specific disease risk index. RESULTS: We identified 5701 patients hospitalized with a first-ever seizure and matched them with 21,872 controls. Relative to bupropion, the risk of new-onset seizure during therapeutic use was highest for escitalopram (adjusted odds ratio [OR] 1.79; 95% confidence interval [CI] 1.42-2.25) and citalopram (OR 1.67; 95% CI 1.35-2.07), while no incremental risk was found for fluoxetine (OR 1.02; 95%CI 0.78-1.33) and duloxetine (OR 0.94; 95%CI 0.75-1.22). Other anti-depressants were associated with modest increase in seizure risk. CONCLUSIONS: The risk of seizure during therapeutic use among elderly patients varies among second-generation anti-depressants. Escitalopram and citalopram are associated with the highest risk. Prescribers should consider the seizure risk of individual anti-depressants and use discretion when selecting an anti-depressant, especially for patients with other risk factors for seizure. Frontline clinicians should be cognizant of this differential risk.