Climate forcing controls on carbon terrestrial fluxes during shale weathering.

Climate influences near-surface biogeochemical processes and thereby determines the partitioning of carbon dioxide (CO2) in shale, and yet the controls on carbon (C) weathering fluxes remain poorly constrained. Using a dataset that characterizes biogeochemical responses to climate forcing in shale regolith, we implement a numerical model that describes the effects of water infiltration events, gas exchange, and temperature fluctuations on soil respiration and mineral weathering at a seasonal timescale. Our modeling approach allows us to quantitatively disentangle the controls of transient climate forcing and biogeochemical mechanisms on C partitioning. We find that ~3% of soil CO2 (1.02 mol C/m2/y) is exported to the subsurface during large infiltration events. Here, net atmospheric CO2 drawdown primarily occurs during spring snowmelt, governs the aqueous C exports (61%), and exceeds the CO2 flux generated by pyrite and petrogenic organic matter oxidation (~0.2 mol C/m2/y). We show that shale CO2 consumption results from the temporal coupling between soil microbial respiration and carbonate weathering. This coupling is driven by the impacts of hydrologic fluctuations on fresh organic matter availability and CO2 transport to the weathering front. Diffusion-limited transport of gases under transient hydrological conditions exerts an important control on CO2(g) egress patterns and thus must be considered when inferring soil CO2 drawdown from the gas phase composition. Our findings emphasize the importance of seasonal climate forcing in shaping the net contribution of shale weathering to terrestrial C fluxes and suggest that warmer conditions could reduce the potential for shale weathering to act as a CO2 sink.

Early Detection of Ventilator-associated Pneumonia From Exhaled Breath in Intensive Care Unit Patients.

OBJECTIVE: Evaluate associations between volatile organic compounds (VOCs) in heat and moisture exchange (HME) filters and the presence of ventilator-associated pneumonia (VAP). BACKGROUND: Clinical diagnostic criteria for VAP have poor interobserver reliability, and cultures are slow to result. Exhaled breath contains VOCs related to gram-negative bacterial proliferation, the most identified organisms in VAP. We hypothesized that exhaled VOCs on HME filters can predict nascent VAP in mechanically ventilated intensive care unit patients. METHODS: Gas chromatography-mass spectrometry was used to analyze 111 HME filters from 12 intubated patients who developed VAP. Identities and relative amounts of VOCs were associated with dates of clinical suspicion and culture confirmation of VAP. Matched pairs t tests were performed to compare VOC abundances in HME filters collected within 3 days pre and postclinical suspicion of VAP (pneumonia days), versus outside of these days (non-pneumonia days). A receiver operating characteristic curve was generated to determine the diagnostic potential of VOCs. RESULTS: Carbon disulfide, associated with the proliferation of certain gram-negative bacteria, was found in samples collected during pneumonia days for 11 of 12 patients. Carbon disulfide levels were significantly greater ( P = 0.0163) for filters on pneumonia days. The Area Under the Curve of the Reciever Operating Characteristic curve (AUC ROC) for carbon disulfide was 0.649 (95% CI: 0.419-0.88). CONCLUSIONS: Carbon disulfide associated with gram-negative VAP can be identified on HME filters up to 3 days before the initial clinical suspicion, and approximately a week before culture confirmation. This suggests VOC sensors may have potential as an adjunctive method for early detection of VAP.

Optimal Timing for Initiation of Thromboprophylaxis After Hepatic Angioembolization.

OBJECTIVE: To evaluate the optimal timing of thromboprophylaxis (TPX) initiation after hepatic angioembolization in trauma patients. BACKGROUND: TPX after hepatic trauma is complicated by the risk of bleeding, but the relative risk after hepatic angioembolization is unknown. METHODS: Patients who underwent hepatic angioembolization within 24 hours were retrospectively identified from the 2017 to 2019 American College of Surgeons Trauma Quality Improvement Project data sets. Cases with <24-hour length of stay and other serious injuries were excluded. Venous thromboembolism (VTE) included deep venous thrombosis and PE. Bleeding complications included hepatic surgery, additional angioembolization, or blood transfusion after TPX initiation. Differences were tested with univariate and multivariate analyses. RESULTS: Of 1550 patients, 1370 had initial angioembolization. Bleeding complications were higher in those with TPX initiation within 24 hours (20.0% vs 8.9%, P <0.001) and 48 hours (13.2% vs 8.4%, P =0.013). However, VTE was higher in those with TPX initiation after 48 hours (6.3% vs 3.3%, P =0.025). In the 180 patients with hepatic surgery before angioembolization, bleeding complications were higher in those with TPX initiation within 24 hours (72% vs 20%, P <0.001), 48 hours (50% vs 17%, P <0.001), and 72 hours (37% vs 14%, P =0.001). Moreover, deep venous thrombosis was higher in those with TPX initiation after 96 hours (14.3% vs 3.1%, P =0.023). CONCLUSIONS: This is the first study to address the timing of TPX after hepatic angioembolization in a national sample of trauma patients. For these patients, initiation of TPX at 48 to 72 hours achieves the safest balance in minimizing bleeding while reducing the risk of VTE. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Phosphorylation of cardiac sodium channel at Ser571 anticipates manifestations of the aging myopathy.

Diastolic dysfunction and delayed ventricular repolarization are typically observed in the elderly, but whether these defects are intimately associated with the progressive manifestation of the aging myopathy remains to be determined. In this regard, aging in experimental animals is coupled with increased late Na+ current (INa,L) in cardiomyocytes, raising the possibility that INa,L conditions the modality of electrical recovery and myocardial relaxation of the aged heart. For this purpose, aging male and female wild-type (WT) C57Bl/6 mice were studied together with genetically engineered mice with phosphomimetic (gain of function, GoF) or ablated (loss of function, LoF) mutations of the sodium channel Nav1.5 at Ser571 associated with, respectively, increased and stabilized INa,L. At ∼18 mo of age, WT mice developed prolonged duration of the QT interval of the electrocardiogram and impaired diastolic left ventricular (LV) filling, defects that were reversed by INa,L inhibition. Prolonged repolarization and impaired LV filling occurred prematurely in adult (∼5 mo) GoF mutant mice, whereas these alterations were largely attenuated in aging LoF mutant animals. Ca2+ transient decay and kinetics of myocyte shortening/relengthening were delayed in aged (∼24 mo) WT myocytes, with respect to adult cells. In contrast, delayed Ca2+ transients and contractile dynamics occurred at adult stage in GoF myocytes and further deteriorated in old age. Conversely, myocyte mechanics were minimally affected in aging LoF cells. Collectively, these results document that Nav1.5 phosphorylation at Ser571 and the late Na+ current modulate the modality of myocyte relaxation, constituting the mechanism linking delayed ventricular repolarization and diastolic dysfunction.NEW & NOTEWORTHY We have investigated the impact of the late Na current (INa,L) on cardiac and myocyte function with aging by using genetically engineered animals with enhanced or stabilized INa,L, due to phosphomimetic or phosphoablated mutations of Nav1.5. Our findings support the notion that phosphorylation of Nav1.5 at Ser571 prolongs myocardial repolarization and impairs diastolic function, contributing to the manifestations of the aging myopathy.

Survival of In-Hospital Cardiopulmonary Arrest in Trauma Patients.

INTRODUCTION: Relative to other hospitalized patients, trauma patients are younger with fewer comorbidities, but the incidence and outcomes of in-hospital cardiopulmonary arrest (IHCA) with cardiopulmonary resuscitation (CPR) in this population is unknown. Therefore, we aimed to investigate factors associated with survival in trauma patients after IHCA to test the hypothesis that compared to other hospitalized patients, trauma patients with IHCA have improved survival. METHODS: Retrospective review of the Trauma Quality Improvement Program database 2017 to 2019 for patients who had IHCA with CPR. Primary outcome was survival to hospital discharge. Secondary outcomes were in-hospital complications, hospital length of stay, intensive care unit length of stay, and ventilator days. Data were compared with univariate and multivariate analyses at P < 0.05. RESULTS: In 22,346,677 admitted trauma patients, 14,056 (0.6%) received CPR. Four thousand three hundred seventy-seven (31.1%) survived to discharge versus 26.4% in a national sample of all hospitalized patients (P < 0.001). In trauma patients, median age was 55 y, the majority were male (72.2%). Mortality was higher for females versus males (70.3% versus 68.3%, P = 0.026). Multivariate regression showed that older age 1.01 (95% confidence interval (CI) 1.01-1.02), Hispanic ethnicity 1.21 (95% CI 1.04-1.40), and penetrating trauma 1.51 (95% CI 1.32-1.72) were risk factors for mortality, while White race was a protective factor 0.36 (95% CI 0.14-0.89). CONCLUSIONS: This is the first study to show that the incidence of IHCA with CPR is approximately six in 1000 trauma admissions and 31% survive to hospital discharge, which is higher than other hospitalized patients. Age, gender, racial, and ethnic disparities also influence survival.

Nationwide Analysis of Firearm Injury Versus Other Penetrating Trauma: It's Not All the Same Caliber.

INTRODUCTION: Ballistic injuries cause both a temporary and permanent cavitation event, making them far more destructive and complex than other penetrating trauma. We hypothesized that global injury scoring and physiologic parameters would fail to capture the lethality of gunshot wounds (GSW) compared to other penetrating mechanisms. METHODS: The 2019 American College of Surgeons Trauma Quality Programs participant use file was queried for the mortality rate for GSW and other penetrating mechanisms. A binomial logistic regression model ascertained the effects of sex, age, hypotension, tachycardia, mechanism, Glasgow Coma Scale, ISS, and volume of blood transfusion on the likelihood of mortality. Subgroup analyses examined isolated injuries by body regions. RESULTS: Among 95,458 cases (82% male), GSW comprised 46.4% of penetrating traumas. GSW was associated with longer hospital length of stay (4 [2-9] versus 3 [2-5] days), longer intensive care unit length of stay (3 [2-6] versus 2 [2-4] days), and more ventilator days (2 [1-4] versus 2 [1-3]) compared to stab wounds, all P < 0.001. The model determined that GSW was linked to increased odds of mortality compared to stab wounds (odds ratio 4.19, 95% confidence interval 3.55-4.93). GSW was an independent risk factor for acute kidney injury, acute respiratory distress syndrome, venous thromboembolism, sepsis, and surgical site infection. CONCLUSIONS: Injury scoring systems based on anatomical or physiological derangements fail to capture the lethality of GSW compared to other mechanisms of penetrating injury. Adjustments in risk stratification and reporting are necessary to reflect the proportion of GSW seen at each trauma center. Improved classification may help providers develop quality processes of care. This information may also help shape public discourse on this highly lethal mechanism.

Neorecovery: A Critical Analysis of the Relationship between Neoliberalism and the Recovery Movement.

"Neorecovery" is a portmanteau used to describe the distortions that neoliberalism engendered in the original recovery philosophy. I describe how neoliberalism as an economic model acted externally to the recovery movement to preclude opportunities to implement a wide range of innovative mental health approaches and to curtail safety net and social justice policies for persons with severe mental illness. In addition, I illustrate how the neoliberalism philosophy acted internally by inducing the recovery movement to adopt an individual-focused ethos that minimized the impact of broader social structures that affect well-being and opportunities for self-realization. Recovery's potentially radical transformative vision can only be achieved by seriously acknowledging the social and political structures that underlie the mental health system and their relationship to the broader society, and ultimately, altering them so that people experiencing severe mental illness can truly flourish.

The Relationships between Caregiver Burden, Physical Frailty, Race, Behavioral and Psychological Symptoms (BPSD), and Other Associated Variables: An Exploratory Study.

Background and Objectives: For persons with dementia, the relationships between caregiver burden, physical frailty, race, behavioral and psychological symptoms (BPSD), and other associated variables are poorly understood. Only one prior study examined the relationships among these variables but did not include race, which is an important social determinant of health outcomes in the United States. To examine these interactions, we conducted a cross-sectional exploratory study based on a model by Sugimoto and colleagues. Materials and Methods: The sample comprised 85 patient-caregiver dyads (58% White) seen in four centers in diverse regions of New York State. All patients met DSM5 criteria for a major neurocognitive disorder, had a Clinical Dementia Rating sum score of ≥3, and Mini-Mental State Examination (MMSE) score of 10 to 26. Other measures included the SHARE-Frailty Instrument(FI), the Neuropsychiatric Inventory (NPI) to assess BPSD, Zarit's Caregiver Burden Interview (CBI), Lawton's Activities of Daily Living (ADL) Scale, the MMSE, the Cumulative Illness Rating Scale for Geriatrics (CIRSG), age, and gender. Results: In our sample, 59% met the criteria for prefrail/subsyndromal or frail/syndromal (SSF) on the SHARE-FI. SSF had significant direct effects on the NPI and significant indirect effects on the CBI mediated through the NPI; the NPI had significant direct effects on the CBI. Race (White) had significant direct effects on the CBI (higher) and SSF (lower) but did not have significant indirect effects on the CBI. MMSE, ADL, and CIRSG were not significantly associated with the NPI or the CBI. Conclusions: Our analysis demonstrated that frailty, race, BPSD, and caregiver burden may directly or indirectly influence one another, and therefore should be considered essential elements of dementia assessment, care, and research. These results must be viewed as provisional and should be replicated longitudinally with larger samples.

Predictors of suicidal ideation severity among treatment-seeking young people with major depressive disorder: The role of state and trait anxiety.

OBJECTIVE: Depression and suicidal ideation are closely intertwined. Yet, among young people with depression, the specific factors that contribute to changes in suicidal ideation over time are uncertain. Factors other than depressive symptom severity, such as comorbid psychopathology and personality traits, might be important contributors. Our aim was to identify contributors to fluctuations in suicidal ideation severity over a 12-week period in young people with major depressive disorder receiving cognitive behavioural therapy. METHODS: Data were drawn from two 12-week randomised, placebo-controlled treatment trials. Participants (N = 283) were 15-25 years old, with moderate to severe major depressive disorder. The primary outcome measure was the Suicidal Ideation Questionnaire, administered at baseline and weeks 4, 8 and 12. A series of linear mixed models was conducted to examine the relationship between Suicidal Ideation Questionnaire score and demographic characteristics, comorbid psychopathology, personality traits and alcohol use. RESULTS: Depression and anxiety symptom severity, and trait anxiety, independently predicted higher suicidal ideation, after adjusting for the effects of time, demographics, affective instability, non-suicidal self-injury and alcohol use. CONCLUSIONS: Both state and trait anxiety are important longitudinal correlates of suicidal ideation in depressed young people receiving cognitive behavioural therapy, independent of depression severity. Reducing acute psychological distress, through reducing depression and anxiety symptom severity, is important, but interventions aimed at treating trait anxiety could also potentially be an effective intervention approach for suicidal ideation in young people with depression.

Examination of the Feasibility, Acceptability, and Efficacy of the Online Personalised Training in Memory Strategies for Everyday Program for Older Adults: Single-Arm Pre-Post Trial.

BACKGROUND: Memory strategy training for older adults helps maintain and improve cognitive health but is traditionally offered face-to-face, which is resource intensive, limits accessibility, and is challenging during a pandemic. Web-based interventions, such as the Online Personalised Training in Memory Strategies for Everyday (OPTIMiSE) program, may overcome such barriers. OBJECTIVE: We report on OPTIMiSE's feasibility, acceptability, and efficacy. METHODS: Australians aged ≥60 years reporting subjective cognitive decline participated in this single-arm pre-post web-based intervention. OPTIMiSE is a 6-module web-based program offered over 8-weeks with a 3-month booster. It has a problem-solving approach to memory issues, focusing on psychoeducation about memory and aging, knowledge and practice of compensatory memory strategies, and personalized content related to individual priorities. We examined the feasibility (recruitment, attrition, and data collection), acceptability (recommendation to others, suggestions for improvement, and withdrawal reasons), and efficacy (change in goal satisfaction, strategy knowledge and use, self-reported memory, memory satisfaction and knowledge, and mood; thematic content analysis of the most significant change; and the application of knowledge and strategies in daily life) of OPTIMiSE. RESULTS: OPTIMiSE was feasible, demonstrated by strong interest (633 individuals screened), a satisfactory level of attrition (158/312, 50.6%), and minimal missing data from those completing the intervention. It was acceptable, with 97.4% (150/154) of participants agreeing they would recommend OPTIMiSE, the main suggestion for improvement being more time to complete modules, and withdrawal reasons similar to those in in-person interventions. OPTIMiSE was also efficacious, with linear mixed-effects analyses revealing improvements, of moderate to large effect sizes, across all primary outcomes (all P<.001): memory goal satisfaction (Cohen d after course=1.24; Cohen d at 3-month booster=1.64), strategy knowledge (Cohen d after course=0.67; Cohen d at 3-month booster=0.72) and use (Cohen d after course=0.79; Cohen d at 3-month booster=0.90), self-reported memory (Cohen d after course=0.80; Cohen d at 3-month booster=0.83), memory satisfaction (Cohen d after course=1.25; Cohen d at 3-month booster=1.29) and knowledge (Cohen d after course=0.96; Cohen d at 3-month booster=0.26), and mood (Cohen d after course=-0.35; nonsignificant Cohen d at booster). Furthermore, the most significant changes reported by participants (strategy use, improvements in daily life, reduced concern about memory, confidence and self-efficacy, and sharing and shame busting with others) reflected the course objectives and were consistent with themes arising from previous in-person interventions. At the 3-month booster, many participants reported continued implementation of knowledge and strategies in their daily lives. CONCLUSIONS: This feasible, acceptable, and efficacious web-based program has the potential to enable access to evidence-based memory interventions for older adults worldwide. Notably, the changes in knowledge, beliefs, and strategy use continued beyond the initial program. This is particularly important for supporting the growing number of older adults living with cognitive concerns. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620000979954; https://tinyurl.com/34cdantv. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3233/ADR-200251.

Social Networks and Residential Status in Community-Dwelling Older Adults With Schizophrenia: Compensation by Reconfiguration?

OBJECTIVE: To address the paucity of data on the structure and content of social networks of older adults with schizophrenia (OAS). METHODS: The OAS group comprised 249 persons aged 55 and older with early-onset schizophrenia living in supportive housing (SS; n = 151), independently (SI; n = 70), or with family (SF; n = 28). The community comparison (CC) group comprised 113 individuals. Social network analysis was used. Multinomial logistic regression with p ≤0.001 and p ≤0.05 was used for overall and pairwise comparisons, respectively. RESULTS: Each OAS subgroup had more total, nonkin, and formal linkages than the CC group. The SS and SI subgroups had fewer kin linkages than the CC group. The CC group had more confidants than the SS subgroup, more reliable linkages than the SS and SI subgroups, and more sustenance linkages than each of the OAS subgroups. Nearly everyone in the CC, SI, and SF subgroups had a confidant, a reliable contact, and a sustenance linkage; 33% of the SS subgroup had no confidants. The SS subgroup displayed more psychiatric symptoms than the SI and SF subgroups. There were no differences in loneliness or relationship satisfaction between the CC and the schizophrenia subgroups. CONCLUSION: Networks were expressed differentially across residential arrangements and differences may reflect dissimilarities in psychiatric functioning. OAS generally had ample levels of companionship and emotional and instrumental support, often comparable to their age peers. Whereas social networks typically decline at illness onset and may be predominantly family-focused, later life may be a time of network reconfiguration and reconstitution.

Global cognitive trajectory patterns in Alzheimer's disease.

OBJECTIVES: The literature on Alzheimer's disease (AD) provides little data about long-term cognitive course trajectories. We identify global cognitive outcome trajectories and associated predictor variables that may inform clinical research and care. DESIGN: Data derived from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set were used to examine the cognitive course of persons with possible or probable AD, a Mini-Mental State Examination (MMSE) of ≥10, and complete annual assessments for 5 years. SETTING: Thirty-six Alzheimer's Disease Research Centers. PARTICIPANTS: Four hundred and fourteen persons. MEASUREMENTS: We used a hybrid approach comprising qualitative analysis of MMSE trajectory graphs that were operationalized empirically and binary logistic regression analyses to assess 19 variables' associations with each trajectory. MMSE scores of ±3 points or greater were considered clinically meaningful. RESULTS: Five distinct cognitive trajectories were identified: fast decliners (32.6%), slow decliners (30.7%), zigzag stable (15.9%), stable (15.9%), and improvers (4.8%). The decliner groups had three subtypes: curvilinear, zigzag, and late decline. The fast decliners were associated with female gender, lower baseline MMSE scores, a shorter illness duration, or receiving a cognitive enhancer. An early MMSE decline of ≥3 points predicted a worse outcome. A higher rate of traumatic brain injury, the absence of an ApoE ϵ4 allele, and male gender were the strongest predictors of favorable outcomes. CONCLUSIONS: Our hybrid approach revealed five distinct cognitive trajectories and a variegated pattern within the decliners and stable/improvers that was more consistent with real-world clinical experience than prior statistically modeled studies. Future investigations need to determine the consistency of the distribution of these categories across settings.

Correlates of suicidality in young people with depressive disorders: A systematic review.

OBJECTIVE: Depression is one of the most prevalent and disabling mental health conditions among young people worldwide. The health and economic burdens associated with depressive illness are substantial. Suicide and depression are closely intertwined, yet a diagnosis of depression itself lacks predictive specificity for suicidal behaviour. To better inform suicide prevention and early intervention strategies for young people, improved identification of modifiable intervention targets is needed. The objective of this review was to identify clinical, psychosocial and biological correlates of suicidality in young people diagnosed with a broad range of unipolar and bipolar depressive disorders. METHOD: Systematic searches were conducted across MEDLINE, Embase and PsycINFO to identify studies of young people aged 15-25 years diagnosed with unipolar or bipolar depressive disorders. An assessment of suicidality was required for inclusion. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 and Synthesis Without Meta-analysis guidelines. RESULTS: We integrated findings from 71 studies including approximately 24,670 young people with clinically diagnosed depression. We identified 26 clinical, psychosocial and biological correlates of suicidality. Depression characteristics (type and severity), psychiatric comorbidity (particularly anxiety and substance use disorders) and neurological characteristics emerged as having the most evidence for being associated with suicidal outcomes. Our ability to pool data and conduct meaningful quantitative synthesis was hampered by substantial heterogeneity across studies and incomplete reporting; thus, meta-analysis was not possible. CONCLUSION: Findings of this review reinforce the notion that suicidality is a complex phenomenon arising from the interplay of multiple contributing factors. Our findings question the utility of considering a diagnosis of depression as a specific risk factor for suicidality in young people. Suicidality itself is transdiagnostic; adoption of a transdiagnostic approach to investigating its aetiology and treatment is perhaps warranted. Future research investigating specific symptoms, or symptom networks, might help to further our understanding of suicidality among young people experiencing mental illness.

Assessing Suicidal Ideation in Young People With Depression: Factor Structure of the Suicidal Ideation Questionnaire.

Evaluating suicidal ideation in young people seeking mental health treatment is an important component of clinical assessment and treatment planning. To reduce the burden of youth suicide, we need to improve our understanding of suicidal ideation, its underlying constructs, and how ideation translates into suicidal behaviour. Using exploratory factor analysis, we investigated the dimensionality of the Suicidal Ideation Questionnaire (SIQ) among 273 participants aged 15-25 with Major Depressive Disorder. Area under the receiver operating characteristic curve (AUROC) analysis was used to explore associations between latent factors and actual suicidal behaviour. Findings suggested that the SIQ assesses multiple factors underlying suicidal ideation. AUROC analyses demonstrated that latent factors relating to both active and passive suicidal ideation predicted past-month suicidal behaviour and suicide attempt. These findings contribute to an improved understanding of the complexities of suicidal ideation and relationships with suicidal behaviour in young people with depression.

New generation antidepressants for depression in children and adolescents: a network meta-analysis.

BACKGROUND: Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and physical and mental health and well-being. There is an association between major depressive disorder and suicidal ideation, suicide attempts, and suicide. Antidepressant medication is used in moderate to severe depression; there is now a range of newer generations of these medications. OBJECTIVES: To investigate, via network meta-analysis (NMA), the comparative effectiveness and safety of different newer generation antidepressants in children and adolescents with a diagnosed major depressive disorder (MDD) in terms of depression, functioning, suicide-related outcomes and other adverse outcomes. The impact of age, treatment duration, baseline severity, and pharmaceutical industry funding was investigated on clinician-rated depression (CDRS-R) and suicide-related outcomes. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews (CDSR)), together with Ovid Embase, MEDLINE and PsycINFO till March 2020. SELECTION CRITERIA: Randomised trials of six to 18 year olds of either sex and any ethnicity with clinically diagnosed major depressive disorder were included. Trials that compared the effectiveness of newer generation antidepressants with each other or with a placebo were included. Newer generation antidepressants included: selective serotonin reuptake inhibitors; selective norepinephrine reuptake inhibitors (SNRIs); norepinephrine reuptake inhibitors; norepinephrine dopamine reuptake inhibitors; norepinephrine dopamine disinhibitors (NDDIs); and tetracyclic antidepressants (TeCAs). DATA COLLECTION AND ANALYSIS: Two reviewers independently screened titles/abstracts and full texts, extracted data, and assessed risk of bias. We analysed dichotomous data as Odds Ratios (ORs), and continuous data as Mean Difference (MD) for the following outcomes: depression symptom severity (clinician rated), response or remission of depression symptoms, depression symptom severity (self-rated), functioning, suicide related outcomes and overall adverse outcomes. Random-effects network meta-analyses were conducted in a frequentist framework using multivariate meta-analysis. Certainty of evidence was assessed using Confidence in Network Meta-analysis (CINeMA). We used "informative statements" to standardise the interpretation and description of the results. MAIN RESULTS: Twenty-six studies were included. There were no data for the two primary outcomes (depressive disorder established via clinical diagnostic interview and suicide), therefore, the results comprise only secondary outcomes. Most antidepressants may be associated with a "small and unimportant" reduction in depression symptoms on the CDRS-R scale (range 17 to 113) compared with placebo (high certainty evidence: paroxetine: MD -1.43, 95% CI -3.90, 1.04; vilazodone: MD -0.84, 95% CI -3.03, 1.35; desvenlafaxine MD -0.07, 95% CI -3.51, 3.36; moderate certainty evidence: sertraline: MD -3.51, 95% CI -6.99, -0.04; fluoxetine: MD -2.84, 95% CI -4.12, -1.56; escitalopram: MD -2.62, 95% CI -5.29, 0.04; low certainty evidence: duloxetine: MD -2.70, 95% CI -5.03, -0.37; vortioxetine: MD 0.60, 95% CI -2.52, 3.72; very low certainty evidence for comparisons between other antidepressants and placebo). There were "small and unimportant" differences between most antidepressants in reduction of depression symptoms (high- or moderate-certainty evidence). Results were similar across other outcomes of benefit. In most studies risk of self-harm or suicide was an exclusion criterion for the study. Proportions of suicide-related outcomes were low for most included studies and 95% confidence intervals were wide for all comparisons. The evidence is very uncertain about the effects of mirtazapine (OR 0.50, 95% CI 0.03, 8.04), duloxetine (OR 1.15, 95% CI 0.72, 1.82), vilazodone (OR 1.01, 95% CI 0.68, 1.48), desvenlafaxine (OR 0.94, 95% CI 0.59, 1.52), citalopram (OR 1.72, 95% CI 0.76, 3.87) or vortioxetine (OR 1.58, 95% CI 0.29, 8.60) on suicide-related outcomes compared with placebo. There is low certainty evidence that escitalopram may "at least slightly" reduce odds of suicide-related outcomes compared with placebo (OR 0.89, 95% CI 0.43, 1.84). There is low certainty evidence that fluoxetine (OR 1.27, 95% CI 0.87, 1.86), paroxetine (OR 1.81, 95% CI 0.85, 3.86), sertraline (OR 3.03, 95% CI 0.60, 15.22), and venlafaxine (OR 13.84, 95% CI 1.79, 106.90) may "at least slightly" increase odds of suicide-related outcomes compared with placebo. There is moderate certainty evidence that venlafaxine probably results in an "at least slightly" increased odds of suicide-related outcomes compared with desvenlafaxine (OR 0.07, 95% CI 0.01, 0.56) and escitalopram (OR 0.06, 95% CI 0.01, 0.56). There was very low certainty evidence regarding other comparisons between antidepressants. AUTHORS' CONCLUSIONS: Overall, methodological shortcomings of the randomised trials make it difficult to interpret the findings with regard to the efficacy and safety of newer antidepressant medications. Findings suggest that most newer antidepressants may reduce depression symptoms in a small and unimportant way compared with placebo. Furthermore, there are likely to be small and unimportant differences in the reduction of depression symptoms between the majority of antidepressants. However, our findings reflect the average effects of the antidepressants, and given depression is a heterogeneous condition, some individuals may experience a greater response. Guideline developers and others making recommendations might therefore consider whether a recommendation for the use of newer generation antidepressants is warranted for some individuals in some circumstances. Our findings suggest sertraline, escitalopram, duloxetine, as well as fluoxetine (which is currently the only treatment recommended for first-line prescribing) could be considered as a first option. Children and adolescents considered at risk of suicide were frequently excluded from trials, so that we cannot be confident about the effects of these medications for these individuals. If an antidepressant is being considered for an individual, this should be done in consultation with the child/adolescent and their family/caregivers and it remains critical to ensure close monitoring of treatment effects and suicide-related outcomes (combined suicidal ideation and suicide attempt) in those treated with newer generation antidepressants, given findings that some of these medications may be associated with greater odds of these events. Consideration of psychotherapy, particularly cognitive behavioural therapy, as per guideline recommendations, remains important.

The utility of self-rated health in older adults with schizophrenia.

OBJECTIVES: Self-rated health is one of the most widely used measures in gerontology, but it has not been evaluated systematically in older adults with schizophrenia (OAS). Therefore, the aim of this study was to determine the utility of self-rated health in OAS by examining its influencing factors and contrasting these findings with a community comparison (CC) group. METHOD: We compared 249 community-dwelling persons aged 55 years and older having a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, diagnosis of schizophrenia arising before age 45 years with a demographically similar group of 113 older adults in the general community. Using a modified version of Ocampo's model of self-rated health, we identified 12 predictor variables within 5 dimensions. RESULTS: There were no significant differences in self-health ratings between the OAS and the CC groups. Six of the 12 variables in the model significantly correlated with self-rated health in both groups. In linear regression analysis, three variables were significantly associated with self-rated health in both groups: Center for Epidemiological Studies-Depression score, number of physical disorders, and perception of self-health versus others. Self-rated health assessment was not associated with positive or negative symptoms or lack of awareness of mental illness. CONCLUSION: There was a striking similarity in the factors influencing self-rated health in the two groups. The findings were consistent with results of previous gerontological studies that self-rated health reflects elements of psychiatric and physical well-being, as well as perceptions of their age peers. Our results support the use of self-rated health as a legitimate clinical and research measure in OAS.

Recovery and Recovering in Older Adults with Schizophrenia: A 5-Tier Model.

RATIONALE: There are little recent data on clinical recovery in older adults with schizophrenia. This exploratory study uses an empirically measurable construct to address this issue. METHODS: From an original sample of 248 community-dwelling persons aged 55 and over with early-onset schizophrenia spectrum disorder, a subsample of 102 persons was reassessed at a mean of 52 months. Clinical recovery required meeting criteria for its two components: clinical remission and community integration. RESULTS: Prospective analysis generated a 5-tier taxonomy of recovery in which 12% remained persistently in clinical recovery at both baseline and follow-up (Tier 1) and 18% never met criteria of clinical recovery (Tier 5). The remaining 70% exhibited a variety of components of clinical recovery at baseline and follow-up (Tiers 2, 3, and 4). CONCLUSION: The findings generated a dynamic picture of recovery, with most persons being in varying states of "recovering." The 5-tier taxonomy of recovery adumbrated potential treatment strategies for each tier.

Dissolved Carbonate and pH Control the Dissolution of Uranyl Phosphate Minerals in Flow-Through Porous Media.

Uranyl phosphate minerals represent an important secondary source of uranium release at contaminated sites. In flow-through column experiments with background porewater (BPW) of typical freshwater aquifer composition (pH 7.0, ∼0.2 mM total carbonate (TC)), dissolution of K-ankoleite (KUO2PO4·3H2O), Na-autunite (NaUO2PO4·3H2O), and Ca-autunite (Ca(UO2)2(PO4)2·6H2O) was controlled by mineral solubility at steady-state U release. Effluent concentrations indicated exchange with BPW cations, and postreaction characterization showed alteration of the initial mineral composition, changes in structure (decreased crystallinity, increased disorder, and distortion of U-P mineral sheets) and possible neoformation of phases of similar structure. Increasing the BPW pH and TC to 8.1-8.2 and 2.2-3.7 mM, respectively, resulted in mineral undersaturation and produced ca. 2 orders-of-magnitude higher U and P release without reaching steady state. Minerals incorporated less BPW cations into their structures compared to low carbonate BPW experiments but showed structural disorder and distortion. Faster dissolution rates were attributed to the formation of binary and ternary uranyl carbonate complexes that accelerate the rate-determining step of uranyl detachment from the uranyl-phosphate layered structure. Calculated dissolution rates (log Rs between -8.95 and -10.32 mol m-2 s-1), accounting for reaction and transport in porous media, were similar to dissolution rates of other classes of uranyl minerals. In undersaturated solutions, dissolution rates for uranyl phosphate, oxyhydroxide, and silicate minerals can be predicted within 1-2 orders-of-magnitude from pH ∼5-10 on the basis of pH/carbonate concentration.

A Longitudinal Study of Illness Awareness in Older Adults With Schizophrenia.

OBJECTIVE: Impaired insight is common in schizophrenia and may be affected by changes that occur with aging. There have been a few nonprospective investigations of insight in older adults with schizophrenia (OAS). This study examines the temporal fluctuations that occur with insight-defined as "awareness of mental illness" (dichotomized into presence or absence)-along with associated factors that influence illness awareness (IA) in OAS. METHODS: The sample consisted of 103 persons derived from an initial sample of 250 community-dwelling persons aged 55 and over with early-onset schizophrenia spectrum disorder. Mean follow-up was 53 months. We examined 27 potential predictor variables of IA along with 5 covariates in bivariate analysis. The significant variables were then examined using multiple regression analyses. RESULTS: 23% of persons transitioned between presence and absence of IA, 62% had persistent IA, and 15% never had IA. At baseline, fewer negative symptoms (blunted affect), higher cognitive functioning (conceptualization), younger age, higher educational levels, and more physical disorders were associated significantly with higher rates of IA at follow-up. Baseline IA did not predict any variables at follow-up. CONCLUSION: IA is often unstable in later life, with nearly one-fourth of persons showing fluctuations. Although younger age predicted IA over time, other factors associated with aging, such as cognitive functioning and physical disorders, had additional independent effects on IA. The impact of IA on clinical and functional variables attenuated over time, suggesting that for many OAS, IA may have a limited role in enhancing long-term outcomes.

Risk Factors and Clinical Outcomes Associated With Augmented Renal Clearance in Trauma Patients.

BACKGROUND: Augmented renal clearance (ARC; i.e., creatinine clearance [CLCr] ≥ 130 mL/min) has an incidence of 14%-80% in critically ill patients and has been associated with therapy failures for renally cleared drugs. However, the clinical implications of ARC are poorly defined. We hypothesize that modifiable risk factors that contribute to ARC can be identified in severely injured trauma patients and that these risk factors influence clinical outcome. METHODS: In 207 trauma intensive care unit patients, 24-h CLCr was correlated with clinical estimates of glomerular filtration rate (by Cockroft-Gault, modification of diet in renal disease, or chronic kidney disease epidemiology), and clinical outcomes (infection, venous thromboembolism [VTE], length of stay, and mortality). RESULTS: The population was 45 ± 20 y, 68% male, 77% blunt injury with injury severity score of 24 (17-30). Admission serum creatinine was 1.02 ± 0.35 mg/dL, CLCr was 154 ± 77 mL/min, VTE incidence was 15%, ARC incidence was 57%, and mortality was 11%. Clinical estimates of glomerular filtration rate by Cockroft-Gault, modification of diet in renal disease, chronic kidney disease epidemiology underestimated actual CLCr by 20%, 22%, or 15% (all P < 0.01). CLCr was higher in males and those who survived, and lower in those with hypertension, diabetes, positive cultures, receiving transfusions, or pressors (all P < 0.05). On multivariate analysis, male gender (odds ratio [OR] 2.9 [1.4-6.1]), age (OR 0.97 [0.95-0.99]), and packed red blood cells transfusion (OR 0.31 [0.15-0.66]) were the only independent predictors of ARC. CONCLUSIONS: ARC occurs in more than half of all high-risk trauma intensive care unit patients and is underestimated by standard clinical equations. ARC was not associated with increased incidence of VTE or infection but rather is associated with younger healthier males and reduced mortality. ARC seems to be a beneficial compensatory response to trauma.