Mental Health Interventions to Improve Psychological Outcomes in Informal Caregivers of Critically Ill Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Determine effect of mental health interventions on psychologic outcomes in informal caregivers of critically ill patients. DATA SOURCES: Searches conducted in MEDLINE, Embase, and other databases from inception to October 31, 2019. STUDY SELECTION: Interventions for informal caregivers of critically ill patients in adult ICU, PICU, or neonatal ICU. DATA EXTRACTION: Two independent, blinded reviewers screened citations and extracted data. Random-effects models with inverse variance weighting pooled outcome data when suitable. Psychologic outcomes categorized: 1) negative (anxiety, depression, post-traumatic stress disorder, distress, and burden) or 2) positive (courage, humanity, justice, transcendence, temperance, and wisdom and knowledge). Stratification according to intervention type and patient population was performed. DATA SYNTHESIS: Of 11,201 studies, 102 interventional trials were included (n = 12,676 informal caregivers). Interventions targeted caregiver experience (n = 58), role (n = 6), or support (n = 38). Meta-analysis (56 randomized controlled trials; n = 22 [39%] in adult ICUs; n = 34 [61%] in neonatal ICU or PICU) demonstrated reduced anxiety (ratio of means = 0.92; 95% CI, 0.87-0.97) and depression (ratio of means = 0.83; 95% CI, 0.69-0.99), but not post-traumatic stress disorder (ratio of means = 0.91; 95% CI, 0.80-1.04) or distress (ratio of means = 1.01; 95% CI, 0.95-1.07) among informal caregivers randomized to mental health interventions compared with controls within 3 months post-ICU discharge. Increased humanity (ratio of means = 1.11; 95% CI, 1.07-1.15), transcendence (ratio of means = 1.11; 95% CI, 1.07-1.15), and caregiver burden (ratio of means = 1.08; 95% CI, 1.05-1.12) were observed. No significant effects of mental health interventions observed after 3 months postdischarge. CONCLUSIONS: Mental health interventions for caregivers of critically ill patients improved short-term anxiety, depression, humanity, and transcendence while increasing burden. Clinicians should consider short-term prescriptions of mental health interventions to informal caregivers of critically ill patients with capacity to manage interventions.

Adverse events associated with administration of vasopressor medications through a peripheral intravenous catheter: a systematic review and meta-analysis.

BACKGROUND: It is unclear whether vasopressors can be safely administered through a peripheral intravenous (PIV). Systematic review and meta-analysis methodology was used to examine the incidence of local anatomic adverse events associated with PIV vasopressor administration in patients of any age cared for in any acute care environment. METHODS: MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of controlled trials, and the Database of Abstracts of Reviews of Effects were searched without restriction from inception to October 2019. References of included studies and related reviews, as well as relevant conference proceedings were also searched. Studies were included if they were: (1) cohort, quasi-experimental, or randomized controlled trial study design; (2) conducted in humans of any age or clinical setting; and (3) reported on local anatomic adverse events associated with PIV vasopressor administration. Risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials or the Joanna Briggs Institute checklist for prevalence studies where appropriate. Incidence estimates were pooled using random effects meta-analysis. Subgroup analyses were used to explore sources of heterogeneity. RESULTS: Twenty-three studies were included in the systematic review, of which 16 and 7 described adults and children, respectively. Meta-analysis from 11 adult studies including 16,055 patients demonstrated a pooled incidence proportion of adverse events associated with PIV vasopressor administration as 1.8% (95% CI 0.1-4.8%, I2 = 93.7%). In children, meta-analysis from four studies and 388 patients demonstrated a pooled incidence proportion of adverse events as 3.3% (95% CI 0.0-10.1%, I2 = 82.4%). Subgroup analyses did not detect any statistically significant effects associated with stratification based on differences in clinical location, risk of bias or design between studies, PIV location and size, or vasopressor type or duration. Most studies had high or some concern for risk of bias. CONCLUSION: The incidence of adverse events associated with PIV vasopressor administration is low. Additional research is required to examine the effects of PIV location and size, vasopressor type and dose, and patient characteristics on the safety of PIV vasopressor administration.

Influence of GTP on system specific chaperone - Twin arginine signal peptide interaction.

Many bacterial respiratory redox enzymes depend on the twin-arginine translocase (Tat) system for translocation and membrane insertion. Tat substrates contain an N-terminal twin-arginine (SRRxFLK) motif serving as the targeting signal towards the translocon. Many Tat substrates have a system specific chaperone - redox enzyme maturation protein (REMP) - for final folding and assembly prior to Tat binding. The REMP DmsD strongly interacts with the twin-arginine motif of the DmsA signal sequence of dimethyl sulfoxide (DMSO) reductase. In this study, we have utilized the in vitro protein-protein interaction technique of an affinity pull down assay, as well as protein thermal stability measurement via differential scanning fluorimetry (DSF) to investigate the interaction of guanosine nucleotides (GNPs) with DmsD. Here we have shown highly cooperative binding of DmsD with GTP. A dissociative ligand-binding style isotherm was generated upon GTP titration into the DmsD:DmsAL interaction, yielding sigmoidal release of DmsD with a Hill coefficient of 2.09 and a dissociation constant of 0.99 mM. DSF further illustrated the change in thermal stability upon DmsD interaction with DmsAL and GTP. These results imply the possibility of DmsD detection and binding of GTP during the DMSO protein maturation mechanism, from ribosomal translation to membrane targeting and final assembly. Conceivably, GTP is shown to act as a molecular regulator in the biochemical pathway.

Exploring the impact of the COVID-19 pandemic on medical learner wellness: a needs assessment for the development of learner wellness interventions.

BACKGROUND: On March 11, 2020 the World Health Organization declared the novel coronavirus SARS-CoV-2 disease (COVID-19) a global pandemic. We sought to understand impact of COVID-19 on learner wellness at a large tertiary care academic institution to inform the future development of learner wellness interventions during the COVID-19 pandemic. METHODS: A cross-sectional, internet-based survey collected quantitative and qualitative data from learners April-June 2020. Descriptive statistics and univariate analyses were reported for quantitative data. Open-ended, qualitative responses were analyzed deductively using thematic analysis. RESULTS: Twenty percent of enrolled learners in that faculty of medicine (540/2741) participated including undergraduate [Bachelor's] students (25.7%), graduate [science] students (27.5%), undergraduate medical students (22.8%), and postgraduate resident physicians (23.5%). We found that learner wellness across all stages of training was negatively impacted and the ways in which learners were impacted varied as a result of their program's response to the COVID-19 pandemic. CONCLUSIONS: Learners in health sciences and medical education report worsening well-being because of the programs and the systems in which they function with the added burden of the COVID-19 pandemic. Future interventions would benefit from a holistic framework of learner wellness while engaging in systems thinking to understand how individuals, programs and respective systems intersect. The importance of acknowledging equity, diversity and inclusion, fostering psychological safety and engaging learners as active participants in their journey during a pandemic and beyond are key elements in developing wellness interventions.

CONTEXTE: Le 11 mars 2020, l'Organisation mondiale de la santé a déclaré que le nouveau coronavirus SRAS-CoV-2 (COVID-19) était pandémique. Nous avons tenté de cerner l'impact de la COVID-19 sur le bien-être des apprenants dans un grand centre universitaire de soins tertiaires afin d'étayer le développement futur d'interventions en faveur du bien-être des apprenants en contexte de pandémie. MÉTHODES: Une enquête transversale par sondage en ligne, menée entre les mois d'avril et juin 2020, a permis de recueillir des données quantitatives et qualitatives auprès des apprenants. Des statistiques descriptives et des analyses univariées ont été présentées comme données quantitatives. Les réponses ouvertes, qualitatives, ont été analysées de manière déductive par le biais d'une analyse thématique. RÉSULTATS: Vingt pour cent des étudiants de la faculté de médecine (540/2741) ont participé, dont 25,7 % étaient inscrits au premier cycle (baccalauréat), 27,5 % au deuxième cycle (sciences), 22,8 % au premier cycle en médecine et 23,5 % étaient résidents. Nous avons constaté que la pandémie a négativement affecté le bien-être des apprenants à tous les niveaux de formation et que les effets précis sur les étudiants pouvaient varier en fonction de la réponse de leur programme à la situation sanitaire. CONCLUSIONS: Les étudiants en médecine et en sciences de la santé signalent une détérioration de leur bien-être liée aux programmes et aux systèmes dans lesquels ils évoluent, auxquels s'ajoute le fardeau supplémentaire de la pandémie de la COVID-19. Il conviendrait de définir les interventions futures sur la base d'un cadre holistique du bien-être des apprenants tout en adoptant une réflexion systémique pour appréhender l'entrecroisement entre individus, programmes et systèmes. Reconnaître l'importance de l'équité, de la diversité et de l'inclusion, favoriser la sécurité psychologique et assurer la participation active des apprenants dans leur parcours pendant la pandémie et au-delà, constituent des éléments clés dans l'élaboration d'interventions au profit de leur bien-être.

Wellness in medical education: definition and five domains for wellness among medical learners during the COVID-19 pandemic and beyond.

Problem: The novel coronavirus SARS-CoV-2 disease (COVID-19) impacted medical learner well-being and serves as a unique opportunity to understand medical learner wellness. The authors designed a formal needs assessment to assess medical learners' perspectives regarding distress related to disrupted training environments. This Rapid Communication describes findings from a qualitative study which defined medical learner wellness and validated five wellness domains.Approach: We conducted follow-up telephone interviews to an online needs assessment survey to identify a learner definition for wellness and to validate five wellness domains, including social, mental, physical, intellectual, and occupational wellness. Using purposive and maximal variation sampling, 27 students were interviewed from July-August 2020. Thematic analysis was performed using a deductive thematic approach to qualitative analysis.Outcomes: Medical learners defined wellness as a general [holistic] sense of personal well-being - the opportunity to be and to do what they most need and value. Learners validated all five wellness domains for medical education. Learners acknowledged the need for an adoptable and adaptable holistic framework for wellness in medical education.Next steps: We recommend academic medical institutions consider learner wellness a key component of medical education to cultivate learners as a competent collective of self-reliant, scholarly experts. We encourage evaluation of wellness domains in diverse medical learner populations to identify feasible interventions potentially associated with improvements in medical learner wellness.

Development and validation of delirium prediction model for critically ill adults parameterized to ICU admission acuity.

BACKGROUND: Risk prediction models allow clinicians to forecast which individuals are at a higher risk for developing a particular outcome. We developed and internally validated a delirium prediction model for incident delirium parameterized to patient ICU admission acuity. METHODS: This retrospective, observational, fourteen medical-surgical ICU cohort study evaluated consecutive delirium-free adults surviving hospital stay with ICU length of stay (LOS) greater than or equal to 24 hours with both an admission APACHE II score and an admission type (e.g., elective post-surgery, emergency post-surgery, non-surgical) in whom delirium was assessed using the Intensive Care Delirium Screening Checklist (ICDSC). Risk factors included in the model were readily available in electric medical records. Least absolute shrinkage and selection operator logistic (LASSO) regression was used for model development. Discrimination was determined using area under the receiver operating characteristic curve (AUC). Internal validation was performed by cross-validation. Predictive performance was determined using measures of accuracy and clinical utility was assessed by decision-curve analysis. RESULTS: A total of 8,878 patients were included. Delirium incidence was 49.9% (n = 4,431). The delirium prediction model was parameterized to seven patient cohorts, admission type (3 cohorts) or mean quartile APACHE II score (4 cohorts). All parameterized cohort models were well calibrated. The AUC ranged from 0.67 to 0.78 (95% confidence intervals [CI] ranged from 0.63 to 0.79). Model accuracy varied across admission types; sensitivity ranged from 53.2% to 63.9% while specificity ranged from 69.0% to 74.6%. Across mean quartile APACHE II scores, sensitivity ranged from 58.2% to 59.7% while specificity ranged from 70.1% to 73.6%. The clinical utility of the parameterized cohort prediction model to predict and prevent incident delirium was greater than preventing incident delirium by treating all or none of the patients. CONCLUSIONS: Our results support external validation of a prediction model parameterized to patient ICU admission acuity to predict a patients' risk for ICU delirium. Classification of patients' risk for ICU delirium by admission acuity may allow for efficient initiation of prevention measures based on individual risk profiles.

Impact of social media interventions and tools among informal caregivers of critically ill patients after patient admission to the intensive care unit: A scoping review.

BACKGROUND: The use of social media in healthcare continues to evolve. The purpose of this scoping review was to summarize existing research on the impact of social media interventions and tools among informal caregivers of critically ill patients after patient admission to the intensive care unit (ICU). METHODS: This review followed established scoping review methods, including an extensive a priori-defined search strategy implemented in the MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane CENTRAL Register of Controlled Trials databases to July 10, 2020. Primary research studies reporting on the use of social media by informal caregivers for critically ill patients were included. RESULTS: We identified 400 unique citations and thirty-one studies met the inclusion criteria. Nine were interventional trials-four randomized controlled trials (RCTs)-and a majority (n = 14) were conducted (i.e., data collected) between 2013 to 2015. Communication platforms (e.g., Text Messaging, Web Camera) were the most commonly used social media tool (n = 17), followed by social networking sites (e.g., Facebook, Instagram) (n = 6), and content communities (e.g., YouTube, SlideShare) (n = 5). Nine studies' primary objective was caregiver satisfaction, followed by self-care (n = 6), and health literacy (n = 5). Nearly every study reported an outcome on usage feasibility (e.g., user attitudes, preferences, demographics) (n = 30), and twenty-three studies reported an outcome related to patient and caregiver satisfaction. Among the studies that assessed statistical significance (n = 18), 12 reported statistically significant positive effects of social media use. Overall, 16 of the 31 studies reported positive conclusions (e.g., increased knowledge, satisfaction, involvement) regarding the use of social media among informal caregivers for critically ill patients. CONCLUSIONS: Social media has potential benefits for caregivers of the critically ill. More robust and clinically relevant studies are required to identify effective social media strategies used among caregivers for the critically ill.

Late-pregnancy uterine artery ligation increases susceptibility to postnatal Western diet-induced fat accumulation in adult female offspring.

Stressors during the fetal and postnatal period affect the growth and developmental trajectories of offspring, causing lasting effects on physiologic regulatory systems. Here, we tested whether reduced uterine artery blood flow in late pregnancy would alter body composition in the offspring, and whether feeding offspring a western diet (WD) would aggravate these programming effects. Pregnant rats underwent bilateral uterine artery ligation (BUAL) or sham surgery on gestational day (GD)18 (term = GD22). At weaning, offspring from each group received either a normal diet (ND) or a WD. BUAL surgery increased fetal loss and caused offspring growth restriction, albeit body weights were no longer different at weaning, suggesting postnatal catch-up growth. BUAL did not affect body weight gain, fat accumulation, or plasma lipid profile in adult male offspring. In contrast, while ND-fed females from BUAL group were smaller and leaner than their sham-littermates, WD consumption resulted in excess weight gain, fat accumulation, and visceral adiposity. Moreover, WD increased plasma triglycerides and cholesterol in the BUAL-treated female offspring without any effect on sham littermates. These results demonstrate that reduced uterine artery blood flow during late pregnancy in rodents can impact body composition in the offspring in a sex-dependent manner, and these effects may be exacerbated by postnatal chronic WD consumption.

Nutrition interventions in populations with mental health conditions: a scoping review.

Nutrition is a modifiable factor for intervention in mental disorders. This scoping review characterized nutrition intervention research in mental disorders. A 3-category framework characterized nutrition interventions: Guide (e.g., counselling), Provide (e.g., food provisions), and Add (e.g., supplementation). Nutrition interventions were classified as single-component (e.g., Guide) or complex (e.g., Guide-Provide). Sixty-nine trials met inclusion criteria, 96% were randomized controlled trials. Most commonly diagnosed mental disorders were depressive disorder (i.e., persistent) or major depressive disorder (n = 39), schizophrenia (n = 17), and other psychotic disorders (n = 13). Few trials included patients with anxiety disorders (n = 2) or bipolar disorders (n = 3). Several trials (n = 15, 22%) assessed and implemented nutrition interventions to improve dietary patterns, of which 11 (73%) reported statistically significant and clinically important positive effects of nutrition interventions on mental disorders. The majority of the trials (n = 61, 90%) investigated supplementation, most commonly adding essential fatty acids, vitamins, or minerals. The majority (n = 48, 70%) reported either statistically significant or clinically important effect and 31 (51%) reported both. Though most interventions led to statistically significant improvements, trials were heterogeneous for targeted mental disorders, nutrition interventions, and outcomes assessed. Given considerable heterogeneity, further research from robust and clinically relevant trials is required to support high-quality health care with effective nutrition interventions. Novelty Future research on whole-diet interventions powered to detect changes in mental health outcomes as primary objectives is needed. Dietitians may be an opportunity to improve feasibility and efficacy of nutrition interventions for mental disorder patients. Dietitians may be of value to educate mental health practitioners on the importance of nutrition.

Principal component analysis of the relationship between pelvic inclination and lumbar lordosis.

BACKGROUND: The purpose of this study was to describe the relationship between pelvic inclination (PI) and lumbar lordosis (LL). Pelvic inclination and pelvic tilt are two different names for the same metric. The geometrical parameters of the spine and pelvis were measured using surface topography scanning, and the data was explored for any physical relationships using principal component analysis.Once widely assumed to be a direct correlation, research in the 1980s first cast doubt upon the PI to LL relationship. And yet, other studies have suggested a relationship does exist. Decades later, the rehabilitation professionals often still rely on this supposed correlation when making decisions about rehabilitation treatment interventions. This theoretical relationship requires further clarification, which is explored herein. METHODS: Surface topography imaging is a technology that has proven to be a radiation-free way to produce accurate, reliable skeletal alignment measures. Patient data from one physical rehabilitation clinic was collected at the time of initial assessment. Patients presented with a wide range of musculoskeletal complaints. Surface topography scans were performed on 107 patients at the commencement and completion of their therapy. Principal component analysis was performed on the collected data to determine how these spine and pelvic alignment parameters changed between the two points in time and what trends and/or relationships exist between the parameters. Our analysis evaluated eight spinal and pelvic measurements as input and focused on LL and PI as the two principal components at time points of beginning and completion of treatment. RESULTS: Pelvic inclination and lumbar lordosis changed during treatment but were not correlated. CONCLUSION: Our data demonstrates that pelvic inclination and lumbar lordosis do not have a predictable relationship as previously assumed.

Quantitative meta-analysis of maternal prenatal salivary cortisol and newborn birthweight does not identify effect of fetal sex.

BACKGROUND: Heightened concentration of maternal cortisol is a frequently proposed mechanism linking adverse maternal environments with poor birth outcomes, including birth weight. It is commonly hypothesized that prenatal exposures have sexually dimorphic effects on fetal development, however few studies have assessed the effects of fetal sex on the relationship between maternal cortisol and birth outcomes. METHODS: In a previous systematic review and meta-analysis we obtained data from authors of included studies to calculate trimester-specific correlations between maternal prenatal salivary cortisol and newborn birth weight. Given that this data was well-poised to address the unknown effects of fetal sex on the relationship between maternal cortisol and birth outcomes, we contacted authors a second time with request to unblind sex into the correlations. An updated database search was conducted to identify potentially relevant articles published within 2018 and two additional articles were included. RESULTS AND DISCUSSION: Eleven studies with a total of 2236 maternal-fetal dyads demonstrated negative correlations for both males, -0.15 (95% CI -0.24 to -0.06, I2 = 98.5%, p < 0.001) and females -0.21 (95% CI -0.25 to -0.17, I2 = 93.3%, p < 0.001). Sex difference were not statistically significant, p = 0.62. Despite greater exposure to cortisol and lower birth weight among females, the association did not differ by sex.

The effect of gestational period on the association between maternal prenatal salivary cortisol and birth weight: A systematic review and meta-analysis.

BACKGROUND: Studies exploring the relations between maternal stress and fetal development show an association between increased maternal stress and adverse birth outcomes. A frequently proposed mechanism linking maternal prenatal stress and adverse birth outcomes is heightened concentrations of maternal cortisol. To date, studies exploring this association have reported conflicting results because of the diverse approaches taken to measuring cortisol and the wide variety of possible birth outcomes explored. To add clarity to the growing body of literature, this systematic review and meta-analysis reports empirical findings on the association between maternal prenatal salivary cortisol and newborn birth weight. METHODS: Searches for relevant papers published up until November 2017 were run in MEDLINE, EMBASE, PsycINFO, and CINAHL. Non-English language papers were included and experts were contacted when necessary. We included data from human observational studies that were designed or had an underlying intention to measure maternal prenatal salivary cortisol and newborn birth weight. We only included data from measurements of salivary cortisol to prevent rendering of the review unsuitable for meta-analysis. Two independent reviewers assessed study eligibility and quality. For every maternal-fetal dyad, an area under the curve with respect to ground (AUCg) of maternal cortisol was calculated to determine a Pearson's correlation coefficient with a continuous measure of newborn birth weight. Correlation coefficients were then pooled across all stages of gestation. To examine if there are critical gestational periods in which the fetus may be more susceptible to elevated concentration of maternal salivary cortisol, a meta-analysis was performed on separate correlations calculated from gestational trimesters. RESULTS: Nine studies with a total of 1606 maternal-fetal dyads demonstrated a negative correlation between pooled maternal salivary cortisol and birth weight (-0.24, 95% CI -0.28 to -0.20), but there was a high degree of heterogeneity between studies (I2 = 88.9%). To investigate heterogeneity, subgroup analysis by trimester of the pooled correlation between salivary cortisol and birth weight was performed with the following correlations found: first trimester, -0.18 (95% CI -0.32 to -0.03, I2 = 97.3%); second trimester, -0.20 (95% CI -0.28 to -0.12, I2 = 98.3%); and third trimester, -0.30 (95% CI -0.33 to -0.26, I2 = 85.4%). DISCUSSION: A consistently negative association was observed between maternal cortisol and infant birth weight. The review highlights specific gaps in the literature on the relationship between maternal prenatal salivary cortisol and newborn birth weight. Although a significant negative correlation was found, substantial heterogeneity of effects and the likelihood of publication bias exist. The third trimester was revealed as a possible critical gestational period for heightened maternal cortisol concentration to affect birth weight. Challenges faced in this body of research and recommendations for future research are discussed.

Assembly pathway of a bacterial complex iron sulfur molybdoenzyme.

Protein folding and assembly into macromolecule complexes within the living cell are complex processes requiring intimate coordination. The biogenesis of complex iron sulfur molybdoenzymes (CISM) requires use of a system specific chaperone - a redox enzyme maturation protein (REMP) - to help mediate final folding and assembly. The CISM dimethyl sulfoxide (DMSO) reductase is a bacterial oxidoreductase that utilizes DMSO as a final electron acceptor for anaerobic respiration. The REMP DmsD strongly interacts with DMSO reductase to facilitate folding, cofactor-insertion, subunit assembly and targeting of the multi-subunit enzyme prior to membrane translocation and final assembly and maturation into a bioenergetic catalytic unit. In this article, we discuss the biogenesis of DMSO reductase as an example of the participant network for bacterial CISM maturation pathways.

Modest and Severe Maternal Iron Deficiency in Pregnancy are Associated with Fetal Anaemia and Organ-Specific Hypoxia in Rats.

Prenatal iron-deficiency (ID) is known to alter fetal developmental trajectories, which predisposes the offspring to chronic disease in later life, although the underlying mechanisms remain unclear. Here, we sought to determine whether varying degrees of maternal anaemia could induce organ-specific patterns of hypoxia in the fetuses. Pregnant female Sprague Dawley rats were fed iron-restricted or iron-replete diets to induce a state of moderate (M-ID) or severe ID (S-ID) alongside respective controls. Ultrasound biomicroscopy was performed on gestational day (GD)20 to assess uterine and umbilical artery blood flow patterns. On GD21, tissues were collected and assessed for hypoxia using pimonidazole staining. Compared to controls, maternal haemoglobin (Hb) in M- and S-ID were reduced 17% (P < 0.01) and 48% (P < 0.001), corresponding to 39% (P < 0.001) and 65% (P < 0.001) decreases in fetal Hb. Prenatal ID caused asymmetric fetal growth restriction, which was most pronounced in S-ID. In both severities of ID, umbilical artery resistive index was increased (P < 0.01), while pulsatility index only increased in S-ID (P < 0.05). In both M-and S-ID, fetal kidneys and livers showed evidence of hypoxia (P < 0.01 vs. controls), whereas fetal brains and placentae remained normoxic. These findings indicate prenatal ID causes organ-specific fetal hypoxia, even in the absence of severe maternal anaemia.