Development and preliminary evaluation of EMPOWER for surrogate decision-makers of critically ill patients

OBJECTIVE: The objectives of this study were to develop and refine EMPOWER (Enhancing and Mobilizing the POtential for Wellness and Resilience), a brief manualized cognitive-behavioral, acceptance-based intervention for surrogate decision-makers of critically ill patients and to evaluate its preliminary feasibility, acceptability, and promise in improving surrogates' mental health and patient outcomes. METHOD: Part 1 involved obtaining qualitative stakeholder feedback from 5 bereaved surrogates and 10 critical care and mental health clinicians. Stakeholders were provided with the manual and prompted for feedback on its content, format, and language. Feedback was organized and incorporated into the manual, which was then re-circulated until consensus. In Part 2, surrogates of critically ill patients admitted to an intensive care unit (ICU) reporting moderate anxiety or close attachment were enrolled in an open trial of EMPOWER. Surrogates completed six, 15-20 min modules, totaling 1.5-2 h. Surrogates were administered measures of peritraumatic distress, experiential avoidance, prolonged grief, distress tolerance, anxiety, and depression at pre-intervention, post-intervention, and at 1-month and 3-month follow-up assessments. RESULTS: Part 1 resulted in changes to the EMPOWER manual, including reducing jargon, improving navigability, making EMPOWER applicable for a range of illness scenarios, rearranging the modules, and adding further instructions and psychoeducation. Part 2 findings suggested that EMPOWER is feasible, with 100% of participants completing all modules. The acceptability of EMPOWER appeared strong, with high ratings of effectiveness and helpfulness (M = 8/10). Results showed immediate post-intervention improvements in anxiety (d = -0.41), peritraumatic distress (d = -0.24), and experiential avoidance (d = -0.23). At the 3-month follow-up assessments, surrogates exhibited improvements in prolonged grief symptoms (d = -0.94), depression (d = -0.23), anxiety (d = -0.29), and experiential avoidance (d = -0.30). SIGNIFICANCE OF RESULTS: Preliminary data suggest that EMPOWER is feasible, acceptable, and associated with notable improvements in psychological symptoms among surrogates. Future research should examine EMPOWER with a larger sample in a randomized controlled trial

Enhancing & Mobilizing the POtential for Wellness & Emotional Resilience (EMPOWER) among Surrogate Decision-Makers of ICU Patients: study protocol for a randomized controlled trial

Background Critical illness increases the risk for poor mental health outcomes among both patients and their informal caregivers, especially their surrogate decision-makers. Surrogates who must make life-and-death medical decisions on behalf of incapacitated patients may experience additional distress. EMPOWER (Enhancing & Mobilizing the POtential for Wellness & Emotional Resilience) is a novel cognitive-behavioral, acceptance-based intervention delivered in the intensive care unit (ICU) setting to surrogate decision-makers designed to improve both patients’ quality of life and death and dying as well as surrogates’ mental health. Methods Clinician stakeholder and surrogate participant feedback (n = 15), as well as results from an open trial (n = 10), will be used to refine the intervention, which will then be evaluated through a multisite randomized controlled trial (RCT) (n = 60) to examine clinical superiority to usual care. Feasibility, tolerability, and acceptability of the intervention will be evaluated through self-report assessments. Hierarchical linear modeling will be used to adjust for clustering within interventionists to determine the effect of EMPOWER on surrogate differences in the primary outcome, peritraumatic stress. Secondary outcomes will include symptoms of post-traumatic stress disorder, prolonged grief disorder, and experiential avoidance. Exploratory outcomes will include symptoms of anxiety, depression, and decision regret, all measured at 1 and 3 months from post-intervention assessment. Linear regression models will examine the effects of assignment to EMPOWER versus the enhanced usual care group on patient quality of life or quality of death and intensity of care the patient received during the indexed ICU stay assessed at the time of the post-intervention assessment. Participant exit interviews will be conducted at the 3-month assessment time point and will be analyzed using qualitative thematic data analysis methods. Discussion The EMPOWER study is unique in its application of evidence-based psychotherapy targeting peritraumatic stress to improve patient and caregiver outcomes in the setting of critical illness. The experimental intervention will be strengthened through the input of a variety of ICU stakeholders, including behavioral health clinicians, physicians, bereaved informal caregivers, and open trial participants. Results of the RCT will be submitted for publication in a peer-reviewed journal and serve as preliminary data for a larger, multisite RCT grant application

Prospective Randomized Controlled Trial to Analyze the Effects of Intermittent Pneumatic Compression on Edema Following Autologous Femoropopliteal Bypass Surgery

Background: Patients who undergo autologous femoropopliteal bypass surgery develop postoperative edema in the revascularized leg. The effects of intermittent pneumatic compression (IPC) to treat and to prevent postreconstructive edema were examined in this study. Methods: In a prospective randomized trial, patients were assigned to one of two groups. All patients suffered from peripheral arterial disease, and all were subjected to autologous femoropopliteal bypass reconstruction. Patients in group 1 used a compression stocking (CS) above the knee exerting 18 mmHg (class I) on the leg postoperatively for 1 week (day and night). Patients in group 2 used IPC on the foot postoperatively at night for 1 week. The lower leg circumference was measured preoperatively and at five postoperative time points. A multivariate analysis was done using a mixed model analysis of variance. Results: A total of 57 patients were analyzed (CS 28; IPC 29). Indications for operation were severe claudication (CS 13; IPC 13), rest pain (10/5), or tissue loss (7/11). Revascularization was performed with either a supragenicular (CS 13; IPC10) or an infragenicular (CS 15; IPC 19) autologous bypass. Leg circumference increased on day 1 (CS/IPC): 0.4%/2.7%, day 4 (2.1%/6.1%), day 7 (2.5%/7.9%), day 14 (4.7%/7.3%), and day 90 (1.0%/3.3%) from baseline (preoperative situation). On days 1, 4, and 7 there was a significant difference in leg circumference between the two treatment groups. Conclusions: Edema following femoropopliteal bypass surgery occurs in all patients. For the prevention and treatment of that edema the use of a class I CS proved superior to treatment with IPC. The use of CS remains the recommended practice following femoropopliteal bypass surgery

The history of Coast Salish “woolly dogs” revealed by ancient genomics and Indigenous Knowledge

Ancestral Coast Salish societies in the Pacific Northwest kept long-haired "woolly dogs" that were bred and cared for over millennia. However, the dog wool-weaving tradition declined during the 19th century, and the population was lost. In this study, we analyzed genomic and isotopic data from a preserved woolly dog pelt from "Mutton," collected in 1859. Mutton is the only known example of an Indigenous North American dog with dominant precolonial ancestry postdating the onset of settler colonialism. We identified candidate genetic variants potentially linked with their distinct woolly phenotype. We integrated these data with interviews from Coast Salish Elders, Knowledge Keepers, and weavers about shared traditional knowledge and memories surrounding woolly dogs, their importance within Coast Salish societies, and how colonial policies led directly to their disappearance

Cholesterol-Lowering Drugs and Incident Open-Angle Glaucoma: A Population-Based Cohort Study

Background: Open-angle glaucoma (OAG) is a progressive neurodegenerative disease that may lead to blindness. An elevated intraocular pressure (IOP) is its major risk factor. OAG treatment is currently exclusively directed towards the lowering of the IOP. IOP lowering does not prevent disease progression in all patients and thus other treatment modalities are needed. Earlier studies reported cholesterol-lowering drugs to have neuroprotective properties. The aim of this study was to determine the associations between the use of cholesterol-lowering drugs and incident OAG. Methodology/Principal Findings: Participants in a prospective population-based cohort study underwent ophthalmic examinations, including IOP measurements and perimetry, at baseline and follow-up. The use of statins and non-statin cholesterol-lowering drugs was monitored continuously during the study. Associations between the use of cholesterol-lowering drugs and incident OAG were analyzed with Cox regression; associations between cholesterol-lowering drugs and IOP at follow-up were analyzed with multiple linear regression. During a mean follow-up of 9.8 years, 108 of 3939 eligible participants (2.7%) developed OAG. The hazard ratio for statin use was 0.54 (95% confidence interval 0.31-0.96; P = 0.034) and for non-statin cholesterol-lowering drugs 2.07 (0.81-5.33; P = 0.13). The effect of statins was more pronounced with prolonged use (hazard ratio 0.

Communally breeding bats use physiological and behavioural adjustments to optimise daily energy expenditure

Small endotherms must change roosting and thermoregulatory behaviour in response to changes in ambient conditions if they are to achieve positive energy balance. In social species, for example many bats, energy expenditure is influenced by environmental conditions, such as ambient temperature, and also by social thermoregulation. Direct measurements of daily fluctuations in metabolic rates in response to ambient and behavioural variables in the field have not been technologically feasible until recently. During different reproductive periods, we investigated the relationships between ambient temperature, group size and energy expenditure in wild maternity colonies of Bechstein’s bats (Myotis bechsteinii). Bats used behavioural and physiological adjustments to regulate energy expenditure. Whether bats maintained normothermia or used torpor, the number of bats in the roosts as well changed with reproductive status and ambient temperature. During pregnancy and lactation, bats remained mostly normothermic and daily group sizes were relatively large, presumably to participate in the energetic benefits of social thermoregulation. In contrast, smaller groups were formed on days when bats used torpor, which occurred mostly during the post-lactation period. Thus, we were able to demonstrate on wild animals under natural conditions the significance of behavioural and physiological flexibility for optimal thermoregulatory behaviour in small endotherms

Asynchronous Antarctic and Greenland ice-volume contributions to the last interglacial sea-level highstand

The last interglacial (LIG; ~130 to ~118 thousand years ago, ka) was the last time global sea level rose well above the present level. Greenland Ice Sheet (GrIS) contributions were insufficient to explain the highstand, so that substantial Antarctic Ice Sheet (AIS) reduction is implied. However, the nature and drivers of GrIS and AIS reductions remain enigmatic, even though they may be critical for understanding future sea-level rise. Here we complement existing records with new data, and reveal that the LIG contained an AIS-derived highstand from ~129.5 to ~125 ka, a lowstand centred on 125–124 ka, and joint AIS + GrIS contributions from ~123.5 to ~118 ka. Moreover, a dual substructure within the first highstand suggests temporal variability in the AIS contributions. Implied rates of sea-level rise are high (up to several meters per century; m c−1), and lend credibility to high rates inferred by ice modelling under certain ice-shelf instability parameterisations

Shorter courses of parenteral antibiotic therapy do not appear to influence response rates for children with acute hematogenous osteomyelitis: a systematic review

BACKGROUND: Acute hematogenous osteomyelitis (AHO) occurs primarily in children and is believed to evolve from bacteremia followed by localization of infection to the metaphysis of bones. Currently, there is no consensus on the route and duration of antimicrobial therapy to treat AHO. METHODS: We conducted a systematic review of a short versus long course of treatment for AHO due primarily to Staphylococcus aureus in children aged 3 months to 16 years. We searched Medline, Embase and the Cochrane trials registry for controlled trials. Clinical cure rate at 6 months was the primary outcome variable, and groups receiving less than 7 days of intravenous therapy were compared with groups receiving one week or longer of intravenous antimicrobials. RESULTS: 12 eligible prospective studies, one of which was randomized, were identified. The overall cure rate at 6 months for the short course of intravenous therapy was 95.2% (95% CI = 90.4, 97.7) compared to 98.8% (95% CI = 93.6, 99.8) for the longer course of therapy. There was no significant difference in the duration of oral therapy between the two groups. CONCLUSIONS: Given the potential increased morbidity and cost associated with longer courses of intravenous therapy, this finding should be confirmed through a randomized controlled equivalence trial

Transcriptome Sequencing Revealed Significant Alteration of Cortical Promoter Usage and Splicing in Schizophrenia

While hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression.The data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22) from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDR<0.05). Both types of transcriptional isoforms were exemplified by reads aligned to the neurodevelopmentally significant doublecortin-like kinase 1 (DCLK1) gene.This study provided the first deep and un-biased analysis of schizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia