Impact and Sustainability of a Palliative Care Education Module in Patients With Heart Failure.

BACKGROUND: Approximately 6.7 million American adults are living with heart failure (HF). Current therapies are geared toward preventing progression and managing symptoms, as there is no cure. Multiple studies have shown the benefit of including palliative care (PC) in patients with HF to improve symptoms and quality of life. Heart failure guidelines recommend the inclusion of PC in therapy, but referrals are often delayed. A previous pilot project demonstrated increased involvement of PC when targeted education was given to patients with HF. OBJECTIVE: Educate patients with HF on PC and examine the impact on PC consults, readmission, mortality, intensive care unit (ICU) transfers and evaluate sustainability of the intervention. METHODS: Patients (n = 124) admitted to an academic hospital with a diagnosis of HF were asked to view an educational module on PC. Patients who completed the module were placed in the intervention group (n = 39). Patients who declined were placed in the usual care group (n = 38). The number of PC consults, re-admissions, mortality, and transfers to the ICU were compared among participants and those who declined. Results were compared to previous pilot project. RESULTS: Eleven patients in the intervention group (IG) requested a PC consult vs one in the usual care group (UCG) (P = .006). There was no statistically significant difference in readmissions, mortality, or ICU transfers between groups. CONCLUSIONS: This sustainable project again demonstrated education on PC increases utilization of PC but does not statistically impact mortality, re-admissions, or transfers to higher levels of care.

In-Hospital Virtual Peer-to-Peer Consultation to Increase Guideline-Directed Medical Therapy for Heart Failure: A Pilot Randomized Trial.

BACKGROUND: Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) improves clinical outcomes and quality of life. Optimizing GDMT in the hospital is associated with greater long-term use in HFrEF. This study aimed to describe the efficacy of a multidisciplinary virtual HF intervention on GDMT optimization among patients with HFrEF admitted for any cause. METHODS: In this pilot randomized, controlled study, consecutive patients with HFrEF admitted to noncardiology medicine services for any cause were identified at a large academic tertiary care hospital between May to September 2021. Major exclusions were end-stage renal disease, hemodynamic instability, concurrent COVID-19 infection, and current enrollment in hospice care. Patients were randomized to a clinician-level virtual peer-to-peer consult intervention providing GDMT recommendations and information on medication costs versus usual care. Primary end points included (1) proportion of patients with new GDMT initiation or use and (2) changes to HF optimal medical therapy scores which included target dosing (range, 0-9). RESULTS: Of 242 patients identified, 91 (38%) were eligible and randomized to intervention (N=52) or usual care (N=39). Baseline characteristics were similar between intervention and usual care (mean age 63 versus 67 years, 23% versus 26% female, 46% versus 49% Black, mean ejection fraction 33% versus 31%). GDMT use on admission was also similar. There were greater proportions of patients with GDMT initiation or continuation with the intervention compared with usual care. After adjusting for optimal medical therapy score on admission, changes to optimal medical therapy score at discharge were higher for the intervention group compared with usual care (+0.44 versus -0.31, absolute difference +0.75, adjusted estimate 0.86±0.42; P=0.041). CONCLUSIONS: Among eligible patients with HFrEF hospitalized for any cause on noncardiology services, a multidisciplinary pilot virtual HF consultation increased new GDMT initiation and dose optimization at discharge.

Traumatic peripheral nerve injuries: diagnosis and management.

PURPOSE OF REVIEW: To review advances in the diagnostic evaluation and management of traumatic peripheral nerve injuries. RECENT FINDINGS: Serial multimodal assessment of peripheral nerve injuries facilitates assessment of spontaneous axonal regeneration and selection of appropriate patients for early surgical intervention. Novel surgical and rehabilitative approaches have been developed to complement established strategies, particularly in the area of nerve grafting, targeted rehabilitation strategies and interventions to promote nerve regeneration. However, several management challenges remain, including incomplete reinnervation, traumatic neuroma development, maladaptive central remodeling and management of fatigue, which compromise functional recovery. SUMMARY: Innovative approaches to the assessment and treatment of peripheral nerve injuries hold promise in improving the degree of functional recovery; however, this remains a complex and evolving area.

Elevation of C-reactive protein in adolescent bipolar disorder vs. anxiety disorders.

Bipolar disorder (BD) largely begins in adolescence, but diagnosis lags for years, causing significant morbidity and mortality, and demonstrating the need for better diagnostic tools. Suggesting an association between BD and immune activity, elevated levels of peripheral inflammatory markers, including C-reactive protein (CRP), have been found in adults with BD. As similar data are extremely limited in adolescents, this study examined CRP levels in adolescents with BD (n = 37) compared to those with anxiety disorders (ADs, n = 157) and healthy controls with no psychiatric diagnoses (HCs, n = 2760). CRP blood levels for patients aged 12-17 years were retrieved from a nationwide repository of deidentified clinical data. After excluding patients with inflammatory conditions, differences in CRP were examined using multivariate and weighted regressions (covariates: demographics and BMI). Mean CRP levels were significantly elevated in adolescents with BD relative to those with ADs and HCs. Mean CRP levels were lower in the ADs cohort versus HCs. Although CRP levels were significantly higher in males and younger patients, the significant between-cohort differences in CRP remained after controlling for multiple confounders. To our knowledge, our study is the first to compare CRP levels between adolescent BD, ADs, and HCs, comprising a novel and essential contribution. Our results suggest the presence of a unique immune process in adolescents with BD and indicate that CRP may represent a biomarker with a crucial role in the diagnostic assessment of adolescent BD.

Regional extent, environmental relevance, and spatiotemporal variability of neonicotinoid insecticides detected in Florida's ambient flowing waters.

The use of imidacloprid and, to a lesser degree, other neonicotinoid insecticides is widespread in FL (and globally). The moderate to high water solubility and environmental persistence of neonicotinoids allows these compounds to readily enter, and be retained in, water resources where they may harm nontarget organisms and impact biological communities and associated trophic structures negatively. To better understand imidacloprid's chronic long-term exposure potential to aquatic invertebrate communities in FL, grab water samples were collected monthly in 2015 at 77 monitoring stations statewide. Fifty-eight stations (75%), representing 24 of the 25 drainage basins sampled, had detectable concentrations of imidacloprid, with concentrations ranging from 2 to 660 nanograms per liter [ng/L]. Imidacloprid basin medians were found to be correlated with two of six land use categories (urban, transportation, agriculture, and three crop classes) examined; urban (rho = 0.43, p-value = 0.03), and orchards and vineyards (rho 0.49, p-value = 0.01). The resampling of 12 select stations, representing eight basins, between August 2019 and July 2020, for the neonicotinoids acetamiprid, clothianidin, dinotefuran, imidacloprid, and thiamethoxam, showed that (1) median values of imidacloprid continued to exceed the US EPA chronic freshwater Invertebrate Aquatic Life Benchmark (IALB) (10 ng/L), (2) imidacloprid concentration was directly correlated with flow measurements, and (3) while median imidacloprid concentration decreased between the two sampling events (48.5 vs. 34.5 ng/L, p-value = 0.01) differences in event 1 and 2 streamflow regimes and disruptions due to the COVID-19 pandemic likely affected this outcome. Clothianidin was the only other neonicotinoid found to have values greater than a US EPA IALB, with detections at three stations exceeding the chronic IALB (50 ng/L). This study highlights the challenges associated with limiting neonicotinoids from entering water resources and identifies means to reduce their entry into and persistence within FL water resources.

Long read sequencing overcomes challenges in the diagnosis of SORD neuropathy.

Biallelic mutations in sorbitol dehydrogenase (SORD) have been recently identified as a common cause of recessive axonal Charcot-Marie-Tooth neuropathy (CMT2). We aimed to assess a novel long-read sequencing approach to overcome current limitations in SORD neuropathy diagnostics due to the SORD2P pseudogene and the phasing of biallelic mutations in recessive disease. We conducted a screen of our Australian whole exome sequencing (WES) CMT cohort to identify individuals with homozygous or compound heterozygous SORD variants. Individuals detected with SORD mutations then underwent long-read sequencing, clinical assessment, and serum sorbitol analysis. An individual was detected with compound heterozygous truncating mutations in SORD exon 7, NM_003104.5:c.625C>T (p.Arg209Ter) and NM_003104.5:c.757del (p.Ala253GlnfsTer27). Subsequent Oxford Nanopore Tech (ONT) long-read sequencing was used to successfully differentiate SORD from the highly homologous non-functional SORD2P pseudogene and confirmed that the mutations were biallelic through haplotype-resolved analysis. The patient presented with axonal sensorimotor polyneuropathy (CMT2) and ulnar neuropathy without compression at the elbow. Burning neuropathic pain in the forearms and feet was also reported and was exacerbated by alcohol consumption and improved with alcohol cessation. UPLC-tandem mass spectrometry confirmed that the patient had elevated serum sorbitol levels (12.0 mg/L) consistent with levels previously observed in patients with biallelic SORD mutations. This represents a novel clinical presentation and expands the phenotype associated with biallelic SORD mutations causing CMT2. Our study is the first report of long-read sequencing for an individual with CMT and demonstrates the utility of this approach for clinical genomics.

Arrhythmia Recurrence After Atrial Fibrillation Ablation: Impact of Warfarin vs. Non-Vitamin K Antagonist Oral Anticoagulants.

PURPOSE: Both warfarin and non-vitamin K antagonist oral anticoagulants (NOACs) have pleiotropic effects including anti-inflammatory and anti-fibrotic properties. This study aims to explore whether arrhythmia recurrence after AF ablation is influenced by the choice of oral anticoagulant. METHODS: We retrospectively studied all patients who underwent primary AF ablation between 2011 and 2017 and divided them into two groups according to the anticoagulant used: Warfarin vs. NOACs. The primary endpoint was atrial tachyarrhythmia recurrence after ablation. RESULTS: Of the 1106 patients who underwent AF ablation in the study period (median age 62.5 years; 71.5% males, 48.2% persistent AF), 697 (63%) received warfarin and 409 (37%) received NOACs. After a median of 26.4 months follow-up, arrhythmia recurrence was noted in 368 patients in warfarin group and 173 patients in NOACs group, with a 1-year recurrence probability of 35% vs. 36% (log rank P = 0.81) and 5-year recurrence probability of 62% vs. 63% (Log rank P = 0.32). However, NOACs use was associated with a higher probability of recurrence (46% for 1 year, 68% for 5 years) in patients with persistent AF compared with those taking warfarin (34% for 1 year, 63% for 5 years; log rank P = 0.01 and P = 0.02 respectively). Multivariate analysis indicated that in patients with persistent AF, use of NOACs was an independent risk factor of atrial tachyarrhythmia recurrence after ablation (HR 1.39, 95% CI 1.07-1.81, P = 0.013). CONCLUSION: In this large contemporary cohort, overall AF recurrence after ablation was similar with NOACs or warfarin use. However, in patients with persistent AF, NOACs use was associated with a higher probability of arrhythmia recurrence and was an independent risk factor of recurrence at long-term follow-up.

Nitrous oxide-induced myeloneuropathy.

BACKGROUND AND PURPOSE: Nitrous oxide misuse is a recognized issue worldwide. Prolonged misuse inactivates vitamin B12, causing a myeloneuropathy. METHODS: Twenty patients presenting between 2016 and 2020 to tertiary hospitals in Sydney with myeloneuropathy due to nitrous oxide misuse were reviewed. RESULTS: The average age was 24 years, and mean canister consumption was 148 per day for 9 months. At presentation, paresthesias and gait unsteadiness were common, and seven patients were bedbound. Mean serum B12 was normal (258 pmol/L, normal range [NR] = 140-750) as was active B12 (87 pmol/L, normal > 35). In contrast, mean serum homocysteine was high (51 µmol/L, NR = 5-15). Spinal magnetic resonance imaging (MRI) showed characteristic dorsal column T2 hyperintensities in all 20 patients. Nerve conduction studies showed a predominantly axonal sensorimotor neuropathy (n = 5). Patients were treated with intramuscular vitamin B12, with variable functional recovery. Three of the seven patients who were bedbound at presentation were able to walk again with an aid at discharge. Of eight patients with follow-up data, most had persistent paresthesias and/or sensory ataxia. Mobility scores at admission and discharge were not significantly correlated with the serum total and active B12 levels or cumulative nitrous oxide use. There were no significant trends between serum active B12 level and cumulative nitrous oxide use (Spearman rho = -0.331, p = 0.195). CONCLUSIONS: Nitrous oxide misuse can cause a severe but potentially reversible subacute myeloneuropathy. Serum and active B12 can be normal, while elevated homocysteine and dorsal column high T2 signal on MRI strongly suggest the diagnosis. Neurological deficits can improve with abstinence and B12 supplementation, even in the most severely affected patients.

Radical Knowledge Management: Using Lessons Learned From Artists to Create Sustainable Workplaces.

This study weaves together research that has been published over the last 20 years and creates a narrative about how we can change our organisations so that they are fit-for-purpose in the 21st century. Using knowledge management as the starting point, the question "How do we move forward in a sustainable, holistic way to create organisations that are healthy and balanced among social, environmental, and financial performance (triple bottom line)?" needs to be answered. This brand new form of knowledge management is called radical knowledge management (radical KM).

Sinus rhythm heart rate increase after atrial fibrillation ablation is associated with lower risk of arrhythmia recurrence.

BACKGROUND: Pulmonary vein isolation (PVI) with autonomic modulation may be more successful than PVI alone for atrial fibrillation (AF) ablation and may be signaled by changes in sinus rhythm heart rate (HR) post ablation. We sought to determine if a change in sinus rhythm HR predicted AF recurrence post PVI. METHODS: Patients who underwent AF ablation from 2000 to 2011 were included if sinus rhythm was noted on ECG within 90 days pre and 7 days post ablation. Basic ECG interval and HR changes were analyzed and outcomes determined. RESULTS: A total of 1152 patients were identified (74.3% male, mean age 57 ± 11 years). Mean AF duration was 5.2 ± 5.3 years. Paroxysmal AF was noted in 712 (61.8%) of the patients. Mean EF was 61% ± 6%. Sinus rhythm HR was 61 ± 11 pre-ablation and 76 ± 13 bpm post-ablation (27% ± 24% increase, p < .001). The ability of relative HR change post-ablation to predict AF recurrence was borderline (hazard ratio 0.65 [0.41-1.01], p = .067). With patients separated into quartiles based on the relative HR change, the upper quartile with the largest relative increase in HR had a significantly lower rate of AF recurrence compared to the lowest quartile following multi variable modeling (p = .038). There were significant changes in PR (171 ± 28 to 167 ± 30 ms) and QTc (424 ± 25 to 434 ± 29 ms) intervals (both p < .001) but these were not predictive of outcome. CONCLUSION: Relative changes in HR post AF ablation correlates with AF recurrence. Further prospective studies are needed to confirm this relationship.

Structural and functional markers of optic nerve damage in myelin oligodendrocyte glycoprotein antibody-associated optic neuritis.

BACKGROUND: Optic neuritis (ON) occurs in immune-mediated disorders including multiple sclerosis (MS), aquaporin-4 antibody-positive (AQP4) neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination (MOGAD). Accurate determination of aetiology is critical for appropriate treatment and prognostication. OBJECTIVE: To evaluate demyelination and axonal loss in MOG-ON to facilitate differentiation from MS-ON and AQP4-ON. METHODS: 15 MOGAD patients with previous ON (25 eyes) underwent multifocal visual evoked potential (mfVEP) recordings and optical coherence tomography scans. Comparison was made to previously reported MS patients (n = 67, 69 eyes) and AQP4-NMOSD patients (n = 15, 23 eyes) with prior ON and healthy controls (n = 37, 74 eyes). RESULTS: MOG-ON patients had less retinal nerve fibre layer (RNFL) loss than AQP4-ON patients (p < 0.05) and less mfVEP latency prolongation than MS-ON patients (p < 0.01). Number of ON episodes in MOGAD was associated with reduced RNFL thickness (global, p = 0.07; temporal, p < 0.001) and mfVEP amplitude (p < 0.001). There was no abnormality in non-ON eyes. CONCLUSIONS: Our study demonstrated a distinct pattern of damage in MOG-ON compared to AQP4-ON and MS-ON. ON in MOGAD produces less axonal loss than AQP4-NMOSD. Damage accumulates with relapses, supporting the role of maintenance immunosuppression to induce remission. Compared to MS, MOGAD causes less demyelination.

Dissociation of functional and structural plasticity of dendritic spines during NMDAR and mGluR-dependent long-term synaptic depression in wild-type and fragile X model mice.

Many neurodevelopmental disorders are characterized by impaired functional synaptic plasticity and abnormal dendritic spine morphology, but little is known about how these are related. Previous work in the Fmr1-/y mouse model of fragile X (FX) suggests that increased constitutive dendritic protein synthesis yields exaggerated mGluR5-dependent long-term synaptic depression (LTD) in area CA1 of the hippocampus, but an effect on spine structural plasticity remains to be determined. In the current study, we used simultaneous electrophysiology and time-lapse two photon imaging to examine how spines change their structure during LTD induced by activation of mGluRs or NMDA receptors (NMDARs), and how this plasticity is altered in Fmr1-/y mice. We were surprised to find that mGluR activation causes LTD and AMPA receptor internalization, but no spine shrinkage in either wildtype or Fmr1-/y mice. In contrast, NMDAR activation caused spine shrinkage as well as LTD in both genotypes. Spine shrinkage was initiated by non-ionotropic (metabotropic) signaling through NMDARs, and in wild-type mice this structural plasticity required activation of mTORC1 and new protein synthesis. In striking contrast, NMDA-induced spine plasticity in Fmr1-/y mice was no longer dependent on acute activation of mTORC1 or de novo protein synthesis. These findings reveal that the structural consequences of mGluR and metabotropic NMDAR activation differ, and that a brake on spine structural plasticity, normally provided by mTORC1 regulation of protein synthesis, is absent in FX. Increased constitutive protein synthesis in FX appears to modify functional and structural plasticity induced through different glutamate receptors.

Spatial Multiplexing of Fluorescent Reporters for Imaging Signaling Network Dynamics.

In order to analyze how a signal transduction network converts cellular inputs into cellular outputs, ideally one would measure the dynamics of many signals within the network simultaneously. We found that, by fusing a fluorescent reporter to a pair of self-assembling peptides, it could be stably clustered within cells at random points, distant enough to be resolved by a microscope but close enough to spatially sample the relevant biology. Because such clusters, which we call signaling reporter islands (SiRIs), can be modularly designed, they permit a set of fluorescent reporters to be efficiently adapted for simultaneous measurement of multiple nodes of a signal transduction network within single cells. We created SiRIs for indicators of second messengers and kinases and used them, in hippocampal neurons in culture and intact brain slices, to discover relationships between the speed of calcium signaling, and the amplitude of PKA signaling, upon receiving a cAMP-driving stimulus.