Effectiveness of a multi-modal hospital-wide doctor mental health and wellness intervention.

BACKGROUND: Doctors report high rates of workplace stress and are at increased risk of mental health disorders. However, there are few real-world studies evaluating the effectiveness of interventions aimed at addressing workplace risk factors and improving doctors' mental health in a hospital setting. This study was conducted over two years (2017-2019) to assess the effects of a multi-modal intervention on working conditions doctors' mental health and help-seeking for mental health problems in two Australian teaching hospitals. METHODS: The multimodal intervention consisted of organisational changes, such as reducing unrostered overtime, as well as strategies for individual doctors, such as mental health training programs. Hospital-based doctors at all career stages were eligible to participate in two cross-sectional surveys. 279 doctors completed the baseline survey (19.2% response rate) and 344 doctors completed the follow-up survey (31.3% response rate). A range of workplace risk and protective factors, mental health (psychological distress and suicidal ideation) and help-seeking outcomes were assessed. RESULTS: There were significant improvements in key workplace protective factors, with small effects found for doctors' job satisfaction, stress, work-life balance and perceived workplace support and a significant reduction in workplace risk factors including a moderate reduction in reported bullying behaviour between baseline to follow-up (job satisfaction p < 0.05, all other outcomes p < 0.01). However, no significant changes in doctors' mental health or help-seeking outcomes were found over the intervention period. CONCLUSION: Following the implementation of individual and organisational-level strategies in two Australian tertiary hospitals, doctors reported a reduction in some key workplace stressors, but no significant changes to their mental health or help-seeking for mental health problems. Further research is warranted, particularly to determine if these workplace changes will lead to improved mental health outcomes for doctors once maintained for a longer period.

A Review of Chlorhexidine Oral Care in Patients Receiving Mechanical Ventilation.

BACKGROUND: Chlorhexidine gluconate has been considered the criterion standard of oral care for patients receiving mechanical ventilation because of its ability to reduce the incidence of ventilator-associated events. Optimal concentrations and frequencies remain unclear, as do adverse events related to mortality in various intensive care unit populations. OBJECTIVE: To examine the current evidence for the efficacy of chlorhexidine gluconate in reducing the incidence of ventilator-associated events, mortality, intensive care unit length of stay, and duration of mechanical ventilation in patients receiving ventilator support. METHODS: In this integrative review, CINAHL (Cumulative Index to Nursing and Allied Health Literature), MEDLINE, and Health Source: Nursing/Academic Edition were searched using terms related to mechanical ventilation and chlorhexidine gluconate oral care with dates ranging from 2012 to 2023. RESULTS: Seventeen articles were included in this review: 8 systematic reviews, 8 randomized clinical trials (3 of which were not included in any systematic review), and 1 quasi-experimental study. Chlorhexidine gluconate oral care was associated with a reduced incidence of ventilator-associated events, but efficacy depended on concentration and frequency of administration. With stratification by intensive care unit population type, a nonsignificant trend toward increased mortality was found among non-cardiac surgical patients who received this care. CONCLUSION: The evidence regarding the efficacy of chlorhexidine gluconate oral care in reducing ventilator-associated events in specific intensive care unit populations is contradictory. Recently published guidelines recommend de-implementation of chlorhexidine gluconate oral care in all patients receiving mechanical ventilation. Such care may be beneficial only in the cardiac surgical population.

Discovery and characterization of NVP-QAV680, a potent and selective CRTh2 receptor antagonist suitable for clinical testing in allergic diseases.

Optimization of a 7-azaindole-3-acetic acid CRTh2 receptor antagonist chemotype derived from high throughput screening furnished a highly selective compound NVP-QAV680 with low nM functional potency for inhibition of CRTh2 driven human eosinophil and Th2 lymphocyte activation in vitro. The molecule exhibited good oral bioavailability in the rat, combined with efficacy in rodent CRTh2-dependent mechanistic and allergic disease models and was suitable for clinical development.

Case report: imaging features in a renal transplant patient with calcineurin inhibitor-induced pain syndrome (CIPS).

Post-transplant distal limb bone marrow edema syndrome or calcineurin inhibitor-induced pain syndrome (CIPS) is generally a self-limiting but debilitating acute pain syndrome that has been reported in 2-14 % of renal transplant recipients. The disease is extensively described in the transplant literature in patients receiving the calcineurin inhibitors cyclosporine and tacrolimus. We present a case of CIPS arising in a patient 73 days after renal allograft, review the imaging findings, and discuss proposed etiologies and differential diagnoses. To the authors' knowledge, CIPS has not been characterized as a distinct entity in the radiology literature.

Generation of a thermostable, oral Zika vaccine that protects against virus challenge in non-human primates.

Here we report the development of a thermally stable, orally administered, candidate Zika vaccine using human serotype 5 adenovirus (AdHu5). We engineered AdHu5 to express the genes for the envelope and NS1 proteins of Zika virus. AdHu5 was formulated using a proprietary platform, OraPro, comprising a mix of sugars and modified amino acids that can overcome elevated temperatures (37 C), and an enteric coated capsule that protects the integrity of the AdHu5 from the acid in the stomach. This enables the delivery AdHu5 to the immune system of the small intestine. We show that oral delivery of AdHu5 elicited antigen-specific serum IgG immune responses in a mouse model and in a non-human primate model. Importantly, these immune responses were able reduce viral counts in mice and to prevent detectable viraemia in the non-human primates on challenge with live Zika virus. This candidate vaccine has significant advantages over many current vaccines that are maintained in a cold or ultra-cold chain and require parenteral administration.

Protein disulphide isomerase family members show distinct substrate specificity: P5 is targeted to BiP client proteins.

At least 17 members of the protein disulphide isomerase (PDI) family of oxidoreductases are present in the endoplasmic reticulum (ER) of mammalian cells. They are thought to catalyse disulphide formation to aid folding or to regulate protein function; however, little is known about their individual functions. Here, we show that some proteins that enter the ER are clients for single oxidoreductases, whereas others are clients for several PDI-like enzymes. We previously identified potential substrates for ERp57, and here identify substrates for ERp18 and ERp46. In addition, we analysed the specificity of substrates towards PDI, ERp72, ERp57, ERp46, ERp18 and P5. Strikingly, ERp18 shows specificity towards a component of the complement cascade, pentraxin-related protein PTX3, whereas ERp46 has specificity towards peroxiredoxin-4, a thioredoxin peroxidase. By contrast, most PDI family members react with Ero1alpha. Moreover, P5 forms a non-covalent complex with immunoglobulin heavy chain binding protein (BiP) and shows specificity towards BiP client proteins. These findings highlight cooperation between BiP and P5, and demonstrate that individual PDI family members recognise specific substrate proteins.

Regulation of neuregulin 1beta1-induced MUC5AC and MUC5B expression in human airway epithelium.

Excessive mucus production has been linked to many of the pathologic features of respiratory diseases, including obstruction of the airways, decline in lung function, increased rates of mortality, and increased infections. The mucins, MUC5AC and MUC5B, contribute to the viscoelastic properties of mucus, and are found at elevated levels in the airways of individuals with chronic respiratory diseases. The T helper type 2 cell cytokine, IL-13, is known to regulate MUC5AC expression in goblet cells of the airways, although much less is known about the regulation of MUC5B expression. In a study to further understand the mediators of MUC5AC and MUC5B expression, neuregulin (NRG) 1beta1 was identified as novel regulator of goblet cell formation in primary cultures of human bronchial epithelial cells (HBECs). NRG1beta1 increased expression of MUCAC and MUC5B proteins in a time- and dose-dependent fashion in HBEC cultures. NRG1beta1-induced expression of MU5AC and MUC5B was shown to involve v-erb-b2 erythroblastic leukemia viral oncogene homolog (ErbB) and ErbB3 receptors, but not ErbB4 receptors. Treatment of HBECs with inhibitors of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase1/2, and phosphatidylinositol 3-kinase indicated that these kinases were involved in NRG1beta1-induced MUC5AC and MUC5B expression. Additionally, NRG1beta1 was shown to induce the phosphorylation of the ErbB2 receptor, AKT, and extracellular signal-regulated kinase 1/2. NRG1beta1 protein was found increased in the airways of antigen-challenged mice, together with increases in MUC5AC and MUC5B message. Together, these data indicate that NRG1beta1 is a novel mediator of MUC5AC and MUC5B expression in HBECs, and may represent a novel therapeutic target for mucus hypersecretion in respiratory diseases.

Association of asymptomatic peripheral arterial disease with vascular events in patients with stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Patients with stroke and patients with transient ischemic attack (TIA) are at high risk for vascular events and may not exhibit the signs and symptoms of peripheral arterial disease (PAD). We investigated if asymptomatic PAD detected by ankle brachial index <0.9 is independently associated with recurrent vascular events in patients with stroke or TIA. METHODS: In this prospective longitudinal hospital-based cohort study, asymptomatic PAD was detected by ankle brachial index measurement in consecutive patients with stroke and patients with TIA. They were assessed for stroke risk factors, ankle brachial index measurement, and laboratory parameters known to be associated with stroke risk. These patients were followed for composite vascular events, including stroke, TIA, myocardial infarction, and vascular death. RESULTS: In a 1-year period, 102 patients were evaluated, of whom 26% had asymptomatic PAD. All patients were followed for a median period of 2.1 years from the index stroke/TIA (range, 1.0 to 2.7 years) for vascular events. Kaplan-Meier curve showed fewer patients with asymptomatic PAD remained free of composite vascular events (48% compared with 84% in the no-PAD group; log rank, P=0.0001). Asymptomatic PAD was significantly associated with composite vascular events before (hazard ratio, 4.2; 95% CI, 1.9 to 9.3; P=0.0003) and after adjustment for confounders (hazard ratio, from Model 1, 2.8; 95% CI, 1.1 to 7.2; P=0.03 and Model 2, 3.4; 95% CI, 1.4 to 8.2, P=0.006). Asymptomatic PAD was also significantly associated with stroke before (hazard ratio, 6.5; 95% CI, 2.1 to 19.9; P=0.001) and after adjustment for confounders (hazard ratio from Model 1, 4.8; 95% CI, 1.5 to 15.3; P=0.009 and Model 2, 5.2; 95% CI, 1.5 to 17.6; P=0.008). CONCLUSIONS: In patients with stroke or TIA, asymptomatic PAD is independently associated with recurrent vascular events and stroke.

Aortic arch atheroma progression and recurrent vascular events in patients with stroke or transient ischemic attack.

BACKGROUND: It is not known whether progression of aortic arch (AA) atheroma is associated with vascular events in patients with stroke or transient ischemic attack (TIA). METHODS AND RESULTS: AA atheroma was detected on baseline transesophageal echocardiogram in 167 consecutive patients who had prevalent stroke or TIA. Of these, 125 consented to a follow-up transesophageal echocardiogram at 12 months. Adequate paired AA images were obtained in 117 (78 with strokes, 39 with TIAs), which allowed detailed measurements of plaques. On admission for their index stroke or TIA, patients were assessed for stroke risk factors, stroke subtypes, baseline AA plaque characteristics, and laboratory parameters. Progression of AA atheroma was observed in 33 patients (28%) on 12-month follow-up transesophageal echocardiogram. It was determined that the progression group had significantly higher adjusted homocysteine levels (P<0.0001) and neutrophil counts (P<0.0001) than the no-progression group. These patients were followed up for a median of 1.7 years from the index stroke/TIA (range 0.5 to 4.5 years) for vascular events including stroke, TIA, myocardial infarction, and death due to vascular causes. Kaplan-Meier curves showed fewer patients with AA atheroma progression remained free of the composite vascular end point (49% compared with 89% in the no-progression group; P<0.0001). AA atheroma progression was associated with composite vascular events (hazard ratio 5.8, 95% confidence interval 2.3 to 14.5, P=0.0002) after adjustment for a propensity score based on confounders. CONCLUSIONS: In this preliminary study of stroke/TIA patients with AA atheroma on transesophageal echocardiogram, AA atheroma progression was associated with recurrent vascular events.

Mindfulness-Based Cognitive Therapy for Young People and Their Carers: a Mixed-Method Feasibility Study.

We aimed to evaluate whether mindfulness-based cognitive therapy (MBCT) was feasible and acceptable for young people, their parents and the clinicians working with them; whether a parallel course for parents was a useful addition; and whether attendance at MBCT was associated with improved outcomes. The design was a mixed-method service evaluation of an eight-session MBCT programme for young people who were recovering from depression. The course was a manualised eight-session group intervention. Both young people (n = 18) and parents (n = 21) completed validated measures before and after the course. Semi-structured interviews were completed with some group participants and clinical staff working in the service. Care records were searched for additional contact following the intervention. Qualitative data from young people, parents and clinicians suggested that MBCT was acceptable and feasible and provided strategies to cope. The parent course was reported to provide personal support to parents and helped them cope with their child's depression whilst also impacting the family, promoted shared understanding of depression and strategies to combat it and addressed intergenerational aspects of depression. Eighty-four per cent of participants attended at least 6/8 sessions, and 48% required no further intervention within the following year. Young people had statistically significant improvements across all outcome measures, whilst parents had statistically significant improvements in rumination, self-compassion and decentring.

Association of leukocyte count with progression of aortic atheroma in stroke/transient ischemic attack patients.

BACKGROUND AND PURPOSE: Leukocyte count is an independent predictor of stroke. We investigated the association between leukocyte count and progression of aortic atheroma over 12 months in stroke/transient ischemic attack (TIA) patients. METHODS: Consecutive ischemic stroke and transient ischemic attack patients underwent 12-month sequential transesophageal echocardiography and were assessed for total and differential leukocyte counts on admission. Paired aortic plaque images were assessed for several parameters, including changes in grade, intimal-medial thickness (IMT), and cross-sectional area. Multivariate linear and logistic regressions were used to calculate the effect of leukocyte count on the change in aortic atheromas over 12 months. RESULTS: Of the 115 participants (mean+/-SD age, 64.6+/-11.9 years; 53.1% men; 73.4% white, 24.2% black, and 2.3% Asian), 45 (35%) showed clinically significant progression of aortic atheromas (maximal change in IMT >0.70 mm over 12 months). The mean admission leukocyte count was higher in the progression group compared with the no-progression group (8.6+/-2.2 vs 7.3+/-2.2 x 10(9)/L respectively, P=0.002). Each unit increase in leukocyte count was associated with a 0.26-mm increase in aortic arch IMT over 12 months (P=0.006). After adjustment for other atherosclerosis risk factors, the relation persisted (mean increase in aortic arch IMT per unit increase in leukocyte count=0.27 mm, P=0.007). Each unit increase in leukocyte count was associated with an increased risk of significant progression of aortic atheromas (adjusted odds ratio=1.33; 95% CI, 1.09 to 1.61). CONCLUSIONS: In stroke/transient ischemic attack patients, leukocyte count is independently associated with the progression of aortic atheroma over 12 months (>0.70 mm), which is associated with cardiovascular risk.

Assessment of comparative treatment satisfaction with sildenafil citrate and penile injection therapy in patients responding to both.

OBJECTIVE: To survey patient satisfaction, using validated questionnaires, in a group of men with erectile dysfunction who had used and responded to both sildenafil citrate and intracavernosal injection (ICI) therapy. PATIENTS AND METHODS: In all, 300 patients on ICI therapy were mailed questionnaire packets containing a survey enquiring about the patients' medical history, and two sets of the International Index of Erectile Function (IIEF) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) sexual function surveys. If patients were using sildenafil alternating with ICI they were asked to complete the IIEF and EDITS questionnaires for each therapy. To identify only patients who had an adequate response to each agent, a score of >/=22 on the EF domain of the IIEF for sildenafil and ICI was required for inclusion in the final analysis. RESULTS: In all, 178 packets were evaluable; 123 men (69%) responded to ICI but not sildenafil, and 11 (6%) responded only to sildenafil and not ICI, leaving 37 patients who responded to both; these patients comprised the study population. There was no difference in EF domain score of the IIEF between the treatments; EDITS scores were significantly higher for ICI therapy than for sildenafil (P < 0.001). CONCLUSIONS: In patients who alternate the use of sildenafil and ICI therapy, satisfaction appears to be higher with ICI, although the erectogenic performance is similar. This suggests that patient satisfaction does not depend solely on erection performance, and that patients might benefit from various treatment options.

Chemotherapeutic Medications and Their Emergent Complications.

Patients with complications of chemotherapy, either acute or chronic, are frequently encountered in the emergency department (ED). Some patients present with complaints immediately after chemotherapy administration, whereas others may show subtle, secondary signs or may have no signs or symptoms of chemotoxicity. An increased index of suspicion prompts early recognition, diagnosis, and prevention of further iatrogenic injury. This article reviews characteristic hypersensitivity reactions, typical organ system dysfunction, and treatment strategies for adult patients who present to the ED with complications after chemotherapy.

Long-Term Deficits in Cortical Circuit Function after Asphyxial Cardiac Arrest and Resuscitation in Developing Rats.

Cardiac arrest is a common cause of global hypoxic-ischemic brain injury. Poor neurologic outcome among cardiac arrest survivors results not only from direct cellular injury but also from subsequent long-term dysfunction of neuronal circuits. Here, we investigated the long-term impact of cardiac arrest during development on the function of cortical layer IV (L4) barrel circuits in the rat primary somatosensory cortex. We used multielectrode single-neuron recordings to examine responses of presumed excitatory L4 barrel neurons to controlled whisker stimuli in adult (8 ± 2-mo-old) rats that had undergone 9 min of asphyxial cardiac arrest and resuscitation during the third postnatal week. Results indicate that responses to deflections of the topographically appropriate principal whisker (PW) are smaller in magnitude in cardiac arrest survivors than in control rats. Responses to adjacent whisker (AW) deflections are similar in magnitude between the two groups. Because of a disproportionate decrease in PW-evoked responses, receptive fields of L4 barrel neurons are less spatially focused in cardiac arrest survivors than in control rats. In addition, spiking activity among L4 barrel neurons is more correlated in cardiac arrest survivors than in controls. Computational modeling demonstrates that experimentally observed disruptions in barrel circuit function after cardiac arrest can emerge from a balanced increase in background excitatory and inhibitory conductances in L4 neurons. Experimental and modeling data together suggest that after a hypoxic-ischemic insult, cortical sensory circuits are less responsive and less spatially tuned. Modulation of these deficits may represent a therapeutic approach to improving neurologic outcome after cardiac arrest.

Effect of surface treatments on the mechanical properties and antimicrobial activity of desiccated glass ionomers.

OBJECTIVES: The purpose of this study was to evaluate the effect of various surface treatments on the mechanical properties and antibacterial activity of desiccated glass-ionomer (GI) and resin-modified glass-ionomer (RMGI) materials. METHODS: One hundred GI and RMGI specimens were fabricated in a mold, stored in 100% humidity for 24h, placed in air to desiccate for 24h, and then stored for one week in one of the five media [casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), chlorhexidine (CHX), sodium fluoride (NaF), cetylpyridinium chloride (CPC), or 100% humidity (control)]. Fifty GI and RMGI specimens were tested in flexure to determine flexural strength and modulus, with the fragments used for Knoop hardness testing. The remaining 50 GI and RMGI specimens were covered with a suspension of Streptococcus mutans and incubated for 24h. The bacterial suspension was removed and the specimens were washed. Sterile saline was added, vortex mixed, serially diluted, and plated. CFU/mLs were calculated after 3days of incubation. RESULTS: Compared to the 100% humidity control group, surface treatment of the desiccated GI and RMGI materials had a variable effect on the mechanical properties. In general, NaF provided the greatest improvement in flexural strength and modulus. Surface treatment of the desiccated GI or RMGI specimens with CHX or CPC resulted in no growth of the S. mutans. NaF resulted in significantly lower CFU/mL than CPP-ACP, which was significantly lower than the control group. SIGNIFICANCE: Surface treatment with 5% NaF provides improved antimicrobial and strength properties of desiccated GI or RMGI materials.

Dissipation of [(14)C]acetochlor herbicide under anaerobic aquatic conditions in flooded soil microcosms.

Acetochlor degradation was studied under anaerobic conditions representative of conditions in flooded soils. Soil-water microcosms were prepared with a saturated Drummer clay loam and made anaerobic by either glucose pretreatment or N(2) sparging. Sparged microcosms consisted of sulfate-amended, unamended, and gamma-irradiated microcosms. The microcosms were sampled in triplicate at predetermined time intervals during a 371 day incubation period. Volatile, aqueous, extractable, and bound (unextractable) (14)C residues were quantified with liquid scintillation counting and characterized using high-performance liquid radiochromatography (HPLRC) and soil combustion. SO(4)(2)(-), Fe(II), CH(4), and pH were monitored. Complete anaerobic degradation of [(14)C]acetochlor was observed in all viable treatments. The time observed for 50% acetochlor disappearance (DT(50)) was 10 days for iron-reducing and sulfate-reducing conditions (sulfate-amended), 15 days for iron-reducing conditions (unamended), and 16 days for methanogenic conditions (glucose-pretreated). Acetochlor remained after 371 days in the gamma-irradiated microcosms, and metabolites were observed. [(14)C]Metabolites were detected throughout the study. Formation of one of the metabolites correlated with Fe(II) formation (r(2)(), 0.83). A significant portion of the (14)C activity was eventually incorporated into soil-bound residue (30-50% of applied acetochlor) in all treatments.

Chemotherapeutic medications and their emergent complications.

Patients with complications of chemotherapy, either acute or chronic, are frequently encountered in the emergency department (ED). Some patients present with complaints immediately after chemotherapy administration, whereas others may show subtle, secondary signs or may have no signs or symptoms of chemotoxicity. An increased index of suspicion prompts early recognition, diagnosis, and prevention of further iatrogenic injury. This article reviews characteristic hypersensitivity reactions, typical organ system dysfunction, and treatment strategies for adult patients who present to the ED with complications after chemotherapy.