The use of interventional procedures for cancer pain. A brief review.

CONTEXT: Pain is a common experience in people living with cancer. Concerns around opioid prescribing have seen a move toward a multi-modality management approach, which includes interventional pain procedures. PURPOSE: In this paper we discuss the interventional pain procedures used to treat cancer pain at two major tertiary centers in Australia. METHODS AND RESULTS: This expert review provides practical insights on cancer pain management from healthcare providers in different specialties. These insights can be used to guide the management of a wide range of cancer pain types. CONCLUSIONS: Furthermore, this review identifies the need for a systematic and comprehensive approach to the management of cancer pain that is broader than that of a single specialty. With recent advances in pain management procedures, an interdisciplinary approach is essential in order to provide an up to date, patient tailored approach to pain management. This review will help inform the development of a cancer pain intervention registry.

Current Practices and Attitudes of Cardiac Nurses Regarding Cognitive Screening in Patients With Acute Coronary Syndrome.

BACKGROUND: Cognitive impairment (CI) is common in patients with acute coronary syndrome (ACS) but is often undetected and may affect recovery and secondary prevention uptake. Nurses play a crucial role providing care for patients with ACS and promoting secondary prevention. AIM: This study aimed to explore current nursing practices and barriers regarding CI screening in patients with ACS. METHODS: Cardiac nurses were recruited from three metropolitan teaching hospitals and two professional associations in Australia and undertook a 38-question purpose-built survey. RESULTS: A total of 95 nurses participated (mean age 38±13 years; 78% [n=74] female): 69 were registered nurses, and 48% had received CI training. Only 16% of nurses in our sample reported that they regularly screen for CI, and 23% reported that they never screen; however, 59% believed screening should be part of everyday practice. Nurses mostly screened when ward policy required admission/daily cognitive screening (34%) or when they suspected cognitive problems or decline (39%). Nurses in acute settings (vs non-acute) were nine times more likely to screen when adjusting for confounders. The typically used screening instruments assessed delirium/confusion and dementia but not milder CI. Common barriers to screening included communication difficulties, patients too unstable/unwell, time constraints requiring clinical care prioritisation, and being unaware of patients' normal cognition status. CONCLUSIONS: Screening practices for CI in the context of ACS were found to be suboptimal, with only 16% of nurses in our sample reporting regularly screening. The most used methods focus on screening for delirium. Given current practice, many CI cases will be missed, especially mild CI, which will negatively affect secondary prevention efforts. Further research is required to identify appropriate methods to implement routine screening within the nursing clinical workflow and establish a suitable screening tool.

Management of pain in cancer patients- lessons from practices during the COVID-19: a qualitative study of cancer care providers' perspectives.

BACKGROUND: The ongoing COVID-19 pandemic has impacted health systems globally and affected managing many chronic conditions, including cancer. This study aimed to explore the perceptions of multi-disciplinary cancer care providers on how cancer pain management was affected by the COVID-19 pandemic. METHODS: Participants were eligible if they were cancer care providers of any specialty and discipline from two tertiary hospitals in Australia. Data were collected using semi-structured interviews to explore cancer care providers' perspectives on cancer pain management within COVID-19. Thematic analysis of interview transcripts used an integrated approach that started with inductive coding before coding deductively against a behaviour framework called the COM-B Model, which proposes that 'capability', 'motivation' and 'opportunity' are requisites for any behaviour. RESULTS: Twenty-three providers participated. Five themes were developed and interpreted from the analysis of data, namely: "Telehealth enables remote access to cancer pain management but also created a digital divide", "Access to cancer pain management in the community is compromised due to the pandemic", "COVID-19 negatively impacts hospital resource allocation", "Patients were required to trade off cancer pain management against other health priorities" and "Hospital restrictions result in decreased social and psychological support for patients with cancer pain". CONCLUSIONS: The landscape of cancer pain management in the Australian health system underwent substantial shifts during the COVID-19 pandemic, with lasting impacts. Cancer care providers perceived the pandemic to have significant adverse effects on pain management across multiple levels, with repercussions for patients experiencing cancer-related pain. A more adaptive health system model needs to be established in the future to accommodate vulnerable cancer patients.

Lower cardiac rehabilitation enrolment occurs in acute coronary syndrome patients who report low levels of physical activity at four weeks post-event: A prospective observational study using physical activity tracker data.

BACKGROUND: Physical activity (PA) and cardiac rehabilitation (CR) attendance are important for recovery and prognosis following acute coronary syndrome (ACS). However, PA patterns early post-ACS are not well known. OBJECTIVES: Investigate the level of PA at 4-weeks post-ACS and any potential associations with CR enrolment. METHODS: We recruited patients admitted for ACS from cardiac wards and clinics at two hospital sites in Sydney, Australia. PA data were collected using wearable activity trackers worn at 4-weeks post-ACS, and CR enrolment was self-reported. RESULTS: Participants (n = 61) were aged 66.7 ± 10.3 years, 74 % male, 61 % were married or partnered, and 33 % were diagnosed with ST-elevation myocardial infarction. Patients engaged in 7514±3355 steps per day and 44.6 ± 37.5 min of moderate-to-vigorous physical activity (MVPA). Patients who enrolled in CR exhibited higher daily step counts (p = 0.044), MVPA minutes (p = 0.001), and were more likely to meet PA guidelines. ACS patients who engaged in higher levels of MVPA were more likely to enrol in CR (odds ratio [OR] 1.46; 95 % confidence interval [CI] 1.08, 1.98). CR enrolment was also positively associated with being married or in an intimate partnership (OR 9.93; 95 % CI 1.83, 53.85) and absence of depressive symptoms (OR 11.86; 95 % CI 1.91, 73.74). CONCLUSION: Lower CR enrolment rates were observed among less physically active patients at 4-weeks post-ACS. However, each 10 min increment in MVPA increased the odds of CR enrolment by 46 %. Future research should explore strategies to target this inactive and high-risk group, given the potential for a large prognostic gain with CR participation.

Age and Marital Status Predict Mild Cognitive Impairment During Acute Coronary Syndrome Admission: An Observational Study of Acute Coronary Syndrome Inpatients.

BACKGROUND: Mild cognitive impairment (MCI) has been reported after acute coronary syndrome (ACS), but it is uncertain who is at risk, particularly during inpatient admission. OBJECTIVE: In this study, we aimed to explore the prevalence and cognitive domains affected in MCI during ACS admission and determine factors that identify patients most at risk of MCI. METHODS: Inpatients with ACS were consecutively recruited from 2 tertiary hospital cardiac wards and screened with the Montreal Cognitive Assessment and the Hopkins Verbal Learning Test. Screening included health literacy (Newest Vital Sign), depressive symptoms (Patient Health Questionnaire-9), and physical activity (Physical Activity Scale for the Elderly). Factors associated with MCI were determined using logistic regression. RESULTS: Participants (n = 81) had a mean (SD) age of 63.5 (10.9) years, and 82.7% were male. In total, MCI was identified in 52.5%, 42.5% with 1 screen and 10% with both. Individually, the Montreal Cognitive Assessment identified MCI in 48.1%, and the Hopkins Verbal Learning Test identified MCI in 13.8%. In Montreal Cognitive Assessment screening, the cognitive domains in which participants most frequently did not achieve the maximum points available were delayed recall (81.5%), visuospatial executive function (48.1%), and attention (30.9%). Accounting for education, depression, physical activity, and ACS diagnosis, the likelihood of an MCI positive screen increased by 11% per year of age (odds ratio, 1.11; 95% confidence interval, 1.04-1.18) and by 3.6 times for those who are unmarried/unpartnered (odds ratio, 3.61; 95% confidence interval, 1.09-11.89). CONCLUSION: An estimated half of patients with ACS screen positive for MCI during admission, with single and older patients most at risk. Multiple areas of thinking were affected with potential impact on capacity for learning heart disease management.

Segmentation-Assisted Fully Convolutional Neural Network Enhances Deep Learning Performance to Identify Proliferative Diabetic Retinopathy.

With the progression of diabetic retinopathy (DR) from the non-proliferative (NPDR) to proliferative (PDR) stage, the possibility of vision impairment increases significantly. Therefore, it is clinically important to detect the progression to PDR stage for proper intervention. We propose a segmentation-assisted DR classification methodology, that builds on (and improves) current methods by using a fully convolutional network (FCN) to segment retinal neovascularizations (NV) in retinal images prior to image classification. This study utilizes the Kaggle EyePacs dataset, containing retinal photographs from patients with varying degrees of DR (mild, moderate, severe NPDR and PDR. Two graders annotated the NV (a board-certified ophthalmologist and a trained medical student). Segmentation was performed by training an FCN to locate neovascularization on 669 retinal fundus photographs labeled with PDR status according to NV presence. The trained segmentation model was used to locate probable NV in images from the classification dataset. Finally, a CNN was trained to classify the combined images and probability maps into categories of PDR. The mean accuracy of segmentation-assisted classification was 87.71% on the test set (SD = 7.71%). Segmentation-assisted classification of PDR achieved accuracy that was 7.74% better than classification alone. Our study shows that segmentation assistance improves identification of the most severe stage of diabetic retinopathy and has the potential to improve deep learning performance in other imaging problems with limited data availability.

Cognitive Function and the Relationship With Health Literacy and Secondary Prevention in Patients With Acute Coronary Syndrome at Early Discharge: A Prospective Observational Study.

BACKGROUND: Cognitive impairment (CI) may contribute to difficulties in understanding and implementing secondary prevention behavior change after acute coronary syndrome (ACS), but the association is poorly understood. OBJECTIVES: The aim of this study was to explore the prevalence of CI in patients 4 weeks post ACS and the association with health literacy and secondary prevention. METHODS: Patients with ACS who were free from visual deficits, auditory impairment, and dementia diagnoses were recruited and assessed 4 weeks post discharge for cognitive function (Montreal Cognitive Assessment and Hopkins Verbal Learning Test), health literacy (Newest Vital Sign), depression (Patient Health Questionnaire), physical activity (Fitbit Activity Tracker and Physical Activity Scale for the Elderly), and medication knowledge and adherence. RESULTS: Participants (n = 45) had an average age of 65 ± 11 years, 82% were male, 64% were married/partnered, and 82% had high school education or higher. Overall CI was identified in 28.9% (n = 13/45) of the patients 4 weeks after discharge, which was composed of patients detected on both the Montreal Cognitive Assessment and Hopkins Verbal Learning Test (n = 3), patients detected on Montreal Cognitive Assessment alone (n = 6), and patients detected on Hopkins Verbal Learning Test alone (n = 4). Fewer patients with CI had adequate health literacy (61.4%) than patients with normal cognition (90.3%, P = .024). Significant correlations were found between Hopkins Verbal Learning Test scores and medication knowledge (0.4, P = .008) and adherence (0.33, P = .029). CONCLUSIONS: In this exploratory study, 30% of patients with ACS demonstrated CI at 4 weeks post discharge. Two screening instruments were required to identify all cases. Cognitive impairment was significantly associated with health literacy and worth further investigation.

Sensitivity and specificity of 5 min cognitive screening tests in patients with acute coronary syndrome.

AIMS: This study aimed to determine the sensitivity and specificity of the National Institute of Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) brief (5 min) screen composed of three items of the Montreal Cognitive Assessment (MoCA), in acute coronary syndrome (ACS) patients during hospital admission, relative to the full MoCA and potential alternative combinations of other items. METHODS AND RESULTS: Participants were consecutively recruited during ACS admission and administered the MoCA before discharge. The three NINDS-CSN screen items were extracted, collated and compared to the full MoCA. Receiver operator characteristic (ROC) curves were created to determine the sensitivity, specificity, and appropriate cut-off scores of the screens. The mean age of the sample (n = 81) was 63.49 [standard deviation (SD) 10.85] years and 49.4% screened positive for cognitive impairment. The NINDS-CSN mean score was 9.22 (SD 2.09 of the potential range 0-12). Area under the ROC (AUC) indicated high accuracy levels for screening for cognitive impairment (AUC = 0.89, P < 0.01, 95% confidence interval 0.82, 0.96) with none of the alternative combination screens performing better on both sensitivity and specificity. A cut-off score of ≤10 on the NINDS-CSN protocol provided 83% sensitivity and 80% specificity for classifying cognitive impairment. CONCLUSION: The NINDS-CSN protocol presents an accurate, feasible screen for cognitive impairment in patients following ACS for use at the bedside and potentially also for telephone screens. Diagnostic accuracy should be confirmed using a neurocognitive battery.

Effects of hypnosis versus enhanced standard of care on postoperative opioid use after total knee arthroplasty: the HYPNO-TKA randomized clinical trial.

BACKGROUND: Hypnosis decreases perioperative pain and has opioid-sparing potential but has not been rigorously studied in knee arthroplasty. This trial investigates the impact of perioperative hypnosis on inpatient opioid use following total knee arthroplasty. METHODS: This prospective randomized controlled trial was conducted at a single academic medical center. The hypnosis arm underwent a scripted 10 min hypnosis session prior to surgery and had access to the recorded script. The control arm received hypnosis education only. The primary outcome was opioid use in milligram oral morphine equivalents per 24 hours during hospital admission. A secondary analysis was performed for patients taking opioids preoperatively. RESULTS: 64 primary knee arthroplasty patients were randomized 1:1 to hypnosis (n=31) versus control (n=33) and included in the intent-to-treat analysis. The mean (SD) postoperative opioid use in oral morphine equivalents per 24 hours was 70.5 (48.4) in the hypnosis versus 90.7 (74.4) in the control arm, a difference that was not statistically significant (difference -20.1; 95% CI -51.8 to 11.4; p=0.20). In the subgroup analysis of the opioid-experienced patients, there was a 54% daily reduction in opioid use in the hypnosis group (82.4 (56.2) vs 179.1 (74.5) difference of -96.7; 95% CI -164.4 to -29.0; p=<0.01), equivalent to sparing 65 mg of oxycodone per day. CONCLUSION: Perioperative hypnosis significantly reduced inpatient opioid use among opioid-experienced patients only. A larger study examining these findings is warranted. TRIAL REGISTRATION NUMBER: NCT03308071.

Cognitive impairment and psychological state in acute coronary syndrome patients: A prospective descriptive study at cardiac rehabilitation entry, completion and follow-up.

BACKGROUND: Cognitive impairment may limit the uptake of secondary prevention in acute coronary syndrome patients, but is poorly understood, including in cardiac rehabilitation participants. AIM: The aim of this study was to explore cognitive impairment in relation to psychological state in acute coronary syndrome patients over the course of cardiac rehabilitation and follow-up. METHODS: Acute coronary syndrome patients without diagnosed dementia were assessed on verbal learning, processing speed, executive function and visual attention, at cardiac rehabilitation entry, completion and follow-up and scores adjusted using normative data. The hospital anxiety and depression scale measured psychological state. RESULTS: Participants (n = 40) had an average age of 66.2 (±8.22) years and were 70% men. Mild cognitive impairment occurred at cardiac rehabilitation entry in single 62.5% and multiple 22.5% domains but was significantly less prevalent by cardiac rehabilitation completion (52.5% and 15.0%) and follow-up (32.5% and 7.0%). Domains most often impaired were verbal learning (52.5%) and processing speed (25.6%), again decreasing significantly with time (verbal learning cardiac rehabilitation completion 42.5%, follow-up 22.5%; processing speed cardiac rehabilitation completion 15.0%, follow-up 15.0%). A small group of patients had persistent multiple domain cognitive impairment. At cardiac rehabilitation entry patients with cognitive impairment in processing speed, a single domain or multiple domains had more depression, and patients with cognitive impairment in executive function had more depression and anxiety. CONCLUSIONS: At cardiac rehabilitation entry, mild cognitive impairment is very common in post-acute coronary syndrome patients and worse in patients who have depression or anxiety symptoms. Cognitive impairment decreases significantly by cardiac rehabilitation follow-up. A small proportion of patients has persistent, multiple domain cognitive impairment flagging potential long-term changes and the need for further investigations and cognitive rehabilitation.

Testing Hypnotizability by Phone: Development and Validation of the Remote Hypnotic Induction Profile (rHIP).

Standard hypnotizability scales require physical contact or direct observation by tester and participant. The authors addressed this limitation by developing and testing the remote Hypnotic Induction Profile (rHIP), a hypnotizability test derived from the Hypnotic Induction Profile that is completed by telephone. To assess the validity of the rHIP, 56 volunteers naïve to hypnotizability testing completed both the HIP and the rHIP, with order of testing randomized. Results indicate a strong correlation between HIP and rHIP scores, r s =.71(0.53-0.84), p <.0001, and good concordance, difference =.03(-0.53, 0.59), p =.91, independent of testing order. The rHIP had few complications. Possible advantages of using the rHIP include improving patient expectancy prior to scheduling a hypnosis session, increasing access to hypnotizability testing for remote interventions, and obviating resource-intensive in-person hypnotizability screening for trials that exclude subjects with certain scores.

Prevalence and patterns of cognitive impairment in acute coronary syndrome patients: A systematic review.

BACKGROUND: Minimising risk factors through secondary prevention behaviour is challenging for patients following an acute coronary syndrome. Cognitive impairment can potentially make these changes more difficult. However, cognitive impairment prevalence in acute coronary syndrome patients is poorly understood. DESIGN: This study was based on a systematic review. METHODS: A systematic review was conducted of PubMed, Medline, PsycINFO and Cochrane databases up to March 2019, to identify studies reporting the prevalence of cognitive impairment in acute coronary syndrome patients. Predefined inclusion criteria were specified, including use of a validated cognitive impairment screening tool. Studies were excluded if patients had diagnosed dementia or coronary artery bypass graft surgery. Strengthening The Reporting of Observational Studies in Epidemiology and Cochrane Risk of Bias tools were used to assess quality. RESULTS: From 747 potential studies, nine were included. The total sample size was 6457 (range 53-2174), mean age range was 51.3-77.4 years, and range of proportions of males was 57-100%. Reported cognitive impairment prevalence rates varied substantially (9-85%) with no clear pattern over time. From the two studies which examined domains, verbal fluency, memory and language were affected the most. Meta-analysis could not be undertaken due to diverse screening tools (n = 9), cut-off scores and screening timepoints. CONCLUSIONS: Cognitive impairment in acute coronary syndrome patients is currently poorly described, and likely affects a substantial number of acute coronary syndrome patients who remain undetected and have the potential to develop to dementia in the future. As domains are most affected, this could impact understanding and retention of health education. Research is needed to accurately determine the prevalence of cognitive impairment in acute coronary syndrome patients and create suitable standardised measures and thresholds.

Silica Exposure Differentially Modulates Autoimmunity in Lupus Strains and Autoantibody Transgenic Mice.

Inhalational exposure to crystalline silica is linked to several debilitating systemic autoimmune diseases characterized by a prominent humoral immune component, but the mechanisms by which silica induces autoantibodies is poorly understood. To better understand how silica lung exposure breaks B cell tolerance and unleashes autoreactive B cells, we exposed both wildtype mice of healthy C57BL/6 and lupus-prone BXSB, MRL, and NZB strains and mice carrying an autoantibody transgene on each of these backgrounds to instilled silica or vehicle and monitored lung injury, autoimmunity, and B cell fate. Silica exposure induced lung damage and pulmonary lymphoid aggregates in all strains, including in genetically diverse backgrounds and in autoantibody transgenic models. In wildtype mice strain differences were observed in specificity of autoantibodies and site of enhanced autoantibody production, consistent with genetic modulation of the autoimmune response to silica. The unique autoantibody transgene reporter system permitted the in vivo fate of autoreactive B cells and tolerance mechanisms to be tracked directly, and demonstrated the presence of transgenic B cells and antibody in pulmonary lymphoid aggregates and bronchoalveolar lavage fluid, respectively, as well as in spleen and serum. Nonetheless, B cell enumeration and transgenic antibody quantitation indicated that B cell deletion and anergy were intact in the different genetic backgrounds. Thus, silica exposure sufficient to induce substantial lung immunopathology did not overtly disrupt central B cell tolerance, even when superimposed on autoimmune genetic susceptibility. This suggests that silica exposure subverts tolerance at alternative checkpoints, such as regulatory cells or follicle entry, or requires additional interactions or co-exposures to induce loss of tolerance. This possibility is supported by results of differentiation assays that demonstrated transgenic autoantibodies in supernatants of Toll-like receptor (TLR)7/TLR9-stimulated splenocytes harvested from silica-exposed, but not vehicle-exposed, C57BL/6 mice. This suggests that lung injury induced by silica exposure has systemic effects that subtly alter autoreactive B cell regulation, possibly modulating B cell anergy, and that can be unmasked by superimposed exposure to TLR ligands or other immunostimulants.

A long wait: barriers to discharge for long length of stay patients.

INTRODUCTION: Reducing long length of stay (LLOS, or inpatient stays lasting over 30 days) is an important way for hospitals to improve cost efficiency, bed availability and health outcomes. Discharge delays can cost hundreds to thousands of dollars per patient, and LLOS represents a burden on bed availability for other potential patients. However, most research studies investigating discharge barriers are not LLOS-specific. Of those that do, nearly all are limited by further patient subpopulation focus or small sample size. To our knowledge, our study is the first to describe LLOS discharge barriers in an entire Department of Medicine. METHODS: We conducted a chart review of 172 LLOS patients in the Department of Medicine at an academic tertiary care hospital and quantified the most frequent causes of delay as well as factors causing the greatest amount of delay time. We also interviewed healthcare staff for their perceptions on barriers to discharge. RESULTS: Discharge site coordination was the most frequent cause of delay, affecting 56% of patients and accounting for 80% of total non-medical postponement days. Goals of care issues and establishment of follow-up care were the next most frequent contributors to delay. CONCLUSION: Together with perspectives from interviewed staff, these results highlight multiple different areas of opportunity for reducing LLOS and maximising the care capacity of inpatient hospitals.

Two-color fluorescent in situ hybridization using chromogenic substrates in zebrafish.

Two-color fluorescent in situ hybridization (FISH) is a widely used technique for comparing relative gene expression patterns. Current two-color FISH protocols are not ideal for detecting weakly expressed transcripts or monitoring signal strength and background levels during the course of the reaction. Here we describe an improved FISH protocol using the conventional highly sensitive chromogenic substrates nitro blue tetrazolium (NBT)/5-bromo-4-chloro-3-indolyl phosphate (BCIP) and Vector Red in zebrafish embryos. This protocol substantially improves on existing FISH techniques by combining the advantages of long reactivity of alkaline phosphatase, chromogenic monitoring of both developing reactions, and the ability to perform subsequent high-resolution fluorescent imaging. Although tested in zebrafish, a similar approach is expected to be applicable to ISH in any model organism.

Distinct regulation of the anterior and posterior myeloperoxidase expression by Etv2 and Gata1 during primitive Granulopoiesis in zebrafish.

Neutrophilic granulocytes are the most abundant type of myeloid cells and form an essential part of the innate immune system. In vertebrates the first neutrophils are thought to originate during primitive hematopoiesis, which precedes hematopoietic stem cell formation. In zebrafish embryos, it has been suggested that primitive neutrophils may originate in two distinct sites, the anterior (ALPM) and posterior lateral plate mesoderm (PLPM). An ETS-family transcription factor Etsrp/Etv2/ER71 has been implicated in vasculogenesis and hematopoiesis in multiple vertebrates. However, its role during neutrophil development is not well understood. Here we demonstrate using zebrafish embryos that Etv2 has a specific cell-autonomous function during primitive neutropoiesis in the anterior lateral plate mesoderm (ALPM) but has little effect on erythropoiesis or the posterior lateral plate mesoderm (PLPM) expression of neutrophil marker myeloperoxidase mpo/mpx. Our results argue that ALPM-derived neutrophils originate from etv2-expressing cells which downregulate etv2 during neutropoiesis. We further show that Scl functions downstream of Etv2 in anterior neutropoiesis. Additionally, we demonstrate that mpx expression within the PLPM overlaps with gata1 expression, potentially marking the cells with a dual myelo-erythroid potential. Intriguingly, initiation of mpx expression in the PLPM is dependent on gata1 but not etv2 function. Our results demonstrate that mpx expression is controlled differently in the ALPM and PLPM regions and describe novel roles for etv2 and gata1 during primitive neutropoiesis.