Multicenter Evaluation of the Acuitas AMR Gene Panel for Detection of an Extended Panel of Antimicrobial Resistance Genes among Bacterial Isolates.

The Acuitas antimicrobial resistance (AMR) gene panel is a qualitative, multiplex, nucleic acid-based in vitro diagnostic test for the detection and differentiation of 28 antimicrobial resistance markers associated with not susceptible results (NS; i.e., intermediate or resistant) to one or more antimicrobial agents among cultured isolates of select Enterobacterales, Pseudomonas aeruginosa, and Enterococcus faecalis. This study was conducted at four sites and included testing of 1,224 deidentified stocks created from 584 retrospectively collected isolates and 83 prospectively collected clinical isolates. The Acuitas results were compared with a combined reference standard including whole-genome sequencing, organism identification, and phenotypic antimicrobial susceptibility testing. The positive percent agreement (PPA) for FDA-cleared AMR targets ranged from 94.4% for MCR-1 to 100% for armA, CTX-M-2, DHA, IMP, OXA-9, SHV, vanA, and VEB. The negative percent agreement (NPA) for the majority of targets was ≥99%, except for AAC, AAD, CMY-41, P. aeruginosa gyrA mutant, Sul1, Sul2, and TEM targets (range, 96.5% to 98.5%). Three AMR markers did not meet FDA inclusion criteria (GES, SPM, and MCR-2). For each organism, 1 to 22 AMR targets met the minimum reportable PPA/NPA and correlated with ≥80% positive predictive value with associated NS results for at least one agent (i.e., the probability of an organism carrying an AMR marker testing NS to the associated agent). We demonstrate that the Acuitas AMR gene panel is an accurate method to detect a broad array of AMR markers among cultured isolates. The AMR markers were further associated with expected NS results for specific agent-organism combinations.

Neurological improvement predicts clinical outcome after acute basilar artery stroke thrombectomy.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is the standard of care for patients with anterior circulation large vessel occlusion. Early neurological improvement (ENI), defined as a reduction of ≥ 8 on the National Institutes of Health Stroke Scale (NIHSS) compared with baseline score, or an NIHSS score of 0 or 1 at 24 h after MT, is a strong predictor of 3-month favorable outcome in such patients. The impact of ENI after MT in stroke patients with basilar artery occlusion (BAO) on 3-month outcome is not clear. We aimed to study the effects of ENI in patients with BAO. METHODS: We performed a retrospective analysis of a multicenter prospective cohort of all consecutive stroke patients with BAO who underwent MT. We compared clinical outcomes between BAO patient groups according to ENI status. Multivariate analyses were performed to determine the impact of ENI on favorable 90-day outcome (modified Rankin scale score 0-3) and to report factors contributing to ENI. RESULTS: A total of 237 patients were included. ENI was observed in 70 patients (30%). Outcomes were significantly better in ENI-positive patients, with 84% achieving favorable outcome (mRS score 0-3) at 3 months versus 30% for ENI-negative patients (P < 0.0001). In multivariate analysis, ENI was an independent predictive factor associated with higher rates of favorable outcome {odds ratio (OR) 18.12 [95% confidence interval (CI) 3.95-83.10]; P = 0.0001}. Higher number of passes [OR 0.62 (95% CI 0.43-0.89); P = 0.010] and need for stenting [OR 0.27 (95% CI 0.07-0.95); P = 0.041] were negatively associated with ENI. CONCLUSION: Early neurological improvement on day 1 following MT for BAO is a strong independent predictor of a favorable 3-month clinical outcome.

Psychological defence mechanisms during the COVID-19 pandemic: A case series.

BACKGROUND AND OBJECTIVES: COVID-19 has had a negative effect on mental health across the world's population. Healthcare workers in particular have experienced increased levels of psychological distress, depression and anxiety. Any perceived stress to an individual can provoke psychological defence mechanisms. Using psychoanalytic theory, a defence mechanism is described as an unconscious psychological strategy, with or without resulting behaviour, which aims to reduce or eliminate anxiety arising from unacceptable or potentially harmful stimuli. This paper aims to describe a range of psychological defence mechanisms encountered within colleagues in relation to the COVID-19 pandemic. METHODS: Using the methodology of a case series, specific defence mechanisms are explored with reference to further literature in the field. RESULTS: The author has encountered varying psychological defence mechanisms, both within himself and in other members of the multidisciplinary team. These have been illustrated in the attached clinical vignettes, relating to the specific psychological coping mechanisms of; denial, hypochondriasis, altruism, sublimation and humour. CONCLUSION: We encourage acknowledgement of psychological defence mechanisms and their implications on day to day practice. Whilst defence mechanisms can have a number of negative consequences as described in this article, they also have an important role, particularly in the case of mature defence mechanisms, as protective factors against psychological distress and symptom formation. Deeper understanding of the gold-standard hierarchical organisation of defence mechanisms could help increase utilisation of specific therapeutic interventions for enhancing changes from immature to mature defensive responses to stressful experiences as the COVID-19 pandemic progresses.

Co-occurrence of hearing loss and posttraumatic stress disorder among injured military personnel: a retrospective study.

BACKGROUND: Posttraumatic stress disorder (PTSD) and hearing loss are hallmark public health issues related to military service in Iraq and Afghanistan. Although both are significant individual contributors to disability among veterans, their co-occurrence has not been specifically explored. METHODS: A total of 1179 male U.S. military personnel who sustained an injury between 2004 and 2012 during operations in Iraq or Afghanistan were identified from clinical records. Pre- and postinjury audiometric data were used to define new-onset hearing loss, which was categorized as unilateral or bilateral. Diagnosed PTSD was abstracted from electronic medical records. Logistic regression analysis examined the relationship between hearing loss and PTSD, while adjusting for age, year of injury, occupation, injury severity, injury mechanism, and presence of concussion. RESULTS: The majority of the study sample were aged 18-25 years (79.9%) and sustained mild-moderate injuries (94.6%). New-onset hearing loss was present in 14.4% of casualties (10.3% unilateral, 4.1% bilateral). Rates of diagnosed PTSD were 9.1, 13.9, and 29.2% for those with no hearing loss, unilateral hearing loss, and bilateral hearing loss, respectively. After adjusting for covariates, those with bilateral hearing loss had nearly three-times higher odds of PTSD (odds ratio = 2.92; 95% CI, 1.47-5.81) compared to those with no hearing loss. Unilateral hearing loss was not associated with PTSD. CONCLUSIONS: Both PTSD and hearing loss are frequent consequences of modern warfare that adversely affect the overall health of the military. Bilateral, but not unilateral, hearing loss was associated with a greater burden of PTSD. This has implications for warfighter rehabilitation and should encourage collaboration between audiology and mental health professionals.

Predicting Antibiotic Resistance in Gram-Negative Bacilli from Resistance Genes.

We developed a rapid high-throughput PCR test and evaluated highly antibiotic-resistant clinical isolates of Escherichia coli (n = 2,919), Klebsiella pneumoniae (n = 1,974), Proteus mirabilis (n = 1,150), and Pseudomonas aeruginosa (n = 1,484) for several antibiotic resistance genes for comparison with phenotypic resistance across penicillins, cephalosporins, carbapenems, aminoglycosides, trimethoprim-sulfamethoxazole, fluoroquinolones, and macrolides. The isolates originated from hospitals in North America (34%), Europe (23%), Asia (13%), South America (12%), Africa (7%), or Oceania (1%) or were of unknown origin (9%). We developed statistical methods to predict phenotypic resistance from resistance genes for 49 antibiotic-organism combinations, including gentamicin, tobramycin, ciprofloxacin, levofloxacin, trimethoprim-sulfamethoxazole, ertapenem, imipenem, cefazolin, cefepime, cefotaxime, ceftazidime, ceftriaxone, ampicillin, and aztreonam. Average positive predictive values for genotypic prediction of phenotypic resistance were 91% for E. coli, 93% for K. pneumoniae, 87% for P. mirabilis, and 92% for P. aeruginosa across the various antibiotics for this highly resistant cohort of bacterial isolates.

Structured education using Dose Adjustment for Normal Eating (DAFNE) reduces long-term HbA1c and HbA1c variability.

AIMS: Previous evidence has demonstrated that participation in the Dose Adjustment for Normal Eating (DAFNE) education programme can reduce HbA1c and severe hypoglycaemia in people with Type 1 diabetes. In a number of studies, increased HbA1c variability has been associated with higher diabetic morbidity and mortality. No studies have examined the impact of structured education on HbA1c variability in Type 1 diabetes. METHODS: People with Type 1 diabetes who had attended DAFNE were identified for inclusion from the Scottish Care Information-Diabetes dataset. HbA1c median and variability, expressed as coefficient of variation (CV) before and after DAFNE was calculated. RESULTS: Some 1061 individuals participated in DAFNE education and 687 met the inclusion criteria. A significant median reduction in HbA1c [-3.5 mmol/mol (-0.3%)] was seen at 12 months with a significant reduction [-1.5 mmol/mol (-0.1%)] still seen at 60 months of follow-up. HbA1c variability as measured by CV was significantly lower during the post-DAFNE period: 0.08 (IQR 0.05-0.12) reduced to 0.07 (IQR 0.05-0.10); P = 0.002. CONCLUSION: The data confirm that DAFNE participation improves glycaemic control in Type 1 diabetes with benefits being sustained for 5 years. This study is the first to demonstrate reduced HbA1c variability after completion of structured education. This is new evidence of the beneficial impact of DAFNE on glycaemic profile.

Percutaneous endoscopic gastrostomy placement in paediatric Crohn's disease patients contributes to both improved nutrition and growth.

AIM: This paper describes the outcomes of gastrostomy feeding in patients with Crohn's disease (CD). METHODS: Patients with CD who attended the Royal Hospital for Children, Glasgow and received gastrostomy feeding for at least two years between 2003 and 2010 were identified from the clinical database. The data recorded included the anthropometric data, CD phenotype, the surgical technique that was used, complications, medication, feed type, median feed, calories, volume and clinical outcomes. RESULTS: The study identified 16 patients (14 male) who had a gastrostomy inserted using a pull technique at a median age of 12.6 years. Of these two required laparoscopic placement. Short-term complications lasting less than one month were experienced by nine (56%) patients and one (6%) experienced long-term complications. Anthropometry significantly improved at follow-up compared to baseline: at 12 months, the body mass index z-score was 1.11 (p = 0.005) and the weight z-score was 0.19 (p < 0.05). At 24 months, the height z-score was -1.03 (p = 0.04). The daily median volume and calories from feeds increased significantly from baseline to post-PEG insertion, from 400 to 738 mL and 705 to 860 kcal/day (p ≤ 0.01). CONCLUSION: Gastrostomy feeding for paediatric patients with CD was associated with improved nutrition, weight gain and growth outcomes.

Investigation into the potential for post-mortem formation of carboxyhemoglobin in bodies retrieved from fires.

The forensic investigation of a deceased person retrieved following a fire includes measuring carboxyhemoglobin. A carboxyhemoglobin saturation above 10% is considered indicative of respiration during a fire, implying the person had been alive. This relies on the assumption that carbon monoxide will not diffuse into blood used for toxicological analysis. This project investigated the potential for carbon monoxide to passively diffuse into a body and if carboxyhemoglobin levels could become elevated post-mortem. Stillborn piglets with intact skin were exposed to carbon monoxide. Carboxyhemoglobin formed in the hypostasis of the skin, but carboxyhemoglobin levels in blood from the heart and chest cavities were not significantly elevated. However, defects in the skin over body cavities (producing breaches to replicate cases with stab wounds or heat damage) resulted in cavity blood carboxyhemoglobin levels above 10%. A review of fire death cases in South Australia 2000-2015 was performed to determine the origin of the blood samples used for toxicological analysis and the incidence of cases with breaches of body cavities. This revealed a small number of cases in which blood from the cavities had been analyzed when cavity breaches were present. Thus, there is a potential for significant elevation of carboxyhemoglobin saturation post-mortem in forensic casework involving bodies retrieved from fires.

Review of autopsy reports of deaths relating to fire in South Australia 2000-2015.

It has been noted there are gaps and inconsistencies in data pertaining to fire related deaths in Australia, which poses difficulties for analysis of national statistics. A search of post-mortem examination reports at Forensic Science SA from 2000 to 2015 revealed 275 cases regarded as fire related in which the body had been involved in a fire. The autopsy reports were evaluated to determine parameters including the location of the fire event, age and sex of victim, as well as the presence of soot in the airways and cherry-red coloration to the blood and/or organs, in addtion to toxicological levels of carboxyhemoglobin and alcohol. Fire events were clasified as structural, transportation or open air in type. Males were more commonly victims than females, especially in transportation fires, where males aged below 50 years were most at risk of death. Carboxyhemoglobin levels tended to be lower in victims of transportation fires. This study has confirmed that presence of soot in the respiratory tract and cherry-red coloration of a body retrieved from a fire are both linked to an increased level of blood carboxyhemoglobin. These findings significantly contribute to the documentation of fire deaths in Australia.

HbA1c variability is associated with increased mortality and earlier hospital admission in people with Type 1 diabetes.

AIM: Despite evidence of morbidity, no evidence exists on the relationship between HbA1c variability and mortality in Type 1 diabetes. We performed an observational study to investigate whether the association between HbA1c variability and mortality exists in a population of people with Type 1 diabetes. As a secondary outcome, we compared onset of first hospital admission between groups. METHODS: People with Type 1 diabetes were identified for inclusion from the Scottish Care Information - Diabetes data set. This database includes data of all people known to have diabetes who live within Scotland. A survival analysis was carried out over a 47-month period comparing two groups; group 1 with a HbA1c coefficient of variation (CV) above the median CV value, and group 2 with a CV below the median value. Time to death or first admission was also analysed. A Cox proportional hazard model was used to compare time to death, adjusting for appropriate covariables. RESULTS: Some 6048 individuals with Type 1 diabetes were included in the analysis. Median HbA1c CV was 7.9. The hazard ratio (HR) for mortality for those with an HbA1c CV above the median value is 1.5 over 47 months of follow-up (P < 0.001). HR for survival to either the first admission to hospital or death for those with an HbA1c CV above the median value was 1.35 (95% confidence interval 1.25-1.45) over 730 days of follow-up (P < 0.001). CONCLUSION: Our results show that people with greater HbA1c variability have a higher rate of mortality and earlier hospital admission in Type 1 diabetes.

Adverse Health Effects Associated with Living in a Former Methamphetamine Drug Laboratory - Victoria, Australia, 2015.

The manufacture of methamphetamine in clandestine drug laboratories occurs in various locations, including residential houses and apartments. Unlike the controlled manufacture of chemicals and drugs, clandestine manufacture results in the uncontrolled storage, use, generation, and disposal of a wide range of chemicals and the deposit of methamphetamine drug residues on indoor surfaces (1). These residues have been found at high levels on porous and nonporous surfaces and have been shown to persist for months to years (1). Persons exposed to these environments often have poorly defined exposures and health effects. It is commonly assumed that these levels of exposure are low compared with those related to illicit drug use or therapeutic use of amphetamine-based drugs for managing behavioral issues such as attention deficit hyperactivity disorder (2). In 2015, a family that was unknowingly exposed to methamphetamine residues in a house in Australia was found to have adverse health effects and elevated methamphetamine levels in hair samples, highlighting the potential for public health risks for persons who might live in methamphetamine-contaminated dwellings. This case study highlights the importance of the identification and effective decontamination of former clandestine drug laboratories.

State-of-science: situation awareness in individuals, teams and systems.

Our review addresses one of the most used, but debated, topics in Ergonomics: Situation Awareness (SA). We examine and elaborate upon key SA models. These models are divided into individual SA, team SA and systems SA categories. Despite, or perhaps because of, the debates surrounding SA it remains an enduring theme for research and practice in the domain of Ergonomics, now for over two decades. A contingent approach, which seeks to match different models of SA to different types of ergonomics problem, enables the differences between positions to be revealed and reconciled, and the practitioner guided towards optimum methodological solutions. Practitioner Summary: Measuring SA in individuals, teams and systems has become a key objective in Ergonomics. One single approach to SA does not fit all problems encountered. This review shows the importance of considering all three types of models and achieving a match between them and the problem at hand.

Analytical Performance of Multiplexed Screening Test for 10 Antibiotic Resistance Genes from Perianal Swab Samples.

BACKGROUND: Multiantibiotic-resistant bacteria pose a threat to patients and place an economic burden on health care systems. Carbapenem-resistant bacilli and extended-spectrum ß-lactamase (ESBL) producers drive the need to screen infected and colonized patients for patient management and infection control. METHODS: We describe a multiplex microfluidic PCR test for perianal swab samples (Acuitas(®) MDRO Gene Test, OpGen) that detects the vancomycin-resistance gene vanA plus hundreds of gene subtypes from the carbapenemase and ESBL families Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-ß-lactamase (NDM), Verona integron-mediated metallo-ß-lactamase (VIM), imipenemase metallo-ß-lactamase (IMP), OXA-23, OXA-48, OXA-51, CTX-M-1, and CTX-M-2, regardless of the bacterial species harboring the antibiotic resistance. RESULTS: Analytical test sensitivity per perianal swab is 11-250 CFU of bacteria harboring the antibiotic resistance genes. Test throughput is 182 samples per test run (1820 antibiotic resistance gene family results). We demonstrate reproducible test performance and 100% gene specificity for 265 clinical bacterial organisms harboring a variety of antibiotic resistance genes. CONCLUSIONS: The Acuitas MDRO Gene Test is a sensitive, specific, and high-throughput test to screen colonized patients and diagnose infections for several antibiotic resistance genes directly from perianal swab samples, regardless of the bacterial species harboring the resistance genes.

Ethical issues and best practice in clinically based genomic research: Exeter Stakeholders Meeting Report.

Current guidelines on consenting individuals to participate in genomic research are diverse. This creates problems for participants and also for researchers, particularly for clinicians who provide both clinical care and research to their patients. A group of 14 stakeholders met on 7 October 2015 in Exeter to discuss the ethical issues and the best practice arising in clinically based genomic research, with particular emphasis on the issue of returning results to study participants/patients in light of research findings affecting research and clinical practices. The group was deliberately multidisciplinary to ensure that a diversity of views was represented. This report outlines the main ethical issues, areas of best practice and principles underlying ethical clinically based genomic research discussed during the meeting. The main point emerging from the discussion is that ethical principles, rather than being formulaic, should guide researchers/clinicians to identify who the main stakeholders are to consult with for a specific project and to incorporate their voices/views strategically throughout the lifecycle of each project. We believe that the mix of principles and practical guidelines outlined in this report can contribute to current debates on how to conduct ethical clinically based genomic research.

Osteogenic cell response to 3-D hydroxyapatite scaffolds developed via replication of natural marine sponges.

Bone tissue engineering may provide an alternative to autograft, however scaffold optimisation is required to maximize bone ingrowth. In designing scaffolds, pore architecture is important and there is evidence that cells prefer a degree of non-uniformity. The aim of this study was to compare scaffolds derived from a natural porous marine sponge (Spongia agaricina) with unique architecture to those derived from a synthetic polyurethane foam. Hydroxyapatite scaffolds of 1 cm(3) were prepared via ceramic infiltration of a marine sponge and a polyurethane (PU) foam. Human foetal osteoblasts (hFOB) were seeded at 1 × 10(5) cells/scaffold for up to 14 days. Cytotoxicity, cell number, morphology and differentiation were investigated. PU-derived scaffolds had 84-91% porosity and 99.99% pore interconnectivity. In comparison marine sponge-derived scaffolds had 56-61% porosity and 99.9% pore interconnectivity. hFOB studies showed that a greater number of cells were found on marine sponge-derived scaffolds at than on the PU scaffold but there was no significant difference in cell differentiation. X-ray diffraction and inductively coupled plasma mass spectrometry showed that Si ions were released from the marine-derived scaffold. In summary, three dimensional porous constructs have been manufactured that support cell attachment, proliferation and differentiation but significantly more cells were seen on marine-derived scaffolds. This could be due both to the chemistry and pore architecture of the scaffolds with an additional biological stimulus from presence of Si ions. Further in vivo tests in orthotopic models are required but this marine-derived scaffold shows promise for applications in bone tissue engineering.

Mortality from sudden unexpected death in epilepsy (SUDEP) in a cohort of adults with intellectual disability.

BACKGROUND: People with intellectual disability (ID) and epilepsy are more likely to die prematurely than the general population. A significant number of deaths in people with epilepsy may be potentially preventable through better seizure control, regular monitoring and raising awareness among patients and carers. The aim of this project was to study mortality from sudden unexpected death in epilepsy (SUDEP) in adults with ID. METHODS: All adults (≥20 years old) living in Leicester city, Leicestershire and Rutland, UK, with ID between 1993 and 2010 were identified using the Leicestershire Intellectual Disability Register database. People with and without ID who died during the same period were identified using death certificate data from the Office for National Statistics (ONS). Deaths from probable and definite SUDEP were identified. Additional information on adults with ID who had died from probable or definite SUDEP was obtained from case notes and post-mortem reports, where available. Cases of probable and definite SUDEP in adults with ID were compared with the general population using standardised mortality ratios (SMRs). RESULTS: A total of 898 adults with ID had died over the 18-year study period. Of these, 244 deaths (27%) occurred in people with ID who had a diagnosis of epilepsy. Twenty-six people with ID died from probable or definite SUDEP, which was the second most common cause of death among adults with ID and epilepsy. All-cause specific SMRs were 2.2 [95% confidence interval (CI): 2.0-2.4] and 2.8 (95% CI: 2.5-3.1) for men and women with ID respectively. SMRs were 3.2 (95% CI: 2.7-3.8) and 5.6 (95% CI: 4.6-6.7) for men and women with epilepsy and ID respectively. During the same study period, 83 adults without ID had died of probable or definite SUDEP. The SMRs for SUDEP in patients with ID were 37.6 for men (95% CI: 21.9-60.2) and 52.0 for women (95% CI: 23.8-98.8). We found that in the majority of ID cases there was little detailed documentation on the circumstances surrounding deaths, no communication with patients/carers about risk of SUDEP and an absence of post-mortem reports or carers' referral for bereavement counselling. CONCLUSION: The authors believe that a comprehensive risk management under a multiagency/multidisciplinary framework should be undertaken for all adults with ID and epilepsy in day-to-day clinical practice to reduce mortality in people with ID.

Dye adsorption onto mesoporous materials: pH influence, kinetics and equilibrium in buffered and saline media.

Mesoporous materials were used as adsorbents for dye removal in different media: non-ionic, buffered and saline. The mesoporous materials used were commercial (silica gel) as well as as-synthesised materials (SBA-15 and a novel mesoporous carbon). Dye adsorption onto all the materials was very fast and the equilibrium was reached before 1 h. The pH has a significant influence on the adsorption capacity for the siliceous materials since the electrostatic interactions are the driving forces. However, the influence of the pH on the adsorption capacity of the carbonaceous material was lower, since the van der Waals interactions are the driving forces. The ionic strength has a great impact on the siliceous materials adsorption capacity, being their adsorption capacity in a buffered medium six times higher than the corresponding to a non-ionic medium. Nevertheless, ionic strength does not influence on the dye adsorption on the mesoporous carbon. Overall, the as-synthesised carbon material presents a clear potential to treat dye effluents, showing high adsorption capacity (q(e) ≈ 200 mg/g) in all the pH range studied (from 3 to 11); even at low concentrations (C(e) ≈ 10 mg/L) and at short contact times (t(e) < 30 min).