Framing the wider determinants of health: Reflections and learning from a knowledge mobilisation exercise with an English local authority.

Background: Health inequalities remain a persistent problem in the UK. One contributing factor may be how health inequalities are framed in professional and public debate. Dominant understandings of health focus on the individual, personal choice, lifestyle and (un)healthy behaviour. This project sought to reframe health inequalities as a 'systemic' or structural problem using extant guidance. This was intended to support the work of a local authority in England working to address health inequalities. Project design: An academic-practitioner participatory knowledge mobilisation exercise with a local authority public health team using recent guidance and reflective feedback and the iterative development of actionable tools. There were four discrete stages to the exercise. Methods: Two on-line and one face-to-face participatory, deliberative workshops designed to co-create reframed public health challenges and solutions based on team portfolios. Iterative feedback provided by the researcher to support the development of actionable tools. Results: Six topic areas were developed with a systemic framing: 1. Food insecurity, 2. Obesity, 3. Prostate cancer among Black men, 4. Cost of living, 5. Mental health, suicide prevention and Gypsy, Roma, Traveller communities, 6. Healthy streets. Reflections from the process revealed some perceived advantages of engaging in a systemic framing of the wider determinants of health, some limitations and issues to consider in a local setting. Benefits included: Clarity in a complex field; structured thinking about what to communicate and how; eliminated jargon; could be made locally relevant. Challenges included: Sustaining a consistent framing; maintaining the technique; knowing if was making a difference; slipping back into dominant (individualised) framings, especially in free-flowing discussion. Conclusions: The process of reframing the wider determinants of health using recent guidance in a local authority setting was broadly helpful in developing coherence and consistency across the public health team. There were challenges to adopting the approach and evaluation of its impact locally would be beneficial.

Validation of N95 Filtering Facepiece Respirator Decontamination Methods Available at a Large University Hospital.

BACKGROUND: Due to unprecedented shortages in N95 filtering facepiece respirators, healthcare systems have explored N95 reprocessing. No single, full-scale reprocessing publication has reported an evaluation including multiple viruses, bacteria, and fungi along with respirator filtration and fit. METHODS: We explored reprocessing methods using new 3M 1860 N95 respirators, including moist (50%-75% relative humidity [RH]) heat (80-82°C for 30 minutes), ethylene oxide (EtO), pulsed xenon UV-C (UV-PX), hydrogen peroxide gas plasma (HPGP), and hydrogen peroxide vapor (HPV). Respirator samples were analyzed using 4 viruses (MS2, phi6, influenza A virus [IAV], murine hepatitis virus [MHV)]), 3 bacteria (Escherichia coli, Staphylococcus aureus, Geobacillus stearothermophilus spores, and vegetative bacteria), and Aspergillus niger. Different application media were tested. Decontaminated respirators were evaluated for filtration integrity and fit. RESULTS: Heat with moderate RH most effectively inactivated virus, resulting in reductions of >6.6-log10 MS2, >6.7-log10 Phi6, >2.7-log10 MHV, and >3.9-log10 IAV and prokaryotes, except for G stearothermohphilus. Hydrogen peroxide vapor was moderately effective at inactivating tested viruses, resulting in 1.5- to >4-log10 observable inactivation. Staphylococcus aureus inactivation by HPV was limited. Filtration efficiency and proper fit were maintained after 5 cycles of heat with moderate RH and HPV. Although it was effective at decontamination, HPGP resulted in decreased filtration efficiency, and EtO treatment raised toxicity concerns. Observed virus inactivation varied depending upon the application media used. CONCLUSIONS: Both moist heat and HPV are scalable N95 reprocessing options because they achieve high levels of biological indicator inactivation while maintaining respirator fit and integrity.

In Vitro Activities of ß-Lactam-ß-Lactamase Inhibitor Antimicrobial Agents against Cystic Fibrosis Respiratory Pathogens.

We tested the in vitro activities of ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, piperacillin-tazobactam, and 11 other antimicrobial agents against 420 Burkholderia, Achromobacter, Stenotrophomonas, and Pandoraea strains, 89% of which were cultured from respiratory specimens from persons with cystic fibrosis. Among the ß-lactam-ß-lactamase inhibitor agents, meropenem-vaborbactam had the greatest activity against Burkholderia and Achromobacter, including multidrug-resistant and extensively-drug-resistant strains. None of the newer ß-lactam-ß-lactamase combination drugs showed increased activity compared to that of the older agents against Stenotrophomonas maltophilia or Pandoraea spp.

Impact of an Antimicrobial Stewardship Intervention on Within- and Between-Patient Daptomycin Resistance Evolution in Vancomycin-Resistant Enterococcus faecium.

Vancomycin-resistant Enterococcus (VRE) is a leading cause of hospital-acquired infection, with limited treatment options. Resistance to one of the few remaining drugs, daptomycin, is a growing clinical problem and has previously been described in this hospital. In response to increasing resistance, an antimicrobial stewardship intervention was implemented to reduce hospital-wide use of daptomycin. To assess the impact of the intervention, daptomycin prescribing patterns and clinically reported culture results from vancomycin-resistant Enterococcus faecium (VREfm) bloodstream infections (BSIs) from 2011 through 2017 were retrospectively extracted and the impact of the intervention was estimated using interrupted time series analysis (ITS). We corrected for a change in MIC determination methodology by retesting 262 isolates using Etest and broth microdilution. Hospital-wide and within-patient resistance patterns of corrected daptomycin MICs are reported. Our data show that daptomycin prescriptions decreased from an average of 287 days of therapy/month preintervention to 151 days of therapy/month postintervention. Concurrently, the proportion of patients experiencing an increase in daptomycin MIC during an infection declined from 14.6% (7/48 patients) in 2014 to 1.9% (1/54 patients) in 2017. Hospital-wide resistance to daptomycin also decreased in the postintervention period, but this was not maintained. This study shows that an antimicrobial stewardship-guided intervention reduced daptomycin use and improved individual level outcomes but had only transient impact on the hospital-level trend.

Helicobacter pylori Antimicrobial Susceptibility Testing-Guided Salvage Therapy in the USA: A Real Life Experience.

BACKGROUND: The current practice guidelines recommend that Helicobacter pylori (H. pylori) culture and antimicrobial susceptibility testing (AST) be considered after patients failed the second course of H. pylori eradication therapy. AIMS: Here we report the real life experience of following this recommendation in the USA. METHODS: We established an in-house H. pylori culture protocol for AST and identified retrospectively patients who previously failed ≥ 2 courses of anti-H. pylori therapy and underwent esophagogastroduodenoscopy with AST at University of Michigan from 2010 to 2017. We determined the rate of H. pylori antibiotic resistance, the success rates of AST-guided tailored therapy, and the risk factors associated with treatment failure. RESULTS: Forty-seven patients were identified and 34 (72.3%) had successful cultures and AST. The most common antibiotic resistance was to metronidazole (79.4%), followed by clarithromycin (70.6%) and ciprofloxacin (42.9%). None of the patients were resistant to amoxicillin or tetracycline. The overall success rate of AST-guided tailored therapy was low (44.4%, 12/27). In patients infected with metronidazole-resistant H. pylori, bismuth quadruple therapy appears to be superior compared to non-bismuth quadruple therapy (6/8 or 75.0% vs. 3/14 or 21.4%, P = 0.03). High body mass index was significantly associated with tailored therapy failure (OR 1.24, 95% CI 1.00-1.54, P = 0.049). CONCLUSIONS: The success rate of AST-guided salvage therapy in the USA is low particularly in those with high BMI. Bismuth-based therapy appears to be better than non-bismuth-based regimens.

In Vitro Activity of Ceftolozane-Tazobactam and Other Antimicrobial Agents against Burkholderia cepacia Complex and Burkholderia gladioli.

We tested the activities of ceftolozane-tazobactam and 13 other antimicrobial agents against 221 strains of Burkholderia cepacia complex and Burkholderia gladioli Most strains (82%) were cultured from persons with cystic fibrosis, and most (85%) were recovered since 2011. The ceftolozane-tazobactam MIC was ≤8 µg/ml for 77% of the strains. However, the MIC range was broad (≤0.5 to >64 µg/ml; MIC50/90, 2/32 µg/ml). Significant differences in susceptibility to some antimicrobial agents were observed between species.

Reasons for Declining Preconception Expanded Carrier Screening Using Genome Sequencing.

Genomic carrier screening can identify more disease-associated variants than existing carrier screening methodologies, but its utility from patients' perspective is not yet established. A randomized controlled trial for preconception genomic carrier screening provided an opportunity to understand patients' decisions about whether to accept or decline testing. We administered a survey to potential genomic carrier screening recipients who declined participation (N = 240) to evaluate their reasons for doing so. Two thirds of women declined participation. We identified major themes describing reasons these individuals declined to participate; the most common were time limitation, lack of interest, not wanting to know the information, and potential cause of worry or anxiety. Most women eligible for genomic carrier screening indicated that their reasons for opting out were due to logistical issues rather than opposing the rationale for testing. As expanded carrier screening and genomic sequencing become a more routine part of clinical care, it is anticipated there will be variable uptake from individuals for this testing. Thus, the advancement of clinical carrier screening from single genes, to expanded screening panels, to an exome- or genome-wide platform, will require approaches that respect individual choice to receive genetic testing for reproductive risk assessment.

Bacterial Contamination of CT Equipment: Use of ATP Detection and Culture Results to Target Quality Improvement.

RATIONALE AND OBJECTIVE: This study aimed to evaluate the use of an adenosine triphosphate (ATP) monitoring system to minimize surface contamination on inpatient computed tomography (CT) scanners. METHODS: The bore, table, and wrap of two quaternary care inpatient CT scanners (load/scanner: ~ 30-40 CT examinations/day) were assayed with bacterial cultures and an ATP detection system during six prospective iterative plan-do-check-act improvement cycles from January 6, 2016 to October 12, 2016. Per-cycle sampling was for eight consecutive weekdays. ATP detection was expressed as relative light units (RLUs) through a luciferase reaction, with >350 RLU considered contaminated per manufacturer recommendations. Culture swabs were placed into 6.5% NaCl broth, a Staphylococcus enrichment broth, and incubated aerobically at 37°C for 48 hours. Positive broths were plated to chromogenic Staphylococcus media. Culture rates (Fisher exact test) and RLU values (Mann-Whitney U test) were compared. RESULTS: In Cycle 1, both culture results and median RLU values indicated the wrap was the most contaminated item (positive culture rate: 63% [10/16], median RLU interquartile range: 173 [IQR: 56-640]); however, RLU values were not predictive of per-sample culture results (P = .36). Following iterative improvements, RLU values at Cycle 6 were significantly lower than at peak (P = .02-.04) and within manufacturer's recommendations: all samples: 45 (IQR: 16-87), bore: 26 (IQR: 0-51), table: 68 (IQR: 21-89), wrap: 47 (IQR: 38-121). CONCLUSION: The Velcro wrap is the most contaminated item on a CT scanner, and special processes may be needed to ensure adequate cleansing. ATP detection is a crude surrogate for bacterial culture results but benefits from speed, reduced cost, and greater statistical power.

Multicenter Evaluation of MRSASelect II Chromogenic Agar for Identification of Methicillin-Resistant Staphylococcus aureus from Wound and Nasal Specimens.

Hospitals strive to reduce methicillin-resistant Staphylococcus aureus (MRSA) prevalence via active surveillance of inpatient populations. Rapid and inexpensive screening methods are utilized when molecular methods are not operationally feasible. In this multisite clinical trial, the utility of Bio-Rad's MRSASelect II was evaluated for MRSA identification from remnant nares and wound swabs. The prevalence of MRSA was 11.1% (n = 1,384) from nares samples and 18.1% (n = 842) from wound samples. MRSASelect II had an overall concordance of 95.4% (confidence interval [CI] = 94.5% to 96.2%) compared to a broth-enriched reference standard. Comparisons between results, stratified by examination times, exhibited a nonsignificant trend toward increased positivity at prolonged incubation times. Cefoxitin screening of colonies directly from MRSASelect II was 96.7% (95.8% to 97.3%) concordant compared to testing of colonies following broth enrichment. A comparison of MRSASelect and MRSASelect II revealed no statistical differences; however, the latter exhibited earlier positivity, greater selectivity, and more intense indicator staining, which resulted in facilitated differentiation of positive results. MRSASelect II agar is a simple, rapid, and robust method to routinely screen patients for MRSA colonization without the need for additional testing.

Multicenter clinical evaluation of VRESelect agar for identification of vancomycin-resistant Enterococcus faecalis and Enterococcus faecium.

A chromogenic medium for identification of vancomycin-resistant Enterococcus faecalis and Enterococcus faecium, VRESelect, was compared to bile esculin azide agar with 6 µg/ml vancomycin (BEAV) for the isolation of vancomycin-resistant enterococci (VRE) from stool specimens. At 24 to 28 h, VRESelect demonstrated 98.7% (confidence interval [CI], 96.1 to 99.7%) sensitivity and 99.0% (CI, 98.0 to 99.6%) specificity versus 85.1% (CI, 79.8 to 89.5%) and 90.1% (CI, 79.8 to 89.5%) sensitivity and specificity, respectively, for BEAV.

Culture-based method with performance comparable to that of PCR-based methods for detection of group B Streptococcus in screening samples from pregnant women.

We compared five approaches for group B streptococcus (GBS) detection: three culture-based methods and two methods using broth-enhanced real-time PCR. Carrot broth-enhanced subculture to GBS Detect (Hardy Diagnostics, Santa Maria, CA) exhibited sensitivity and specificity comparable to carrot broth- and LIM broth-enhanced real-time PCRs.

Clinical and laboratory features of Streptococcus salivarius meningitis: a case report and literature review.

Streptococcus salivarius is a normal member of the human oral microbiome that is an uncommon cause of invasive infections. Meningitis is a rare but increasingly reported infection caused by S. salivarius. Despite the growing number of reported cases, a comprehensive review of the literature on S. salivarius meningitis is lacking. We sought to gain a better understanding of the clinical presentation, evaluation, management, and outcome of S. salivarius meningitis by analyzing previously reported cases. In addition to a single case reported here, 64 previously published cases of meningitis were identified for this review. The collected data confirm that most patients presented with classical signs and symptoms of bacterial meningitis with a predominance of neutrophils in the cerebrospinal fluid (CSF) and hypoglycorrhachia. The majority of cases followed iatrogenic or traumatic CSF contamination. Most cases were diagnosed by CSF culture within one day of symptom onset. There was no clear evidence of predisposing co-morbid conditions in patients with meningitis, although in most case reports, limited information was given on the medical history of each patient. Outcomes were generally favorable with antibiotic management. Clinicians should suspect S. salivarius meningitis in patients presenting acutely after medical or surgical procedures involving the meninges.

Fractal branching quantifies vascular changes and predicts survival in pulmonary hypertension: a proof of principle study.

OBJECTIVES: To develop a non-invasive method of assessing disease severity in pulmonary hypertension by quantifying the overall degree of vascular pruning using fractal geometry. DESIGN: A retrospective analysis of ECG-gated CT pulmonary angiograms. SETTING: A single national referral centre for the investigation and treatment of children with pulmonary hypertension. PATIENTS: Consecutive CT pulmonary angiograms in children and young adults (mean age 10.3 years, range 0.7-19.1) with pulmonary arterial hypertension assessed between January 2007 and April 2009. MAIN OUTCOME MEASURES: The fractal dimension (FD) of skeletonised CT pulmonary angiograms was calculated using the box counting method. The FD was compared with pulmonary vascular resistance, the percentage of predicted 6-min walk distance, WHO functional class and survival. RESULTS: Diagnostic plots confirmed that the pulmonary artery angiograms were all fractal. The FD correlated negatively with the pulmonary vascular resistance index (r=-0.55, p=0.01, n=21) and with WHO functional class (p<0.01, n=31) while it correlated positively with the percentage of predicted 6-min walk distance (r=0.43, p=0.04, n=24). A lower FD was associated with poorer survival (HR 5.6; 95% CI 1.2 to 25; p=0.027) for every SD reduction in FD. CONCLUSION: The FD derived from CT can be used to quantify vascular changes in pulmonary hypertension. This non-invasive technique may be useful in monitoring disease progression and response to therapy.

Four-dimensional computed tomography: a method of assessing right ventricular outflow tract and pulmonary artery deformations throughout the cardiac cycle.

OBJECTIVE: To characterise 3D deformations of the right ventricular outflow tract (RVOT)/pulmonary arteries (PAs) during the cardiac cycle and estimate the errors of conventional 2D assessments. METHODS: Contrast-enhanced, ECG-gated cardiovascular computed tomography (CT) findings were retrospectively analysed from 12 patients. The acquisition of 3D images over 10 phases of the cardiac cycle created a four-dimensional CT (4DCT) dataset. The datasets were reconstructed and deformation measured at various levels of the RVOT/PAs in both space and time. Section planes were either static or dynamic relative to the motion of the structures. RESULTS: 4DCT enabled measurement and characterisation of in vivo 3D changes of patients' RVOT/PA during the cardiac cycle. The studied patient population showed a wide range of RVOT/PA morphologies, sizes and dynamics that develop late after surgical repair of congenital heart disease. There were also significant differences in the measured cross-sectional areas of the structures between static and dynamic section planes (up to 150%, p<0.05) secondary to large 3D displacements and rotations. CONCLUSIONS: 4DCT imaging data suggest high variability in RVOT/PA dynamics and significant errors in deformation measurements if 3D analysis is not carried out. These findings play an important role for the development of novel percutaneous approaches to pulmonary valve intervention.

Diagnosis of Clostridium difficile infection: comparison of four methods on specimens collected in Cary-Blair transport medium and tcdB PCR on fresh versus frozen samples.

Clostridium difficile infection (CDI) caused by toxigenic strains of C. difficile is primarily a nosocomial infection with increasing prevalence. Stool specimens are typically collected in Cary-Blair transport medium to maximize culture-based detection of common stool pathogens. The goal of this study was to establish an analytically accurate and efficient algorithm for the detection of CDI in our patient population using samples collected in Cary-Blair transport medium. In addition, we wished to determine whether the sensitivity and specificity of PCR was affected by freezing samples before testing. Using 357 specimens, we compared four methods: enzyme immunoassay for the antigen glutamate dehydrogenase (Wampole™ C. DIFF CHEK-60 Assay, GDH), toxin A and B enzyme immunoassay (Remel ProSpecT™ C. difficile Toxin A/B Microplate Assay, Toxin EIA), cell culture cytotoxicity neutralization assay (Bartels™ Cytotoxicity Assay, CT), and real-time PCR targeting the toxin B gene (BD GeneOhm™ Cdiff Assay, PCR). The analytic sensitivity and specificity of each as determined using a combined gold standard were as follows: GDH, 100% and 93.2%; Toxin EIA, 82.9% and 82.9%; CT, 100% and 100%; PCR (performed on frozen specimens) 74.3% and 96.6%; respectively. However, the sensitivity and specificity of PCR improved to 100% when performed on 50 fresh stool samples collected in Cary-Blair. While CT remains a sensitive method for the detection of CDI, GDH offers an excellent initial screening method to rule out CDI. While the performance of each assay did not appear to be affected by collection in Cary-Blair medium, PCR performed better using fresh specimens.

Identifying common competences in health and social care: an example of multi-institutional and inter-professional working.

Students taking programmes of study leading to registration as a nurse or other health and social care professional, must be assessed in practice to ensure that they are competent in a range of skills. As practice placements become more difficult to source, the use of inter-professional assessment is becoming an increasingly important facet of assessment for students in health and social care. This paper describes an innovate collaborative project across 5 Higher Education Institutions and 16 professional groups to develop maps to assess communication, team working and ethical practice, three essential competences for all health professionals. The process used to develop each competency map is detailed along with discussion of the consultation process with professional statutory and regulatory bodies, practice based and academic staff and service users and carers. The completed project is evidence of successful multi-institutional and inter-professional working to develop assessment processes which accurately and fairly measure capabilities to help students develop into proficient and effective practitioners.

Comparison of chromogenic media to BD GeneOhm methicillin-resistant Staphylococcus aureus (MRSA) PCR for detection of MRSA in nasal swabs.

To select a method for detecting methicillin-resistant Staphylococcus aureus (MRSA) in nasal swabs, we compared BD GeneOhm MRSA PCR and various culture media (mannitol salt agar with cefoxitin, MRSASelect, CHROMagar MRSA, and Spectra MRSA). While PCR detection of MRSA was more rapid, MRSASelect and Spectra MRSA demonstrated performance equivalent to that of PCR with maximal detection at 24 h.

GABA type-A activity controls its own developmental polarity switch in the maturing retina.

In the developing CNS, GABA(A) responses switch from early excitation to late mature inhibition. The developmental factors that induce the polarity switch remain to be unraveled. Here, we bring the first experimental evidence in vivo in the retina that chronic activation of GABA(A) receptors is necessary for the switch to occur and for the chloride extrusion mechanism (through the K+/Cl- cotransporter KCC2) to develop. Using a turtle model and calcium imaging, we investigated how chronic blockade of GABA(A) receptors with bicuculline during the period of the GABAergic polarity switch (from 1 week before hatching until 4 weeks after hatching) influences developmental changes in the patterns of spontaneously generated electrical activity in the retinal ganglion cell (RGC) layer. During that period, spontaneous activity normally switches from propagating waves to stationary patches of coactive cells, until correlated activity completely disappears. These changes in activity patterns coincide with the switch of GABA(A) responses from excitation to inhibition. When GABA(A) receptors are chronically blocked, GABA(A) responses remain excitatory and spontaneous waves keep propagating across the RGC layer. Concomitantly, the developmental upregulation of KCC2 is inhibited on dendritic processes in the inner plexiform layer, suggesting that the intracellular concentration of chloride remains higher, as in younger cells. This study presents the first demonstration in vivo that GABA autoregulates its developmental polarity switch, emphasizing the importance of GABAergic activity in controlling activity patterns in the maturing retina.