Impacts of metal mining on river systems: a global assessment.

An estimated 23 million people live on floodplains affected by potentially dangerous concentrations of toxic waste derived from past and present metal mining activity. We analyzed the global dimensions of this hazard, particularly in regard to lead, zinc, copper, and arsenic, using a georeferenced global database detailing all known metal mining sites and intact and failed tailings storage facilities. We then used process-based and empirically tested modeling to produce a global assessment of metal mining contamination in river systems and the numbers of human populations and livestock exposed. Worldwide, metal mines affect 479,200 kilometers of river channels and 164,000 square kilometers of floodplains. The number of people exposed to contamination sourced from long-term discharge of mining waste into rivers is almost 50 times greater than the number directly affected by tailings dam failures.

Artificial intelligence for radiological paediatric fracture assessment: a systematic review.

BACKGROUND: Majority of research and commercial efforts have focussed on use of artificial intelligence (AI) for fracture detection in adults, despite the greater long-term clinical and medicolegal implications of missed fractures in children. The objective of this study was to assess the available literature regarding diagnostic performance of AI tools for paediatric fracture assessment on imaging, and where available, how this compares with the performance of human readers. MATERIALS AND METHODS: MEDLINE, Embase and Cochrane Library databases were queried for studies published between 1 January 2011 and 2021 using terms related to 'fracture', 'artificial intelligence', 'imaging' and 'children'. Risk of bias was assessed using a modified QUADAS-2 tool. Descriptive statistics for diagnostic accuracies were collated. RESULTS: Nine eligible articles from 362 publications were included, with most (8/9) evaluating fracture detection on radiographs, with the elbow being the most common body part. Nearly all articles used data derived from a single institution, and used deep learning methodology with only a few (2/9) performing external validation. Accuracy rates generated by AI ranged from 88.8 to 97.9%. In two of the three articles where AI performance was compared to human readers, sensitivity rates for AI were marginally higher, but this was not statistically significant. CONCLUSIONS: Wide heterogeneity in the literature with limited information on algorithm performance on external datasets makes it difficult to understand how such tools may generalise to a wider paediatric population. Further research using a multicentric dataset with real-world evaluation would help to better understand the impact of these tools.

Validation of the Personality Assessment Inventory (PAI) scale of scales in a mixed clinical sample.

Objective: This exploratory study examined the classification accuracy of three derived scales aimed at detecting cognitive response bias in neuropsychological samples. The derived scales are composed of existing scales from the Personality Assessment Inventory (PAI). A mixed clinical sample of consecutive outpatients referred for neuropsychological assessment at a large Midwestern academic medical center was utilized. Participants and Methods: Participants included 332 patients who completed study's embedded and free-standing performance validity tests (PVTs) and the PAI. PASS and FAIL groups were created based on PVT performance to evaluate the classification accuracy of the derived scales. Three new scales, Cognitive Bias Scale of Scales 1-3, (CB-SOS1-3) were derived by combining existing scales by either summing the scales together and dividing by the total number of scales summed, or by logistically deriving a variable from the contributions of several scales. Results: All of the newly derived scales significantly differentiated between PASS and FAIL groups. All of the derived SOS scales demonstrated acceptable classification accuracy (i.e. CB-SOS1 AUC = 0.72; CB-SOS2 AUC = 0.73; CB-SOS3 AUC = 0.75). Conclusions: This exploratory study demonstrates that attending to scale-level PAI data may be a promising area of research in improving prediction of PVT failure.

Replication and cross-validation of the personality assessment inventory (PAI) cognitive bias scale (CBS) in a mixed clinical sample.

Objective: This study is a cross-validation of the Cognitive Bias Scale (CBS) from the Personality Assessment Inventory (PAI), a ten-item scale designed to assess symptom endorsement associated with performance validity test failure in neuropsychological samples. The study utilized a mixed neuropsychological sample of consecutively referred patients at a large academic medical center in the Midwest. Participants and Methods: Participants were 332 patients who completed embedded and free-standing performance validity tests (PVTs) and the PAI. Pass and fail groups were created based on PVT performance to evaluate classification accuracy of the CBS. Results: The results were generally consistent with the initial study for overall classification accuracy, sensitivity, and cut-off score. Consistent with the validation study, CBS had better classification accuracy than the original PAI validity scales and a comparable effect size to that obtained in the original validation publication; however, the Somatic Complaints scale (SOM) and the Conversion subscale (SOM-C) also demonstrated good classification accuracy. The CBS had incremental predictive ability compared to existing PAI scales. Conclusions: The results supported the CBS, but further research is needed on specific populations. Findings from this present study also suggest the relationship between conversion tendencies and PVT failure may be stronger in some geographic locations or population types (forensic versus clinical patients).

Review of study reporting guidelines for clinical studies using artificial intelligence in healthcare.

High-quality research is essential in guiding evidence-based care, and should be reported in a way that is reproducible, transparent and where appropriate, provide sufficient detail for inclusion in future meta-analyses. Reporting guidelines for various study designs have been widely used for clinical (and preclinical) studies, consisting of checklists with a minimum set of points for inclusion. With the recent rise in volume of research using artificial intelligence (AI), additional factors need to be evaluated, which do not neatly conform to traditional reporting guidelines (eg, details relating to technical algorithm development). In this review, reporting guidelines are highlighted to promote awareness of essential content required for studies evaluating AI interventions in healthcare. These include published and in progress extensions to well-known reporting guidelines such as Standard Protocol Items: Recommendations for Interventional Trials-AI (study protocols), Consolidated Standards of Reporting Trials-AI (randomised controlled trials), Standards for Reporting of Diagnostic Accuracy Studies-AI (diagnostic accuracy studies) and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis-AI (prediction model studies). Additionally there are a number of guidelines that consider AI for health interventions more generally (eg, Checklist for Artificial Intelligence in Medical Imaging (CLAIM), minimum information (MI)-CLAIM, MI for Medical AI Reporting) or address a specific element such as the 'learning curve' (Developmental and Exploratory Clinical Investigation of Decision-AI) . Economic evaluation of AI health interventions is not currently addressed, and may benefit from extension to an existing guideline. In the face of a rapid influx of studies of AI health interventions, reporting guidelines help ensure that investigators and those appraising studies consider both the well-recognised elements of good study design and reporting, while also adequately addressing new challenges posed by AI-specific elements.

Development and implementation of an ultralow-dose CT protocol for the assessment of cerebrospinal shunts in adult hydrocephalus.

BACKGROUND: Cerebrospinal fluid shunts in the treatment of hydrocephalus, although associated with clinical benefit, have a high failure rate with repeat computed tomography (CT) imaging resulting in a substantial cumulative radiation dose. Therefore, we sought to develop a whole-body ultralow-dose (ULD) CT protocol for the investigation of shunt malfunction and compare it with the reference standard, plain radiographic shunt series (PRSS). METHODS: Following ethical approval, using an anthropomorphic phantom and a human cadaveric ventriculoperitoneal shunt model, a whole-body ULD-CT protocol incorporating two iterative reconstruction (IR) algorithms, pure IR and hybrid IR, including 60% filtered back projection and 40% IR was evaluated in 18 adult patients post new shunt implantation or where shunt malfunction was suspected. Effective dose (ED) and image quality were analysed. RESULTS: ULD-CT permitted a 36% radiation dose reduction (median ED 0.16 mSv, range 0.07-0.17, versus 0.25 mSv (0.06-1.69 mSv) for PRSS (p = 0.002). Shunt visualisation in the thoracoabdominal cavities was improved with ULD-CT with pure IR (p = 0.004 and p = 0.031, respectively) and, in contrast to PRSS, permitted visualisation of the entire shunt course (p < 0.001), the distal shunt entry point and location of the shunt tip in all cases. For shunt complications, ULD-CT had a perfect specificity. False positives (3/22, 13.6%) were observed with PRSS. CONCLUSIONS: At a significantly reduced radiation dose, whole body ULD-CT with pure IR demonstrated diagnostic superiority over PRSS in the evaluation of cerebrospinal fluid shunt malfunction.

Assessment of the effects of Syk and BTK inhibitors on GPVI-mediated platelet signaling and function.

Spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (BTK) play critical roles in platelet physiology, facilitating intracellular immunoreceptor tyrosine-based activation motif (ITAM)-mediated signaling downstream of platelet glycoprotein VI (GPVI) and GPIIb/IIIa receptors. Small molecule tyrosine kinase inhibitors (TKIs) targeting Syk and BTK have been developed as antineoplastic and anti-inflammatory therapeutics and have also gained interest as antiplatelet agents. Here, we investigate the effects of 12 different Syk and BTK inhibitors on GPVI-mediated platelet signaling and function. These inhibitors include four Syk inhibitors, Bay 61-3606, R406 (fostamatinib), entospletinib, TAK-659; four irreversible BTK inhibitors, ibrutinib, acalabrutinib, ONO-4059 (tirabrutinib), AVL-292 (spebrutinib); and four reversible BTK inhibitors, CG-806, BMS-935177, BMS-986195, and fenebrutinib. In vitro, TKIs targeting Syk or BTK reduced platelet adhesion to collagen, dense granule secretion, and alpha granule secretion in response to the GPVI agonist cross-linked collagen-related peptide (CRP-XL). Similarly, these TKIs reduced the percentage of activated integrin αIIbß3 on the platelet surface in response to CRP-XL, as determined by PAC-1 binding. Although all TKIs tested inhibited phospholipase C γ2 (PLCγ2) phosphorylation following GPVI-mediated activation, other downstream signaling events proximal to phosphoinositide 3-kinase (PI3K) and PKC were differentially affected. In addition, reversible BTK inhibitors had less pronounced effects on GPIIb/IIIa-mediated platelet spreading on fibrinogen and differentially altered the organization of PI3K around microtubules during platelets spreading on fibrinogen. Select TKIs also inhibited platelet aggregate formation on collagen under physiological flow conditions. Together, our results suggest that TKIs targeting Syk or BTK inhibit central platelet functional responses but may differentially affect protein activities and organization in critical systems downstream of Syk and BTK in platelets.

The Potential Clinical and Economic Value of a Human Papillomavirus Primary Screening Test That Additionally Identifies Genotypes 31, 45, 51, and 52 Individually.

BACKGROUND: Although current human papillomavirus (HPV) genotype screening tests identify genotypes 16 and 18 and do not specifically identify other high-risk types, a new extended genotyping test identifies additional individual (31, 45, 51, and 52) and groups (33/58, 35/39/68, and 56/59/66) of high-risk genotypes. METHODS: We developed a Markov model of the HPV disease course and evaluated the clinical and economic value of HPV primary screening with Onclarity (BD Diagnostics, Franklin Lakes, NJ) capable of extended genotyping in a cohort of women 30 years or older. Women with certain genotypes were later rescreened instead of undergoing immediate colposcopy and varied which genotypes were rescreened, disease progression rate, and test cost. RESULTS: Assuming 100% compliance with screening, HPV primary screening using current tests resulted in 25,194 invasive procedures and 48 invasive cervical cancer (ICC) cases per 100,000 women. Screening with extended genotyping (100% compliance) and later rescreening women with certain genotypes averted 903 to 3163 invasive procedures and resulted in 0 to 3 more ICC cases compared with current HPV primary screening tests. Extended genotyping was cost-effective ($2298-$7236/quality-adjusted life year) when costing $75 and cost saving (median, $0.3-$1.0 million) when costing $43. When the probabilities of disease progression increased (2-4 times), extended genotyping was not cost-effective because it resulted in more ICC cases and accrued fewer quality-adjusted life years. CONCLUSIONS: Our study identified the conditions under which extended genotyping was cost-effective and even cost saving compared with current tests. A key driver of cost-effectiveness is the risk of disease progression, which emphasizes the need to better understand such risks in different populations.

Assessment of structural chromosomal instability phenotypes as biomarkers of carboplatin response in triple negative breast cancer: the TNT trial.

BACKGROUND: In the TNT trial of triple negative breast cancer (NCT00532727), germline BRCA1/2 mutations were present in 28% of carboplatin responders. We assessed quantitative measures of structural chromosomal instability (CIN) to identify a wider patient subgroup within TNT with preferential benefit from carboplatin over docetaxel. PATIENTS AND METHODS: Copy number aberrations (CNAs) were established from 135 formalin-fixed paraffin-embedded primary carcinomas using Illumina OmniExpress SNP-arrays. Seven published [allelic imbalanced CNA (AiCNA); allelic balanced CNA (AbCNA); copy number neutral loss of heterozygosity (CnLOH); number of telomeric allelic imbalances (NtAI); BRCA1-like status; percentage of genome altered (PGA); homologous recombination deficiency (HRD) scores] and two novel [Shannon diversity index (SI); high-level amplifications (HLAMP)] CIN-measurements were derived. HLAMP was defined based on the presence of at least one of the top 5% amplified cytobands located on 1q, 8q and 10p. Continuous CIN-measurements were divided into tertiles. All nine CIN-measurements were used to analyse objective response rate (ORR) and progression-free survival (PFS). RESULTS: Patients with tumours without HLAMP had a numerically higher ORR and significantly longer PFS in the carboplatin (C) than in the docetaxel (D) arm [56% (C) versus 29% (D), PHLAMP,quiet = 0.085; PFS 6.1 months (C) versus 4.1 months (D), Pinteraction/HLAMP = 0.047]. In the carboplatin arm, patients with tumours showing intermediate telomeric NtAI and AiCNA had higher ORR [54% (C) versus 20% (D), PNtAI,intermediate = 0.03; 62% (C) versus 33% (D), PAiCNA,intermediate = 0.076]. Patients with high AiCNA and PGA had shorter PFS in the carboplatin arm [3.4 months (high) versus 5.7 months (low/intermediate); and 3.8 months (high) versus 5.6 months (low/intermediate), respectively; Pinteraction/AiCNA = 0.027, Padj.interaction/AiCNA = 0.125 and Pinteraction/PGA = 0.053, Padj.interaction/PGA = 0.176], whilst no difference was observed in the docetaxel arm. CONCLUSIONS: Patients with tumours lacking HLAMP and demonstrating intermediate CIN-measurements formed a subgroup benefitting from carboplatin relative to docetaxel treatment within the TNT trial. This suggests a complex and paradoxical relationship between the extent of genomic instability in primary tumours and treatment response in the metastatic setting.

Micro-computed tomography (micro-CT) for the assessment of myocardial disarray, fibrosis and ventricular mass in a feline model of hypertrophic cardiomyopathy.

Micro-computed tomography (micro-CT) is a high-resolution imaging modality that provides accurate tissue characterization. Hypertrophic cardiomyopathy (HCM) occurs as a spontaneous disease in cats, and is characterized by myocardial hypertrophy, disarray and fibrosis, as in humans. While hypertrophy/mass (LVM) can be objectively measured, fibrosis and myocyte disarray are difficult to assess. We evaluated the accuracy of micro-CT for detection and quantification of myocardial disarray and fibrosis by direct comparison with histopathology. 29 cat hearts (12 normal and 17 HCM hearts) underwent micro-CT and pathologic examination. Myocyte orientation was assessed using structure tensor analysis by determination of helical angle (HA), fractional anisotropy (FA) and myocardial disarray index (MDI). Fibrosis was segmented and quantified based on comparison of gray-scale values in normal and fibrotic myocardium. LVM was obtained by determining myocardial volume. Myocardial segments with low FA, low MDI and disruption of normal HA transmural profile on micro-CT were associated with myocardial disarray on histopathology. FA was consistently lower in HCM than normal hearts. Assessment of fibrosis on micro-CT closely matched the histopathologic evaluation. LVM determined by micro-CT was higher in HCM than normal hearts. Micro-CT can be used to detect and quantify myocardial disarray and fibrosis and determine myocardial mass in HCM.

Registry-based trials: a potential model for cost savings?

BACKGROUND/AIMS: Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials. METHODS: We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design. RESULTS: Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field. CONCLUSIONS: Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.

The potential economic value of a therapeutic Chagas disease vaccine for pregnant women to prevent congenital transmission.

BACKGROUND: Currently, there are no solutions to prevent congenital transmission of Chagas disease during pregnancy, which affects 1-40% of pregnant women in Latin America and is associated with a 5% transmission risk. With therapeutic vaccines under development, now is the right time to determine the economic value of such a vaccine to prevent congenital transmission. METHODS: We developed a computational decision model that represented the clinical outcomes and diagnostic testing strategies for an infant born to a Chagas-positive woman in Mexico and evaluated the impact of vaccination. RESULTS: Compared to no vaccination, a 25% efficacious vaccine averted 125 [95% uncertainty interval (UI): 122-128] congenital cases, 1.9 (95% UI: 1.6-2.2) infant deaths, and 78 (95% UI: 66-91) DALYs per 10,000 infected pregnant women; a 50% efficacious vaccine averted 251 (95% UI: 248-254) cases, 3.8 (95% UI: 3.6-4.2) deaths, and 160 (95% UI: 148-171) DALYs; and a 75% efficacious vaccine averted 376 (95% UI: 374-378) cases, 5.8 (95% UI: 5.5-6.1) deaths, and 238 (95% UI: 227-249) DALYs. A 25% efficacious vaccine was cost-effective (incremental cost-effectiveness ratio <3× Mexico's gross domestic product per capita, <$29,698/DALY averted) when the vaccine cost ≤$240 and ≤$310 and cost-saving when ≤$10 and ≤$80 from the third-party payer and societal perspectives, respectively. A 50% efficacious vaccine was cost-effective when costing ≤$490 and ≤$615 and cost-saving when ≤$25 and ≤$160, from the third-party payer and societal perspectives, respectively. A 75% efficacious vaccine was cost-effective when ≤$720 and ≤$930 and cost-saving when ≤$40 and ≤$250 from the third-party payer and societal perspectives, respectively. Additionally, 13-42 fewer infants progressed to chronic disease, saving $0.41-$1.21 million to society. CONCLUSION: We delineated the thresholds at which therapeutic vaccination of Chagas-positive pregnant women would be cost-effective and cost-saving, providing economic guidance for decision-makers to consider when developing and bringing such a vaccine to market.

The Potential Economic Value of a Zika Vaccine for a Woman of Childbearing Age.

INTRODUCTION: With Zika vaccine candidates under development and women of childbearing age being the primary target population, now is the time to map the vaccine (e.g., efficacy and duration of protection) and vaccination (e.g., cost) characteristic thresholds at which vaccination becomes cost effective, highly cost effective, and cost saving. METHODS: A Markov model was developed (to represent 2019 circumstances, US$ and INT$, Region of the Americas) to simulate a woman of childbearing age and the potential risk and clinical course of a Zika infection. RESULTS: Compared with no vaccination, vaccination was cost effective (incremental cost-effectiveness ratio: US$1,254-$82,900/disability-adjusted life years averted) when the risk of infection was ≥0.05%-0.08% (varying with country income), vaccine efficacy was ≥25%, and vaccination cost was US$1-$7,500 (INT$5-$10,000 depending on country income level). Vaccination was dominant (i.e., saved costs and provided beneficial health effects) when the infection risk was ≥0.1% for a vaccine efficacy ≥75% and when the infection risk was ≥0.5% for a vaccine efficacy ≥25%, for scenarios where vaccination conferred a 1-year duration of protection and cost ≤$200. In some cases, the vaccine was cost effective when the risk was as low as 0.015%, the cost was as high as $7,500 (INT$10,000), the efficacy was as low as 25%, and the duration of protection was 1 year. CONCLUSIONS: The thresholds at which vaccination becomes cost effective and cost saving can provide targets for Zika vaccine development and implementation.

Utility of the Modified Isolated-check Visual Evoked Potential Technique in Functional Glaucoma Assessment.

PRE[COMBINING ACUTE ACCENT]CIS:: Cortical response to low-contrast stimuli, as measured by isolated-check visual evoked potential (icVEP) technology, has the potential to provide functional assessment that may complement standard achromatic perimetry in assessing glaucomatous change. PURPOSE: To evaluate the utility of modified icVEP testing in detecting functional glaucomatous damage. MATERIALS AND METHODS: Subjects who met predetermined criteria of controls, glaucoma suspects, preperimetric glaucoma, or glaucoma were enrolled in this prospective cross-sectional study from a single tertiary care center. Glaucoma patients were further categorized as early, moderate, advanced, or severe on the basis of Hodapp-Anderson-Parrish criteria. icVEP testing was performed with ten 2-second runs per qualified eye using the EvokeDx testing software. Multivariate statistics were used to calculate signal-to-noise ratios (SNR) and perform outlier analysis. RESULTS: In total, 140 eyes met criteria (mean±SD; age of 63±14 y; 49% male; logMAR visual acuity, 0.11±0.089). There was no significant difference in age, sex, or logMAR visual acuity among the groups. Controls had a significantly higher SNR than all other groups (P<0.003), including patients with preperimetric glaucoma. Among those with glaucoma, the early glaucoma patients had significantly higher SNR than the moderate, advanced, or severe glaucoma cohorts (P<0.04). The optimal SNR cutoff for differentiating between glaucomatous and nonglaucomatous eyes was 0.95, both with (sensitivity 82%, specificity 76%) and without (sensitivity 82%, specificity 100%) glaucoma suspects included in analysis. CONCLUSIONS: icVEP technology has the potential to complement standard achromatic perimetry in functional assessment of glaucomatous defects.

Assessment of neonatal, cord, and adult platelet granule trafficking and secretion.

Despite the transient hyporeactivity of neonatal platelets, full-term neonates do not display a bleeding tendency, suggesting potential compensatory mechanisms which allow for balanced and efficient neonatal hemostasis. This study aimed to utilize small-volume, whole blood platelet functional assays to assess the neonatal platelet response downstream of the hemostatic platelet agonists thrombin and adenosine diphosphate (ADP). Thrombin activates platelets via the protease-activated receptors (PARs) 1 and 4, whereas ADP signals via the receptors P2Y1 and P2Y12 as a positive feedback mediator of platelet activation. We observed that neonatal and cord blood-derived platelets exhibited diminished PAR1-mediated granule secretion and integrin activation relative to adult platelets, correlating to reduced PAR1 expression by neonatal platelets. PAR4-mediated granule secretion was blunted in neonatal platelets, correlating to lower PAR4 expression as compared to adult platelets, while PAR4 mediated GPIIb/IIIa activation was similar between neonatal and adult platelets. Under high shear stress, cord blood-derived platelets yielded similar thrombin generation rates but reduced phosphatidylserine expression as compared to adult platelets. Interestingly, we observed enhanced P2Y1/P2Y12-mediated dense granule trafficking in neonatal platelets relative to adults, although P2Y1/P2Y12 expression in neonatal, cord, and adult platelets were similar, suggesting that neonatal platelets may employ an ADP-mediated positive feedback loop as a potential compensatory mechanism for neonatal platelet hyporeactivity.

Assessing the perceived impact of post Minamata amalgam phase down on oral health inequalities: a mixed-methods investigation.

BACKGROUND: Data from countries that have implemented a complete phase out of dental amalgam following the Minamata agreement suggest increased costs and time related to the placement of alternatives with consumers absorbing the additional costs. This aim of this study was to investigate the impact of a complete phase out of dental amalgam on oral health inequalities in particular for countries dependent on state run oral health services. METHODS: A mixed methods component design quantitative and qualitative study in the United Kingdom. The quantitative study involved acquisition and analysis of datasets from NHS Scotland to compare trends in placement of dental amalgam and a survey of GDPs in Yorkshire, UK. The qualitative study involved analysis of the free text of the survey and a supplementary secondary analysis of semi-structured interviews and focus groups with GDPs (private and NHS), dental school teaching leads and NHS dental commissioners to understand the impact of amalgam phase down on oral health inequalities. RESULTS: Time-trends for amalgam placement showed that there was a significant (p < 0.05) reduction in amalgam use compared with composites and glass ionomers. However dental amalgam still represented a large proportion (42%) of the restorations (circa 1.8 million) placed in the 2016-2017 financial year. Survey respondents suggest that direct impacts of a phase down were related to increased costs and time to place alternative restorations and reduced quality of care. This in turn would lead to increased tooth extractions, reduced access to care and privatisation of dental services with the greatest impact on deprived populations. CONCLUSION: Amalgam is still a widely placed material in state run oral health services. The complete phase down of dental amalgam poses a threat to such services and threatens to widen oral health inequalities. Our data suggest that a complete phase out is not currently feasible unless appropriate measures are in place to ensure cheaper, long-lasting and easy to use alternatives are available and can be readily adopted by primary care oral health providers.

Does exposure to bentonite dust during tunnel hyperbaric interventions increase health risks for compressed air workers? A prospective qualitative and quantitative safety assessment.

INTRODUCTION: The mining and tunneling industries are historically associated with hazardous exposures that result in significant occupational health concerns. Occupational respiratory exposures causing pneumoconiosis and silicosis are of great concern, silicosis being non-curable. This work demonstrates that compressed-air workers (CAWs) performing tunnel hyperbaric interventions (HIs) may be at risk for hazards related to bentonite exposure, increasing the likelihood of developing harmful illnesses including cancer. Bentonite dust inhalation may result in respiratory levels of silica exceeding acceptable industrial hygiene standards. METHODS: A qualitative observational exposure assessment was conducted on CAWs while they were performing their HI duties. This was followed by quantitative data collection using personal and area air sample techniques. The results were analyzed and interpreted using standard industrial hygiene principles and guidelines from NIOSH and OSHA. RESULTS: Our work suggests bentonite dust exposure may be an emerging particulate matter concern among CAWs in the tunneling industry. Aerosolized bentonite particles may have potential deleterious effects that include pneumoconiosis and silicosis. Silicosis can result in the development of pulmonary carcinoma. CONCLUSIONS: The modern tunneling industry and required hyperbaric interventional tasks represent a potential public health and occupational concern for CAWs. This paper introduces the modern tunneling industry and the duties of CAWs, the hazardous environment in which they perform their duties, and describes the risks and potential harmful health effects associated with these hazardous exposures.

Minimally invasive autopsy for fetuses and children based on a combination of post-mortem MRI and endoscopic examination: a feasibility study.

BACKGROUND: Less invasive perinatal and paediatric autopsy methods, such as imaging alongside targeted endoscopy and organ biopsy, may address declining consent rates for traditional autopsy, but their acceptability and accuracy are not known. OBJECTIVES: The aims of this study were to provide empirical data on the acceptability and likely uptake for different types of autopsy among key stakeholders (study 1); and to analyse existing autopsy data sources to provide estimates of the potential efficacy of less invasive autopsy (LIA) and its projected utility in clinical practice (study 2). REVIEW METHODS: Study 1: this was a mixed-methods study. Parents were involved in research design and interpretation of findings. Substudy 1: a cross-sectional survey of 859 parents who had experienced miscarriage, termination of pregnancy for fetal anomaly, stillbirth, infant or child death, and interviews with 20 responders. Substudy 2: interviews with 25 health professionals and four coroners. Substudy 3: interviews with 16 religious leaders and eight focus groups, with 76 members of the Muslim and Jewish community. Study 2: a retrospective analysis of national data in addition to detailed information from an existing in-house autopsy database of > 5000 clinical cases that had undergone standard autopsy to determine the proportion of cases by clinical indication group for which tissue sampling of specific internal organs significantly contributed to the diagnosis. RESULTS: Substudy 1: 91% of participants indicated that they would consent to some form of LIA, 54% would consent to standard autopsy, 74% to minimally invasive autopsy (MIA) and 77% to non-invasive autopsy (NIA). Substudy 2: participants viewed LIA as a positive development, but had concerns around the limitations of the technology and de-skilling the workforce. Cost implications, skills and training requirements were identified as implementation challenges. Substudy 3: religious leaders agreed that NIA was religiously permissible, but MIA was considered less acceptable. Community members indicated that they might consent to NIA if the body could be returned for burial within 24 hours. Study 2: in 5-10% of cases of sudden unexplained death in childhood and sudden unexplained death in infants, the final cause of death is determined by routine histological sampling of macroscopically normal organs, predominantly the heart and lungs, and in this group routine histological sampling therefore remains an important aspect of investigation. In contrast, routine histological examination of macroscopically normal organs rarely (< 0.5%) provides the cause of death in fetal cases, making LIA and NIA approaches potentially highly applicable. LIMITATIONS: A key limitation of the empirical research is that it is hypothetical. Further research is required to determine actual uptake. Furthermore, because of the retrospective nature of the autopsy data set, findings regarding the likely contribution of organ sampling to final diagnosis are based on extrapolation of findings from historical autopsies, and prospective data collection is required to validate the conclusions. CONCLUSIONS: LIA is viable and acceptable (except for unexplained deaths), and likely to increase uptake. Further health economic, performance and implementation studies are required to determine the optimal service configuration required to offer this as routine clinical care. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Autopsy (post-mortem) examination of babies and children who die is often necessary to help doctors or coroners find out the cause of death. It may also be useful for research. However, many bereaved parents dislike the idea of their child being cut and some religious communities prohibit the procedure. Over the past 30 years, consent rates for autopsies have declined. In order to address parental concerns and declining uptake, a number of less invasive options have been developed. These include X-ray and magnetic resonance imaging, by doing keyhole internal examination and needle organ biopsy. However, it is not known to what extent such methods are acceptable to parents, nor how accurate they are. We surveyed the attitudes of bereaved parents and religious group leaders to such less invasive methods. The less invasive option was considered acceptable and would be chosen by almost 1000 bereaved parents. Such an approach is also acceptable to those religious groups for whom standard autopsy examination is not. We also examined a database of > 5000 standard autopsies to determine the extent to which specific internal organ biopsy contributed to the diagnosis. In > 5000 standard autopsies, traditional organ biopsy rarely contributed to determination of the cause of death or the main diagnosis. Therefore, a more limited and targeted tissue sampling protocol could be introduced without significant reduction in the accuracy of final diagnosis. The specific approaches required will depend on individual circumstances and are likely to include a range, from targeted organ biopsy with an open incision, through incisionless image-guided needle biopsies, to non-invasive imaging-only techniques. Future studies may focus on how the NHS could implement offering less invasive approaches nationally, what the cost­benefit of such an approach could be and what the impact could be on real-world uptake if this were to be offered routinely.

Diagnostic assessment of foetal brain malformations with intra-uterine MRI versus perinatal post-mortem MRI.

PURPOSE: To evaluate differences in diagnostic yield of intra-uterine foetal (iuMR) and post-mortem MRI (PMMR) for complex brain malformations, using autopsy as the reference standard. METHODS: In this retrospective, multicentre study spanning 2 years, we reviewed 13 terminated singleton pregnancies with a prenatal ultrasound finding of complex foetal cerebral abnormalities, referred for both iuMR and PMMR. The iuMR and PMMR studies of the brain were reported independently by two groups of radiologists, blinded to each other's reports. Descriptive statistics were used to compare differences in intracranial abnormalities with autopsy (and genetic testing, where present) as reference standard. RESULTS: The median gestational age at termination was 24.6 weeks (IQR 22-29) with median time between delivery and PMMR of 133 h (IQR 101-165). There was full concordance between iuMR and PMMR findings and autopsy in 2/13 (15.3%) cases. Partial concordance between both imaging modalities was present in 6/13 (46.2%) and total discordance in the remainder (5/13, 38.5%). When compared to autopsy, PMMR missed important key findings specifically for neuronal migration and cerebellar anomalies, whereas iuMR appeared to overcall CSF space abnormalities which were less crucial to reaching the final overall diagnosis. CONCLUSIONS: iuMR should be performed to improve foetal phenotyping where there is a prenatal ultrasound for complex foetal brain abnormalities. Reliance on PMMR alone is likely to result in misdiagnosis in a majority of cases.