Assessment of inspiration and technical quality in anteroposterior thoracic radiographs using machine learning.

INTRODUCTION: Chest radiographs are the most performed radiographic procedure, but suboptimal technical factors can impact clinical interpretation. A deep learning model was developed to assess technical and inspiratory adequacy of anteroposterior chest radiographs. METHODS: Adult anteroposterior chest radiographs (n = 2375) were assessed for technical adequacy, and if otherwise technically adequate, for adequacy of inspiration. Images were labelled by an experienced radiologist with one of three ground truth labels: inadequate technique (n = 605, 25.5 %), adequate inspiration (n = 900, 37.9 %), and inadequate inspiration (n = 870, 36.6 %). A convolutional neural network was then iteratively trained to predict these labels and evaluated using recall, precision, F1 and micro-F1, and Gradient-weighted Class Activation Mapping analysis on a hold-out test set. Impact of kyphosis on model accuracy was assessed. RESULTS: The model performed best for radiographs with adequate technique, and worst for images with inadequate technique. Recall was highest (89 %) for radiographs with both adequate technique and inspiration, with recall of 81 % for images with adequate technique and inadequate inspiration, and 60 % for images with inadequate technique, although precision was highest (85 %) for this category. Per-class F1 was 80 %, 81 % and 70 % for adequate inspiration, inadequate inspiration, and inadequate technique respectively. Weighted F1 and Micro F1 scores were 78 %. Presence or absence of kyphosis had no significant impact on model accuracy in images with adequate technique. CONCLUSION: This study explores the promising performance of a machine learning algorithm for assessment of inspiratory adequacy and overall technical adequacy for anteroposterior chest radiograph acquisition. IMPLICATIONS FOR PRACTICE: With further refinement, machine learning can contribute to education and quality improvement in radiology departments.

Correlation of frailty assessment metrics in one-year follow-up of aged care residents: a sub-study of a randomised controlled trial.

INTRODUCTION: Frailty is increasingly recognised as a dynamic syndrome, with multiple causes, dimensions and consequences. There is little understanding of how those frailty assessment metrics interact over time. The aim of this study was to describe the longitudinal correlation between five frailty metrics, namely multimorbidity, muscular strength, mood alterations, cognitive capacity, and functional capacity in a cohort study of aged care (nursing home) residents. METHODS: 248 aged care residents with Frailty Index at baseline of < 0.4 and no dementia were followed for 12 months. A multimorbidity score and an activity of daily living limitation score were created using individual items of the Frailty Index. Muscular strength was measured by grip strength. Cognitive capacity was measured using the Montreal Cognitive Assessment (MoCA) test. Mood alterations were measured using the anxiety/depression screening question from EQ-5D. We analysed the inter-individual correlation at baseline, association between baseline and future change, and within-individual correlation at baseline, 6 and 12 months. RESULTS: Population analysis shows that metrics were not associated at baseline. All of the studied metrics at baseline were associated with change in 12 months, with the exception of anxiety/depression scores. Pairwise within-individual correlation was strong between MoCA and grip strength (0.13, p = 0.02) and activity of daily living (- 0.48, p < 0.001), and between activities of daily living and multimorbidity index (0.28, p < 0.001). No within-individual correlation was found between anxiety depression score and other metrics. CONCLUSION: The results suggest an interdependence between comorbidities, physical capacity, cognition and activities of daily living in aged care residents. Comprehensive measurement of frailty-related metrics may provide improved understanding of frailty progression at later life stages.

Adaptive Biomedical Innovation: Evolving Our Global System to Sustainably and Safely Bring New Medicines to Patients in Need.

The current system of biomedical innovation is unable to keep pace with scientific advancements. We propose to address this gap by reengineering innovation processes to accelerate reliable delivery of products that address unmet medical needs. Adaptive biomedical innovation (ABI) provides an integrative, strategic approach for process innovation. Although the term "ABI" is new, it encompasses fragmented "tools" that have been developed across the global pharmaceutical industry, and could accelerate the evolution of the system through more coordinated application. ABI involves bringing stakeholders together to set shared objectives, foster trust, structure decision-making, and manage expectations through rapid-cycle feedback loops that maximize product knowledge and reduce uncertainty in a continuous, adaptive, and sustainable learning healthcare system. Adaptive decision-making, a core element of ABI, provides a framework for structuring decision-making designed to manage two types of uncertainty - the maturity of scientific and clinical knowledge, and the behaviors of other critical stakeholders.

Real World Data in Adaptive Biomedical Innovation: A Framework for Generating Evidence Fit for Decision-Making.

Analyses of healthcare databases (claims, electronic health records [EHRs]) are useful supplements to clinical trials for generating evidence on the effectiveness, harm, use, and value of medical products in routine care. A constant stream of data from the routine operation of modern healthcare systems, which can be analyzed in rapid cycles, enables incremental evidence development to support accelerated and appropriate access to innovative medicines. Evidentiary needs by regulators, Health Technology Assessment, payers, clinicians, and patients after marketing authorization comprise (1) monitoring of medication performance in routine care, including the materialized effectiveness, harm, and value; (2) identifying new patient strata with added value or unacceptable harms; and (3) monitoring targeted utilization. Adaptive biomedical innovation (ABI) with rapid cycle database analytics is successfully enabled if evidence is meaningful, valid, expedited, and transparent. These principles will bring rigor and credibility to current efforts to increase research efficiency while upholding evidentiary standards required for effective decision-making in healthcare.

Accelerated access to innovative medicines for patients in need.

There is broad agreement among health-care stakeholders that more must be done to ensure that patients have timely access to new and innovative medicines. Assuming that industry will continue to develop such medicines at a sustainable rate, regulators and payers become the gatekeepers. Regulators, starting in the late 1980s/early 1990s, and, more recently, payers have implemented a variety of early-access pathways or initiatives, and this practice is continuing even today. This article describes the specific approaches that have been taken in four economically developed regions, reviews their success rates, and suggests possible new directions.

Adaptive licensing: taking the next step in the evolution of drug approval.

Traditional drug licensing approaches are based on binary decisions. At the moment of licensing, an experimental therapy is presumptively transformed into a fully vetted, safe, efficacious therapy. By contrast, adaptive licensing (AL) approaches are based on stepwise learning under conditions of acknowledged uncertainty, with iterative phases of data gathering and regulatory evaluation. This approach allows approval to align more closely with patient needs for timely access to new technologies and for data to inform medical decisions. The concept of AL embraces a range of perspectives. Some see AL as an evolutionary step, extending elements that are now in place. Others envision a transformative framework that may require legislative action before implementation. This article summarizes recent AL proposals; discusses how proposals might be translated into practice, with illustrations in different therapeutic areas; and identifies unresolved issues to inform decisions on the design and implementation of AL.

A comparison of mixture toxicity assessment: examining the chronic toxicity of atrazine, permethrin and chlorothalonil in mixtures to Ceriodaphnia cf. dubia.

Pesticides predominantly occur in aquatic ecosystems as mixtures of varying complexity, yet relatively few studies have examined the toxicity of pesticide mixtures. Atrazine, chlorothalonil and permethrin are widely used pesticides that have different modes of action. This study examined the chronic toxicities (7-d reproductive impairment) of these pesticides in binary and ternary mixtures to the freshwater cladoceran Ceriodaphnia cf. dubia. The toxicity of the mixtures was compared to that predicted by the independent action (IA) model for mixtures, as this is the most appropriate model for chemicals with different modes of action. Following this they were compared to the toxicity predicted by the concentration addition (CA) model for mixtures. According to the IA model, the toxicity of the chlorothalonil plus atrazine mixture conformed to antagonism, while that of chlorothalonil and permethrin conformed to synergism. The toxicity of the atrazine and permethrin mixture as well as the ternary mixture conformed to IA implying there was either no interaction between the components of these mixtures and/or in the case of the ternary mixture the interactions cancelled each other out to result in IA. The synergistic and antagonistic mixtures deviated from IA by factors greater than 3 and less than 2.5, respectively. When the toxicity of the mixtures was compared to the predictions of the CA model, the binary mixture of chlorothalonil plus atrazine, permethrin plus atrazine and the ternary mixture all conformed to antagonism, while the binary mixture of chlorothalonil plus permethrin conformed to CA. Using the CA model provided estimates of mixture toxicity that did not markedly underestimate the measured toxicity, unlike the IA model, and therefore the CA model is the most suitable to use in ecological risk assessments of these pesticides.

Assessment of metal toxicity in sediment pore water from Lake Macquarie, Australia.

Recent investigations into the level of heavy metal enrichment in the sediments of Lake Macquarie have indicated that significant contamination has occurred over the past 100 years, with elevated levels of lead, zinc, cadmium, copper, and selenium being observed in most parts of the lake. Pore water extracted from sediments showing the greatest contamination by these metals exhibited toxicity to the larval development of the sea urchin Heliocidaris tuberculata. However, an analysis of pore water metal concentrations revealed that the concentrations of these metals were too low to cause toxicity. Rather, pore water toxicity was highly correlated with manganese for the majority of sites sampled; subsequent spiking experiments confirmed manganese as a cause of toxicity. Current levels of manganese in the sediments of Lake Macquarie have arisen from natural sources and are not the result of anthropogenic activities. These results reiterate the importance of identifying the causes of toxicity in assessments of sediment contamination, particularly when testing sediment pore waters using sensitive early life stages.

Development of an improved rapid enzyme inhibition bioassay with marine and freshwater microalgae using flow cytometry.

A rapid toxicity test based on inhibition of esterase activity in marine and freshwater microalgae (Selenastrum capricornutum, Chlorella sp., Dunaliella tertiolecta, Phaeodactylum tricornutum, Tetraselmis sp., Entomoneis cf. punctulata, Nitzschia cf. paleacea) was developed using flow cytometry. Uptake of fluorescein diacetate (FDA) was optimized for each species by varying the substrate concentration, incubation time, and media pH. Propidium iodide (PI) was utilized to assess membrane integrity. The optimized FDA/PI staining procedure was then used to assess the toxicity of copper in short-term exposures (1-24 h). Esterase activity was a sensitive indicator of copper toxicity in S. capricornutum and E. cf. punctulata. As copper concentrations increased, esterase activity decreased in a concentration-dependent manner. The 3- and 24-h EC50 values (based on mean activity states) were 112 microg Cu L(-1) (95% confidence limits 88-143) and 51 microg Cu L(-1) (95% confidence limits 38-70) for S. capricornutum and 47 microg Cu L(-1) (95% confidence limits 43-51) and 9.1 microg Cu L(-1) (95% confidence limits 7.6-11) for E. cf. punctulata, respectively. This enzyme inhibition endpoint showed similar sensitivity to chronic growth rate inhibition in E. cf. punctulata (48-h and 72-h EC50 values of 17 and 18 microg L(-1), respectively) but was less sensitive compared to growth for S. capricornutum (48-h and 72-h EC50 values of 4.9 and 7.5 microg L(-1), respectively). For the other five species tested, inhibition of FDA fluorescence was relatively insensitive to copper, even at copper concentrations that severely inhibited cell division rate. These short-term bioassays that detect sublethal endpoints may provide a more rapid and cost-effective way of monitoring contaminant impacts in natural waters.

Valoración en niños de la aceptabilidad de antibióticos resistentes a beta-lactamasas / Assessment of the palatability of beta-lactamase-resistant antibiotics in children

Se evaluó la aceptabilidad de tres antibióticos conocidos por su resistencia a beta-lactamasas en una muestra integrada por niños. Los resultados fueron comparados con los obtenidos en adultos. La aceptabilidad al sabor de los antibióticos en suspensión fue calificada con base en una escala analógica de 10 cm. Tanto en niños como en adultos, se asignó la calificación más alta a la azitromicina. Las significativas diferencias entre los sabores sugieren que este factor debe ser tomado en cuenta en todo estudio de aceptabilidad

Assessment of the palatability of beta-lactamase-resistant antibiotics in children.

OBJECTIVES: To evaluate the palatability of antibiotics effective against beta-lactamase-producing bacteria in children and to compare the results obtained with those obtained in adults. DESIGN: A taste test of 4 antibiotic suspensions: a combination of amoxicillin and clavulanic acid (banana), azithromycin (cherry), clarithromycin (wild fruit), and a combination of erythromycin and sulfisoxazole (strawberry-banana). SETTING: Outpatient setting. SUBJECTS: A volunteer sample of 50 healthy children (mean +/- SD age, 6.3 +/- 1.3 years) and 20 adults. MAIN OUTCOME MEASURES: After each antibiotic test dose, subjects rated its taste on a 10-cm visual analog scale incorporating a facial hedonic scale. RESULTS: The mean +/- SD taste scores of the antibiotics as rated by the children were as follows: amoxicillin-clavulanic acid, 5.7 +/- 3.6 cm; azithromycin, 6.8 +/- 3.2 cm; clarithromycin, 3.7 +/- 3.6 cm; and erythromycin-sulfisoxazole, 4.9 +/- 3.5 cm. The mean +/- SD taste score for erythromycin-sulfisoxazole (ie, 2.7 +/- 2.3) assigned by the adults was significantly different than that given by the children (P = .01) with no difference noted for the other 3 drugs. Children and adults both selected azithromycin most often as best tasting. There was a significant difference in the proportions selecting each antibiotic as worst tasting, with the children tending to dislike clarithromycin and the adults tending to dislike erythromycin-sulfisoxazole (P = .03). CONCLUSIONS: The taste of azithromycin was rated most highly by both children and adults, who also selected this antibiotic most often as best tasting. Differences in taste-testing results between children and adults suggest that evaluation of the palatability of medications intended for use in pediatrics should be conducted in children.

Objective assessment of "cardioprotective" efficacy as a prognostic guide to management of mildly symptomatic revascularizable coronary artery disease.

OBJECTIVES: The concept of "cardioprotection" based on ejection fraction was tested to see whether patients with coronary artery disease in whom medical treatment fails to be cardioprotective can be distinguished from those in whom it is safe to continue such treatment. BACKGROUND: Ejection fraction is of fundamental prognostic importance. Its modification by anti-ischemic medication may allow assessment of cardioprotection from adverse outcome. METHODS: Exercise ejection fraction and the change in ejection fraction from rest to exercise were measured by radionuclide ventriculography with and without background medication in 102 mildly symptomatic patients with coronary artery disease suitable for revascularization but initially treated medically. RESULTS: Over 20 months, 23 patients experienced an adverse event. With medication, exercise ejection fraction increased in patients with and without events. By contrast, the ejection fraction response to exercise improved significantly in the event-free group only; the group with events had a persistent decrease in ejection fraction. By Cox analysis, the ejection fraction response to exercise performed with medication made the most significant independent contribution to event-free survival. Comparison of areas under receiver operating characteristic curves suggested that this index is the most useful clinical measure of cardioprotection. CONCLUSIONS: An exercise-induced decrease in ejection fraction despite anti-ischemic medication implies failure of cardioprotection and a greater short-term risk of adverse outcome and crossover to revascularization in patients initially treated medically. Conversely, a preserved left ventricular performance confers a satisfactory prognosis while continuing with that treatment. Thus, the effect of medication on the ejection fraction response to exercise--a reasonable estimate of its cardioprotective efficacy--may influence the choice of continuing with such treatment or performing early revascularization.

Prescription of oxygen concentrators for long term oxygen treatment: reassessment in one district.

When oxygen concentrators became available on form FP10 in 1985 the Department of Health and Social Security issued clear guidelines for their prescription for long term treatment. Reassessment of those patients prescribed a concentrator in one district showed that 29 out of 61 patients did not fulfil these criteria. Furthermore, in only 28 cases was the daily use of the machine appropriate, though this did not reflect poor patient cooperation but was a result of inadequate prescribing instructions. In addition, 12 out of 54 patients continued to smoke. Overall, in only 18 of the 61 cases was both the prescription appropriate and the concentrator properly used. These results suggest a need for better cooperation between general practitioner and hospital in the initial assessment of patients for long term oxygen treatment and better education of both doctor and patient in the use of oxygen concentrators.

Hepatocellular carcinoma: assessment of resectability by computed tomography and ultrasound.

A retrospective review of the CT and ultrasound scans from examinations of 30 patients who had hepatocellular carcinoma (hepatoma) was undertaken with special emphasis placed on evaluation of hepatic distribution of tumor, vascular invasion, and extrahepatic spread. Although both CT and ultrasound detected hepatoma in 29 of 30 patients (96%), CT showed more extensive hepatic parenchymal involvement in eight of the patients. Vascular invasion was seen more frequently with ultrasound than with CT. Invasion into the main portal vein was seen by ultrasound in 11 of 30 patients (37%). Extrahepatic spread of tumor was much more frequently detected by CT and was present in 21 of 30 patients (70%). A reasoned approach to the diagnostic workup of hepatomas that will minimize invasive procedures and unnecessary surgery is presented.

Nutritional assessment by comparative growth achievement in Malay children below school age.

Measurements of child growth have become the most accepted means of assessing the protein-calorie nutritional status of economically developing populations. International reference standards have been suggested for a number of body measurements, but there has been little evaluation of their applicability in South-East Asia.In order to delineate the present range of nutritional standards in West Malaysia, and to aid in the development of guidelines for further nutritional work in this region, anthropometric tests were made on 3 groups of children below school age belonging to the Malay ethnic group and living under diverse conditions. Children of Malaysian Army personnel differed significantly in most measurements from rural village children in Trengganu and children from a small urban elite in Kuala Lumpur. Measurements for the latter group approximated to internationally used standards of height and weight. Parental height data suggest that these differences are not primarily genetic. Anaemia, malaria, and ascariasis were common among the Trengganu children.Weight and height emerge as the measurements that are most sensitive in differentiating between the groups; arm circumferences and skinfold measurements are also useful because they are relatively independent of age. Measurement of chest and head circumferences and of crown-rump lengths appeared to be of little value.