Leveraging machine learning to examine engagement with a digital therapeutic.

Digital Therapeutics (DTx) are evidence-based software-driven interventions for the prevention, management, and treatment of medical disorders or diseases. DTx offer the unique ability to capture rich objective data about when and how a patient engages with a treatment. Not only can one measure the quantity of patient interactions with a digital treatment with high temporal precision, but one can also assess the quality of these interactions. This is particularly useful for treatments such as cognitive interventions, where the specific manner in which a patient engages may impact likelihood of treatment success. Here, we present a technique for measuring the quality of user interactions with a digital treatment in near-real time. This approach produces evaluations at the level of a roughly four-minute gameplay session (mission). Each mission required users to engage in adaptive and personalized multitasking training. The training included simultaneous presentation of a sensory-motor navigation task and a perceptual discrimination task. We trained a machine learning model to classify user interactions with the digital treatment to determine if they were "using it as intended" or "not using it as intended" based on labeled data created by subject matter experts (SME). On a held-out test set, the classifier was able to reliably predict the SME-derived labels (Accuracy = .94; F1 Score = .94). We discuss the value of this approach and highlight exciting future directions for shared decision-making and communication between caregivers, patients and healthcare providers. Additionally, the output of this technique can be useful for clinical trials and personalized intervention.

Under the influence of light: How light pollution disrupts personality and metabolism in hermit crabs.

Anthropogenic disturbances are known to cause significant physiological and behavioural changes in animals and, thus, are the critical focus of numerous studies. Light pollution is an increasingly recognised source of disturbance that has the potential to impact animal physiology and behaviour. Here, we investigate the effect of constant light on a personality trait and metabolic rate in the European hermit crab Pagurus bernhardus. We used Bayesian mixed models to estimate average behavioural change (i.e. sample mean level behavioural plasticity) and between- and within-individual variation in boldness in response to laboratory light. Hermit crabs experiencing constant light were consistently less bold and had a higher metabolic rate than those kept under a standard laboratory light regime (12:12 h light/dark). However, there was no effect of light on individual consistency in behaviour. As boldness is associated with coping with risk, hermit crabs exposed to light pollution at night may experience increased perceived predation risk, adjusting their behaviour to compensate for the increased conspicuousness. However, reduced boldness could lead to lower rates of foraging and this, in combination with elevated metabolic rate, has the potential for a reduction in energy balance.

Rapid Formation of Methemoglobin via Nitric Oxide Delivery for Potential Use as an MRI Contrast Agent.

Contrast-enhanced magnetic resonance angiography is a vital tool for evaluating vascular pathology. However, concerns about the limitations and safety of gadolinium-based contrast agents have led to an interest in alternative agents. Methemoglobin (metHb) increases the T1-weighted signal intensity of the magnetic resonance image of blood and could provide a safe and effective alternative. MetHb can be produced by the reaction of nitric oxide (NO) gas with oxyhemoglobin followed by natural conversion back to hemoglobin by cytochrome b5 reductase. Since rapid production of metHb via NO has not been studied, the effectiveness of producing metHb via NO delivery to blood was evaluated using a hollow-fiber module. MetHb production began immediately and > 90% conversion was achieved within 10 min. MetHb remained stable for at least 90 min when NO delivery was removed following metHb formation. Comparison of experimental data for metHb formation with model predictions showed that only a fraction of the NO delivered was utilized for metHb production, suggesting an additional fast reaction of NO with other blood constituents. Directly delivering NO to blood for the rapid formation of metHb provides a potential platform for producing metHb as an alternative contrast agent.

International shipments of Wolbachia-infected mosquito eggs: towards the scaling-up of World Mosquito Program operations.

The Wolbachia insect control method, employed by the World Mosquito Program (WMP), relies on introgressing Wolbachia through target Aedes aegypti populations to reduce the incidence of dengue. Since 2010, the WMP has been producing Wolbachia-infected mosquitoes at numerous sites across the globe for release in 11 countries. As the technology has matured, greater focus has been placed on mosquito production at larger central facilities for transport to remote release sites, both domestically and internationally. Of particular note is the production of Wolbachia-infected mosquitoes at the WMP's Australian production facility for successful international deployments in Fiji, Vanuatu, Kiribati and Sri Lanka. This requires careful management of both production and supply-chain processes to ensure that the quality of the mosquito eggs, specifically the hatch rate and Wolbachia infection rate, is maintained. To ensure the cost-effectiveness and scalability of the Wolbachia method, these processes will be further refined to facilitate deployment from large centralised production facilities.

La méthode de contrôle des insectes mise en oeuvre par le World Mosquito Program (WMP) recourt à la bactérie Wolbachia et repose sur l'introgression de cette dernière par le biais des populations cibles d'Aedes aegypti dans le but de réduire l'incidence de la dengue. Depuis 2010, le WMP produit des moustiques infectés par Wolbachia à partir de nombreux sites répartis dans le monde entier en vue de leur lâcher dans 11 pays. Cette technologie s'étant bien développée, l'accent est désormais mis sur la production de moustiques dans des établissements centralisés de plus grande envergure afin de les expédier vers des sites de lâcher éloignés, tant sur le territoire national qu'à l'échelle internationale. Il importe de souligner la production de moustiques infectés par Wolbachia conduite par le WMP sur son site australien et leur déploiement international couronné de succès aux Fidji, au Vanuatu, à Kiribati et au Sri Lanka. Cela nécessite une gestion rigoureuse des procédures aussi bien lors de la production que tout au long de la chaîne d'approvisionnement afin de veiller au maintien de la qualité des oeufs de moustiques et plus spécifiquement du taux d'éclosion et du taux d'infection par Wolbachia. Afin d'assurer la rentabilité et l'évolutivité de la méthode basée sur Wolbachia, ces procédures seront encore affinées afin de faciliter le déploiement à partir de sites de production à grande échelle centralisés.

El método de control de insectos con Wolbachia que emplea el World Mosquito Program (WMP) reposa en la introgresión de Wolbachia a través de poblaciones de Aedes aegypti para reducir la incidencia del dengue. Desde 2010, el WMP viene generando mosquitos infectados por Wolbachia en numerosas instalaciones repartidas por todo el globo, mosquitos que después son liberados en 11 países. A medida que la tecnología ha ido madurando, la tendencia ha sido cada vez más la de concentrar la producción de mosquitos en grandes instalaciones centrales y desde allí enviarlos a los remotos lugares de suelta, ya estén en el mismo país o en otros países. Especialmente destacable es la producción de mosquitos infectados por Wolbachia en las instalaciones que el WMP tiene en Australia, utilizadas con éxito como centro de operaciones para aplicar el método en otros países como Fiji, Vanuatu, Kiribati y Sri Lanka. Ello exige una cuidadosa gestión de los procesos tanto de producción como de la cadena de suministro, que garantice un nivel constante de calidad de los huevos de mosquito, y más concretamente de las tasas de eclosión y de infección por Wolbachia. A fin de asegurar que el método ofrezca una buena relación costo-eficacia y sea reproducible a mayor escala, esos procesos serán perfeccionados para facilitar el despliegue de los insectos a partir de grandes instalaciones de producción centralizada.

A novel digital intervention for actively reducing severity of paediatric ADHD (STARS-ADHD): a randomised controlled trial.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a common paediatric neurodevelopmental disorder with substantial effect on families and society. Alternatives to traditional care, including novel digital therapeutics, have shown promise to remediate cognitive deficits associated with this disorder and may address barriers to standard therapies, such as pharmacological interventions and behavioural therapy. AKL-T01 is an investigational digital therapeutic designed to target attention and cognitive control delivered through a video game-like interface via at-home play for 25 min per day, 5 days per week for 4 weeks. This study aimed to assess whether AKL-T01 improved attentional performance in paediatric patients with ADHD. METHODS: The Software Treatment for Actively Reducing Severity of ADHD (STARS-ADHD) was a randomised, double-blind, parallel-group, controlled trial of paediatric patients (aged 8-12 years, without disorder-related medications) with confirmed ADHD and Test of Variables of Attention (TOVA) Attention Performance Index (API) scores of -1·8 and below done by 20 research institutions in the USA. Patients were randomly assigned 1:1 to AKL-T01 or a digital control intervention. The primary outcome was mean change in TOVA API from pre-intervention to post-intervention. Safety, tolerability, and compliance were also assessed. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02674633 and is completed. FINDINGS: Between July 15, 2016, and Nov 30, 2017, 857 patients were evaluated and 348 were randomly assigned to receive AKL-T01 or control. Among patients who received AKL-T01 (n=180 [52%]; mean [SD] age, 9·7 [1·3] years) or control (n=168 [48%]; mean [SD] age, 9·6 [1·3] years), the non-parametric estimate of the population median change from baseline TOVA API was 0·88 (95% CI 0·24-1·49; p=0·0060). The mean (SD) change from baseline on the TOVA API was 0·93 (3·15) in the AKL-T01 group and 0·03 (3·16) in the control group. There were no serious adverse events or discontinuations. Treatment-related adverse events were mild and included frustration (5 [3%] of 180) and headache (3 [2%] of 180). Patient compliance was a mean of 83 (83%) of 100 expected sessions played (SD, 29·2 sessions). INTERPRETATION: Although future research is needed for this digital intervention, this study provides evidence that AKL-T01 might be used to improve objectively measured inattention in paediatric patients with ADHD, while presenting minimal adverse events. FUNDING: Sponsored by Akili Interactive Labs.

Osseous impingement occurs early in flexion in cam-type femoroacetabular impingement: a 4D CT model.

AIMS: The aim of this study was to examine the real time in vivo kinematics of the hip in patients with cam-type femoroacetabular impingement (FAI). PATIENTS AND METHODS: A total of 50 patients (83 hips) underwent 4D dynamic CT scanning of the hip, producing real time osseous models of the pelvis and femur being moved through flexion, adduction, and internal rotation. The location and size of the cam deformity and its relationship to the angle of flexion of the hip and pelvic tilt, and the position of impingement were recorded. RESULTS: In these patients with cam-type FAI, there was significant correlation between the alpha angle and flexion to the point of impingement (mean 41.36°; 14.32° to 57.95°) (R = -0.5815 and p = < 0.001). Patients with a large cam deformity (alpha angle > 78°) had significantly less flexion to the point of impingement (mean 36.30°; 14.32° to 55.18°) than patients with a small cam deformity (alpha angle 60° to 78°) (mean 45.34°; 27.25° to 57.95°) (p = < 0.001). CONCLUSION: This study has shown that cam-type impingement can occur early in flexion (40°), particularly in patients with large anterior deformities. These patients risk chondrolabral damage during routine activities such as walking, and going up stairs. These findings offer important insights into the cause of the symptoms, the mechanisms of screening and the forms of treatment available for these patients. Cite this article: Bone Joint J 2017;99-B(4 Supple B):41-8.

Aging, Spatial Disparity, and the Sound-Induced Flash Illusion.

The present study examined age-related differences in multisensory integration and the effect of spatial disparity on the sound-induced flash illusion--an illusion used in previous research to assess age-related differences in multisensory integration. Prior to participation in the study, both younger and older participants demonstrated their ability to detect 1-2 visual flashes and 1-2 auditory beep presented unimodally. After passing the pre-test, participants were then presented 1-2 flashes paired with 0-2 beeps that originated from one of five speakers positioned equidistantly 100 cm from the participant. One speaker was positioned directly below the screen, two speakers were positioned 50 cm to the left and right from the center of the screen, and two more speakers positioned to the left and right 100 cm from the center of the screen. Participants were told to report the number of flashes presented and to ignore the beeps. Both age groups showed a significant effect of the beeps on the perceived number of flashes. However, neither younger nor older individuals showed any significant effect of spatial disparity on the sound-induced flash illusion. The presence of a congruent number of beeps increased accuracy for both older and younger individuals. Reaction time data was also analyzed. As expected, older individuals showed significantly longer reaction times when compared to younger individuals. In addition, both older and younger individuals showed a significant increase in reaction time for fusion trials, where two flashes and one beep are perceived as a single flash, as compared to congruent single flash trials. This increase in reaction time was not found for fission trials, where one flash and two beeps were perceived as two flashes. This suggests that processing may differ for the two forms for fission as compared to fusion illusions.

Creating a Common Data Model for Comparative Effectiveness with the Observational Medical Outcomes Partnership.

BACKGROUND: Adoption of a common data model across health systems is a key infrastructure requirement to allow large scale distributed comparative effectiveness analyses. There are a growing number of common data models (CDM), such as Mini-Sentinel, and the Observational Medical Outcomes Partnership (OMOP) CDMs. OBJECTIVES: In this case study, we describe the challenges and opportunities of a study specific use of the OMOP CDM by two health systems and describe three comparative effectiveness use cases developed from the CDM. METHODS: The project transformed two health system databases (using crosswalks provided) into the OMOP CDM. Cohorts were developed from the transformed CDMs for three comparative effectiveness use case examples. Administrative/billing, demographic, order history, medication, and laboratory were included in the CDM transformation and cohort development rules. RESULTS: Record counts per person month are presented for the eligible cohorts, highlighting differences between the civilian and federal datasets, e.g. the federal data set had more outpatient visits per person month (6.44 vs. 2.05 per person month). The count of medications per person month reflected the fact that one system's medications were extracted from orders while the other system had pharmacy fills and medication administration records. The federal system also had a higher prevalence of the conditions in all three use cases. Both systems required manual coding of some types of data to convert to the CDM. CONCLUSIONS: The data transformation to the CDM was time consuming and resources required were substantial, beyond requirements for collecting native source data. The need to manually code subsets of data limited the conversion. However, once the native data was converted to the CDM, both systems were then able to use the same queries to identify cohorts. Thus, the CDM minimized the effort to develop cohorts and analyze the results across the sites.

Behavioral training to improve collision detection.

Young drivers are a high-risk group for vehicle crashes due to inexperience in detecting an impending collision and are one group that may benefit from perceptual learning (PL) training. The present study assessed whether PL could be used to improve performance in collision detection. Ten college-aged subjects participated in the first experiment, which consisted of seven 1-hr sessions conducted on separate days. Thresholds at three observer/object speeds were measured prior to training using a two-alternative forced choice procedure during which they indicated whether an approaching object would result in a collision or noncollision event. Participants were then trained near threshold at one of these speeds for 5 days. After training, participants showed a significant reduction in the time needed to detect a collision at the trained speed. This improvement was also found to transfer to the higher observer speed condition. A second experiment was conducted to determine whether this improvement was due to training near threshold or whether this improvement was merely due to practice with the task. Training with stimuli well above threshold showed no significant improvement in performance, indicating that the improvement seen in the first experiment was not solely due to task practice.

Improving vision among older adults: behavioral training to improve sight.

A major problem for the rapidly growing population of older adults (age 65 and over) is age-related declines in vision, which have been associated with increased risk of falls and vehicle crashes. Research suggests that this increased risk is associated with declines in contrast sensitivity and visual acuity. We examined whether a perceptual-learning task could be used to improve age-related declines in contrast sensitivity. Older and younger adults were trained over 7 days using a forced-choice orientation-discrimination task with stimuli that varied in contrast with multiple levels of additive noise. Older adults performed as well after training as did college-age younger adults prior to training. Improvements transferred to performance for an untrained stimulus orientation and were not associated with changes in retinal illuminance. Improvements in far acuity in younger adults and in near acuity in older adults were also found. These findings indicate that behavioral interventions can greatly improve visual performance for older adults.

Optimization of perceptual learning: effects of task difficulty and external noise in older adults.

Previous research has shown a wide array of age-related declines in vision. The current study examined the effects of perceptual learning (PL), external noise, and task difficulty in fine orientation discrimination with older individuals (mean age 71.73, range 65-91). Thirty-two older subjects participated in seven 1.5-h sessions conducted on separate days over a three-week period. A two-alternative forced choice procedure was used in discriminating the orientation of Gabor patches. Four training groups were examined in which the standard orientations for training were either easy or difficult and included either external noise (additive Gaussian noise) or no external noise. In addition, the transfer to an untrained orientation and noise levels were examined. An analysis of the four groups prior to training indicated no significant differences between the groups. An analysis of the change in performance post-training indicated that the degree of learning was related to task difficulty and the presence of external noise during training. In addition, measurements of pupil diameter indicated that changes in orientation discrimination were not associated with changes in retinal illuminance. These results suggest that task difficulty and training in noise are factors important for optimizing the effects of training among older individuals.

Evaluation of new geological reference materials for uranium-series measurements: Chinese Geological Standard Glasses (CGSG) and macusanite obsidian.

Recent advances in high-resolution, rapid, in situ microanalytical techniques present numerous opportunities for the analytical community, provided accurately characterized reference materials are available. Here, we present multicollector thermal ionization mass spectrometry (MC-TIMS) and multicollector inductively coupled plasma mass spectrometry (MC-ICP-MS) uranium and thorium concentration and isotopic data obtained by isotope dilution for a suite of newly available Chinese Geological Standard Glasses (CGSG) designed for microanalysis. These glasses exhibit a range of compositions including basalt, syenite, andesite, and a soil. Uranium concentrations for these glasses range from ∼2 to 14 µg g(-1), Th/U weight ratios range from ∼4 to 6, (234)U/(238)U activity ratios range from 0.93 to 1.02, and (230)Th/(238)U activity ratios range from 0.98 to 1.12. Uranium and thorium concentration and isotopic data are also presented for a rhyolitic obsidian from Macusani, SE Peru (macusanite). This glass can also be used as a rhyolitic reference material, has a very low Th/U weight ratio (around 0.077), and is approximately in (238)U-(234)U-(230)Th secular equilibrium. The U-Th concentration data agree with but are significantly more precise than those previously measured. U-Th concentration and isotopic data agree within estimated errors for the two measurement techniques, providing validation of the two methods. The large (238)U-(234)U-(230)Th disequilibria for some of the glasses, along with the wide range in their chemical compositions and Th/U ratios should provide useful reference points for the U-series analytical community.

Multisensory integration, aging, and the sound-induced flash illusion.

The present study examined age-related differences in multisensory integration and the role of attention in age-related differences in multisensory integration. The sound-induced flash illusion--the misperception of the number of visual flashes due to the simultaneous presentation of a different number of auditory beeps--was used to examine the strength of multisensory integration in older and younger observers. The effects of integration were examined when discriminating 1-3 flashes, 1-3 beeps, or 1-3 flashes presented with 1-3 beeps. Stimulus conditions were blocked according to these conditions with baseline (unisensory) performance assessed during the multisensory block. Older participants demonstrated greater multisensory integration--a greater influence of the beeps when judging the number of visual flashes--than younger observers. In a second experiment, the role of attention was assessed using a go/no-go paradigm. The results of Experiment 2 replicated those of Experiment 1. In addition, the strength of the illusion was modulated by the sensory domain of the go/no-go task, though this did not differ by age group. In the visual go/no-go task we found a decrease in the illusion, yet in the auditory go/no-go task we found an increase in the illusion. These results demonstrate that older individuals exhibit increased multisensory integration compared with younger individuals. Attention was also found to modulate the strength of the sound-induced flash illusion. However, the results also suggest that attention was not likely to be a factor in the age-related differences in multisensory integration.

An in depth analysis of histopathological characteristics found in keratoconus.

AIMS: The aims of this study were to re-assess the histopathology of the disease by introducing more modern measuring techniques and to determine if axial stromal thinning, which is the most apparent change, is related to the other alterations observed. METHODS: Recipient keratoconic corneas from 36 patients following corneal transplantation were studied. Haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were used to identify breaks in Bowman's layer and Descemet's membrane. Thickness of corneal layers was measured by Leica QWin software. Epithelial and stromal thickness were measured in each sample at the periphery of the corneal button and at the area of maximal stromal thinning. The presence of apoptotic cells in Bowman's layer breaks was detected by terminal deoxynucleotidyl transferase mediated dUTP-X nick end labelling. RESULTS: In all 36 corneal samples the central stroma, at the apex of the cone, was thinner than the peripheral. There was a negative correlation between central stromal and central epithelial thickness (p = 0.009). Bowman's layer breaks were found in 92% of corneas. Apoptotic cells were detected at the level of Bowman's breaks membrane. We found a positive correlation between epithelial thickness and the number of Bowman's layer breaks (p = 0.009 for central epithelial thickness and p = 0.003 for peripheral epithelial thickness). Descemet's membrane deformities were observed in 19% of corneas and central stromal thickness of these corneas was significantly less than corneas without breaks (p = 0.006). CONCLUSIONS: There are various different histopathological features associated with keratoconus and some of them are very subtle and not very well studied. Accurate measurements also suggest some correlations between them. Stromal thinning is associated with the number of breaks in Descemet's membrane, but it is the thickening of the epithelium which is associated with breaks in Bowman's layer.

Headache after substance abuse: a diagnostic dilemma.

An 18-year-old man inhaled a substance containing synthetic cannabinoids and 1 hour later developed a severe global headache. Imaging revealed a perimesencephalic subarachnoid haemorrhage. An angiogram suggested that a small superior cerebellar artery aneurysm was the culprit. This report discusses the, as yet undefined, relationship between "herbal highs" and intracranial haemorrhage.

Functional evaluation of TNFAIP3 (A20) in rheumatoid arthritis.

OBJECTIVES: To determine the protein expression of TNFAIP3 in synovium and to show the capability of 6q23 intergenic SNPs, associated with rheumatoid arthritis (RA) susceptibility, to influence TNFAIP3 gene transcription. METHODS: Immunohistochemistry for TNFAIP3, NF-kB p65 and phosphorylated NF-kB p65 protein expression was performed in 6 RA knee joint synovium samples compared to 9 osteoarthritis (OA) samples. Luciferase reporter gene assays were used to examine the regulatory ability of RA associated SNP variants on TNFAIP3 promoter activity. Sense and antisense constructs were prepared for rs6920220 alleles, together with each of the 4 SNPs in r2=1 with it (rs6933404, rs2327832, rs6927172 and rs17264332), coupled to the TNFAIP3 promoter. Transient transfections were performed in a human T lymphoblastoid (CEMC7A) cell line. Bioinformatic software was utilised to prioritise SNPs for further investigation. Electrophoretic mobility shift assays (EMSA), using CEMC7A nuclear extracts, were conducted for the rs6927172 SNP alleles. RESULTS: TNFAIP3 protein expression was seen in the synovium samples and differential TNFAIP3 protein expression between RA vs. OA synoviocytes observed. Within RA synoviocytes TNFAIP3 expression is predominately cytoplasmic, whereas in OA its expression is strongly nuclear and cytoplasmic. For 3 of the 5 SNPs investigated (rs6920220, rs6933404, rs6927172) evidence of repressor activity of TNFAIP3 transcription was seen and EMSA data showed evidence of differential transcription factor binding to rs6927172 alleles. CONCLUSIONS: This is the first observation of TNFAIP3 protein expression in RA and OA synovium. In vitro analysis of 6q23 intergenic SNPs supports the possibility of the functional regulation of TNFAIP3.

Phenol-oxidizing laccases from the termite gut.

cDNAs encoding two gut laccase isoforms (RfLacA and RfLacB) were sequenced from the termite Reticulitermes flavipes. Phylogenetic analyses comparing translated R. flavipes laccases to 67 others from prokaryotes and eukaryotes indicate that the R. flavipes laccases are evolutionarily unique. Alignments with crystallography-verified laccases confirmed that peptide motifs involved in metal binding are 100% conserved in both isoforms. Laccase transcripts and phenoloxidase activity were most abundant in symbiont-free salivary gland and foregut tissue, verifying that the genes and activities are host-derived. Using a baculovirus-insect expression system, the two isoforms were functionally expressed with histidine tags and purified to near homogeneity. ICP-MS (inductively coupled plasma - mass spectrometry) analysis of RfLacA identified bound metals consisting mainly of copper (∼4 copper molecules per laccase protein molecule and ∼3 per histidine tag) with lesser amounts of calcium, manganese and zinc. Both recombinant enzyme preparations showed strong activity towards the lignin monomer sinapinic acid and four other phenolic substrates. By contrast, both isoforms displayed much lower or no activity against four melanin precursors, suggesting that neither isoform is involved in integument formation. Modification of lignin alkali by the recombinant RfLacA preparation was also observed. These findings provide evidence that R. flavipes gut laccases are evolutionarily distinct, host-derived, produced in the salivary gland, secreted into the foregut, bind copper, and play a role in lignocellulose digestion. These findings contribute to a better understanding of termite digestion and gut physiology, and will assist future translational studies that examine the contributions of individual termite enzymes in lignocellulose digestion.

A fatal complication of a vena caval filter associated with pulmonary thromboembolism.

Vena caval filters are increasingly used for the prevention of pulmonary thromboembolism in patients with deep vein thrombosis ever since the introduction of the stainless steel Greenfield filter in the 1970s. Although complications associated with their use are rare, they can be fatal, and therefore it is important for forensic pathologists to be aware of their occurrence. Because of the ramifications of a medical device failure, a thorough documentation of the autopsy findings is essential. We describe an unusual case of a 75-year-old woman who developed a fatal pulmonary thromboembolism with concurrent migration of a lesser known type of vena caval filter to the right ventricle occurring 19 days after filter placement. A review of the types of vena caval filters in current use, and their complications, are discussed.

Fentanyl epidemic in Chicago, Illinois and surrounding Cook County.

INTRODUCTION: Epidemics related to illicit fentanyl abuse have been reported and the potential exists for a national epidemic associated with high mortality. This report describes emergency department visits for opioid toxicity and a recent outbreak of illicit fentanyl fatalities in Chicago, Illinois and surrounding Cook County. METHODS: Retrospective chart review of opioid-related overdoses seen in our emergency department and a retrospective review of data from the Cook County Medical Examiner's Office Fentanyl Fatality Database from April 2005 through December 2006. RESULTS: Our emergency department treated 43 patients with a total of 55 emergency department visits during this time. Paramedic transport was utilized for 83.6% of the emergency department visits and naloxone was administered during 80.4% of transports. Naloxone was administered during 47.3% of emergency department visits with total doses ranging from 0.4 mg to 12 mg. Eighty percent of cases were treated and discharged from the emergency department. During this same time frame, the Medical Examiner's office identified 342 fentanyl-related fatalities. In 2006, illicit fentanyl fatalities represented 6.9% of all Medical Examiner cases for that year. Approximately 80% of deaths occurred in Chicago. A peak in fentanyl-related deaths occurred in the spring of 2006 and again in the fall of 2006 while the number of emergency department visits peaked during May of 2006. CONCLUSION: Chicago and surrounding Cook County experienced an outbreak of 342 fentanyl-related deaths between April 2005 and December 2006. The experience demonstrated a clear need for an interdisciplinary approach to identifying, communicating, and managing an outbreak.