Measuring problem prescription opioid use among patients receiving long-term opioid analgesic treatment: development and evaluation of an algorithm for use in EHR and claims data.

Objective: Opioid surveillance in response to the opioid epidemic will benefit from scalable, automated algorithms for identifying patients with clinically documented signs of problem prescription opioid use. Existing algorithms lack accuracy. We sought to develop a high-sensitivity, high-specificity classification algorithm based on widely available structured health data to identify patients receiving chronic extended-release/long-acting (ER/LA) therapy with evidence of problem use to support subsequent epidemiologic investigations. Methods: Outpatient medical records of a probability sample of 2,000 Kaiser Permanente Washington patients receiving ≥60 days' supply of ER/LA opioids in a 90-day period from 1 January 2006 to 30 June 2015 were manually reviewed to determine the presence of clinically documented signs of problem use and used as a reference standard for algorithm development. Using 1,400 patients as training data, we constructed candidate predictors from demographic, enrollment, encounter, diagnosis, procedure, and medication data extracted from medical claims records or the equivalent from electronic health record (EHR) systems, and we used adaptive least absolute shrinkage and selection operator (LASSO) regression to develop a model. We evaluated this model in a comparable 600-patient validation set. We compared this model to ICD-9 diagnostic codes for opioid abuse, dependence, and poisoning. This study was registered with ClinicalTrials.gov as study NCT02667262 on 28 January 2016. Results: We operationalized 1,126 potential predictors characterizing patient demographics, procedures, diagnoses, timing, dose, and location of medication dispensing. The final model incorporating 53 predictors had a sensitivity of 0.582 at positive predictive value (PPV) of 0.572. ICD-9 codes for opioid abuse, dependence, and poisoning had a sensitivity of 0.390 at PPV of 0.599 in the same cohort. Conclusions: Scalable methods using widely available structured EHR/claims data to accurately identify problem opioid use among patients receiving long-term ER/LA therapy were unsuccessful. This approach may be useful for identifying patients needing clinical evaluation.

Using natural language processing of clinical text to enhance identification of opioid-related overdoses in electronic health records data.

PURPOSE: To enhance automated methods for accurately identifying opioid-related overdoses and classifying types of overdose using electronic health record (EHR) databases. METHODS: We developed a natural language processing (NLP) software application to code clinical text documentation of overdose, including identification of intention for self-harm, substances involved, substance abuse, and error in medication usage. Using datasets balanced with cases of suspected overdose and records of individuals at elevated risk for overdose, we developed and validated the application using Kaiser Permanente Northwest data, then tested portability of the application using Kaiser Permanente Washington data. Datasets were chart-reviewed to provide a gold standard for comparison and evaluation of the automated method. RESULTS: The method performed well in identifying overdose (sensitivity = 0.80, specificity = 0.93), intentional overdose (sensitivity = 0.81, specificity = 0.98), and involvement of opioids (excluding heroin, sensitivity = 0.72, specificity = 0.96) and heroin (sensitivity = 0.84, specificity = 1.0). The method performed poorly at identifying adverse drug reactions and overdose due to patient error and fairly at identifying substance abuse in opioid-related unintentional overdose (sensitivity = 0.67, specificity = 0.96). Evaluation using validation datasets yielded significant reductions, in specificity and negative predictive values only, for many classifications mentioned above. However, these measures remained above 0.80, thus, performance observed during development was largely maintained during validation. Similar results were obtained when evaluating portability, although there was a significant reduction in sensitivity for unintentional overdose that was attributed to missing text clinical notes in the database. CONCLUSIONS: Methods that process text clinical notes show promise for improving accuracy and fidelity at identifying and classifying overdoses according to type using EHR data.

Physician characteristics associated with higher adenoma detection rate.

BACKGROUND AND AIMS: Patients who receive a colonoscopy from a physician with a low adenoma detection rate (ADR) are at higher risk of subsequent colorectal cancer. It is unclear what drives the variation across physicians in ADR. We describe physician characteristics associated with higher ADR. METHODS: In this retrospective cohort study a natural language processing system was used to analyze all outpatient colonoscopy examinations and their associated pathology reports from October 2013 to September 2015 for adults age 40 years and older across physicians from 4 diverse health systems. Physician performance on ADR was risk adjusted for differences in patient population and procedure indication. Our sample included 201 physicians performing at least 30 colonoscopy examinations during the study period, totaling 104,618 colonoscopy examinations. RESULTS: The mean ADR was 33.2% (range, 6.3%-58.7%). Higher ADR was seen among female physicians (4.2 percentage points higher than men, P = .020), gastroenterologists (9.4 percentage points higher than nongastroenterologists, P < .001), and physicians with ≤9 years since their residency completion (6.0 percentage points higher than physicians who have had 27-51 years of practice, P = .004). CONCLUSIONS: Gastroenterologists, female physicians, and more recently trained physicians had higher performance in adenoma detection.

Population-Based Analysis of Histologically Confirmed Melanocytic Proliferations Using Natural Language Processing.

Importance: Population-based information on the distribution of histologic diagnoses associated with skin biopsies is unknown. Electronic medical records (EMRs) enable automated extraction of pathology report data to improve our epidemiologic understanding of skin biopsy outcomes, specifically those of melanocytic origin. Objective: To determine population-based frequencies and distribution of histologically confirmed melanocytic lesions. Design, Setting, and Participants: A natural language processing (NLP)-based analysis of EMR pathology reports of adult patients who underwent skin biopsies at a large integrated health care delivery system in the US Pacific Northwest from January 1, 2007, through December 31, 2012. Exposures: Skin biopsy procedure. Main Outcomes and Measures: The primary outcome was histopathologic diagnosis, obtained using an NLP-based system to process EMR pathology reports. We determined the percentage of diagnoses classified as melanocytic vs nonmelanocytic lesions. Diagnoses classified as melanocytic were further subclassified using the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) reporting schema into the following categories: class I (nevi and other benign proliferations such as mildly dysplastic lesions typically requiring no further treatment), class II (moderately dysplastic and other low-risk lesions that may merit narrow reexcision with <5-mm margins), class III (eg, melanoma in situ and other higher-risk lesions warranting reexcision with 5-mm to 1-cm margins), and class IV/V (invasive melanoma requiring wide reexcision with ≥1-cm margins and potential adjunctive therapy). Health system cancer registry data were used to define the percentage of invasive melanoma cases within MPATH-Dx class IV (stage T1a) vs V (≥stage T1b). Results: A total of 80 368 skin biopsies, performed on 47 529 patients, were examined. Nearly 1 in 4 skin biopsies were of melanocytic lesions (23%; n = 18 715), which were distributed according to MPATH-Dx categories as follows: class I, 83.1% (n = 15 558); class II, 8.3% (n = 1548); class III, 4.5% (n = 842); class IV, 2.2% (n = 405); and class V, 1.9% (n = 362). Conclusions and Relevance: Approximately one-quarter of skin biopsies resulted in diagnoses of melanocytic proliferations. These data provide the first population-based estimates across the spectrum of melanocytic lesions ranging from benign through dysplastic to malignant. These results may serve as a foundation for future research seeking to understand the epidemiology of melanocytic proliferations and optimization of skin biopsy utilization.

Preventing torture for people deprived of freedom: The Atlantic Hope and Black Swan Prison Model.

International law and minimum standards provide certain protection for detainees and prisoners of war (POW) against torture and ill-treatment. Places of detention and parties to conflicts are often monitored to ensure that they adhere to the required standards through, for example, visits to individual detainees and the assessment of facilities. However, monitoring between the point of arrest and eventual remand in prisons is largely inadequate. This paper explains an emerging model to enhance protection of prisoners through readiness training for prospective humanitarian personnel. The Atlantic Hope simulation exercise on monitoring detainees and visits to the mock Black Swan prison represents a teaching model to enhance sustainable protection of detainees and POW during incarceration. The simulation entails comprehensive monitoring, assessment, visits and provision of services to prisoners from the point of arrest, during the transition to places of custody, and imprisonment. These enhance protection of detainees to avoid deaths in custody, disappearance and torture throughout the chain of imprisonment.

Challenges in adapting existing clinical natural language processing systems to multiple, diverse health care settings.

OBJECTIVE: Widespread application of clinical natural language processing (NLP) systems requires taking existing NLP systems and adapting them to diverse and heterogeneous settings. We describe the challenges faced and lessons learned in adapting an existing NLP system for measuring colonoscopy quality. MATERIALS AND METHODS: Colonoscopy and pathology reports from 4 settings during 2013-2015, varying by geographic location, practice type, compensation structure, and electronic health record. RESULTS: Though successful, adaptation required considerably more time and effort than anticipated. Typical NLP challenges in assembling corpora, diverse report structures, and idiosyncratic linguistic content were greatly magnified. DISCUSSION: Strategies for addressing adaptation challenges include assessing site-specific diversity, setting realistic timelines, leveraging local electronic health record expertise, and undertaking extensive iterative development. More research is needed on how to make it easier to adapt NLP systems to new clinical settings. CONCLUSIONS: A key challenge in widespread application of NLP is adapting existing systems to new clinical settings.

Determining the molecular interactions of perfluorinated carboxylic acids with human sera and isolated human serum albumin using nuclear magnetic resonance spectroscopy.

Perfluorooctanoate (PFOA) is ubiquitous in North American human sera and has a serum half-life of 3.5 years in humans. The molecular interactions that lead to the bioaccumulation of these hydrophobic and lipophobic molecules in human blood are not well understood. Perfluorohexanoic acid (PFHxA) and PFOA were used as model perfluorinated carboxylic acids (PFCAs) to characterize the major site of PFCA interaction in human sera. Using novel heteronuclear saturation transfer difference nuclear magnetic resonance spectroscopy experiments, human serum albumin (HSA) was identified as the major site of interaction for both PFHxA and PFOA in human sera. Heteronuclear single quantum coherence nuclear magnetic resonance experiments were then performed to interrogate site-specific interactions of PFHxA and PFOA with isolated HSA. Perfluorohexanoic acid was found to bind specifically to Sudlow's drug-binding site II, whereas PFOA interacted preferentially with Sudlow's drug-binding site I at the lower concentration, with additional interactions developing at the higher concentration. These experiments highlight the utility of nuclear magnetic resonance spectrometry as a tool to observe the in situ interactions of chemical contaminants with biological systems. Both PFCAs displaced the endogenous HSA ligand oleic acid at concentrations lower than observed for the drugs ibuprofen and phenylbutazone, which are established HSA ligands. Interactions between PFCAs and HSA may affect the pharmacokinetics and distribution of fatty acids and certain drugs in the human body and warrant further investigation.

Molecular interactions of pesticides at the soil-water interface.

High-resolution magic angle spinning (HR-MAS) NMR spectroscopy combined with saturation-transfer double difference (STDD) NMR can be used to analyze the molecular-level interactions of pesticides and whole soils occurring at the soil-water interface. Here 1H HR-MAS STDD NMR has been applied to some common pesticides (trifluralin, acifluorfen, and (4-nitro-3-(trifluoromethyl) phenol) and a pesticide degradation product (1-naphthol). Results indicate that dipolar interactions, H-bonding, hydrophobic associations, and potentially pi-pi interactions are the predominant sorption mechanisms for these molecules at the soil-aqueous interface. It is evident that the physical and chemical characteristics of soil are highly influential in determining the mechanisms of pesticide sorption, as they significantly affect soil conformation. In particular, different binding mechanisms were observed for 1-naphthol in soil swollen using a buffer versus D2O, indicating that the K(oc) alone may not be enough to accurately predict the behavior of a molecule in a real soil environment. Preliminary kinetic-based studies suggest that both the swelling solvent and soil moisture content significantly influence the sequestration of trifluralin. These studies demonstrate that HR-MAS and STDD NMR are powerful and versatile tools which can be applied to expand our knowledge of the mechanistic interactions of agrochemicals at the molecular level.

Major structural components in freshwater dissolved organic matter.

Dissolved organic matter (DOM) contains a complex array of chemical components that are intimately linked to many environmental processes, including the global carbon cycle, and the fate and transport of chemical pollutants. Despite its importance, fundamental aspects, such as the structural components in DOM remain elusive, due in part to the molecular complexity of the material. Here, we utilize multidimensional nuclear magnetic resonance spectroscopy to demonstrate the major structural components in Lake Ontario DOM. These include carboxyl-rich alicyclic molecules (CRAM), heteropolysaccharides, and aromatic compounds, which are consistent with components recently identified in marine dissolved organic matter. In addition, long-range proton-carbon correlations are obtained for DOM, which support the existence of material derived from linear terpenoids (MDLT). It is tentatively suggested that the bulk of freshwater dissolved organic matter is aliphatic in nature, with CRAM derived from cyclic terpenoids, and MDLT derived from linear terpenoids. This is in agreement with previous reports which indicate terpenoids as major precursors of DOM. At this time it is not clear in Lake Ontario whether these precursors are of terrestrial or aquatic origin or whether transformations proceed via biological and/ or photochemical processes.

Orientational isomers of alpha-cyclodextrin [2]semi-rotaxanes with asymmetric dicationic threads.

Two series of novel dicationic threading molecules [Quin(CH2)10R]2+ and [3,5-Lut(CH2)10R]2+, where Quin+ = quinuclidinium, 3,5-Lut+ = 3,5-lutidinium, and R+ = N(CH3)3+ and N(CH3)2CH2CH3+, form [2]semi-rotaxanes with [small alpha]-cyclodextrin (alpha-CD) in aqueous solution. The quinuclidinium and 3,5-lutidinium are sufficiently bulky to prevent threading while the R+ groups allow for slow threading by alpha-CD at 25 degrees C. The resulting [2]semi-rotaxanes exist in two orientational isomers owing to the asymmetry of both the alpha-CD cavity and the threading molecules. Two-dimensional 1H NMR spectroscopy and kinetics experiments reveal that the isomer in which the narrower rim (primary OHs) is positioned near the R+ group is the kinetically preferred isomer, while the other isomer is the thermodynamically preferred product. The kinetics and mechanism of the formation, dissociation, and interconversion of the two isomers have been determined at 25 degrees C.

The electrocardiographic toxidrome: the ECG presentation of hydrofluoric acid ingestion.

The clinician can approach the poisoned patient using the toxidrome system of toxin identification; this approach makes use of findings noted on the physical examination, highlighting the importance of abnormalities in blood pressure, heart rate, respiratory effort, body temperature, mental status, pupillary size, skin color, diaphoresis, and gastrointestinal sounds. Such a method provides structure and guidance to the clinical evaluation, providing the clinician with rapid diagnostic information and suggesting urgent management issues. A case of hydrofluoric acid poisoning is used as an example of this diagnostic approach. The patient demonstrated systemic toxicity accompanied by oral irritation and electrocardiographic abnormality (QRS complex widening and QT interval prolongation). The constellation of these findings suggested the possibility of a caustic agent (history and examination) with potential effect on potassium and calcium metabolism (electrocardiographic abnormalities). Such a constellation strongly suggested hydrofluoric acid as the culprit toxin.

Dynamic behavior in diplatinum metalloreceptors.

Diplatinum metalloreceptors anti-4a and anti-4b exhibit dynamic behavior in solution that is modified by anion binding. An X-ray crystal structure determination of anti-4a supports its proposed solution structure.