Risk Factors for Incident Polycystic Ovary Syndrome Diagnosis.

Objective: While highly prevalent, risk factors for incident polycystic ovary syndrome (PCOS) are poorly delineated. Using a population-based cohort, we sought to identify predictors of incident PCOS diagnosis. Materials and Methods: A matched case-control analysis was completed utilizing patients enrolled in Kaiser Permanente Washington from 2006 to 2019. Inclusion criteria included female sex, age 16-40 years, and ≥3 years of prior enrollment with ≥1 health care encounter. PCOS cases were identified using International Classification of Diseases codes. For each incident case (n = 2,491), 5 patients without PCOS (n = 12,455) were matched based on birth year and enrollment status. Potential risk factors preceding diagnosis included family history of PCOS, premature menarche, parity, race, weight gain, obesity, valproate use, metabolic syndrome, epilepsy, prediabetes, and types 1 and 2 diabetes. Potential risk factors for incident PCOS diagnosis were assessed with univariate and multivariable conditional logistic regressions. Results: Mean age of PCOS cases was 26.9 years (SD 6.8). PCOS cases, compared with non-PCOS, were more frequently nulliparous (70.9% versus 62.4%) and in the 3 years prior to index date were more likely to have obesity (53.8% versus 20.7%), metabolic syndrome (14.5% versus 4.3%), prediabetes (7.4% versus 1.6%), and type 2 diabetes (4.1% versus 1.7%) (p < 0.001 for all comparisons). In multivariable models, factors associated with higher risk for incident PCOS included the following: obesity (compared with nonobese) Class I-II (body-mass index [BMI], 30-40 kg/m2; odds ratio [OR], 3.8; 95% confidence interval [CI], 3.4-4.2), Class III (BMI > 40 kg/m2; OR, 7.5, 95% CI, 6.5-8.7), weight gain (compared with weight loss or maintenance) of 1-10% (OR, 1.7, 95% CI, 1.3-2.1), 10-20% (OR, 1.9; 95% CI, 1.5-2.4), and >20% (OR, 2.6; 95% CI, 1.9-3.6), prediabetes (OR, 2.7; 95% CI, 2.1-3.4), and metabolic syndrome (OR, 1.8: 95% CI, 1.5-2.1). Conclusion: Excess weight gain, obesity, and metabolic dysfunction may play a key role in the ensuing phenotypic expression of PCOS. Treatment and prevention strategies targeted at preventing weight gain in early reproductive years may help reduce the risk of this syndrome.

Data-driven automated classification algorithms for acute health conditions: applying PheNorm to COVID-19 disease.

OBJECTIVES: Automated phenotyping algorithms can reduce development time and operator dependence compared to manually developed algorithms. One such approach, PheNorm, has performed well for identifying chronic health conditions, but its performance for acute conditions is largely unknown. Herein, we implement and evaluate PheNorm applied to symptomatic COVID-19 disease to investigate its potential feasibility for rapid phenotyping of acute health conditions. MATERIALS AND METHODS: PheNorm is a general-purpose automated approach to creating computable phenotype algorithms based on natural language processing, machine learning, and (low cost) silver-standard training labels. We applied PheNorm to cohorts of potential COVID-19 patients from 2 institutions and used gold-standard manual chart review data to investigate the impact on performance of alternative feature engineering options and implementing externally trained models without local retraining. RESULTS: Models at each institution achieved AUC, sensitivity, and positive predictive value of 0.853, 0.879, 0.851 and 0.804, 0.976, and 0.885, respectively, at quantiles of model-predicted risk that maximize F1. We report performance metrics for all combinations of silver labels, feature engineering options, and models trained internally versus externally. DISCUSSION: Phenotyping algorithms developed using PheNorm performed well at both institutions. Performance varied with different silver-standard labels and feature engineering options. Models developed locally at one site also worked well when implemented externally at the other site. CONCLUSION: PheNorm models successfully identified an acute health condition, symptomatic COVID-19. The simplicity of the PheNorm approach allows it to be applied at multiple study sites with substantially reduced overhead compared to traditional approaches.

Incidence, prevalence, and trends in polycystic ovary syndrome diagnosis: a United States population-based study from 2006 to 2019.

BACKGROUND: Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age, yet US incidence estimates do not exist, and prevalence estimates vary widely. OBJECTIVE: A population-based US study estimated the incidence, prevalence, and trends of polycystic ovary syndrome by age, race and ethnicity, and diagnosing provider type. STUDY DESIGN: A retrospective cohort study of patients enrolled in Kaiser Permanente Washington from 2006 to 2019 was conducted. All members identified as female, aged 16 to 40 years with at least 3 years of enrollment and at least 1 healthcare encounter during that time, were eligible for inclusion. Individuals were excluded if they had a history of oophorectomy or hysterectomy. Polycystic ovary syndrome cases were identified using the International Classification of Diseases diagnosis codes (International Classification of Diseases, Ninth Revision, 256.4 or International Classification of Diseases, Tenth Revision, E28.2). Individuals with a polycystic ovary syndrome diagnosis before study entry were excluded from incidence rate estimations. The incidence rates were adjusted by age using direct standardization to the 2010 US census data. Temporal trends in incidence were assessed using weighted linear regression (overall) and Poisson regression (by age, race and ethnicity, and provider type). Prevalent cases were defined as patients with a polycystic ovary syndrome diagnosis at any time before the end of 2019. Medical record review of 700 incident cases diagnosed in 2011-2019 was performed to validate incident cases identified by International Classification of Diseases codes using the Rotterdam criteria. RESULTS: Among 177,527 eligible patients who contributed 586,470 person-years, 2491 incident polycystic ovary syndrome cases were identified. The mean age at diagnosis was 26.9 years, and the mean body mass index was 31.6 kg/m2. Overall incidence was 42.5 per 10,000 person-years; the rates were similar over time but increased in individuals aged 16 to 20 years from 31.0 to 51.9 per 10,000 person-years (P=.01) and decreased among those aged 26 to 30 years from 82.8 to 45.0 per 10,000 person-years (P=.02). A small decreasing temporal trend in incidence rates was only observed among non-Hispanic White individuals (P=.01). The incidence rates by diagnosing provider type varied little over time. Among the 58,241 patients who contributed person-time in 2019, 3036 (5.2%) had a polycystic ovary syndrome International Classification of Diseases diagnosis code; the prevalence was the highest among the Hawaiian and Pacific Islander group (7.6%) followed by Native American and Hispanic groups. Medical record review classified 60% as definite or probable incident, 14% as possible incident, and 17% as prevalent polycystic ovary syndrome. The overall positive predictive value of polycystic ovary syndrome International Classification of Diseases diagnosis code for identifying definite, probable, or possible incident polycystic ovary syndrome was 76% (95% confidence interval, 72%-79%). CONCLUSION: Among a cohort of nonselected females in the United States, we observed stable rates of incident polycystic ovary syndrome diagnoses over time. The incidence of polycystic ovary syndrome was 4- to 5-fold greater than reported for the United Kingdom. The prevalence of polycystic ovary syndrome (5.2%) was almost double before the published US estimates (2.9%) based on the International Classification of Diseases codes. Race and ethnicity and provider type did not seem to have a major impact on temporal rates. Incident diagnoses increased over time in younger and decreased in older age groups, perhaps related to shifting practice patterns with greater awareness among practitioners of the impact of polycystic ovary syndrome on long-term health outcomes and improved prevention efforts. Moreover, increasing obesity rates may be a factor driving the earlier ages at diagnosis.

Using natural language processing to identify child maltreatment in health systems.

BACKGROUND: Rates of child maltreatment (CM) obtained from electronic health records are much lower than national child welfare prevalence rates indicate. There is a need to understand how CM is documented to improve reporting and surveillance. OBJECTIVES: To examine whether using natural language processing (NLP) in outpatient chart notes can identify cases of CM not documented by ICD diagnosis code, the overlap between the coding of child maltreatment by ICD and NLP, and any differences by age, gender, or race/ethnicity. METHODS: Outpatient chart notes of children age 0-18 years old within Kaiser Permanente Washington (KPWA) 2018-2020 were used to examine a selected set of maltreatment-related terms categorized into concept unique identifiers (CUI). Manual review of text snippets for each CUI was completed to flag for validated cases and retrain the NLP algorithm. RESULTS: The NLP results indicated a crude rate of 1.55 % to 2.36 % (2018-2020) of notes with reference to CM. The rate of CM identified by ICD code was 3.32 per 1000 children, whereas the rate identified by NLP was 37.38 per 1000 children. The groups that increased the most in identification of maltreatment from ICD to NLP were adolescents (13-18 yrs. old), females, Native American children, and those on Medicaid. Of note, all subgroups had substantially higher rates of maltreatment when using NLP. CONCLUSIONS: Use of NLP substantially increased the estimated number of children who have been impacted by CM. Accurately capturing this population will improve identification of vulnerable youth at high risk for mental health symptoms.

Evaluation of the portability of computable phenotypes with natural language processing in the eMERGE network.

The electronic Medical Records and Genomics (eMERGE) Network assessed the feasibility of deploying portable phenotype rule-based algorithms with natural language processing (NLP) components added to improve performance of existing algorithms using electronic health records (EHRs). Based on scientific merit and predicted difficulty, eMERGE selected six existing phenotypes to enhance with NLP. We assessed performance, portability, and ease of use. We summarized lessons learned by: (1) challenges; (2) best practices to address challenges based on existing evidence and/or eMERGE experience; and (3) opportunities for future research. Adding NLP resulted in improved, or the same, precision and/or recall for all but one algorithm. Portability, phenotyping workflow/process, and technology were major themes. With NLP, development and validation took longer. Besides portability of NLP technology and algorithm replicability, factors to ensure success include privacy protection, technical infrastructure setup, intellectual property agreement, and efficient communication. Workflow improvements can improve communication and reduce implementation time. NLP performance varied mainly due to clinical document heterogeneity; therefore, we suggest using semi-structured notes, comprehensive documentation, and customization options. NLP portability is possible with improved phenotype algorithm performance, but careful planning and architecture of the algorithms is essential to support local customizations.

Improving Methods of Identifying Anaphylaxis for Medical Product Safety Surveillance Using Natural Language Processing and Machine Learning.

We sought to determine whether machine learning and natural language processing (NLP) applied to electronic medical records could improve performance of automated health-care claims-based algorithms to identify anaphylaxis events using data on 516 patients with outpatient, emergency department, or inpatient anaphylaxis diagnosis codes during 2015-2019 in 2 integrated health-care institutions in the Northwest United States. We used one site's manually reviewed gold-standard outcomes data for model development and the other's for external validation based on cross-validated area under the receiver operating characteristic curve (AUC), positive predictive value (PPV), and sensitivity. In the development site 154 (64%) of 239 potential events met adjudication criteria for anaphylaxis compared with 180 (65%) of 277 in the validation site. Logistic regression models using only structured claims data achieved a cross-validated AUC of 0.58 (95% CI: 0.54, 0.63). Machine learning improved cross-validated AUC to 0.62 (0.58, 0.66); incorporating NLP-derived covariates further increased cross-validated AUCs to 0.70 (0.66, 0.75) in development and 0.67 (0.63, 0.71) in external validation data. A classification threshold with cross-validated PPV of 79% and cross-validated sensitivity of 66% in development data had cross-validated PPV of 78% and cross-validated sensitivity of 56% in external data. Machine learning and NLP-derived data improved identification of validated anaphylaxis events.

Anaplastic Transformation of Differentiated Thyroid Carcinoma.

OBJECTIVES: Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive form of thyroid cancer. Increasingly, patients with ATC present with concurrent foci of well-differentiated thyroid carcinoma (WDTC); however, the significance of these pathologic findings remains unclear. The objective of this study is to determine whether the presence of WDTC within anaplastic tumors is a prognosticator of survival. METHODS: A retrospective cohort study of all cases of biopsy-proven ATC managed at a tertiary care academic medical center from 2002 to 2020 was performed. Mean age at diagnosis, median survival time, and locations of distant metastases were assessed. The impact of clinical markers such as presence of differentiation, demographic variables, and oncologic information on overall survival was also determined via univariate and multivariate analysis. RESULTS: Forty-five patients were included in this study. The mean age at diagnosis was 69.1 years. Median survival time was 6.1 months after diagnosis. The most common location of distant metastases was the lung (40%). The presence of limited areas of WDTC in patients with predominantly anaplastic thyroid tumors was not significantly associated with improved outcomes (p = 0.509). Smaller tumor size and use of chemotherapy in ATC patients were significantly associated with prolonged survival (p = 0.026 and 0.010, respectively). CONCLUSIONS: Clinical outcomes for ATC remain poor. The presence of foci of differentiation within anaplastic thyroid tumors does not appear to improve overall survival-the anaplastic component evidently drives outcomes. Further studies into novel therapies are needed to improve survival in ATC. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:437-442, 2023.

Improving physical activity among prostate cancer survivors through a peer-based digital walking program.

Physical activity is important for prostate cancer survivors. Yet survivors face significant barriers to traditional structured exercise programs, limiting engagement and impact. Digital programs that incorporate fitness trackers and peer support via social media have potential to improve the reach and impact of traditional support. Using a digital walking program with prostate cancer survivors, we employed mixed methods to assess program outcomes, engagement, perceived utility, and social influence. After 6 weeks of program use, survivors and loved ones (n=18) significantly increased their average daily step count. Although engagement and perceived utility of using a fitness tracker and interacting with walking buddies was high, social media engagement and utility were limited. Group strategies associated with social influence were driven more by group attraction to the collective task of walking than by interpersonal bonds. Findings demonstrate the feasibility of a digital walking program to improve physical activity and extend the reach of traditional support.

Hearing outcomes in children with Congenital Cytomegalovirus: A multi-center, single-enterprise experience.

BACKGROUND: Cytomegalovirus (CMV) is the most common cause of non-genetic sensorineural hearing loss (SNHL) in the United States; yet screening for congenital CMV (cCMV) remains controversial. CMV related SNHL can be present at birth, or develop in a delayed manner, and it is a consistent feature in children with either symptomatic or asymptomatic disease. A retrospective chart review was performed to determine the characteristics of patients diagnosed with cCMV and SNHL. METHODS: The electronic database warehouse of the Nemours Children's Health System (NCHS) was queried from 01/01/2004 to 10/05/2019. ICD 9 (771.1) and ICD 10 (B25.9, P35.1) diagnostic codes were used to identify patients throughout the system with a diagnosis of cCMV infection. Patient demographics including gender, race/ethnicity, age of diagnosis, results of newborn hearing screening (NBHS), detection and progression of hearing loss, presence of antiviral therapy, and frequency of monitoring were collected, and descriptive statistics performed. RESULTS: Of the 170 patients confirmed to have cCMV, 153 (90%) were symptomatic and 17 (10%) were asymptomatic. CNS involvement (63.5%), radiographic evidence of disease present (69.4%), and SNHL (50.6%) were the most common manifestations of the disease. Of these 170 patients, 83 (48.8%) were determined to have SNHL eligible for evaluation. For these patients with SNHL, the average time of hearing monitoring was 50.6 months. At the time of initial reported detection 63 of 83 (76%) had bilateral hearing loss and 20 (24%) had unilateral loss. Over the study period 3 (15%) progressed from unilateral to bilateral involvement, and 32 (47%) had a deterioration in hearing, with severe to profound SNHL in at least one ear identified at the last visit in 53 (64%) patients. Newborn hearing testing results were available for 69 (83%) of those with hearing loss and 26 patients passed initial testing. However, of the 26 patients who passed, 22 (85%) eventually developed SNHL by their last visit. Within our cohort, females with cCMV were significantly more likely to have SNHL than males with cCMV (62.3% versus 37.6%; p < 0.01). CONCLUSION: In the absence of targeted or universal cCMV screening, the majority of children identified with this condition present symptomatically. Approximately one half of children with symptomatic cCMV failed NBHS at birth while at least 25% develop SNHL later in life. Children with cCMV are at high risk of delayed onset loss and such children, particularly females, should be monitored closely.

Development of a machine learning model to predict mild cognitive impairment using natural language processing in the absence of screening.

BACKGROUND: Patients and their loved ones often report symptoms or complaints of cognitive decline that clinicians note in free clinical text, but no structured screening or diagnostic data are recorded. These symptoms/complaints may be signals that predict who will go on to be diagnosed with mild cognitive impairment (MCI) and ultimately develop Alzheimer's Disease or related dementias. Our objective was to develop a natural language processing system and prediction model for identification of MCI from clinical text in the absence of screening or other structured diagnostic information. METHODS: There were two populations of patients: 1794 participants in the Adult Changes in Thought (ACT) study and 2391 patients in the general population of Kaiser Permanente Washington. All individuals had standardized cognitive assessment scores. We excluded patients with a diagnosis of Alzheimer's Disease, Dementia or use of donepezil. We manually annotated 10,391 clinic notes to train the NLP model. Standard Python code was used to extract phrases from notes and map each phrase to a cognitive functioning concept. Concepts derived from the NLP system were used to predict future MCI. The prediction model was trained on the ACT cohort and 60% of the general population cohort with 40% withheld for validation. We used a least absolute shrinkage and selection operator logistic regression approach (LASSO) to fit a prediction model with MCI as the prediction target. Using the predicted case status from the LASSO model and known MCI from standardized scores, we constructed receiver operating curves to measure model performance. RESULTS: Chart abstraction identified 42 MCI concepts. Prediction model performance in the validation data set was modest with an area under the curve of 0.67. Setting the cutoff for correct classification at 0.60, the classifier yielded sensitivity of 1.7%, specificity of 99.7%, PPV of 70% and NPV of 70.5% in the validation cohort. DISCUSSION AND CONCLUSION: Although the sensitivity of the machine learning model was poor, negative predictive value was high, an important characteristic of models used for population-based screening. While an AUC of 0.67 is generally considered moderate performance, it is also comparable to several tests that are widely used in clinical practice.

Clinical documentation of patient-reported medical cannabis use in primary care: Toward scalable extraction using natural language processing methods.

Background: Most states have legalized medical cannabis, yet little is known about how medical cannabis use is documented in patients' electronic health records (EHRs). We used natural language processing (NLP) to calculate the prevalence of clinician-documented medical cannabis use among adults in an integrated health system in Washington State where medical and recreational use are legal. Methods: We analyzed EHRs of patients ≥18 years old screened for past-year cannabis use (November 1, 2017-October 31, 2018), to identify clinician-documented medical cannabis use. We defined medical use as any documentation of cannabis that was recommended by a clinician or described by the clinician or patient as intended to manage health conditions or symptoms. We developed and applied an NLP system that included NLP-assisted manual review to identify such documentation in encounter notes. Results: Medical cannabis use was documented for 16,684 (5.6%) of 299,597 outpatient encounters with routine screening for cannabis use among 203,489 patients seeing 1,274 clinicians. The validated NLP system identified 54% of documentation and NLP-assisted manual review the remainder. Language documenting reasons for cannabis use included 125 terms indicating medical use, 28 terms indicating non-medical use and 41 ambiguous terms. Implicit documentation of medical use (e.g., "edible THC nightly for lumbar pain") was more common than explicit (e.g., "continues medical cannabis use"). Conclusions: Clinicians use diverse and often ambiguous language to document patients' reasons for cannabis use. Automating extraction of documentation about patients' cannabis use could facilitate clinical decision support and epidemiological investigation but will require large amounts of gold standard training data.

Prevalence of Medical Cannabis Use and Associated Health Conditions Documented in Electronic Health Records Among Primary Care Patients in Washington State.

Importance: Many people use cannabis for medical reasons despite limited evidence of therapeutic benefit and potential risks. Little is known about medical practitioners' documentation of medical cannabis use or clinical characteristics of patients with documented medical cannabis use. Objectives: To estimate the prevalence of past-year medical cannabis use documented in electronic health records (EHRs) and to describe patients with EHR-documented medical cannabis use, EHR-documented cannabis use without evidence of medical use (other cannabis use), and no EHR-documented cannabis use. Design, Setting, and Participants: This cross-sectional study assessed adult primary care patients who completed a cannabis screen during a visit between November 1, 2017, and October 31, 2018, at a large health system that conducts routine cannabis screening in a US state with legal medical and recreational cannabis use. Exposures: Three mutually exclusive categories of EHR-documented cannabis use (medical, other, and no use) based on practitioner documentation of medical cannabis use in the EHR and patient report of past-year cannabis use at screening. Main Outcomes and Measures: Health conditions for which cannabis use has potential benefits or risks were defined based on National Academies of Sciences, Engineering, and Medicine's review. The adjusted prevalence of conditions diagnosed in the prior year were estimated across 3 categories of EHR-documented cannabis use with logistic regression. Results: A total of 185 565 patients (mean [SD] age, 52.0 [18.1] years; 59% female, 73% White, 94% non-Hispanic, and 61% commercially insured) were screened for cannabis use in a primary care visit during the study period. Among these patients, 3551 (2%) had EHR-documented medical cannabis use, 36 599 (20%) had EHR-documented other cannabis use, and 145 415 (78%) had no documented cannabis use. Patients with medical cannabis use had a higher prevalence of health conditions for which cannabis has potential benefits (49.8%; 95% CI, 48.3%-51.3%) compared with patients with other cannabis use (39.9%; 95% CI, 39.4%-40.3%) or no cannabis use (40.0%; 95% CI, 39.8%-40.2%). In addition, patients with medical cannabis use had a higher prevalence of health conditions for which cannabis has potential risks (60.7%; 95% CI, 59.0%-62.3%) compared with patients with other cannabis use (50.5%; 95% CI, 50.0%-51.0%) or no cannabis use (42.7%; 95% CI, 42.4%-42.9%). Conclusions and Relevance: In this cross-sectional study, primary care patients with documented medical cannabis use had a high prevalence of health conditions for which cannabis use has potential benefits, yet a higher prevalence of conditions with potential risks from cannabis use. These findings suggest that practitioners should be prepared to discuss potential risks and benefits of cannabis use with patients.

Design of digital walking programs that engage prostate cancer survivors: Needs and preferences from focus groups.

The majority of prostate cancer survivors do not meet physical activity (PA) recommendations. Although technology has shown to promote PA, engagement has been a challenge. This mixed method study characterizes survivors' needs and preferences for digital walking programs Through focus groups and surveys, we engaged prostate cancer support groups to describe PA motivators and barriers, interest in improving PA, and preferences for design features of a future digital walking program. Identified motivators (peers, positive thinking) and barriers (health issues) reflect PA needs that impact engagement. The most preferred features include: (1) well-curated, specific content, (2) individualized feedback from trusted sources, (3) moderated peer discussion, and (4) support from small teams and peer mentors. These findings inform digital PA programs that survivors will find engaging and can promote PA.

Loci identified by a genome-wide association study of carotid artery stenosis in the eMERGE network.

Carotid artery atherosclerotic disease (CAAD) is a risk factor for stroke. We used a genome-wide association (GWAS) approach to discover genetic variants associated with CAAD in participants in the electronic Medical Records and Genomics (eMERGE) Network. We identified adult CAAD cases with unilateral or bilateral carotid artery stenosis and controls without evidence of stenosis from electronic health records at eight eMERGE sites. We performed GWAS with a model adjusting for age, sex, study site, and genetic principal components of ancestry. In eMERGE we found 1793 CAAD cases and 17,958 controls. Two loci reached genome-wide significance, on chr6 in LPA (rs10455872, odds ratio [OR] (95% confidence interval [CI]) = 1.50 (1.30-1.73), p = 2.1 × 10-8 ) and on chr7, an intergenic single nucleotide variant (SNV; rs6952610, OR (95% CI) = 1.25 (1.16-1.36), p = 4.3 × 10-8 ). The chr7 association remained significant in the presence of the LPA SNV as a covariate. The LPA SNV was also associated with coronary heart disease (CHD; 4199 cases and 11,679 controls) in this study (OR (95% CI) = 1.27 (1.13-1.43), p = 5 × 10-5 ) but the chr7 SNV was not (OR (95% CI) = 1.03 (0.97-1.09), p = .37). Both variants replicated in UK Biobank. Elevated lipoprotein(a) concentrations ([Lp(a)]) and LPA variants associated with elevated [Lp(a)] have previously been associated with CAAD and CHD, including rs10455872. With electronic health record phenotypes in eMERGE and UKB, we replicated a previously known association and identified a novel locus associated with CAAD.

Resilience of clinical text de-identified with "hiding in plain sight" to hostile reidentification attacks by human readers.

OBJECTIVE: Effective, scalable de-identification of personally identifying information (PII) for information-rich clinical text is critical to support secondary use, but no method is 100% effective. The hiding-in-plain-sight (HIPS) approach attempts to solve this "residual PII problem." HIPS replaces PII tagged by a de-identification system with realistic but fictitious (resynthesized) content, making it harder to detect remaining unredacted PII. MATERIALS AND METHODS: Using 2000 representative clinical documents from 2 healthcare settings (4000 total), we used a novel method to generate 2 de-identified 100-document corpora (200 documents total) in which PII tagged by a typical automated machine-learned tagger was replaced by HIPS-resynthesized content. Four readers conducted aggressive reidentification attacks to isolate leaked PII: 2 readers from within the originating institution and 2 external readers. RESULTS: Overall, mean recall of leaked PII was 26.8% and mean precision was 37.2%. Mean recall was 9% (mean precision = 37%) for patient ages, 32% (mean precision = 26%) for dates, 25% (mean precision = 37%) for doctor names, 45% (mean precision = 55%) for organization names, and 23% (mean precision = 57%) for patient names. Recall was 32% (precision = 40%) for internal and 22% (precision =33%) for external readers. DISCUSSION AND CONCLUSIONS: Approximately 70% of leaked PII "hiding" in a corpus de-identified with HIPS resynthesis is resilient to detection by human readers in a realistic, aggressive reidentification attack scenario-more than double the rate reported in previous studies but less than the rate reported for an attack assisted by machine learning methods.

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.

Primary Care Opioid Taper Plans Are Associated with Sustained Opioid Dose Reduction.

BACKGROUND: Primary care providers prescribe most long-term opioid therapy and are increasingly asked to taper the opioid doses of these patients to safer levels. A recent systematic review suggests that multiple interventions may facilitate opioid taper, but many of these are not feasible within the usual primary care practice. OBJECTIVE: To determine if opioid taper plans documented by primary care providers in the electronic health record are associated with significant and sustained opioid dose reductions among patients on long-term opioid therapy. DESIGN: A nested case-control design was used to compare cases (patients with a sustained opioid taper defined as average daily opioid dose of ≤ 30 mg morphine equivalent (MME) or a 50% reduction in MME) to controls (patients matched to cases on year and quarter of cohort entry, sex, and age group, who had not achieved a sustained taper). Each case was matched with four controls. PARTICIPANTS: Two thousand four hundred nine patients receiving a ≥ 60-day supply of opioids with an average daily dose of ≥ 50 MME during 2011-2015. MAIN MEASURES: Opioid taper plans documented in prescription instructions or clinical notes within the electronic health record identified through natural language processing; opioid dosing, patient characteristics, and taper plan components also abstracted from the electronic health record. KEY RESULTS: Primary care taper plans were associated with an increased likelihood of sustained opioid taper after adjusting for all patient covariates and near peak dose (OR = 3.63 [95% CI 2.96-4.46], p < 0.0001). Both taper plans in prescription instructions (OR = 4.03 [95% CI 3.19-5.09], p < 0.0001) and in clinical notes (OR = 2.82 [95% CI 2.00-3.99], p < 0.0001) were associated with sustained taper. CONCLUSIONS: These results suggest that planning for opioid taper during primary care visits may facilitate significant and sustained opioid dose reduction.

The machine giveth and the machine taketh away: a parrot attack on clinical text deidentified with hiding in plain sight.

OBJECTIVE: Clinical corpora can be deidentified using a combination of machine-learned automated taggers and hiding in plain sight (HIPS) resynthesis. The latter replaces detected personally identifiable information (PII) with random surrogates, allowing leaked PII to blend in or "hide in plain sight." We evaluated the extent to which a malicious attacker could expose leaked PII in such a corpus. MATERIALS AND METHODS: We modeled a scenario where an institution (the defender) externally shared an 800-note corpus of actual outpatient clinical encounter notes from a large, integrated health care delivery system in Washington State. These notes were deidentified by a machine-learned PII tagger and HIPS resynthesis. A malicious attacker obtained and performed a parrot attack intending to expose leaked PII in this corpus. Specifically, the attacker mimicked the defender's process by manually annotating all PII-like content in half of the released corpus, training a PII tagger on these data, and using the trained model to tag the remaining encounter notes. The attacker hypothesized that untagged identifiers would be leaked PII, discoverable by manual review. We evaluated the attacker's success using measures of leak-detection rate and accuracy. RESULTS: The attacker correctly hypothesized that 211 (68%) of 310 actual PII leaks in the corpus were leaks, and wrongly hypothesized that 191 resynthesized PII instances were also leaks. One-third of actual leaks remained undetected. DISCUSSION AND CONCLUSION: A malicious parrot attack to reveal leaked PII in clinical text deidentified by machine-learned HIPS resynthesis can attenuate but not eliminate the protective effect of HIPS deidentification.

Identification and validation of uterine perforation, intrauterine device expulsion, and breastfeeding in four health care systems with electronic health records.

OBJECTIVE: To validate algorithms identifying uterine perforations and intrauterine device (IUD) expulsions and to ascertain availability of breastfeeding status at the time of IUD insertion. STUDY DESIGN AND SETTING: Four health care systems with electronic health records (EHRs) participated: Kaiser Permanente Northern California (KPNC), Kaiser Permanente Southern California (KPSC), Kaiser Permanente Washington (KPWA), and Regenstrief Institute (RI). The study included women ≤50 years of age with an IUD insertion. Site-specific algorithms using structured and unstructured data were developed and a sample validated by EHR review. Positive predictive values (PPVs) of the algorithms were calculated. Breastfeeding status was assessed in a random sample of 125 women at each research site with IUD placement within 52 weeks postpartum. RESULTS: The study population included 282,028 women with 325,582 IUD insertions. The PPVs for uterine perforation were KPNC 77%, KPSC 81%, KPWA 82%, and RI 47%; PPVs for IUD expulsion were KPNC 77%, KPSC 87%, KPWA 68%, and RI 37%. Across all research sites, breastfeeding status at the time of IUD insertion was determined for 94% of those sampled. CONCLUSIONS: Algorithms with a high PPV for uterine perforation and IUD expulsion were developed at 3 of the 4 research sites. Breastfeeding status at the time of IUD insertion could be determined at all research sites. Our findings suggest that a study to evaluate the associations of breastfeeding and postpartum IUD insertions with risk of uterine perforation and IUD expulsion can be successfully conducted retrospectively; however, automated application of algorithms must be supplemented with chart review for some outcomes at one research site due to low PPV.

The Regulation of Inflammation by Innate and Adaptive Lymphocytes.

Inflammation plays an essential role in the control of pathogens and in shaping the ensuing adaptive immune responses. Traditionally, innate immunity has been described as a rapid response triggered through generic and nonspecific means that by definition lacks the ability to remember. Recently, it has become clear that some innate immune cells are epigenetically reprogrammed or "imprinted" by past experiences. These "trained" innate immune cells display altered inflammatory responses upon subsequent pathogen encounter. Remembrance of past pathogen encounters has classically been attributed to cohorts of antigen-specific memory T and B cells following the resolution of infection. During recall responses, memory T and B cells quickly respond by proliferating, producing effector cytokines, and performing various effector functions. An often-overlooked effector function of memory CD4 and CD8 T cells is the promotion of an inflammatory milieu at the initial site of infection that mirrors the primary encounter. This memory-conditioned inflammatory response, in conjunction with other secondary effector T cell functions, results in better control and more rapid resolution of both infection and the associated tissue pathology. Recent advancements in our understanding of inflammatory triggers, imprinting of the innate immune responses, and the role of T cell memory in regulating inflammation are discussed.