Incidence of von Willebrand disease in Denmark, 1995-2016: A cohort study.

INTRODUCTION: Information about temporal development of von Willebrand disease (VWD) incidence at a population level is scarce. To our knowledge, no study has described the incidence of VWD at a population level. AIM: To estimate overall and annual incidence rates of hospital diagnosed VWD in Denmark between 1995 and 2016 as well as the frequency of hospital treated bleeding episodes before and after VWD diagnosis. METHODS: A registry-based cohort study that included all Danish patients with a first diagnosis of VWD in Denmark, identified in the Danish National Patient Registry through 1995-2016. RESULTS: We identified 1,035 patients with a diagnosis of VWD. The overall incidence rate of VWD in 1995-2016 was 8.6 (95% CI: 8.1-9.2). The annual age-standardized incidence rate per 100 000 person-years varied between 4.1 (95% CI: 2.4-5.9) in 1998 and 16.7 (95% CI: 13.1-20.3) in 2005. A prominent peak in rates appeared from 2002 to 2008. One and five years before VWD diagnosis, 6% and 11.5% of the patients had at least one hospital treated bleeding episode. One and five years after diagnosis, the corresponding percentages were 7.9% and 13.4%. CONCLUSION: These results are the first population-based estimates of VWD incidence. The incidence may be underestimated because asymptomatic individuals may not be diagnosed. The observed peak in incidence from 2002-2008 may be explained by increased medical attention, leading to more patients being diagnosed, rather than an actual increase in VWD incidence. However, overall, we observed no systematic changes in VWD incidence over the study period.

Alpha-1 Antitrypsin Deficiency-Associated Clinical Manifestations and Healthcare Resource Use in the United States.

Pulmonary events (PEs) associated with alpha-1 antitrypsin deficiency (AATD) can have a severe clinical course and increase healthcare resource use (HRU). However, AATD-associated HRU and healthcare costs have not been extensively described. This study describes and compares real-world HRU and healthcare costs among US patients with severe (requiring hospitalization after AATD-related PE) versus nonsevere AATD clinical course. Administrative healthcare claims for patients with a second primary AATD diagnosis between 6/1/2008 and 12/31/2017 were analyzed from 2 databases (requiring continuous enrollment 6 months preceding diagnosis). Patient baseline characteristics and AATD-associated PE incidence rates, HRU, and healthcare costs during follow-up were compared in patients with severe versus nonsevere AATD. Of 5109 patients with a second AATD diagnosis, 2674 (severe, n = 711 [26.6%]; nonsevere, n = 1963 [73.4%]) had ≥1 AATD-associated PE. PE incidence per 100 person-years was higher in patients with severe versus nonsevere AATD. Annual incidences (mean ± SD) of emergency department (1.2 ± 5.7 vs. 0.4 ± 1.2), inpatient (1.3 ± 2.5 vs. 0.1 ± 0.5), and outpatient (10.3 ± 15.9 vs. 5.7 ± 13.2) visits were higher in patients with severe versus nonsevere AATD. Median (interquartile range) annual costs were also higher for patients with severe versus nonsevere AATD for emergency department ($185 [$0-$1665] vs. $0 [$0-$264]), inpatient ($16,038 [$2968-$70,941] vs. $0 [$0-$0]), and outpatient ($2663 [$412-$10,277] vs. $1114 [$134-$4195]) visits. Higher percentages of patients with severe AATD were prescribed augmentation therapy, antibiotics, or corticosteroids. These findings suggest that patients with severe AATD have higher incidence of AATD-associated PEs, as well as higher HRU and healthcare costs.

Alveolar echinococcosis in an Ontario dog resembling an hepatic abscess.

A boxer dog was evaluated because of lethargy, vomiting, and abdominal pain. Ultrasonography revealed multiple cystic structures in the abdomen. Exploratory laparotomy revealed 3 well-encapsulated hepatic masses and abdominal effusion with suppurative inflammation. Collectively, these findings suggested the hepatic masses were most likely abscesses. However, histologic examination of the hepatic masses revealed multi-cystic structures, consistent with alveolar echinococcosis. The diagnosis was confirmed by DNA sequencing. The dog was treated with daily albendazole, but within a few weeks exhibited adverse side effects. After 6 months, the dog's condition deteriorated, and it was euthanized.

Échinococcose alvéolaire ressemblant à un abcès hépatique chez un chien en Ontario. Un chien de race boxer fut évalué à cause de léthargie, vomissements, et douleur abdominale. Une échographie révéla de multiples structures kystiques dans l'abdomen. Une laparotomie exploratoire révéla trois masses hépatiques bien encapsulées et une effusion abdominale avec inflammation suppurative. Collectivement, ces données suggéraient que les masses hépatiques étaient fort probablement des abcès. Toutefois, l'examen histologique des masses hépatiques révéla des structures multi-kystiques, compatibles avec une échinococcose alvéolaire. Le diagnostic fut confirmé par séquençage d'ADN. Le chien fut traité avec de l'albendazole quotidiennement, mais en quelques semaines il montra des signes d'effets adverses. Après 6 mois la condition du chien se détériora et il fut euthanasié.(Traduit par Dr Serge Messier).

ECHINOCOCCUS EQUINUS HYDATID CYST IN THE LIVER OF A PRZEWALSKI'S HORSE ( EQUUS PRZEWALSKII) IN A CANADIAN ZOO.

A 23-yr-old captive-born Przewalski's horse mare ( Equus przewalskii) was euthanized at a Canadian zoo because of severe colic resulting from rupture of a jejunal pseudodiverticulum. An incidental finding of an encysted larval cestode within a hepatic granuloma was diagnosed on histopathology. Gel-based polymerase chain reaction (PCR) on liver tissue was positive for Echinococcus granulosus sensu lato, and deoxyribonucleic acid sequencing of the PCR product was 100% homologous with Echinococcus equinus. This appears to be the first molecular confirmation of E. equinus in North America, and the first report of cystic echinococcosis in a Przewalski's horse.

Retro-orbital and disseminated B-cell lymphoma in a yellow-collared macaw (Primolius auricollis).

A yellow-collared macaw was presented with unilateral left exophthalmia. The complete blood cell count and biochemistry revealed a heterophilic leukocytosis and elevation in liver parameters, respectively. A computed tomography scan showed a contrast-enhancing retrobulbar mass and hepatomegaly. Cytology of the liver was consistent with a round cell tumor, most likely lymphoma. The bird died after 2 months of palliative care. Postmortem examination confirmed a retro-orbital and disseminated B-cell lymphoma.

Lymphome B rétro-orbital et disséminé chez un ara à collier jaune(Primolius auricollis). Un ara à collier jaune a été présenté avec de l'exophtalmie unilatérale gauche. La formule sanguine complète et la biochimie ont révélé une leucocytose hétérophile et une élévation des paramètres hépatiques, respectivement. La tomodensitométrie à l'aide d'une injection de milieu de contraste a montré une masse rétrobulbaire et une hépatomégalie. La cytologie du foie était conforme à une tumeur à cellules rondes, le plus probablement un lymphome. L'oiseau est mort après 2 mois de soins palliatifs. L'examen postmortem a confirmé un lymphome B rétro-orbital et disséminé.(Traduit par Isabelle Vallières).

Validation of Medicaid Claims-based Diagnosis of Myocardial Infarction Using an HIV Clinical Cohort.

BACKGROUND: In nonexperimental comparative effectiveness research using health care databases, outcome measurements must be validated to evaluate and potentially adjust for misclassification bias. We aimed to validate claims-based myocardial infarction (MI) algorithms in a Medicaid population using an HIV clinical cohort as the gold standard. METHODS: Medicaid administrative data were obtained for the years 2002-2008 and linked to the UNC CFAR HIV Clinical Cohort based on social security number, first name, and last name and MI were adjudicated. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: There were 1063 individuals included in the study. Over a median observed time of 2.5 years, 17 had an MI. Specificity ranged from 0.979 to 0.993 with the highest specificity obtained using the ICD-9 code 410.xx in the primary or secondary position and a length of stay >3 days. Sensitivity of MI ascertainment varied from 0.588 to 0.824 depending on algorithm. CONCLUSIONS: Specificities of varying claims-based MI ascertainment criteria are high but small changes impact positive predictive value in a cohort with low incidence. Sensitivities vary based on ascertainment criteria. Type of algorithm used should be prioritized based on study question and maximization of specific validation parameters that will minimize bias while also considering precision.

Evaluating the incident user design in the HIV population: incident use versus naive?

INTRODUCTION: The incident user design is the preferred study design in comparative effectiveness (CER) research. Usually, 180-365 days of exposure free time is adequate to remove biases associated with inclusion of prevalent users. In HIV research, the use of antiretrovirals (ARVs) at any time in the past may influence future treatment choices and CER results; thus, identifying naive as opposed to incident users is of importance. We examined misclassification of antiretroviral naive status based on Medicaid administrative data through linkage to the UNC CFAR HIV Clinical Cohort (UCHCC). METHODS: We identified Medicaid patients with incident exposure to common first-line ARV regimens between 2002 and 2008 that were also patients enrolled in the UCHCC. We calculated the proportion of antiretroviral naive patients based on the UCHCC, among patients identified as having incident exposure in Medicaid and examined factors associated with being antiretroviral naive in both data sources using logistic regression to generate prevalence odds ratios and associated 95% confidence intervals. RESULTS: Of the 3500 Medicaid patients with incident antiretroviral (ARV) exposure, 1344 were also enrolled in the UCHCC. In this sample, 34% were antiretroviral naive at the time of first exposure in the Medicaid data based on the UCHCC. In multivariable models, higher CD4 cell counts and log HIV RNA values were associated with being antiretroviral naive in both data sources. CONCLUSIONS: Administrative data are an important source of information related to HIV treatment. As the construction of a durable and long-lasting HIV treatment plan involves knowledge of current and past antiretroviral therapy, augmentation of this data with comprehensive clinical cohort information is necessary.

Effects of combination antiretroviral therapies on the risk of myocardial infarction among HIV patients.

BACKGROUND: Cohort studies have demonstrated greater risk of myocardial infarction (MI) associated with specific antiretroviral use, while meta-analyses of randomized controlled trials (RCTs) have not. These differences may be due to inherent biases in the observational study design or to the limited duration of randomized trials. We conducted a new-user, active-comparator cohort study emulating an RCT comparing the initiation of several antiretrovirals as part of combination antiretroviral therapy (cART) and MI. METHODS: We included North Carolina (NC) Medicaid beneficiaries infected with human immunodeficiency virus between 2002 and 2008 who were previously untreated with cART. We compared hazard ratios (HRs) and 95% confidence intervals (CIs) of MI between abacavir and tenofovir recipients, and lopinavir-ritonavir or atazanavir recipients and nonnucleoside reverse transcriptase inhibitor (NNRTI) recipients. We adjusted for confounding through inverse probability weighting methods. RESULTS: There were 3481 NC Medicaid new cART recipients who contributed 6399 person-years and experienced 38 MI events. Receiving abacavir compared with tenofovir as part of cART was associated with an increased rate of MI (unadjusted HR = 2.70 [95% CI = 1.24-5.91]; adjusted HR = 2.05 [0.72-5.86]). Point estimates also suggest a relationship between receipt of atazanavir or lopinavir-ritonavir compared with an NNRTI and MI, although estimates were imprecise. CONCLUSIONS: We found an increased rate of MI among patients initiating abacavir compared with tenofovir, although the association was decreased after confounding adjustment. Without a very large prospective comparative clinical trial, a much larger observational study of patients initiating cART would be needed to better define this apparent association.

Sex differences in benzodiazepine use in the HIV-infected population.

In the HIV-infected population there is a high prevalence of psychiatric disorders, conditions that often coexist with drug and alcohol dependence. Symptoms associated with psychiatric disorders are frequently managed with benzodiazepines, a class of medication often abused. We examined whether HIV-infected patients were more likely to fill a benzodiazepine prescription than their uninfected counterparts using a privately insured, nationally representative sample receiving clinical care between January 2007 and December 2009. Odds ratios (OR) and 95% confidence intervals (CI) to quantify the likelihood of receiving a benzodiazepine were calculated using multivariate logistic regression models. We examined the presence of interaction between HIV infection and sex using backwards elimination and by comparing stratum-specific OR to identify clinically meaningful differences. Overall, 323,796 beneficiaries were included in the sample, of which 723 were HIV infected. Bivariate analyses showed that compared to the uninfected sample, HIV-infected patients were more likely to have filled a benzodiazepine prescription (24% vs. 19%) during the study period. HIV-infected patients were also more likely to be male (80% vs. 44%), black (21% vs. 7%) and have a diagnosis of depression (12% vs. 8%) or insomnia (6% vs. 3%) than were uninfected patients. Adjusted for other covariates, HIV infection was associated with an increase (OR): 1.68, 95% CI: 1.39, 2.02) in the likelihood of filling a benzodiazepine prescription. When stratified by sex, HIV-infected males were more likely (OR: 1.68, 95% CI: 1.05, 2.67) than uninfected males to fill a benzodiazepine prescription while there was no observed difference in the likelihood of filling a benzodiazepine prescription between HIV-infected and uninfected females (OR: 1.12, 95% CI: 0.73, 1.70). Our findings suggest that HIV-infected patients, particularly HIV-infected males, are more likely to fill benzodiazepine prescriptions than their uninfected counterparts, highlighting the need for further research to investigate reasons for these observed differences.

Comparative effectiveness research using electronic health records: impacts of oral antidiabetic drugs on the development of chronic kidney disease.

PURPOSE: Little is known about the comparative effects of common oral antidiabetic drugs ([OADs] metformin, sulfonylureas, or thiazolidinediones [THZs]) on chronic kidney disease (CKD) outcomes in patients newly diagnosed with type 2 diabetes (T2DM) and followed in community primary care practices. Electronic health records (EHRs) were used to evaluate the relationships between OAD class use and incident proteinuria and prevention of glomerular filtration rate decline. METHODS: A retrospective cohort study on newly diagnosed T2D cases requiring OADs documented in the EHRs of two primary care networks between 1998 and 2009 was conducted. CKD outcomes were new-onset proteinuria and estimated GFR (eGFR) falling below 60 ml/min/1.73 m(2). OAD exposures defined cohorts. Hazard ratios represent differential CKD outcome risk per year of OAD class use. RESULTS: A total of 798 and 977 patients qualified for proteinuria and eGFR outcome analyses, respectively. With metformin as the reference group, sulfonylurea exposure trended toward association with an increased risk of developing proteinuria ([adjusted hazard ratio; 95% CI] 1.27; 0.93, 1.74); proteinuria risk associated with THZ exposure (1.00; 0.70, 1.42) was similar to metformin. Compared with metformin, sulfonylurea exposure was associated with an increased risk of eGFR reduction to <60 ml/min/1.73 m(2) (1.41; 1.05, 1.91). THZ exposure (1.04; 0.71, 1.50) was not associated with change in the risk of eGFR decline. CONCLUSIONS: In a primary care population, metformin appeared to decrease the risk of CKD development compared with sulfonlyureas; risks of CKD development between metformin and THZs were similar. EHR use in pharmacotherapy comparative effectiveness research creates specific challenges and study limitations.

Communicating quantitative risks and benefits in promotional prescription drug labeling or print advertising.

PURPOSE: Under the Food, Drug, and Cosmetic Act, all promotional materials for prescription drugs must strike a fair balance in presentation of risks and benefits. How to best present this information is not clear. We sought to determine if the presentation of quantitative risk and benefit information in drug advertising and labeling influences consumers', patients', and clinicians' information processing, knowledge, and behavior by assessing available empirical evidence. METHODS: We used PubMed for a literature search, limiting to articles published in English from 1990 forward. Two reviewers independently reviewed the titles and abstracts for inclusion, after which we reviewed the full texts to determine if they communicated risk/benefit information either: (i) numerically (e.g., percent) versus non-numerically (e.g., using text such as "increased risk") or (ii) numerically using different formats (e.g., "25% of patients", "one in four patients", or use of pictographs). We abstracted information from included articles into standardized evidence tables. The research team identified a total of 674 relevant publications, of which 52 met our inclusion criteria. Of these, 37 focused on drugs. RESULTS AND CONCLUSIONS: Presenting numeric information appears to improve understanding of risks and benefits relative to non-numeric presentation; presenting both numeric and non-numeric information when possible may be best practice. No single specific format or graphical approach emerged as consistently superior. Numeracy and health literacy also deserve more empirical attention as moderators.

Initial and subsequent therapy for newly diagnosed type 2 diabetes patients treated in primary care using data from a vendor-based electronic health record.

BACKGROUND: Diabetes is a leading cause of death and disability, and its prevalence is increasing. When diet fails, patients with type 2 diabetes mellitus (T2DM) are prescribed oral hypoglycemics for glycemic control. Few studies have explored initial use or change from initial oral hypoglycemic therapy in the primary care setting. We aimed to describe the utilization of initial oral hypoglycemics among newly diagnosed patients with diabetes from 1998-2009 and changes from initial to subsequent therapy among patients prescribed older oral hypoglycemic agents using electronic health records. METHODS: This observational cohort study used electronic health records from newly diagnosed patients with T2DM between 1 January 1998 and 31 March 2009 at two large health systems in the USA. Oral hypoglycemics included older (biguanide, sulfonylurea, and thiazolidinedione) and newer agents (incretin mimetic agents, alpha-glucosidase inhibitors, and D-phenylalanine derivatives). Multinomial regression models were fit to evaluate initial older oral hypoglycemic medication. We used incidence density sampling and conditional logistic regression models to evaluate predictors of regimen change. RESULTS: Most patients were treated from the biguanide class of oral hypoglycemics (67%), but there were differences in initial prescribing by age and race. HbA1c (Odds Ratio for HbA1c 7.0-8.9 vs < 7.0, 5.87 [95% Confidence Interval: 3.62-9.52]; Odds Ratio for HbA1c ≥ 9 vs < 7.0, 20.25 [95% Confidence Interval: 8.32-49.29] and Black people (Odds Ratio, 0.29 [95% Confidence Interval: 0.14, 0.60]) versus White people were associated with regimen change in the adjusted analysis. CONCLUSIONS: Clinical and demographic characteristics influence choice and duration of initial oral hypoglycemic treatment as well as regimen changes.

Experimental infection of aquatic bird bornavirus 1 in domestic chickens.

Aquatic bird bornavirus 1 (ABBV-1), classified in the Orthobornavirus genus, is a neurotropic virus that infects wild waterfowl causing persistent infection of the nervous system. Given the conspicuous presence of wild waterfowl in urban areas and farmlands, spillover of this virus into domesticated poultry species is a concern. The goal of this study was to test the ability of ABBV-1 to infect and cause disease in chickens. Two day-old, White Leghorn chickens (n, 176) were inoculated with ABBV-1 through the oral, intramuscular, or intracranial routes, and sampled at 1, 4, 8, and 12-weeks post infection (wpi) to assess virus replication and lesion development. Chickens became infected only through the intracranial and intramuscular routes, developing earliest infection in the brain by 1 wpi (intracranial group), and spinal cord by 8 wpi (intramuscular group). Except for the kidney of one bird in the intracranial group, no other tissues (including choanal and cloacal swabs) tested positive for the virus. Therefore, while the virus could reach the central nervous tissue (CNS) from the muscle in approximately 20% of birds (centripetal spread), it inefficiently reached peripheral sites after replication in the CNS (centrifugal spread). Inflammation in the CNS was observed in the intracranial and intramuscular groups starting at 8 and 12 wpi, respectively, and consisted of mononuclear perivascular cuffing. This is the first study to document the susceptibility of chickens to ABBV-1 infection, and indicates that this species can become infected with ABBV-1, although less extensively than what is observed in waterfowl. This suggests that ABBV-1 replication is partially restricted in gallinaceous birds.

Histological and histochemical characteristics of lacrimal glands in beluga whales (Delphinapterus leucas).

The objective of this study was to describe the histological and histochemical characteristics of the lacrimal glands of beluga whales. The study was carried out on the formalin-fixed ocular globes from 96 carcasses of beluga whales found stranded in the St. Lawrence estuary in Quebec, Canada. Hematoxylin and eosin (H&E) stained slides from the eyes of each whale were examined for lacrimal glands. Histological description was done with H&E and Masson Trichrome (MT) stains. Period Acid-Schiff (PAS), Alcian blue (AB) pH 1.0 and 2.5, and High Iron Diamine (HID) stains were used for histochemical characterization of glycoproteins. Thirteen ocular samples from animals ranging from neonate to 48 y included sections of lacrimal glands. The H&E stain revealed a tubuloalveolar gland architecture, separated into lobules by dense connective tissue. Each lobule contained a mixture of acini and tubules with ductules. Small and large acini were composed of low and tall columnar cells, respectively. Acinar cells contained basophilic cytoplasmic granules. The ductules were lined with a bi-layered cuboidal-to-squamous epithelium. The MT stain highlighted the connective tissue separating ductules and acini. Large acini were positive for PAS and some small acini had patchy uptake. Positive staining for AB pH 1.0 and 2.5 was mainly seen in tall columnar cells as compared to small acini that had faint to no stain uptake. High Iron Diamine stain revealed 90% staining of all acinar cells, with 10% exhibiting a mixed blue-black tinge. It was concluded that the lacrimal glands of beluga whales have similar histological and histochemical findings to those of artiodactyla and carnivora orders.

L'objectif de cette étude était de décrire les caractéristiques histologiques et histochimiques des glandes lacrymales des bélugas. L'étude a été réalisée sur les globes oculaires fixés au formol de 96 carcasses de bélugas trouvées échouées dans l'estuaire du Saint-Laurent au Québec, Canada. Des lames colorées à l'hématoxyline et à l'éosine (H&E) des yeux de chaque baleine ont été examinées pour la présence de glandes lacrymales. La description histologique a été réalisée avec des colorations H&E et trichrome de Masson (MT). Les colorations Periodic acid-Schiff (PAS), au bleu Alcian (AB) pH 1,0 et 2,5, et diamine à haute teneur en fer (HID) ont été utilisées pour la caractérisation histochimique des glycoprotéines. Treize échantillons oculaires provenant d'animaux allant du nouveau-né à 48 ans comprenaient des sections de glandes lacrymales. La coloration H&E a révélé une architecture de glande tubulo-alvéolaire, séparée en lobules par un tissu conjonctif dense. Chaque lobule contenait un mélange d'acini et de tubules avec des ductules. Les petits et les grands acini étaient respectivement composés de cellules cylindriques basses et hautes. Les cellules acinaires contenaient des granules cytoplasmiques basophiles. Les canaux étaient tapissés d'un épithélium cuboïde à squameux bicouche. La coloration MT a mis en évidence le tissu conjonctif séparant les canaux et les acini. Les grands acini étaient positifs pour le PAS et certains petits acini avaient une absorption inégale. Une coloration positive pour AB pH 1,0 et 2,5 a été principalement observée dans les cellules cylindriques hautes par rapport aux petits acini qui avaient une absorption de coloration faible ou nulle. La coloration HDI a révélé une coloration de 90 % de toutes les cellules acinaires, 10 % présentant une teinte mixte bleu-noir. Il a été conclu que les glandes lacrymales des bélugas présentent des résultats histologiques et histochimiques similaires à ceux des ordres des artiodactyles et des carnivores.(Traduit par Docteur Serge Messier).

Experimental infection of aquatic bird bornavirus in Muscovy ducks.

Aquatic bird bornavirus (ABBV-1), an avian bornavirus, has been reported in wild waterfowl from North America and Europe that presented with neurological signs and inflammation of the central and peripheral nervous systems. The potential of ABBV-1to infect and cause lesions in commercial waterfowl species is unknown. The aim of this study was to determine the ability of ABBV-1 to infect and cause disease in day-old Muscovy ducks (n = 174), selected as a representative domestic waterfowl. Ducklings became infected with ABBV-1 through both intracranial and intramuscular, but not oral, infection routes. Upon intramuscular infection, the virus spread centripetally to the central nervous system (brain and spinal cord), while intracranial infection led to virus spread to the spinal cord, kidneys, proventriculus, and gonads (centrifugal spread). Infected birds developed both encephalitis and myelitis by 4 weeks post infection (wpi), which progressively subsided by 8 and 12 wpi. Despite development of microscopic lesions, clinical signs were not observed. Only five birds had choanal and/or cloacal swabs positive for ABBV-1, suggesting a low potential of Muscovy ducks to shed the virus. This is the first study to document the pathogenesis of ABBV-1 in poultry species, and confirms the ability of ABBV-1 to infect commercial waterfowl.

Early Diagnosis of Primary Immunodeficiency Disease Using Clinical Data and Machine Learning.

BACKGROUND: Primary immunodeficiency diseases (PIDD) are a group of immune-related disorders that have a current median delay of diagnosis between 6 and 9 years. Early diagnosis and treatment of PIDD has been associated with improved patient outcomes. OBJECTIVE: To develop a machine learning model using elements within the electronic health record data that are related to prior symptomatic treatment to predict PIDD. METHODS: We conducted a retrospective study of patients with PIDD identified using inclusion criteria of PIDD-related diagnoses, immunodeficiency-specific medications, and low immunoglobulin levels. We constructed a control group of age-, sex-, and race-matched patients with asthma. The primary outcome was the diagnosis of PIDD. We considered comorbidities, laboratory tests, medications, and radiological orders as features, all before diagnosis and indicative of symptom-related treatment. Features were presented sequentially to logistic regression, elastic net, and random forest classifiers, which were trained using a nested cross-validation approach. RESULTS: Our cohort consisted of 6422 patients, of whom 247 (4%) were diagnosed with PIDD. Our logistic regression model with comorbidities demonstrated good discrimination between patients with PIDD and those with asthma (c-statistic: 0.62 [0.58-0.65]). Adding laboratory results, medications, and radiological orders improved discrimination (c-statistic: 0.70 vs 0.62, P < .001), sensitivity, and specificity. Extending to the advanced machine learning models did not improve performance. CONCLUSIONS: We developed a prediction model for early diagnosis of PIDD using historical data that are related to symptomatic care, which has potential to fill an important need in reducing the time to diagnose PIDD, leading to better outcomes for immunodeficient patients.

Development and external validation of prediction models for adverse health outcomes in rheumatoid arthritis: A multinational real-world cohort analysis.

BACKGROUND: Identification of rheumatoid arthritis (RA) patients at high risk of adverse health outcomes remains a major challenge. We aimed to develop and validate prediction models for a variety of adverse health outcomes in RA patients initiating first-line methotrexate (MTX) monotherapy. METHODS: Data from 15 claims and electronic health record databases across 9 countries were used. Models were developed and internally validated on Optum® De-identified Clinformatics® Data Mart Database using L1-regularized logistic regression to estimate the risk of adverse health outcomes within 3 months (leukopenia, pancytopenia, infection), 2 years (myocardial infarction (MI) and stroke), and 5 years (cancers [colorectal, breast, uterine] after treatment initiation. Candidate predictors included demographic variables and past medical history. Models were externally validated on all other databases. Performance was assessed using the area under the receiver operator characteristic curve (AUC) and calibration plots. FINDINGS: Models were developed and internally validated on 21,547 RA patients and externally validated on 131,928 RA patients. Models for serious infection (AUC: internal 0.74, external ranging from 0.62 to 0.83), MI (AUC: internal 0.76, external ranging from 0.56 to 0.82), and stroke (AUC: internal 0.77, external ranging from 0.63 to 0.95), showed good discrimination and adequate calibration. Models for the other outcomes showed modest internal discrimination (AUC < 0.65) and were not externally validated. INTERPRETATION: We developed and validated prediction models for a variety of adverse health outcomes in RA patients initiating first-line MTX monotherapy. Final models for serious infection, MI, and stroke demonstrated good performance across multiple databases and can be studied for clinical use. FUNDING: This activity under the European Health Data & Evidence Network (EHDEN) has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806968. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA.

Self-report of current and prior antiretroviral drug use in comparison to the medical record among HIV-infected patients receiving primary HIV care.

OBJECTIVE: Patient antiretroviral (ARV) therapy knowledge is essential for regimen adherence, successful therapeutic response, and minimization of resistance evolution. Moreover, a complete and accurate patient ARV history is needed to construct efficacious and tolerable future regimens. In this study we assessed the ability of HIV-infected patients receiving care in a university infectious diseases clinic to accurately recall current and past ARVs. METHODS: A convenience sample (n = 205) of UNC HIV Clinical Cohort participants (n = 1840) completed a comprehensive in-person interview. Patients were asked about current and ever ARV use and were provided proprietary and generic ARV names and photographs. Self-reported sensitivity for current and ever ARV use (proportion that correctly identified all recorded ARVs), was calculated using the medical record as the gold standard. RESULTS: One hundred and eighty-five patients had received ARVs at some point after enrollment in the cohort study (ever users). For current ARV use (n = 138), self-reported sensitivity was 63% (95% CI: 54-71). For ever use (n = 185), sensitivity was 18% (95% CI: 13-24). CONCLUSION: Self-reported cumulative ARV use is not accurate. Since HIV-infected patients are prescribed a number of medications over their treatment course, it is necessary to develop new medication reconciliation techniques that are not dependent on patient memory or knowledge in order to improve patient outcomes.

"If I knew then what I know now": parents' reflections on raising a child with cerebral palsy.

In this study we investigated experiences of parents of children with cerebral palsy (CP) to identify areas in which health care providers and educators could improve practice. A second objective was to create educational material for parents of young children newly diagnosed with CP. A purposive sample of nine parents, who previously participated in the Adolescent Study of Quality of Life, Mobility, and Exercise, was recruited through phone. During an interview, parents reflected on the experience of raising a child with CP from birth to young adulthood. These interviews were audiotaped, transcribed, and coded using the International Classification of Functioning, Disability and Health-informed model and analyzed to identify major themes. Parents elaborated upon what was helpful and what could be changed to improve their children's and families' experiences through supports, advocacy, and education at different levels. The results informed the development of tips for parents and children with CP to enhance their families' experiences and interactions with health care providers, educators, and others.

Leveraging unstructured data to identify hereditary angioedema patients in electronic medical records.

BACKGROUND: The epidemiologic impact of hereditary angioedema (HAE) is difficult to quantify, due to misclassification in retrospective studies resulting from non-specific diagnostic coding. The aim of this study was to identify cohorts of patients with HAE-1/2 by evaluating structured and unstructured data in a US ambulatory electronic medical record (EMR) database. METHODS: A retrospective feasibility study was performed using the GE Centricity EMR Database (2006-2017). Patients with ≥ 1 diagnosis code for HAE-1/2 (International Classification of Diseases, Ninth Revision, Clinical Modification 277.6 or International Classification of Diseases, Tenth Revision, Clinical Modification D84.1) and/or ≥ 1 physician note regarding HAE-1/2 and ≥ 6 months' data before and after the earliest code or note (index date) were included. Two mutually exclusive cohorts were created: probable HAE (≥ 2 codes or ≥ 2 notes on separate days) and suspected HAE (only 1 code or note). The impact of manually reviewing physician notes on cohort formation was assessed, and demographic and clinical characteristics of the 2 final cohorts were described. RESULTS: Initially, 1691 patients were identified: 190 and 1501 in the probable and suspected HAE cohorts, respectively. After physician note review, the confirmed HAE cohort comprised 254 patients and the suspected HAE cohort decreased to 1299 patients; 138 patients were determined not to have HAE and were excluded. The overall false-positive rate for the initial algorithms was 8.2%. Across final cohorts, the median age was 50 years and > 60% of patients were female. HAE-specific prescriptions were identified for 31% and 2% of the confirmed and suspected HAE cohorts, respectively. CONCLUSIONS: Unstructured EMR data can provide valuable information for identifying patients with HAE-1/2. Further research is needed to develop algorithms for more representative HAE cohorts in retrospective studies.