Validation of the Enhanced Opioid Identification and Co-occurring Disorders Algorithms.

Objectives This report documents the results of a validation study conducted to assess the reliability of two algorithms applied to the 2016 National Hospital Care Survey. One algorithm identifies opioid-involved and opioid overdose hospital encounters, and the other identifies encounters with patients that have substance use disorders and selected mental health issues. These algorithms use both medical codes and natural language processing to identify encounters. Methods To validate the algorithms, medical record abstraction was performed on a stratified sample of 900 hospital encounters from the 2016 National Hospital Care Survey. The abstractors recorded their determinations of opioid involvement, opioid overdose, substance use disorder, and mental health issues on a standard form. Abstractors' determinations were compared with algorithm output to assess the overall performance using F-score and Matthews correlation coefficient. The latter provided a secondary measure of performance. The 2016 National Hospital Care Survey data are unweighted and not nationally representative. Results Overall algorithm performance varied by topic and by metric. The opioid-involvement algorithm achieved the highest performance, performing well with an F-score of 0.95, followed by the substance use disorder algorithm (F-score of 0.79), the mental health issues algorithm (F-score of 0.68), and the opioid overdose algorithm (F-score of 0.48). Assessment by Matthews correlation coefficient indicated an overall poorer level of performance, ranging from a high of 0.57 for the mental health issues algorithm to a low of 0.33 for the opioid-involvement algorithm. The causes of false positives and false negatives likewise varied, including both overly broad code and keyword inclusions as well as incompleteness of data submitted to the National Hospital Care Survey. Conclusion The validation study illustrates which aspects of the developed algorithms performed well and which aspects should be altered or discarded in future iterations. It further emphasizes the importance of data completeness, therefore laying the groundwork for improvements to future survey analyses.

Identifying Co-occurring Disorders Among Patients With an Opioid involved Hospital Encounter Using National Hospital Care Survey Data.

This report documents the development of the 2016 National Hospital Care Survey (NHCS) Co-occurring Disorders Algorithm, which can be used to identify patients with an opioid-involved hospital encounter who had lifetime diagnoses of both a substance use disorder and a selected mental health issue. Lifetime diagnoses are defined as diagnoses at any point in the past or during the current encounter. This algorithm was created to complement the earlier NHCS Enhanced Opioid Identification Algorithm designed to improve the classification of patients with opioid-involved hospital encounters.

National Hospital Care Survey Demonstration Projects:Characteristics and Mortality Outcomes of Opioid-involved Hospital Encounters With Co-occurring Disorders.

This report demonstrates the use of National Hospital Care Survey (NHCS) data to describe characteristics of patients experiencing opioid-involved hospital encounters with co-occurring disorders, defined as lifetime diagnoses of both a substance use disorder (SUD) and a selected mental health issue (MHI), that is, diagnosed at any point in the past or during the present encounter.

Seroepidemiologic Investigation of a COVID-19 Outbreak Aboard a U.S. Navy Ship.

The crew of USS Kidd experienced a COVID-19 outbreak identified in April 2020. This is the earliest documented COVID-19 study with RT-PCR, serology, and pre-exposure test data on the entirety of the exposed population (n=333). Case definitions included 121 confirmed (36.3% of crewmembers) and 18 probable (5.4% of crewmembers) based on laboratory diagnostic test results. At the time of testing positive, 62 (44.6%) cases reported no symptoms. Hispanic ethnicity (AOR: 2.71, CI: 1.40-5.25) and non-smoker status (AOR: 2.28, CI: 1.26-4.12) were identified as statistically significant risk factors. This study highlights the value of rapid, onboard diagnostic testing to quickly identify an outbreak and enumerate cases, as well as the serological testing to flag potential cases missed with standard viral case identification methodologies.

Coronavirus Disease Case Definitions, Diagnostic Testing Criteria, and Surveillance in 25 Countries with Highest Reported Case Counts.

We compared case definitions for suspected, probable, and confirmed coronavirus disease (COVID-19), as well as diagnostic testing criteria, used in the 25 countries with the highest reported case counts as of October 1, 2020. Of the identified countries, 56% followed World Health Organization (WHO) recommendations for using a combination of clinical and epidemiologic criteria as part of the suspected case definition. A total of 75% of identified countries followed WHO recommendations on using clinical, epidemiologic, and diagnostic criteria for probable cases; 72% followed WHO recommendations to use PCR testing to confirm COVID-19. Finally, 64% of countries used testing eligibility criteria at least as permissive as WHO. We observed marked heterogeneity in testing eligibility requirements and in how countries define a COVID-19 case. This heterogeneity affects the ability to compare case counts, transmission, and vaccine effectiveness, as well as estimates derived from case surveillance data across countries.

Enhancing Identification of Opioid-involved Health Outcomes Using National Hospital Care Survey Data.

Objectives This report documents the development of the 2016 National Hospital Care Survey (NHCS) Enhanced Opioid Identification Algorithm, an algorithm that can be used to identify opioid-involved and opioid overdose hospital encounters. Additionally, the algorithm can be used to identify opioids and opioid antagonists that can be used to reverse opioid overdose (naloxone) and to treat opioid use disorder (naltrexone).

Opioid-involved Emergency Department Visits in the National Hospital Care Survey and the National Hospital Ambulatory Medical Care Survey.

Purpose-This report compares 2014 National Hospital Care Survey (NHCS) emergency department (ED) data with national estimates of ED visits due to opioid use (i.e., "opioid-involved visits") from the 2013-2015 National Hospital Ambulatory Medical Care Survey (NHAMCS) to determine the potential of researching the impact and outcomes of opioid use on hospital EDs with non-nationally representative NHCS data. The 2014 NHCS data are also linked to records in the 2014 and 2015 National Death Index (NDI) to examine mortality after the opioid-involved ED visit. Methods-A previously published algorithm, which uses a list of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes and external-cause-of-injury codes denoting opioid use, was used to identify opioid-involved visits in NHCS and NHAMCS, which are compared by sex and age. Weighted percentage estimates and their 95% confidence intervals (CIs) are shown for all demographic characteristics using NHAMCS data. Unweighted percentages are presented for all demographic and health care characteristics using NHCS data. Standard errors and CIs are also presented for the NHCS unweighted percentages as a measure of variability. Results-The percentage of opioid-involved ED visits from NHCS fell within measures of statistical variation from NHAMCS by sex and several age groups. Less consistency of NHCS results compared with NHAMCS was seen for sex-specific age groups. NHCS has a higher percentage of opioid-involved ED visits and a higher percentage of opioid-involved ED visits for those aged 25-34, but a lower percentage for those aged 25 and under. NHCS data show that 19.2% of patients with any opioid-involved ED visit made two or more such visits, and 1.2% died within 30 days post-discharge.

Identification of Substance-involved Emergency Department Visits Using Data From the National Hospital Care Survey.

This report describes the development of methods to identify emergency department (ED) visits involving substance use. Two different algorithms are compared using claims data from the 2013 National Hospital Care Survey (NHCS), a facility-based survey. While NHCS was designed to produce national estimates, this report is based on 2013 data, which are not nationally representative.

Emergency department visits and proximity to patients' residences, 2009-2010.

The number of emergency department (ED) visits rose 44% from 1991 through 2010, even as the number of hospital EDs declined 10% over the same period. As a result, EDs have increasingly experienced overcrowding and longer waiting times. However, little is known about which ED patients visit, how often patients go to the ED closest to their home, and how differences in geography, patient demographics, and hospital characteristics are associated with ED selection patterns.

Preclinical activity of the rational combination of selumetinib (AZD6244) in combination with vorinostat in KRAS-mutant colorectal cancer models.

PURPOSE: Despite the availability of several active combination regimens for advanced colorectal cancer (CRC), the 5-year survival rate remains poor at less than 10%, supporting the development of novel therapeutic approaches. In this study, we focused on the preclinical assessment of a rationally based combination against KRAS-mutated CRC by testing the combination of the MEK inhibitor, selumetinib, and vorinostat, a histone deacetylase (HDAC) inhibitor. EXPERIMENTAL DESIGN: Transcriptional profiling and gene set enrichment analysis (baseline and posttreatment) of CRC cell lines provided the rationale for the combination. The activity of selumetinib and vorinostat against the KRAS-mutant SW620 and SW480 CRC cell lines was studied in vitro and in vivo. The effects of this combination on tumor phenotype were assessed using monolayer and 3-dimensional cultures, flow cytometry, apoptosis, and cell migration. In vivo, tumor growth inhibition, (18)F-fluoro-deoxy-glucose positron emission tomography (FDG-PET), and proton nuclear magnetic resonance were carried out to evaluate the growth inhibitory and metabolic responses, respectively, in CRC xenografts. RESULTS: In vitro, treatment with selumetinib and vorinostat resulted in a synergistic inhibition of proliferation and spheroid formation in both CRC cell lines. This inhibition was associated with an increase in apoptosis, cell-cycle arrest in G(1), and reduced cellular migration and VEGF-A secretion. In vivo, the combination resulted in additive tumor growth inhibition. The metabolic response to selumetinib and vorinostat consisted of significant inhibition of membrane phospholipids; no significant changes in glucose uptake or metabolism were observed in any of the treatment groups. CONCLUSION: These data indicate that the rationally based combination of the mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor, selumetinib, with the HDAC inhibitor vorinostat results in synergistic antiproliferative activity against KRAS-mutant CRC cell lines in vitro. In vivo, the combination showed additive effects that were associated with metabolic changes in phospholipid turnover, but not on FDG-PET, indicating that the former is a more sensitive endpoint of the combination effects.

Development of an integrated genomic classifier for a novel agent in colorectal cancer: approach to individualized therapy in early development.

BACKGROUND: A plethora of agents is in early stages of development for colorectal cancer (CRC), including those that target the insulin-like growth factor I receptor (IGFIR) pathway. In the current environment of numerous cancer targets, it is imperative that patient selection strategies be developed with the intent of preliminary testing in the latter stages of phase I trials. The goal of this study was to develop and characterize predictive biomarkers for an IGFIR tyrosine kinase inhibitor, OSI-906, that could be applied in CRC-specific studies of this agent. METHODS: Twenty-seven CRC cell lines were exposed to OSI-906 and classified according to IC(50) value as sensitive (5 micromol/L). Cell lines were subjected to immunoblotting and immunohistochemistry for effector proteins, IGFIR copy number by fluorescence in situ hybridization, KRAS/BRAF/phosphoinositide 3-kinase mutation status, and baseline gene array analysis. The most sensitive and resistant cell lines were used for gene array and pathway analyses, along with shRNA knockdown of highly ranked genes. The resulting integrated genomic classifier was then tested against eight human CRC explants in vivo. RESULTS: Baseline gene array data from cell lines and xenografts were used to develop a k-top scoring pair (k-TSP) classifier, which, in combination with IGFIR fluorescence in situ hybridization and KRAS mutational status, was able to predict with 100% accuracy a test set of patient-derived CRC xenografts. CONCLUSIONS: These results indicate that an integrated approach to the development of individualized therapy is feasible and should be applied early in the development of novel agents, ideally in conjunction with late-stage phase I trials.

Targeting vascular endothelial growth factor receptor-1 and -3 with cediranib (AZD2171): effects on migration and invasion of gastrointestinal cancer cell lines.

The effect of vascular endothelial growth factor (VEGF) ligands and cediranib on tumor cell proliferation, migration, and invasion was determined. It has recently been suggested that autocrine signaling through the VEGF receptor (VEGFR) pathway may play a role in tumor cell survival, invasion, and migration. The purpose of the present study was to determine the expression of VEGFRs and VEGFR ligands in a panel of gastrointestinal carcinoma cells. Additionally, we evaluated the effects of VEGF autocrine signaling on tumor cell proliferation, migration, and invasion utilizing cediranib (AZD2171), a pan-VEGFR inhibitor. Five colorectal, three pancreatic, and two hepatocellular carcinoma cell lines were screened for VEGFR and VEGF expression by several methods. Expression of VEGFR-1 and VEGFR-3 was cell line-dependent, whereas VEGFR-2 was not detected. Secretion of VEGF-A was detected in the supernatants of all cell lines whereas VEGF-C secretion was detected in the Panc-1, MiaPaca2, and Hep1 cells only. Tumor cells showed increased migratory activity, but not proliferation, when stimulated with VEGFs. The pan-VEGFR inhibitor cediranib (100 nmol/L) inhibited tumor cell migration and invasion, with no effects on proliferation. Cediranib decreased VEGFR-1 and VEGFR-3 phosphorylation as well as activation of downstream effectors. VEGFR-1 and VEGFR-3 expression was detected in all the gastrointestinal carcinoma cells evaluated. Although activation of the VEGF pathway did not affect cell proliferation, our data indicate that this pathway seems to play a role in tumor cell migration and invasion in these cell lines. Therefore, inhibition of VEGFR by cediranib may represent a clinically relevant treatment option for gastrointestinal tumors.

Exploring the utility of the Spence Children's Anxiety Scales parent- and child-report forms in a North American sample.

This study examined the psychometric properties of the Spence Children's Anxiety Scale child- and parent-report forms in a sample of 85 children from the community and 85 children with anxiety disorders matched on sex and age. Results indicated that both versions of the scale had good internal reliability, with the exception of the physical injury fears subscale. All subscales and the total scores of both versions discriminated children in the anxious group from community controls. Strong correlations between child and parent reports supported the concurrent validity of the measure. Furthermore, convergent and divergent validity of the scales were supported by significant correlations with negative affect and physiological hyperarousal to a greater extent than with positive affect indicating that SCAS and SCAS-P measured anxiety rather than depressive symptoms. Mean differences with research from other countries were apparent for selected subscales and supported the need for culture-specific norms.

Five-day intensive treatment for adolescent OCD: a case series.

This case series describes the use of an intensive 5-day treatment for obsessive-compulsive disorder (OCD) with three adolescents. The treatment is based on traditional cognitive-behavioral therapy consisting primarily of exposures and response prevention (ERP) and involves 10 sessions over 5 days. In addition, the treatment emphasizes instructing the adolescent and the parents on how to conduct ERP at home following the completion of the 5 days of therapy. The treatment is designed for adolescents who do not have local access to mental health practitioners with expertise in ERP for OCD. The three patients who participated in the experimental program each experienced substantial improvements in their OCD symptoms and overall functioning. The present study suggests that brief, 5-day intensive treatment may be an effective means of delivering CBT for adolescents with OCD and may be of use to mental health practitioners who provide services to large catchments.

Relations among perceived parental rearing behaviors, attachment style, and worry in anxious children.

The present study extended the findings of Muris et al. [Muris, P., Meesters, C., Merckelbach, H., & Hulsenbeck, P. (2000). Worry in children is related to perceived parental rearing and attachment. Behavior Research and Therapy, 38, 487-497] regarding the relations between perceived parental rearing behaviors, self-reported attachment style, and worry in a community sample to a clinical sample of anxious children. Sixty-four children and adolescents, aged 7-18 years, with a primary anxiety disorder completed (a) the EMBU-C, a questionnaire measuring perceptions of parental rearing behaviors, (b) a single-item measure of attachment style, and (c) an index of worry severity. Findings revealed that child rated parental rearing behaviors, particularly parental rejection, were positively related to child worry. Self-reported attachment style was also related to worry, such that children who classified themselves as ambivalently attached reported higher levels of worry than did children who classified themselves as securely attached. Parenting style and attachment were found to make independent contributions to worry. The results are compared to those from Muris et al.'s community study, and implications for future research are discussed.

Parents' perceptions of pharmacological and cognitive-behavioral treatments for childhood anxiety disorders.

Cognitive-behavioral therapy (CBT) and pharmacotherapy are the most well-established treatments for childhood anxiety disorders. This study examined how parents (N=71) seeking treatment for their child's anxiety disorder perceive the acceptability, believability, and effectiveness of these treatments. While both treatments were perceived favorably, CBT was rated as more acceptable, believable, and effective in the short- and long-term. Children's treatment history influenced parents' perceptions of pharmacotherapy, with parents of children with no treatment history perceiving medication treatment as less acceptable and believable than parents of children with a history of medication alone or in combination with behavior therapy. No effect of treatment history was found for perceptions of CBT. Significant positive correlations emerged between parents' perceived acceptance and believability for pharmacotherapy and child age and level of dysfunction due to their child's anxiety, respectively. The level of the child's anxiety was not significantly correlated with parents' perceptions of either CBT or pharmacotherapy. Our results suggest that parents of anxious children prefer CBT to medication for the treatment of their child's anxiety disorder. Directions for future research are discussed.