Adherence and Opportunity Frequency as Predictors of Communication Outcomes from Pivotal Response Parent Training.

PURPOSE: Access to intervention is a barrier for children with autism. As parent-mediated interventions have emerged to address this need, understanding implementation components contributing to child gains is critically important. Existing literature documents relationships between parent treatment adherence and child progress; however, less is understood about components, such as frequency of learning opportunities, which could also affect child outcomes. METHODS: This study is a secondary analysis of data from a randomized controlled trial evaluating Pivotal Response Treatment group parent training (PRTG) compared to psychoeducation. Linear regression and mediational models were employed to identify potential predictors and mediators of outcome. RESULTS: PRTG produced large increases in adherence and learning opportunities. In general, greater frequency of learning opportunities and adherence predicted better child outcomes. The best-fitting cross-sectional mediational models indicated at least partial mediational effects, whereby increased learning opportunities mediated the relationship between greater adherence and improved child outcomes. CONCLUSIONS: This study provides preliminary evidence of how early gains in adherence may support parents to provide more frequent learning opportunities, which, in turn, yield positive effects on child social communication. Future large-scale research, with greater granularity of measurement, is needed to further understand the temporal relationships between these variables.

Understanding the Factors that Affect the Assessment of Student Performance in Pharmacy Practicums.

OBJECTIVE: The purpose of this study was to explore factors that may influence a practice educator's assessment of an entry-to-practice pharmacy student during inpatient direct patient care practicums. METHODS: This was a qualitative analysis of semi-structured interviews of existing practice educators from a variety of hospital practice environments. Participants were asked to assess a fictional case of a student's work, which provided a framework for a broader discussion of assessment practices. Interviews were transcribed and subjectively analyzed for themes and factors that each study participant considered for the case and in their past precepting experiences. RESULTS: A total of 13 participants consented and were interviewed. Identified themes included the quality of student work, key aspects of the student's performance, professionalism, and the complexity of the patient assigned to the student. There was significant heterogeneity in both the assessment of the fictional student and the factors that influenced each participant's assessment. It was clear that not all guidance provided by the academic institution is read or followed. Participants described challenges in applying the assessment rubric, including lack of time, training, resources, knowledge of the degree requirements/structure, and psychological factors inherent in high-stakes courses. CONCLUSION: Complex, varied, and often contradictory factors are used by experiential practice educators in their assessment of pharmacy students on practicum. These findings lead to inconsistency and heterogeneity when assessing a mock case and actual students. Educators should consider mandatory training to ensure those who assess students have an understanding of practicum course expectations and assessments.

Voice outcomes in high-grade Reinke's edema: Comparing microflap excision and microdebrider surgery.

Objectives: Patients presenting with hoarseness and diagnosed with high-grade Reinke's edema (RE) will often require surgical intervention for polypoid changes of the true vocal folds. We compared patient outcomes in patients who had microflap or microdebrider excision surgeries. Methods: Patients with the diagnosis of grade II or grade III RE based on laryngoscopy or videostroboscopy who failed conservative management underwent surgery using the standard excision practice of the primary surgeon. Voice outcomes were compared using VHI-30 (Voice Handicap Index), V-RQOL (Voice-Related Quality of Life), and MPT (maximum phonation time) preoperatively and at 1-month and 6-months postoperatively. Results: Of the 115 patients included, there were 46 RE grade II patients and 69 RE grade III patients with 52 patient undergoing microflap surgery and 63 patients undergoing microdebrider surgery. Both procedures resulted in significant improvement in VHI-30, V-RQOL, and MPT at 1-month and 6-months postoperatively. The microdebrider group had better 6-month VHI scores (40.84) than the microflap group (44.54) (CI -7.27 to -0.12). The microdebrider group also had better 6-month V-RQOL measures (62.56) than the microflap group (57.79) (CI 0.38-9.16). Conclusion: Both microflap excision and microdebrider excision for high-grade RE lesions resulted in significant improvement in VHI-30, V-RQOL, and MPT at 1-month and 6-months postoperatively with the microdebrider excision group scoring statistically significantly better at 6 months in comparison to the microflap group. Overall, the results support the use of both surgical modalities for treating high-grade RE patients. Level of evidence: 3.

Gut microbiota Turicibacter strains differentially modify bile acids and host lipids.

Bacteria from the Turicibacter genus are prominent members of the mammalian gut microbiota and correlate with alterations in dietary fat and body weight, but the specific connections between these symbionts and host physiology are poorly understood. To address this knowledge gap, we characterize a diverse set of mouse- and human-derived Turicibacter isolates, and find they group into clades that differ in their transformations of specific bile acids. We identify Turicibacter bile salt hydrolases that confer strain-specific differences in bile deconjugation. Using male and female gnotobiotic mice, we find colonization with individual Turicibacter strains leads to changes in host bile acid profiles, generally aligning with those produced in vitro. Further, colonizing mice with another bacterium exogenously expressing bile-modifying genes from Turicibacter strains decreases serum cholesterol, triglycerides, and adipose tissue mass. This identifies genes that enable Turicibacter strains to modify host bile acids and lipid metabolism, and positions Turicibacter bacteria as modulators of host fat biology.

Overview of the 2022 n2c2 shared task on contextualized medication event extraction in clinical notes.

BACKGROUND: An accurate medication history, foundational for providing quality medical care, requires understanding of medication change events documented in clinical notes. However, extracting medication changes without the necessary clinical context is insufficient for real-world applications. METHODS: To address this need, Track 1 of the 2022 National NLP Clinical Challenges focused on extracting the context for medication changes documented in clinical notes using the Contextualized Medication Event Dataset. Track 1 consisted of 3 subtasks: extracting medication mentions from clinical notes (NER), determining whether a medication change is being discussed (Event), and determining the action, negation, temporality, certainty, and actor for any change events (Context). Participants were allowed to participate in any one or more of the subtasks. RESULTS: A total of 32 teams with participants from 19 countries submitted a total of 211 systems across all subtasks. Most teams formulated NER as a token classification task and Event and Context as multi-class classification tasks, using transformer-based large language models. Overall, performance for NER was high across submitted systems. However, performance for Event and Context were much lower, often due to indirectly stated change events with no clear action verb, events requiring farther textual clues for understanding, and medication mentions with multiple change events. CONCLUSIONS: This shared task showed that while NLP research on medication extraction is relatively mature, understanding of contextual information surrounding medication events in clinical notes is still an open problem requiring further research to achieve the end goal of supporting real-world clinical applications.

Changes in basic psychological needs, passion, and well-being of first-semester graduate students.

OBJECTIVE: Examine changes in graduate student health and well-being in the first semester. PARTICIPANTS: Full-time, first-semester graduate students (N = 74) from a midsized midwestern university. METHOD: Graduate students were surveyed prior to starting their master's program and 10 weeks later. Passion for academics, basic psychological needs, physical and mental health symptoms, positive and negative affects, and quality of life were assessed. RESULTS: Need satisfaction, harmonious passion, and indicators of well-being decreased across the first semester, whereas need frustration and indicators of ill-being increased over the first semester. Obsessive passion, harmonious passion, need satisfaction, and need frustration were associated with students' well-being at the end of the semester, with need frustration being the most robust predictor. CONCLUSIONS: Although most graduate students reported good general health and moderately low mental health symptoms, findings suggest that a need supportive environment may contribute to better health and well-being.

Extracting medication changes in clinical narratives using pre-trained language models.

An accurate and detailed account of patient medications, including medication changes within the patient timeline, is essential for healthcare providers to provide appropriate patient care. Healthcare providers or the patients themselves may initiate changes to patient medication. Medication changes take many forms, including prescribed medication and associated dosage modification. These changes provide information about the overall health of the patient and the rationale that led to the current care. Future care can then build on the resulting state of the patient. This work explores the automatic extraction of medication change information from free-text clinical notes. The Contextual Medication Event Dataset (CMED) is a corpus of clinical notes with annotations that characterize medication changes through multiple change-related attributes, including the type of change (start, stop, increase, etc.), initiator of the change, temporality, change likelihood, and negation. Using CMED, we identify medication mentions in clinical text and propose three novel high-performing BERT-based systems that resolve the annotated medication change characteristics. We demonstrate that our proposed systems improve medication change classification performance over the initial work exploring CMED.

Postoperative Complications After Total Thyroidectomy for Patients With Graves' Disease.

OBJECTIVE: To identify the rates and types of postoperative complications in patients with and without Graves' disease undergoing total thyroidectomy using the National Surgical Quality Improvement Program (NSQIP) database. STUDY DESIGN: Retrospective cohort study. SETTING: All hospitals participating in NSQIP from 2007 to 2017. METHODS: Thyroidectomy data were abstracted from the NSQIP database from 2007 to 2017 using related Current Procedural Terminology codes. Exclusion criteria included diagnosis of malignancy and partial thyroidectomy. Patients with a diagnosis of Graves' disease were compared against the control group, which consisted of other nononcologic diagnoses. Statistical analysis including matched pair analysis was performed. RESULTS: Unmatched data demonstrated that patients with Graves' disease who underwent total thyroidectomy (n = 5495) had a higher rate of readmission (odds ratio [OR], 1.41; 95% CI, 1.16-1.73) and rate of reoperation (OR, 2.29; 95% CI, 1.88-2.79) in comparison to control patients (n = 24,213). They also had a higher rate of postoperative complication (OR, 1.54; 95% CI, 1.23-1.93) especially for wound-related outcomes (OR, 1.88; 95% CI, 1.32-2.69), readmission for postoperative hypocalcemia (OR, 2.12; 95% CI, 1.54-2.92), and reoperation for hematoma or hemorrhage (OR, 1.88; 95% CI, 1.32-2.69). A matched-pair analysis of the data also demonstrated similar significant results. CONCLUSION: Patients with Graves' disease undergoing total thyroidectomy are at higher risk of complications in comparison to those who do not have Graves' disease, likely due to sequelae of the disease. However, overall rates were low, suggesting that the procedure remains relatively low risk and should continue to be offered to select patients who meet criteria for surgery.

The Use of Race and Socioeconomic Status Variables in Published Otolaryngologic Research.

OBJECTIVE: To characterize the use of race and socioeconomic status (SES) variables in clinical otolarynogologic research. METHODS: Databases were queried for all articles published in 2016 issues of 5 major otolaryngologic journals. One thousand, one hundred and forty of 1593 articles abstracted met inclusion criteria for analysis. RESULTS: In total, 244 (21.4%) studies specified race as a variable. The subspecialty of Head and Neck cancer specified race at statistically higher rates compared to other subspecialties (P = .002). Two hundred nine (34.0%) domestic studies specified race compared to 35 (6.7%) international studies. Of the 244 studies that specified race, 79 (32.4%) defined race using racial and ethnic categories interchangeably. Two hundred twenty-four (91.8%) studies reported data by race, 145 (59.4%) analyzed the data, and 112 (45.9%) discussed race-based results.In total, 94 (8.2%) studies specified SES. All subspecialties specified SES at statistically similar rates. Seventy (11.4%) domestic studies specified SES compared to 24 (4.6%) international studies. Of the 94 studies that specified SES, 42 (44.7%) defined SES using insurance status, 35 (37.2%) used education, and 32 (34.0%) used income. Seventy-eight (83.0%) studies reported data by SES, 71 (75.5%) analyzed the data, and 68 (72.3%) discussed SES-based results. CONCLUSION: In clinical otolaryngologic research, the study of race and SES is limited. To improve quality of research and patient care for all patients, investigators should clearly justify their use of race and SES variables, carefully select their measures of race and SES (if the use of these variables is justified), and study race/SES-based data beyond just a superficial level.

Estimating the size of colorectal polyps endoscopically: random guess or systematic error?

BACKGROUND: Size of colorectal polyps reflects potential for malignancy and helps define advanced lesions. Studies measuring ability of endoscopists to estimate polyp size show significant variation. The aim of this study was to determine if there is a linear relationship between endoscopic and pathologic polyp size. METHODS: Data for adenomas removed completely by snare, in one piece, were retrieved from a prospectively recorded polyp database. Endoscopic estimate of maximum diameter was compared to that on the pathology report by linear regression analysis. RESULTS: There were 126 polyps in 126 patients, 85 men and 41 women. Mean age was 63.2 ± 12.9 years. Mean endoscopic polyp size was 12.2 ± 9.3 mm and mean pathology size was 9.3 ± 6.9 mm. Endoscopically, 16 polyps were ≤ 5 mm, 62 were from 6 to 10 mm, 21 were from 11 to 15 mm, and 27 were from 16 to 55 mm. Twenty-nine polyps were right sided, 86 were left and 11 were rectal. Regression of endoscopic size against pathology size yielded a significant r2 of 0.761. Using the regression formula of endoscopic size = 0.7 + 1.175× pathology size an endoscopic estimate of 10 mm (= advanced adenoma) means a pathologic size of 8 mm. For a pathologic size of 10 mm, an endoscopic estimate of 12 mm is needed. A large polyp is ≥20 mm; for this endoscopist a 20 mm polyp is really 16.4 mm. CONCLUSIONS: The relationship between endoscopic and directly measured size is linear over all polyp diameters, and likely represents a systematic error.

Capturing Individual-level Social Determinants from Clinical Text.

Knowledge of social determinants of health (SDOH), which refer to nonmedical factors influencing health outcomes, can help providers improve patient care. However, SDOH are often documented in unstructured notes, making them more inaccessible. Although previous works have attempted SDOH extraction from clinical notes, most efforts defined SDOH more narrowly and focused on the note's social history (SH) section, where social factors are traditionally documented. Here, we introduce a new SDOH dataset covering a broad range of SDOH content that is annotated over entire notes. We characterize what, where, and how SDOH information is documented in clinical text, present baseline systems using a token classification and generative approach, and investigate whether training only on the SH section can effectively extract SDOH from the entire note. The final dataset, consisting of 2,007 annotations covering 7 open-ended SDOH domains over 500 notes, will be publicly released to encourage further research in this area.

Inhibition of Melanoma Cell-Intrinsic Tim-3 Stimulates MAPK-Dependent Tumorigenesis.

T-cell immunoglobulin mucin family member 3 (Tim-3) is an immune checkpoint receptor that dampens effector functions and causes terminal exhaustion of cytotoxic T cells. Tim-3 inhibitors are under investigation in immuno-oncology (IO) trials, because blockade of T-cell-Tim-3 enhances antitumor immunity. Here, we identify an additional role for Tim-3 as a growth-suppressive receptor intrinsic to melanoma cells. Inhibition of melanoma cell-Tim-3 promoted tumor growth in both immunocompetent and immunocompromised mice, while melanoma-specific Tim-3 overexpression attenuated tumorigenesis. Ab-mediated Tim-3 blockade inhibited growth of immunogenic murine melanomas in T-cell-competent hosts, consistent with established antitumor effects of T-cell-Tim-3 inhibition. In contrast, Tim-3 Ab administration stimulated tumorigenesis of both highly and lesser immunogenic murine and human melanomas in T-cell-deficient mice, confirming growth-promoting effects of melanoma-Tim-3 antagonism. Melanoma-Tim-3 activation suppressed, while its blockade enhanced, phosphorylation of pro-proliferative downstream MAPK signaling mediators. Finally, pharmacologic MAPK inhibition reversed unwanted Tim-3 Ab-mediated tumorigenesis in T-cell-deficient mice and enhanced desired antitumor activity of Tim-3 interference in T-cell-competent hosts. These results identify melanoma-Tim-3 blockade as a mechanism that antagonizes T-cell-Tim-3-directed IO therapeutic efficacy. They further reveal MAPK targeting as a combination strategy for circumventing adverse consequences of unintended melanoma-Tim-3 inhibition. SIGNIFICANCE: Tim-3 is a growth-suppressive receptor intrinsic to melanoma cells, the blockade of which promotes MAPK-dependent tumorigenesis and thus counteracts antitumor activity of T-cell-directed Tim-3 inhibition.

Illustrated Protocols to Improve Undergraduate Student Research Independence.

One big challenge for undergraduate research students is gaining independence in the laboratory. In this curricular project, undergraduate students transformed research protocols developed for experienced scientists into protocols understandable to someone new to a laboratory. This process enabled themselves and other students to more quickly learn and master new techniques and advance to independent projects. Typically, students started with an original research protocol that assumed basic knowledge, such as instructions that came with a kit (i.e. plasmid purification kit instructions). Students created notes that explained the purpose of each step and reagent and provided example calculations. Then students illustrated the protocols with photos of materials needed, equipment used, action shots of difficult steps and screenshots of software programs. This approach has been used by students in laboratory courses and by new independent research students learning laboratory techniques. In the laboratory courses where students contributed to this project as part of a writing assignment, additional professional experience was gained by presenting a talk about their completed Illustrated Protocols to their classmates and by creating group posters that were presented at an undergraduate research symposium. After completion of this activity, undergraduate students gained confidence by applying their new knowledge to create user-friendly protocols. Students reported increased understanding of what is happening in each step, while instructors reported increased student independence and confidence that the protocol was being applied correctly and consistently. Thus, designing Illustrated Protocols enhanced learning and independence for the students creating the protocol and provided valuable help for future students.

Restorative proctocolectomy with ileal pouch-anal anastomosis in elderly patients - is advanced age a contraindication?

AIM: We aimed to determine pouch function and retention rate for restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) in elderly patients. METHODS: We identified patients over 50 years old subjected to IPAA for confirmed pathological UC from 1980 until 2016. Patients were grouped according to age: 50-59, 60-69 and 70+ years. Short and long-term outcomes and quality of life (QOL) were compared among the groups. RESULTS: Six hundred and one patients were identified (399 (66.4%) between 50-59 181 (30.1%) between 60-69, and 21 (3.5%) over 70 years of age). More males were in the 70+ arm, and more two-stage procedures were performed in this group. Wound infection increased with age (P = 0.023). There was a trend of more fistula and pouchitis in the 70+ patients (P = 0.052 and P = 0.055, respectively). Pouch failure rate increased with age, and it was statistically significant in the 70+ cohort (P = 0.015). Multivariate stepwise logistic regression showed that pelvic sepsis (HR 4.8 (95% CI 1.5-15.4), P = 0.009), fistula (HR 6.0 (95% CI 1.7-21.5), and mucosectomy with handsewn anastomosis (HR 4.5 (95% CI 1.4-14.7)), were independently associated with pouch failure. No difference was observed in the QOL among the groups, but pouch function was better for patients younger than 60 years. CONCLUSION: In elderly patients with UC, IPAA may be offered with reasonable functional outcomes, and ileal pouch retention rates, as an alternative to the permanent stoma. Stapled anastomosis increases the chance of pouch retention and should be recommended as long as the distal rectum does not carry dysplasia.

Antimicrobial use in Canadian acute-care hospitals: Findings from three national point-prevalence surveys between 2002 and 2017.

OBJECTIVES: The Canadian Nosocomial Infection Surveillance Program conducted point-prevalence surveys in acute-care hospitals in 2002, 2009, and 2017 to identify trends in antimicrobial use. METHODS: Eligible inpatients were identified from a 24-hour period in February of each survey year. Patients were eligible (1) if they were admitted for ≥48 hours or (2) if they had been admitted to the hospital within a month. Chart reviews were conducted. We calculated the prevalence of antimicrobial use as follows: patients receiving ≥1 antimicrobial during survey period per number of patients surveyed × 100%. RESULTS: In each survey, 28-47 hospitals participated. In 2002, 2,460 (36.5%; 95% CI, 35.3%-37.6%) of 6,747 surveyed patients received ≥1 antimicrobial. In 2009, 3,566 (40.1%, 95% CI, 39.0%-41.1%) of 8,902 patients received ≥1 antimicrobial. In 2017, 3,936 (39.6%, 95% CI, 38.7%-40.6%) of 9,929 patients received ≥1 antimicrobial. Among patients who received ≥1 antimicrobial, penicillin use increased 36.8% between 2002 and 2017, and third-generation cephalosporin use increased from 13.9% to 18.1% (P < .0001). Between 2002 and 2017, fluoroquinolone use decreased from 25.7% to 16.3% (P < .0001) and clindamycin use decreased from 25.7% to 16.3% (P < .0001) among patients who received ≥1 antimicrobial. Aminoglycoside use decreased from 8.8% to 2.4% (P < .0001) and metronidazole use decreased from 18.1% to 9.4% (P < .0001). Carbapenem use increased from 3.9% in 2002 to 6.1% in 2009 (P < .0001) and increased by 4.8% between 2009 and 2017 (P = .60). CONCLUSIONS: The prevalence of antimicrobial use increased between 2002 and 2009 and then stabilized between 2009 and 2017. These data provide important information for antimicrobial stewardship programs.

Hierarchy-aware Adverse Reaction Embeddings for Signal Detection.

Post-market drug surveillance monitors new and evolving treatments for their effectiveness and safety in real-world conditions. A large amount of drug safety surveillance data is captured by spontaneous reporting systems such as the FAERS. Developing automated methods to identify actionable safety signals from these databases is an active area of research. In this paper, we propose two novel network representation learning methods (HARE and T-HARE) for signal detection that jointly utilize association information between drugs and medical outcomes from the FAERS and ancestral information in medical ontologies. We evaluate these methods using two publicly available reference datasets, EU-ADR and OMOP corpus. Experimental results showed that the proposed methods significantly outper-formed standard methodologies based on disproportionality metrics and the existing state-of-the-art aer2vec method with statistically significant improvements on both EU-ADR and OMOP datasets. Through quantitative and qualitative analysis, we demonstrate the potential of the proposed methods for effective signal detection.

Reducing Physicians' Cognitive Load During Chart Review: A Problem-Oriented Summary of the Patient Electronic Record.

Overabundance of information within electronic health records (EHRs) has resulted in a need for automated systems to mitigate the cognitive burden on physicians utilizing today's EHR systems. We present ProSPER, a Problem-oriented Summary of the Patient Electronic Record that displays a patient summary centered around an auto-generated problem list and disease-specific views for chronic conditions. ProSPER was developed using 1,500 longitudinal patient records from two large multi-specialty medical groups in the United States, and leverages multiple natural language processing (NLP) components targeting various fundamental (e.g. syntactic analysis), clinical (e.g. adverse drug event extraction) and summarizing (e.g. problem list generation) tasks. We report evaluation results for each component and discuss how specific components address existing physician challenges in reviewing EHR data. This work demonstrates the need to leverage holistic information in EHRs to build a comprehensive summarization application, and the potential for NLP-based applications to support physicians and improve clinical care.

Toward Understanding Clinical Context of Medication Change Events in Clinical Narratives.

Understanding medication events in clinical narratives is essential to achieving a complete picture of a patient's medication history. While prior research has explored identification of medication changes in clinical notes, due to the longitudinal and narrative nature of clinical documentation, extraction of medication change alone without the necessary clinical context is insufficient for use in real-world applications, such as medication timeline generation and medication reconciliation. Here, we present a framework to capture multi-dimensional context of medication changes documented in clinical notes. We define specific contextual aspects pertinent to medication change events (i.e. Action, Negation, Temporality, Certainty, and Actor), describe the annotation process and challenges encountered while creating the dataset, and explore models based on state-of-the-art transformers to automate the task. The resulting dataset, Contextualized Medication Event Dataset (CMED), consisting of 9,013 medications annotated over 500 clinical notes, will be released to the community as a shared task in 2021-2022.