Quantitative Biomarkers, Genomic Assays, and Demographics Associated with Breast-Conserving Surgery Following Neoadjuvant Therapy in Early-Stage, Hormone Receptor-Positive, HER-Negative Breast Cancer.

BACKGROUND: Given increased neoadjuvant therapy use in early-stage, hormone receptor (HR)-positive/HER2-negative breast cancer, we sought to quantify likelihood of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) or endocrine therapy (NET) as a function of ER%/PR%/Ki-67%, 21-gene recurrence scores (RS), or 70-gene risk groups. METHODS: We analyzed the 2010-2020 National Cancer Database. Surgery was categorized as "mastectomy/BCS." Logistic regression was performed. Adjusted odds ratios (AOR) were per 10-unit increase in ER%/PR%/Ki-67%. RESULTS: Overall, 42.3% underwent BCS after NACT, whereas 64.0% did after NET. Increasing ER% (AOR = 0.96, 95% confidence interval [CI] 0.94-0.97) or PR% (AOR=0.98, 95% CI 0.96-0.99) was associated with lower odds of BCS after NACT. Increasing Ki-67% was associated with greater odds of BCS (AOR = 1.07, 95% CI 1.04-1.10). Breast-conserving surgery rates increased by ~20 percentage points, with Ki-67% ≥15 or RS >20. Patients with a low (43.0%, AOR = 0.50, 95% CI 0.29-0.88) or intermediate (46.4%, AOR = 0.58, 95% CI 0.41-0.81) RS were less likely than patients with a high RS (65.0%) to undergo BCS after NACT. Increasing ER% was associated with higher odds of BCS after NET (AOR = 1.09, 95% CI 1.01-1.17). Breast-conserving surgery rates increased by ~20 percentage points between ER <50% and >80%. In both cohorts, the odds of BCS were similar between 70-gene low-risk and high-risk groups. Asian or uninsured patients had lower odds of BCS. CONCLUSIONS: Neoadjuvant chemotherapy is unlikely to downstage tumors with a low-intermediate RS, higher ER%/PR%, or lower Ki-67%. Breast-conserving surgery after NET was most dependent on ER%. Findings could facilitate treatment decision-making based on tumor biology and racial/socioeconomic disparities and improve patient counseling on the likelihood of successful BCS.

A Multi-Institutional Natural Language Processing Pipeline to Extract Performance Status From Electronic Health Records.

PURPOSE: Performance status (PS), an essential indicator of patients' functional abilities, is often documented in clinical notes of patients with cancer. The use of natural language processing (NLP) in extracting PS from electronic medical records (EMRs) has shown promise in enhancing clinical decision-making, patient monitoring, and research studies. We designed and validated a multi-institute NLP pipeline to automatically extract performance status from free-text patient notes. PATIENTS AND METHODS: We collected data from 19,481 patients in Harris Health System (HHS) and 333,862 patients from veteran affair's corporate data warehouse (VA-CDW) and randomly selected 400 patients from each data source to train and validate (50%) and test (50%) the proposed pipeline. We designed an NLP pipeline using an expert-derived rule-based approach in conjunction with extensive post-processing to solidify its proficiency. To demonstrate the pipeline's application, we tested the compliance of PS documentation suggested by the American Society of Clinical Oncology (ASCO) Quality Metric and investigated the potential disparity in PS reporting for stage IV non-small cell lung cancer (NSCLC). We used a logistic regression test, considering patients in terms of race/ethnicity, conversing language, marital status, and gender. RESULTS: The test results on the HHS cohort showed 92% accuracy, and on VA data demonstrated 98.5% accuracy. For stage IV NSCLC patients, the proposed pipeline achieved an accuracy of 98.5%. Furthermore, our analysis revealed a documentation rate of over 85% for PS among NSCLC patients, surpassing the ASCO Quality Metrics. No disparities were observed in the documentation of PS. CONCLUSION: Our proposed NLP pipeline shows promising results in extracting PS from free-text notes from various health institutions. It may be used in longitudinal cancer data registries.

Opioid Prescribing for Acute Pain Management in Children and Adolescents in Outpatient Settings: Clinical Practice Guideline.

This is the first clinical practice guideline (CPG) from the American Academy of Pediatrics outlining evidence-based approaches to safely prescribing opioids for acute pain in outpatient settings. The central goal is to aid clinicians in understanding when opioids may be indicated to treat acute pain in children and adolescents and how to minimize risks (including opioid use disorder, poisoning, and overdose). The document also seeks to alleviate disparate pain treatment of Black, Hispanic, and American Indian/Alaska Native children and adolescents, who receive pain management that is less adequate and less timely than that provided to white individuals. There may also be disparities in pain treatment based on language, socioeconomic status, geographic location, and other factors, which are discussed. The document recommends that clinicians treat acute pain using a multimodal approach that includes the appropriate use of nonpharmacologic therapies, nonopioid medications, and, when needed, opioid medications. Opioids should not be prescribed as monotherapy for children or adolescents who have acute pain. When using opioids for acute pain management, clinicians should prescribe immediate-release opioid formulations, start with the lowest age- and weight-appropriate doses, and provide an initial supply of 5 or fewer days, unless the pain is related to trauma or surgery with expected duration of pain longer than 5 days. Clinicians should not prescribe codeine or tramadol for patients younger than 12 years; adolescents 12 to 18 years of age who have obesity, obstructive sleep apnea, or severe lung disease; to treat postsurgical pain after tonsillectomy or adenoidectomy in patients younger than 18 years; or for any breastfeeding patient. The CPG recommends providing opioids when appropriate for treating acutely worsened pain in children and adolescents who have a history of chronic pain; clinicians should partner with other opioid-prescribing clinicians involved in the patient's care and/or a specialist in chronic pain or palliative care to determine an appropriate treatment plan. Caution should be used when treating acute pain in those who are taking sedating medications. The CPG describes potential harms of discontinuing or rapidly tapering opioids in individuals who have been on stable, long-term opioids to treat chronic pain. The guideline also recommends providing naloxone and information on naloxone, safe storage and disposal of opioids, and direct observation of medication administration. Clinicians are encouraged to help caregivers develop a plan for safe disposal. The CPG contains 12 key action statements based on evidence from randomized controlled trials, high-quality observational studies, and, when studies are lacking or could not feasibly or ethically be conducted, from expert opinion. Each key action statement includes a level of evidence, the benefit-harm relationship, and the strength of recommendation.

Evidence for the Use of Opioid Medication for Pediatric Acute Pain in the Outpatient Setting: Technical Report.

This technical report summarizes the results of a systematic review designed to support the American Academy of Pediatrics' "Clinical Practice Guideline: Opioid Prescribing for Acute Pain Management in Children and Adolescents in Outpatient Settings." PubMed and Excerpta Medica Database were searched from 2010 to 2023 to identify randomized clinical trials and systematic reviews related to outpatient opioid prescribing to children. Overall, 11 randomized controlled trials were included. Although data were limited, no evidence was found that pain control by opioids is superior to nonopioid alternatives. Further, opioids are often associated with adverse events. The review also suggests that family and patient education and providing disposal methods may decrease risks associated with opioid prescription. Future studies can build on this foundation of evidence to support the appropriate use of opioids for acute pain in children treated in the outpatient setting.

Vaccine patterns among older adults with Guillain-Barré syndrome and matched comparators, 2006-2019.

BACKGROUND: Some vaccines have a small risk of triggering Guillain-Barré syndrome (GBS), an autoimmune disorder where nerve damage leads to paralysis. There is a CDC precaution for patients whose GBS was associated with an influenza or tetanus toxoid-containing vaccine (GBS occurring within 42 days following vaccination). METHODS: We described vaccine patterns before and after a GBS diagnosis with a matched cohort design in a 20% random sample of fee-for-service Medicare enrollees. We defined the index date as an ICD-9-CM or ICD-10-CM GBS diagnosis code in the primary position of an inpatient claim. We matched each GBS patient to five non-GBS comparators on sex, exact age, racial and ethnic category, state of residence and the month of preventive health visits during baseline; used weighting to balance covariates; and measured frequency of vaccines received per 100 people during year before and after the index date using the weighted mean cumulative count (wMCC). RESULTS: We identified 1567 patients with a GBS diagnosis with at least 1 year of prior continuous enrollment in Medicare A and B that matched to five comparators each. The wMCCs in the 1 year before the index date were similar for both groups, with a wMCC of 74 vaccines/100 people in the GBS group (95% CI 71, 77). Within 1 year after the index date, patients with GBS had received 26 vaccines/100 people (95% CI 23, 28), which was 41 fewer vaccines than matched non-GBS comparators (95% CI -44, -38). Among GBS patients, 11% were diagnosed with GBS within 42 days after a vaccine. CONCLUSIONS: GBS diagnosis has a strong impact on reducing subsequent vaccination even though there is no warning or precaution about future vaccines for most patients diagnosed with GBS. These data suggest discordance between clinical practice and current vaccine recommendations.

Health Care Team Interventions to Reduce Distress Behaviors in Older Adults: A Systematic Review.

OBJECTIVES: This review examines health care team-focused interventions on managing persistent or recurrent distress behaviors among older adults in long-term residential or inpatient health care settings. METHODS: We searched interventions addressing health care worker (HCW) knowledge and skills related to distress behavior management using Ovid MEDLINE, Elsevier Embase, and Ovid PsycINFO from December 2002 through December 2022. RESULTS: We screened 6,582 articles; 29 randomized trials met inclusion criteria. Three studies on patient-facing HCW interactions (e.g. medication management, diagnosing distress) showed mixed results on agitation; one study found no effect on quality of life. Six HCW-focused studies suggested short-term reduction in distress behaviors. Quality-of-life improvement or decreased antipsychotic use was not evidenced. Among 17 interventions combining HCW-focused and patient-facing activities, 0 showed significant distress reduction, 8 showed significant antipsychotic reduction (OR = 0.79, 95%CI [0.69, 0.91]) and 9 showed quality of life improvements (SMD = 0.71, 95%CI [0.39, 1.04]). One study evaluating HCW, patient-, and environmental-focused intervention activities showed short-term improvement in agitation. CONCLUSIONS AND CLINICAL IMPLICATIONS: Novel health care models combining HCW training and patient management improve patient quality of life, reduce antipsychotic use, and may reduce distress behaviors. Evaluation of intervention's effects on staff burnout and utilization is needed.

The Role of Intraoperative Radiotherapy Treatment of Locally Advanced Rectal Cancer.

Intraoperative radiation therapy (IORT) has been used in the treatment of locally advanced and recurrent rectal cancers for the last several decades. Given the heterogeneity of patients treated and different indications for use and dosing at different institutions, it has been difficult to discern if IORT adds any appreciable benefit to standard of care therapies. Herein, the rationale for IORT in rectal cancer is discussed along with the most modern and best available data in 2023. IORT is likely indicated in patients with locally advanced and locally recurrent rectal cancer with threatened margins (R0 or R1 resection) to help improve local control. High-quality imaging and multidisciplinary discussion are necessary to ensure optimal patient selection. Appropriate counseling of the patient and excellent team communication are of the utmost importance given the challenging nature of these cases and the prognostic implications of R1 and R2 resections in this patient population.

A Principled Approach to Characterize and Analyze Partially Observed Confounder Data from Electronic Health Records.

Objective: Partially observed confounder data pose challenges to the statistical analysis of electronic health records (EHR) and systematic assessments of potentially underlying missingness mechanisms are lacking. We aimed to provide a principled approach to empirically characterize missing data processes and investigate performance of analytic methods. Methods: Three empirical sub-cohorts of diabetic SGLT2 or DPP4-inhibitor initiators with complete information on HbA1c, BMI and smoking as confounders of interest (COI) formed the basis of data simulation under a plasmode framework. A true null treatment effect, including the COI in the outcome generation model, and four missingness mechanisms for the COI were simulated: completely at random (MCAR), at random (MAR), and two not at random (MNAR) mechanisms, where missingness was dependent on an unmeasured confounder and on the value of the COI itself. We evaluated the ability of three groups of diagnostics to differentiate between mechanisms: 1)-differences in characteristics between patients with or without the observed COI (using averaged standardized mean differences [ASMD]), 2)-predictive ability of the missingness indicator based on observed covariates, and 3)-association of the missingness indicator with the outcome. We then compared analytic methods including "complete case", inverse probability weighting, single and multiple imputation in their ability to recover true treatment effects. Results: The diagnostics successfully identified characteristic patterns of simulated missingness mechanisms. For MAR, but not MCAR, the patient characteristics showed substantial differences (median ASMD 0.20 vs 0.05) and consequently, discrimination of the prediction models for missingness was also higher (0.59 vs 0.50). For MNAR, but not MAR or MCAR, missingness was significantly associated with the outcome even in models adjusting for other observed covariates. Comparing analytic methods, multiple imputation using a random forest algorithm resulted in the lowest root-mean-squared-error. Conclusion: Principled diagnostics provided reliable insights into missingness mechanisms. When assumptions allow, multiple imputation with nonparametric models could help reduce bias.

Evolving Standards of Care in the Management of Localized Colorectal Cancer.

The treatment of patients with localized rectal cancer is complex and requires input from a multidisciplinary team. Baseline local staging and mismatch repair protein testing are vital to develop individualized treatment plans. There are multiple options in terms of treatment modalities and sequencing, including transanal excision, short-course radiation, long-course chemoradiation, chemotherapy doublet or triplet, nonoperative management, and immune checkpoint blockade for patients with mismatch repair deficient tumors. While localized colon cancer is typically treated with surgical resection and consideration of adjuvant chemotherapy, emerging data suggest that neoadjuvant chemotherapy may be beneficial in patients with higher-risk disease. Quality-of-life considerations are imperative to prevent potential chronic effects on psychosocial health, neuropathy, fertility, and bowel, bladder, and sexual function. The omission of radiation or surgery can mitigate these toxicities without diminishing oncologic outcomes. The optimal treatment plan and sequence is not a one-size-fits-all approach but rather should be personalized to the patient's disease burden, tumor location, comorbidities, and preferences.

Long-term fertilization and manuring effects on the nexus between sulphur distribution and SOC in an Inceptisol over five decades under a finger millet-maize cropping system.

Our investigation revealed that alterations in sulphur (S) pools are predominantly governed by soil organic carbon (SOC), soil nitrogen (N), microbial biomass, and soil enzyme activities in sandy clay loam (Vertic Ustropept) soil. We employed ten sets of nutrient management techniques, ranging from suboptimal (50% RDF) to super-optimal doses (150% RDF), including NPK + Zn, NP, N alone, S-free NPK fertilizers, NPK + FYM, and control treatments, to examine the interrelation of S with SOC characteristics. Fourier-transform infrared (FT-IR) spectroscopy was utilized to analyze the functional groups present in SOC characterization across four treatments: 100% NPK, 150% NPK, NPK + FYM, and absolute control plots. Principal component analysis (PCA) was then applied to assess 29 minimal datasets, aiming to pinpoint specific soil characteristics influencing S transformation. In an Inceptisol, the application of fertilizers (100% RDF) in conjunction with 10 t ha-1 of FYM resulted in an increase of S pools from the surface to the subsurface stratum (OS > HSS > SO42--S > WSS), along with an increase in soil N and SOC. FT-IR spectroscopy identified cellulose and thiocyanate functional groups in all four plots, with a pronounced presence of carbohydrate-protein polyphenol, sulfoxide (S=O), and nitrate groups specifically observed in the INM plot. The PCA findings indicated that the primary factors influencing soil quality and crop productivity (r2 of 0.69) are SOC, SMBC, SMBN, SMBS, and the enzyme activity of URE, DHA, and AS. According to the study, the combined application of fertilizer and FYM (10 t ha-1) together exert a positive impact on sulphur transformation, SOC accumulation, and maize yield in sandy clay loam soil.

smdi: an R package to perform structural missing data investigations on partially observed confounders in real-world evidence studies.

Objectives: Partially observed confounder data pose a major challenge in statistical analyses aimed to inform causal inference using electronic health records (EHRs). While analytic approaches such as imputation are available, assumptions on underlying missingness patterns and mechanisms must be verified. We aimed to develop a toolkit to streamline missing data diagnostics to guide choice of analytic approaches based on meeting necessary assumptions. Materials and methods: We developed the smdi (structural missing data investigations) R package based on results of a previous simulation study which considered structural assumptions of common missing data mechanisms in EHR. Results: smdi enables users to run principled missing data investigations on partially observed confounders and implement functions to visualize, describe, and infer potential missingness patterns and mechanisms based on observed data. Conclusions: The smdi R package is freely available on CRAN and can provide valuable insights into underlying missingness patterns and mechanisms and thereby help improve the robustness of real-world evidence studies.

Genomic classifiers and prognosis of localized prostate cancer: a systematic review.

BACKGROUND: Refinement of the risk classification for localized prostate cancer is warranted to aid in clinical decision making. A systematic analysis was undertaken to evaluate the prognostic ability of three genomic classifiers, Decipher, GPS, and Prolaris, for biochemical recurrence, development of metastases and prostate cancer-specific mortality in patients with localized prostate cancer. METHODS: Data sources: MEDLINE, Embase, and Web of Science were queried for reports published from January 2010 to April 2022. STUDY SELECTION: prospective or retrospective studies reporting prognosis for patients with localized prostate cancer. DATA EXTRACTION: relevant data were extracted into a customized database by one researcher with a second overreading. Risk of bias was assessed using a validated tool for prognostic studies, Quality in Prognosis Studies (QUIPS). Disagreements were resolved by consensus or by input from a third reviewer. We assessed the certainty of evidence by GRADE incorporating adaptation for prognostic studies. RESULTS: Data synthesis: a total of 39 studies (37 retrospective) involving over 10,000 patients were identified. Twenty-two assessed Decipher, 5 GPS, and 14 Prolaris. Thirty-four studies included patients who underwent prostatectomy. Based on very low to low certainty of evidence, each of the three genomic classifiers modestly improved upon the prognostic ability for biochemical recurrence, development of metastases, and prostate cancer-specific mortality compared to standard clinical risk-classification schemes. LIMITATIONS: downgrading of confidence in the evidence stemmed largely from bias due to the retrospective nature of the studies, heterogeneity in treatment received, and era in which patients were treated (i.e., prior to the 2000s). CONCLUSIONS: Genomic classifiers provide a small but consistent improvement upon the prognostic ability of clinical classification schemes, which may be helpful when treatment decisions are uncertain. However, evidence from current management-era data and of the predictive ability of these tests is needed.

Variations in antibiotic prescribing among children enrolled in North Carolina Medicaid, 2013-2019.

PURPOSE: The majority of pediatric antibiotic prescribing occurs in the outpatient setting and inappropriate use contributes to antimicrobial resistance. There are regional variations in outpatient antibiotic use with the highest rates occurring in the Southern states, including in Appalachia. The purpose of this study was to describe the rates and risk factors for inappropriate antibiotic prescription among pediatric patients enrolled in North Carolina (NC) Medicaid. METHODS: We used Medicaid prescription claims data from 2013 to 2019 to describe patterns of pediatric antibiotic prescription in NC. We assessed patient and provider factors to identify variations in prescribing. FINDINGS: Children who were less than 2 years of age, non-Hispanic White, and living in a rural area had the highest overall rates of antibiotic prescription. Compared to pediatricians, the risk of inappropriate antibiotic prescription was highest among other specialists and general practioners and lowest among nurse practitioners. Rural areas of NC had the highest rates of inappropriate antibiotic prescribing, and the risk for non-Hispanic Black children compared to children of other races/ethnicities was compounded by rurality. CONCLUSIONS: Prescribing practices in NC differ compared to neighboring states with a lower overall risk of inappropriate prescription in Appalachian regions; however, disparities by race and rurality exist. Outpatient stewardship efforts in NC should focus on ensuring health equity by appreciating racial and geographic variations in prescribing patterns and providing education to all health care providers.

Underimmunization of very low birth weight infants at discharge from the neonatal intensive care unit.

OBJECTIVE: To quantify immunization status among premature infants discharged from neonatal intensive care units (NICUs), and identify risk factors for underimmunization. STUDY DESIGN: We performed a cohort study of infants <33 weeks gestation discharged home between 2011 and 2020 from 241 NICUs. Using multivariable logistic regression, we examined the association between risk factors and underimmunization at discharge, defined as <1 dose of 5 vaccine types when discharged at 60-119 days of age and <2 doses when discharged at 120-179 days of age. RESULTS: Of 30,766 infants discharged at 60-119 days of age, 14% were underimmunized. Among 4358 infants discharged at 120-179 days of age, 53% were underimmunized. For infants discharged at 60-119 days of age, ventilator support within 30 days of discharge was associated with underimmunization. Having a surgical procedure was associated with underimmunization in both groups. CONCLUSION: A large proportion of premature infants discharged from the NICU are underimmunized.

Overview of global real-world data sources for pediatric pharmacoepidemiologic research.

PURPOSE: Given limited information available on real-world data (RWD) sources with pediatric populations, this study describes features of globally available RWD sources for pediatric pharmacoepidemiologic research. METHODS: An online questionnaire about pediatric RWD sources and their attributes and capabilities was completed by members and affiliates of the International Society for Pharmacoepidemiology and representatives of nominated databases. All responses were verified by database representatives and summarized. RESULTS: Of 93 RWD sources identified, 55 unique pediatric RWD sources were verified, including data from Europe (47%), United States (38%), multiregion (7%), Asia-Pacific (5%), and South America (2%). Most databases had nationwide coverage (82%), contained electronic health/medical records (47%) and/or administrative claims data (42%) and were linkable to other databases (65%). Most (71%) had limited outside access (e.g., by approval or through local collaborators); only 10 (18%) databases were publicly available. Six databases (11%) reported having >20 million pediatric observations. Most (91%) included children of all ages (birth until 18th birthday) and contained outpatient medication data (93%), while half (49%) contained inpatient medication data. Many databases captured vaccine information for children (71%), and one-third had regularly updated data on pediatric height (31%) and weight (33%). Other pediatric data attributes captured include diagnoses and comorbidities (89%), lab results (58%), vital signs (55%), devices (55%), imaging results (42%), narrative patient histories (35%), and genetic/biomarker data (22%). CONCLUSIONS: This study provides an overview with key details about diverse databases that allow researchers to identify fit-for-purpose RWD sources suitable for pediatric pharmacoepidemiologic research.

Lithium-associated primary hyperparathyroidism:: An evaluation of screening and referral patterns in a southeastern veteran population.

BACKGROUND: Long-term lithium therapy has a well-established but under-recognized association with primary hyperparathyroidism. Rates of hypercalcemia, screening for primary hyperparathyroidism, and referral for parathyroidectomy were evaluated among United States veterans on long-term lithium therapy. METHODS: Patients undergoing chronic long-term lithium therapy (>12 months) were identified from 1999 to 2022. Demographics, long-term lithium therapy duration, post-treatment calcium, parathyroid hormone, creatinine, and vitamin D levels were abstracted. Rates of screening for hypercalcemia (calcium ≥10.2 mg/dL), primary hyperparathyroidism (parathyroid hormone ≥30 pg/mL in the setting of hypercalcemia), referral for parathyroidectomy, and outcomes were evaluated. RESULTS: A total of 1,356 patients underwent long-term lithium therapy, 514 of whom received chronic long-term lithium therapy. Baseline characteristics of patients with and without post-treatment hypercalcemia were compared. Of 148 patients with post-treatment hypercalcemia, 112 (74.7%) underwent no further evaluation for primary hyperparathyroidism, while 36 (25.3%) patients had a parathyroid hormone level recorded. Although 33 (91.7%) hypercalcemic patients screened positive for primary hyperparathyroidism, only 5 (13%) were referred for parathyroidectomy. Of the 4 patients who underwent parathyroidectomy, mean calcium was 11.2 mg/dL (range 11.1-11.4), and mean parathyroid hormone was 272 pg/mL (range 108-622). Three patients were localized on preoperative imaging, 2 of whom underwent unilateral exploration with cure, with 1 experiencing recurrence at 31 months. The remaining patient who localized preoperatively underwent bilateral exploration and had 2 ipsilateral glands resected and persistence. The patient who did not localize preoperatively underwent bilateral exploration with 3 gland resection and cure. CONCLUSIONS: Screening for primary hyperparathyroidism and referral for parathyroidectomy are underutilized in United States veterans undergoing chronic long-term lithium therapy. Institutional protocols to standardize screening, surveillance, and referrals to endocrinology/endocrine surgery could benefit this population at increased risk for primary hyperparathyroidism.

Optimizing data integration in trials that use EHR data: lessons learned from a multi-center randomized clinical trial.

BACKGROUND: Despite great promise, trials that ascertain patient clinical data from electronic health records (EHR), referred to here as "EHR-sourced" trials, are limited by uncertainty about how existing trial sites and infrastructure can be best used to operationalize study goals. Evidence is needed to support the practical use of EHRs in contemporary clinical trial settings. MAIN TEXT: We describe a demonstration project that used EHR data to complement data collected for a contemporary multi-center pharmaceutical industry outcomes trial, and how a central coordinating center supported participating sites through the technical, governance, and operational aspects of this type of activity. We discuss operational considerations related to site selection, data extraction, site performance, and data transfer and quality review, and we outline challenges and lessons learned. We surveyed potential sites and used their responses to assess feasibility, determine the potential capabilities of sites and choose an appropriate data extraction strategy. We designed a flexible, multimodal approach for data extraction, enabling each site to either leverage an existing data source, create a new research datamart, or send all data to the central coordinating center to produce the requisite data elements. We evaluated site performance, as reflected by the speed of contracting and IRB approval, total patients enrolled, enrollment yield, data quality, and compared performance by data collection strategy. CONCLUSION: While broadening the type of sites able to participate in EHR-sourced trials may lead to greater generalizability and improved enrollment, sites with fewer technical resources may require additional support to participate. Central coordinating center support is essential to facilitate the execution of operational processes. Future work should focus on sharing lessons learned and creating reusable tools to facilitate participation of heterogeneous trial sites.

Vaccine patterns among patients diagnosed with Guillain-Barré Syndrome and matched counterparts in a Medicare supplemental population, 2000-2020.

Some vaccines have a small risk of Guillain-Barré Syndrome (GBS), a rare autoimmune disorder characterized by paralysis if untreated. The CDC's Advisory Committee on Immunization Practices (ACIP) guidelines do not consider GBS a precaution for future vaccines unless GBS developed within six weeks after a tetanus-toxoid-containing vaccine or influenza vaccine. Our goal was to describe vaccine patterns before and after GBS diagnosis. We matched each of 709 patients diagnosed with GBS from 2002 to 2020 with Medicare supplemental insurance to 10 counterparts without GBS (1:10) on age and sex. Propensity score-based weighting balanced covariates between groups, and we estimated weighted mean cumulative counts (wMCC) of vaccines/person before and after GBS diagnosis. Among patients with GBS, 7% were diagnosed within 42 days after a vaccine. Prior to GBS diagnosis, the wMCC of vaccines per person was similar between GBS cases and matched counterparts, but after two years of follow-up, GBS patients received 21 fewer vaccines/100 people than counterparts (wMCC difference -0.21 vaccines/person, 95% CI -0.24 to -0.18); GBS patients received 16 vaccines/100 people while matched counterparts received 36/100. Vaccine use was reduced following GBS diagnosis despite no ACIP precaution for most (93%) patients in this study. The observed drop in vaccines after GBS diagnosis indicates a disconnect between clinical practice and current recommendations.

Non-overdose acute care hospitalizations for opioid use disorder among commercially-insured adults: a retrospective cohort study.

BACKGROUND: Acute care inpatient admissions outside of psychiatric facilities have been increasingly identified as a critical touchpoint for opioid use disorder (OUD) treatment. We sought to describe non-opioid overdose hospitalizations with documented OUD and examine receipt of post-discharge outpatient buprenorphine. METHODS: We examined acute care hospitalizations with an OUD diagnosis in any position within US commercially-insured adults age 18-64 years (IBM MarketScan claims, 2013-2017), excluding opioid overdose diagnoses. We included individuals with ≥ 6 months of continuous enrollment prior to the index hospitalization and ≥ 10 days following discharge. We described demographic and hospitalization characteristics, including outpatient buprenorphine receipt within 10 days of discharge. RESULTS: Most (87%) hospitalizations with documented OUD did not include opioid overdose. Of 56,717 hospitalizations (49,959 individuals), 56.8% had a primary diagnosis other than OUD, 37.0% had documentation of an alcohol-related diagnosis code, and 5.8% end in a self-directed discharge. Where opioid use disorder was not the primary diagnosis, 36.5% were due to other substance use disorders, and 23.1% were due to psychiatric disorders. Of all non-overdose hospitalizations who had prescription medication insurance coverage and who were discharged to an outpatient setting (n = 49, 237), 8.8% filled an outpatient buprenorphine prescription within 10 days of discharge. CONCLUSIONS: Non-overdose OUD hospitalizations often occur with substance use disorders and psychiatric disorders, and very few are followed by timely outpatient buprenorphine. Addressing the OUD treatment gap during hospitalization may include implementing medication for OUD for inpatients with a broad range of diagnoses.