Associations Between Volume of Early Intravenous Fluid and Hospital Outcomes in Septic Patients With and Without Heart Failure: A Retrospective Cohort Study.

OBJECTIVES: To evaluate the relationship between early IV fluid volume and hospital outcomes, including death in-hospital or discharge to hospice, in septic patients with and without heart failure (HF). DESIGN: A retrospective cohort study using logistic regression with restricted cubic splines to assess for nonlinear relationships between fluid volume and outcomes, stratified by HF status and adjusted for propensity to receive a given fluid volume in the first 6 hours. An ICU subgroup analysis was performed. Secondary outcomes of vasopressor use, mechanical ventilation, and length of stay in survivors were assessed. SETTING: An urban university-based hospital. PATIENTS: A total of 9613 adult patients were admitted from the emergency department from 2012 to 2021 that met electronic health record-based Sepsis-3 criteria. Preexisting HF diagnosis was identified by the International Classification of Diseases codes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 1449 admissions from patients with HF. The relationship between fluid volume and death or discharge to hospice was nonlinear in patients without HF, and approximately linear in patients with HF. Receiving 0-15 mL/kg in the first 6 hours was associated with lower likelihood of death or discharge to hospice compared with 30-45 mL/kg (odds ratio = 0.61; 95% CI, 0.41-0.90; p = 0.01) in HF patients, but no significant difference for non-HF patients. A similar pattern was identified in ICU admissions and some secondary outcomes. Volumes larger than 15-30 mL/kg for non-HF patients and 30-45 mL/kg for ICU-admitted non-HF patients were not associated with improved outcomes. CONCLUSIONS: Early fluid resuscitation showed distinct patterns of potential harm and benefit between patients with and without HF who met Sepsis-3 criteria. Restricted cubic splines analysis highlighted the importance of considering nonlinear fluid outcomes relationships and identified potential points of diminishing returns (15-30 mL/kg across all patients without HF and 30-45 mL/kg when admitted to the ICU). Receiving less than 15 mL/kg was associated with better outcomes in HF patients, suggesting small volumes may be appropriate in select patients. Future studies may benefit from investigating nonlinear fluid-outcome associations and a focus on other conditions like HF.

Stigmatizing Language, Patient Demographics, and Errors in the Diagnostic Process.

This cohort study assesses the association between stigmatizing language, demographic characteristics, and errors in the diagnostic process among hospitalized adults.

Diagnostic Errors in Hospitalized Adults Who Died or Were Transferred to Intensive Care.

Importance: Diagnostic errors contribute to patient harm, though few data exist to describe their prevalence or underlying causes among medical inpatients. Objective: To determine the prevalence, underlying cause, and harms of diagnostic errors among hospitalized adults transferred to an intensive care unit (ICU) or who died. Design, Setting, and Participants: Retrospective cohort study conducted at 29 academic medical centers in the US in a random sample of adults hospitalized with general medical conditions and who were transferred to an ICU, died, or both from January 1 to December 31, 2019. Each record was reviewed by 2 trained clinicians to determine whether a diagnostic error occurred (ie, missed or delayed diagnosis), identify diagnostic process faults, and classify harms. Multivariable models estimated association between process faults and diagnostic error. Opportunity for diagnostic error reduction associated with each fault was estimated using the adjusted proportion attributable fraction (aPAF). Data analysis was performed from April through September 2023. Main Outcomes and Measures: Whether or not a diagnostic error took place, the frequency of underlying causes of errors, and harms associated with those errors. Results: Of 2428 patient records at 29 hospitals that underwent review (mean [SD] patient age, 63.9 [17.0] years; 1107 [45.6%] female and 1321 male individuals [54.4%]), 550 patients (23.0%; 95% CI, 20.9%-25.3%) had experienced a diagnostic error. Errors were judged to have contributed to temporary harm, permanent harm, or death in 436 patients (17.8%; 95% CI, 15.9%-19.8%); among the 1863 patients who died, diagnostic error was judged to have contributed to death in 121 (6.6%; 95% CI, 5.3%-8.2%). In multivariable models examining process faults associated with any diagnostic error, patient assessment problems (aPAF, 21.4%; 95% CI, 16.4%-26.4%) and problems with test ordering and interpretation (aPAF, 19.9%; 95% CI, 14.7%-25.1%) had the highest opportunity to reduce diagnostic errors; similar ranking was seen in multivariable models examining harmful diagnostic errors. Conclusions and Relevance: In this cohort study, diagnostic errors in hospitalized adults who died or were transferred to the ICU were common and associated with patient harm. Problems with choosing and interpreting tests and the processes involved with clinician assessment are high-priority areas for improvement efforts.

Racial, Ethnic, and Language-Based Inequities in Inpatient Opioid Prescribing by Diagnosis from Internal Medicine Services, a Retrospective Cohort Study.

Introduction: Opioid administration is extremely common in the inpatient setting, yet we do not know how the administration of opioids varies across different medical conditions and patient characteristics on internal medicine services. Our goal was to assess racial, ethnic, and language-based inequities in opioid prescribing practices for patients admitted to internal medicine services. Methods: We conducted a retrospective cohort study of all adult patients admitted to internal medicine services from 2013 to 2021 and identified subcohorts of patients treated for the six most frequent primary hospital conditions (pneumonia, sepsis, cellulitis, gastrointestinal bleed, pyelonephritis/urinary tract infection, and respiratory disease) and three select conditions typically associated with pain (abdominal pain, acute back pain, and pancreatitis). We conducted a negative binomial regression analysis to determine how average administered daily opioids, measured as morphine milligram equivalents (MMEs), were associated with race, ethnicity, and language, while adjusting for additional patient demographics, hospitalization characteristics, medical comorbidities, prior opioid therapy, and substance use disorders. Results: The study cohort included 61,831 patient hospitalizations. In adjusted models, we found that patients with limited English proficiency received significantly fewer opioids (66 MMEs, 95% CI: 52, 80) compared to English-speaking patients (101 MMEs, 95% CI: 91, 111). Asian (59 MMEs, 95% CI: 51, 66), Latinx (89 MMEs, 95% CI: 79, 100), and multi-race/ethnicity patients (81 MMEs, 95% CI: 65, 97) received significantly fewer opioids compared to white patients (103 MMEs, 95% CI: 94, 112). American Indian/Alaska Native (227 MMEs, 95% CI: 110, 344) patients received significantly more opioids. Significant inequities were also identified across race, ethnicity, and language groups when analyses were conducted within the subcohorts. Most notably, Asian and Latinx patients received significantly fewer MMEs and American Indian/Alaska Native patients received significantly more MMEs compared to white patients for the top six most frequent conditions. Most patients from minority groups also received fewer MMEs compared to white patients for three select pain conditions. Discussion. There are notable inequities in opioid prescribing based on patient race, ethnicity, and language status for those admitted to inpatient internal medicine services across all conditions and in the subcohorts of the six most frequent hospital conditions and three pain-associated conditions. This represents an institutional and societal opportunity for quality improvement initiatives to promote equitable pain management.

Opioid and High-Risk Prescribing Among Racial and Ethnic Minority Veterans.

INTRODUCTION: The purpose of this study is to compare opioid prescribing and high-risk prescribing by race and ethnicity in a national cohort of U.S. veterans. METHODS: A cross-sectional analysis of veteran characteristics and healthcare use was performed on electronic health record data for 2018 Veterans Health Administration users and enrollees in 2022. RESULTS: Overall, 14.8% received an opioid prescription. The adjusted odds of being prescribed an opioid were lower for all race/ethnicity groups than for non-Hispanic White veterans, except for non-Hispanic multiracial (AOR=1.03; 95% CI=0.999, 1.05) and non-Hispanic American Indian/Alaska Native (AOR=1.06; 95% CI=1.03, 1.09) veterans. The odds of any day of overlapping opioid prescriptions (i.e., opioid overlap) were lower for all race/ethnicity groups than for the non-Hispanic White group, except for the non-Hispanic American Indian/Alaska Native group (AOR=1.01; 95% CI=0.96, 1.07). Similarly, all race/ethnicity groups had lower odds of any day of daily dose >120 morphine milligram equivalents than the non-Hispanic White group, except for the non-Hispanic multiracial (AOR=0.96; 95% CI=0.87, 1.07) and non-Hispanic American Indian/Alaska Native (AOR=1.06; 95% CI=0.96, 1.17) groups. Non-Hispanic Asian veterans had the lowest odds for any day of opioid overlap (AOR=0.54; 95% CI=0.50, 0.57) and daily dose >120 morphine milligram equivalents (AOR=0.43; 95% CI=0.36, 0.52). For any day of opioid-benzodiazepine overlap, all races/ethnicities had lower odds than non-Hispanic White. Non-Hispanic Black/African American (AOR=0.71; 95% CI=0.70, 0.72) and non-Hispanic Asian (AOR=0.73; 95% CI=0.68, 0.77) veterans had the lowest odds of any day of opioid-benzodiazepine overlap. CONCLUSIONS: Non-Hispanic White and non-Hispanic American Indian/Alaska Native veterans had the greatest likelihood to receive an opioid prescription. When an opioid was prescribed, high-risk prescribing was more common in White and American Indian/Alaska Native veterans than in all other racial/ethnic groups. As the nation's largest integrated healthcare system, the Veterans Health Administration can develop and test interventions to achieve health equity for patients experiencing pain.

Prevalence and Causes of Diagnostic Errors in Hospitalized Patients Under Investigation for COVID-19.

BACKGROUND: The COVID-19 pandemic required clinicians to care for a disease with evolving characteristics while also adhering to care changes (e.g., physical distancing practices) that might lead to diagnostic errors (DEs). OBJECTIVE: To determine the frequency of DEs and their causes among patients hospitalized under investigation (PUI) for COVID-19. DESIGN: Retrospective cohort. SETTING: Eight medical centers affiliated with the Hospital Medicine ReEngineering Network (HOMERuN). TARGET POPULATION: Adults hospitalized under investigation (PUI) for COVID-19 infection between February and July 2020. MEASUREMENTS: We randomly selected up to 8 cases per site per month for review, with each case reviewed by two clinicians to determine whether a DE (defined as a missed or delayed diagnosis) occurred, and whether any diagnostic process faults took place. We used bivariable statistics to compare patients with and without DE and multivariable models to determine which process faults or patient factors were associated with DEs. RESULTS: Two hundred and fifty-seven patient charts underwent review, of which 36 (14%) had a diagnostic error. Patients with and without DE were statistically similar in terms of socioeconomic factors, comorbidities, risk factors for COVID-19, and COVID-19 test turnaround time and eventual positivity. Most common diagnostic process faults contributing to DE were problems with clinical assessment, testing choices, history taking, and physical examination (all p < 0.01). Diagnostic process faults associated with policies and procedures related to COVID-19 were not associated with DE risk. Fourteen patients (35.9% of patients with errors and 5.4% overall) suffered harm or death due to diagnostic error. LIMITATIONS: Results are limited by available documentation and do not capture communication between providers and patients. CONCLUSION: Among PUI patients, DEs were common and not associated with pandemic-related care changes, suggesting the importance of more general diagnostic process gaps in error propagation.

Adverse outcomes associated with opioid prescription by dentists in the Veterans Health Administration: A national cross-sectional study from 2015 to 2018.

OBJECTIVES: Opioids prescribed by dentists have been associated with serious adverse events, including opioid-related overdose and mortality. However, the downstream outcomes of opioids prescribed by dentists to Veterans who are at high risk for opioid misuse and overdose have yet to be determined. METHODS: This was a national cross-sectional analysis of opioids associated with dental visits within the Veterans Health Administration from 2015 to 2018. Overprescribing was defined per guidelines as >120 morphine milligram equivalents (MME) or >3 days supply. The association of dental visit and patient characteristics was modeled separately for opioid-related poisoning and all-cause mortality using logistic regression. RESULTS: Of 137,273 Veterans prescribed an opioid by a dentist, 0.1% and 1.1% were associated with opioid-related poisoning and mortality, respectively. There was no difference in opioid poisoning within 6 months for Veterans with opioid prescriptions >120 MME (aOR = 1.25 [CI: 0.89-1.78]), but poisoning decreased in Veterans prescribed opioids >3-days supply (aOR = 0.68 [CI: 0.49-0.96]). However, Veterans with opioids >120 MME were associated with higher odds of mortality within 6 months (aOR = 1.17 [95% CI: 1.05-1.32]) while there was no difference in prescriptions >3-days supply (aOR = 1.12 [CI: 0.99-1.25]). CONCLUSION: Serious opioid-related adverse events were rare in Veterans and lower than other reports in the literature. Since nonopioid analgesics have superior efficacy for the treatment of acute dental pain, prescribing opioid alternatives may decrease opioid-related poisoning. Strategies for dentists to identify patients at high risk should be incorporated into the dental record.

The feasibility of academic detailing for acute oral pain management in outpatient dentistry: A pilot study.

BACKGROUND: Opioids are overprescribed in the outpatient dental setting. Therefore, opportunities exist for opioid stewardship. OBJECTIVES: The purpose of this pilot study was to test the feasibility of an academic detailing (AD) intervention to promote appropriate prescribing of opioids in outpatient dentistry. METHODS: We implemented an AD intervention targeting management of acute oral pain in a Midwestern Veterans Affairs outpatient dental facility. The intervention targeted dentists who actively prescribed opioids at the time of the study. The pilot study tested feasibility, adoption, and acceptance of the AD campaign. Visit-based prescribing rates were obtained from the Veterans Health Administration's Corporate Data Warehouse for baseline and postintervention using difference-in-differences analyses to detect potential changes in health service outcomes. RESULTS: Results indicate moderate levels of feasibility through participation rates (n = 5, 55.5%) and high levels of organizational readiness for change (average of 88.6% agree to strongly agree). Furthermore, fidelity of the AD intervention was high. Adoption measures show moderate indication of motivation to change, and trends suggest that participating dentists decreased their visit-based opioid prescribing rates (P > 0.05). CONCLUSION: The intervention demonstrated feasibility with some indications of adoption of intervention techniques and decrease in opioid prescribing. We further recommend working closely with frontline providers to gather feedback and buy-in before scaling and implementing the AD campaign.

Serious opioid-related adverse outcomes associated with opioids prescribed by dentists.

ABSTRACT: Although nonsteroidal anti inflammatory drugs are superior to opioids in dental pain management, opioids are still prescribed for dental pain in the United States. Little is known about the serious adverse outcomes of short-acting opioids within the context of dental prescribing. The objective of this study was to evaluate adverse outcomes and persistent opioid use (POU) after opioid prescriptions by dentists, based on whether opioids were overprescribed or within recommendations. A cross-sectional analysis of adults with a dental visit and corresponding opioid prescription (index) from 2011 to 2018 within a nationwide commercial claims database was conducted. Opioid overprescribing was defined as >120 morphine milligram equivalents per Centers for Disease Control and Prevention guidelines. Generalized estimating equation models were used to assess adverse outcomes (emergency department visits, hospitalizations, newly diagnosed substance use disorder, naloxone administration, or death within 30 days from index) and POU (≥1 prescription 4-90 days postindex). Predicted probabilities are reported. Of 633,387 visits, 2.6% experienced an adverse outcome and 16.6% had POU. Adverse outcome risk was not different whether opioids were overprescribed or within recommendations (predicted probability 9.0%, confidence interval [CI]: 8.0%-10.2% vs 9.1%, CI: 8.1-10.3), but POU was higher when opioids were overprescribed (predicted probability 27.4%, CI: 26.1%-28.8% vs 25.2%, CI: 24.0%-26.5%). Visits associated with mild pain and those with substance use disorders had the highest risk of both outcomes. Findings from this study demonstrate that dental prescribing of opioids was associated with adverse outcomes and POU, even when prescriptions were concordant with guidelines. Additional efforts are required to improve analgesic prescribing in dentistry, especially in groups at high risk of opioid-related adverse outcomes.

Health-related Quality of Life in Hormone Receptor-Positive Early Breast Cancer: Analyses From the Surveillance, Epidemiology, and End Results Medicare Health Outcomes Survey.

This study describes health-related quality of life (HRQoL) among older Medicare beneficiaries with hormone receptor-positive (HR+) early breast cancer (eBC). Women aged ≥65 years diagnosed with stage I-III HR+ eBC between 1997 and 2014 using the Surveillance, Epidemiology, and End Results Medicare Health Outcomes Survey Data Resource were included. HRQoL was measured using the Short Form Health Survey including physical/mental component summary (PCS/MCS) scores and subscales. Patient surveys ≤ 24 months post-diagnosis were matched to non-cancer controls. Mean differences in HRQoL were compared using analysis of covariance. Among 1880 HR+ eBC patients versus 5640 matched non-cancer controls, eBC patients surveyed ≤ 6 months post-diagnosis (n = 530) scored lower on component scores (PCS mean difference = 1.6 [95%CI: 0.6-2.6]; MCS mean difference = 2.0 [95%CI: 1.0-3.0]) and multiple subscales. Among women surveyed 19 to 24 months post-diagnosis (n = 402), mean differences in HRQoL were modest (PCS: 1.2 [95%CI: 0.1-2.4]; MCS: -1.5 [95%CI: -2.7 to -0.3]). Most differences in HRQoL following diagnosis of eBC did not indicate statistical significance or minimally important difference, emphasizing that preservation of HRQoL is an important and realistic goal among patients with eBC.

Impact of socioeconomic status and rurality on cancer-specific survival among women with de novo metastatic breast cancer by race/ethnicity.

PURPOSE: There are approximately 150,000 women living with metastatic breast cancer (mBC) in the United States. Disparities in de novo mBC incidence and mortality exist across race/ethnicity, socioeconomic status (SES), and rurality. However, how SES and rurality independently impact mBC outcomes across different racial/ethnic groups is not fully understood. The purpose of this study was to determine the impact of SES and rurality on cancer-specific mortality among women with mBC by race/ethnicity. METHODS: We conducted a large, population-based retrospective cohort study in women aged 18 + years diagnosed with de novo mBC using the Surveillance, Epidemiology and End Results Census Tract-level SES and Rurality Database (2000-2015). Associations between SES/rurality and cancer-specific mortality were determined using Fine and Gray regression models. Subdistribution hazard ratios (SHR) and 95% confidence intervals (CI) by race/ethnicity and hormone receptor (HR) status were calculated. RESULTS: A cohort of 33,976 women were included with the majority being White (67%), 17% Black, 0.4% American Indian/Alaskan Native, 6% Asian/Pacific Islander, and 10% Latina/Hispanic. We observed the greatest increased risk of BC mortality among Black women with HR-negative mBC residing in neighborhoods with lower SES (lowest versus highest quintile: SHR 1.38, 95% CI 1.00-1.90) and in rural areas compared to urban areas (SHR 1.27, 95% CI 1.01-1.59). CONCLUSION: Overall, BC-specific survival among women with de novo mBC differs by race/ethnicity, with the greatest adverse impacts of SES and rurality affecting Black women with HR-negative disease.

Comparing Outpatient Opioids, High-Risk Prescribing, and Opioid Poisoning Between Transgender and Cisgender Veterans: A Cross-sectional Analysis.

INTRODUCTION: Transgender veterans have a high prevalence of substance use disorder and physical and mental-health comorbidities, which are associated with prescription opioid use and overdose risk. This study compares receipt of outpatient opioids, high-risk opioid prescribing, and opioid poisoning between transgender and cisgender (i.e., nontransgender) veterans. METHODS: A secondary analysis of Veterans Health Administration health record data from January 1, 2018 to December 31, 2018 was conducted in 2021. Transgender veterans (n=9,686) were randomly matched to 3 cisgender veterans (n=29,058) on the basis of age and county. Using the same matching criteria, a second cohort was created of all transgender veterans and a matched sample of cisgender veterans who were prescribed an outpatient opioid (n=7,576). Stratified Cox proportional hazard regression measured the RR of each prescription outcome and opioid poisoning. RESULTS: Transgender veterans had a 20% higher risk of being prescribed any outpatient opioid than cisgender veterans (adjusted RR=1.20, 95% CI=1.13, 1.27). Transgender and cisgender veterans who were prescribed an opioid did not have different risks of high-risk prescribing: overlapping opioid prescriptions (adjusted RR=0.93, 95% CI=0.85, 1.02), daily dose >120 morphine milligram equivalents (adjusted RR=0.86, 95% CI=0.66, 1.10), or overlapping opioid and benzodiazepine prescriptions (adjusted RR=1.05, 95% CI=0.96, 1.14). Overall, transgender veterans had more than twice the risk of opioid poisoning than cisgender veterans (RR=2.76, 95% CI=1.57, 4.86). The risk of opioid poisoning did not differ between transgender and cisgender veterans who were prescribed an opioid (RR=1.09, 95% CI=0.56, 2.11). CONCLUSIONS: Transgender veterans had a greater risk of being prescribed an outpatient opioid than cisgender veterans but did not have different risks of high-risk opioid prescribing.

Opioid Prescribing by Dentists in the Veterans Health Administration.

INTRODUCTION: Nonopioid analgesics are more effective for most oral pain, but data suggest that dental prescribing of opioids is excessive. This study evaluates the extent to which opioids exceed recommendations and the characteristics associated with opioid overprescribing by Veterans Health Administration dentists. METHODS: This was a national cross-sectional study of Veterans' dental visits from 2015 to 2018. Overprescribing was defined per national guidelines as >120 morphine milligram equivalents (primary outcome). The association of dental visit and patient demographic and medical characteristics was modeled with overprescribing (defined as >120 morphine milligram equivalents) using Poisson regression with clustering by facility and patient. A secondary analysis assessed opioid prescriptions >3 days' supply. The dates of analysis were January 2020‒May 2021. RESULTS: Of the 196,595 visits, 28.7% exceeded 120 morphine milligram equivalents. Friday visits and people with chronic oral pain or substance misuse were associated with a higher prevalence of overprescribing. Women, older Veterans, and Black and Latinx Veterans were less likely to be overprescribed than men, younger Veterans, and White Veterans, respectively. Routine dental visits had a higher prevalence of opioid overprescribing than invasive visits. Opioid overprescribing decreased over time. White Veterans were more likely to receive oxycodone and hydrocodone, whereas people of Black race and Latinx ethnicity were more likely to receive codeine and tramadol. In the secondary analysis, 68.5% of opioid prescriptions exceeded a 3-day supply. CONCLUSIONS: Nearly 1 in 3 opioids prescribed by Veterans Health Administration dentists exceed guidelines. Prescribing higher potency and quantities of opioids, especially on Fridays and to certain demographic groups, should be addressed as part of dental opioid stewardship programs.

Trends in Opioid Prescribing by General Dentists and Dental Specialists in the U.S., 2012-2019.

INTRODUCTION: Evidence suggests that U.S. dentists prescribe opioids excessively. There are limited national data on recent trends in opioid prescriptions by U.S. dentists. In this study, we examined trends in opioid prescribing by general dentists and dental specialists in the U.S. from 2012 to 2019. METHODS: Dispensed prescriptions for oral opioid analgesics written by dentists were identified from IQVIA Longitudinal Prescription Data from January 2012 through December 2019. Autoregressive integrated moving average and joinpoint regression models described monthly population-based prescribing rates (prescriptions/100,000 individuals), dentist-based prescribing rates (prescriptions/1,000 dentists), and opioid dosages (mean daily morphine milligram equivalents/day). All analyses were performed in 2020. RESULTS: Over the 8 years, dentists prescribed >87.2 million opioid prescriptions. Population- and dentist-based prescribing rates declined monthly by -1.97 prescriptions/100,000 individuals (95% CI= -9.98, -0.97) and -39.12 prescriptions/1,000 dentists (95% CI= -58.63, -17.65), respectively. Opioid dosages declined monthly by -0.08 morphine milligram equivalents/day (95% CI= -0.13, -0.04). Joinpoint regression identified 4 timepoints (February 2016, May 2017, December 2018, and March 2019) at which monthly prescribing rate trends were often decreasing in greater magnitude than those in the previous time segment. CONCLUSIONS: Following national trends, dentists became more conservative in prescribing opioids. A greater magnitude of decline occurred post 2016 following the implementation of strategies aimed to further regulate opioid prescribing. Understanding the factors that influence prescribing trends can aid in development of tailored resources to encourage and support a conservative approach by dentists, to prescribing opioids.

Antibiotic prophylaxis prescriptions prior to dental visits in the Veterans' Health Administration (VHA), 2015-2019.

OBJECTIVE: To determine prophylaxis appropriateness by Veterans' Affairs (VA) dentists. DESIGN: A cross-sectional study of dental visits, 2015-2019. METHODS: Antibiotics within 7 days before a visit in the absence of an oral infection were included. Appropriate antibiotic prophylaxis was defined as visits with gingival manipulation and further delineated into narrow and broad definitions based on comorbidities. The primary analysis applied a narrow definition of appropriate prophylaxis: cardiac conditions at the highest risk of an adverse outcome from endocarditis. The secondary analysis included a broader definition: cardiac or immunocompromising condition or tooth extractions and/or implants. Multivariable log-linear Poisson generalized estimating equation regression was used to assess the association between covariates and unnecessary prophylaxis prescriptions. RESULTS: In total, 358,078 visits were associated with 369,102 antibiotics. The median prescription duration was 7 days (IQR, 7-10); only 6.5% were prescribed for 1 day. With the narrow definition, 15% of prophylaxis prescriptions were appropriate, which increased to 72% with the broader definition. Prophylaxis inconsistent with guidelines increased over time. For the narrow definition, Black (vs White) race, Latine (vs non-Latine) ethnicity, and visits located in the West census region were associated with unnecessary prophylaxis. Variables associated with a lower risk were older age, prosthetic joints, immunocompromising condition, and rural location. CONCLUSIONS: Of every 6 antibiotic prophylaxis prescriptions, 5 were inconsistent with guidelines. Improving prophylaxis appropriateness and shortening duration may have substantial implications for stewardship. Guidelines should state whether antibiotic prophylaxis is indicated for extractions, implants, and immunocompromised patients.

Appropriateness of Antibiotic Prophylaxis Before Dental Procedures, 2016-2018.

INTRODUCTION: Prescribing antibiotic prophylaxis is common yet unnecessary for many dental visits. In this analysis, our objective was to assess whether the appropriateness of antibiotic prophylaxis has improved over time. METHODS: A retrospective cohort study was conducted using dental visits from 2016 to 2018 (data analyzed in 2021) using medical and prescriptions claims data of patients from the U.S. with commercial dental insurance. Antibiotic prophylaxis was defined as a ≤2 days' supply prescription dispensed within 7 days before a dental visit. Appropriateness of prophylaxis was defined on the basis of the manipulation of the gingiva/tooth periapex or oral mucosa perforation in patients with appropriate cardiac diagnoses. Associations between patient and visit characteristics and appropriateness of antibiotic prophylaxis were assessed using multiple Poisson regression. RESULTS: Unnecessary antibiotic prophylaxis was highly prevalent in this cohort, ranging from 77.0% in 2016 to 78.5% in 2018. In the adjusted analysis, factors associated with unnecessary antibiotic prophylaxis included younger age, female sex, geographic region, rurality, type of antibiotic, and certain dental procedures. The factors associated with the highest risk of unnecessary prophylaxis in the adjusted analysis were orthodontic procedures and having a history of a prosthetic joint. Notably, the risk of unnecessary antibiotic prophylaxis decreased over time in the adjusted analysis. CONCLUSIONS: Unnecessary prescription of antibiotic prophylaxis by dentists continues to be common. Antimicrobial stewardship strategies are needed to improve prescribing by dentists.

Apixaban Concentrations in Routine Clinical Care of Older Adults With Nonvalvular Atrial Fibrillation.

BACKGROUND: Direct-acting oral anticoagulants are first-line agents for prevention of stroke in patients with nonvalvular atrial fibrillation (NVAF), but data are limited for the oldest patients, and with reduced dosing. OBJECTIVES: To determine steady-state apixaban peak and trough concentrations during routine care of older adults with NVAF, compare concentrations to clinical trial concentrations, and explore factors associated with concentrations. METHODS: A cross-sectional study of medically stable older adults with NVAF (≥75 years or ≥70 years if Black) receiving apixaban. Peak (2-4.4 hours post-dose) and trough (before next dose) concentrations were determined by anti-Xa activity calibrated chromogenic assay. Patient characteristics associated with concentrations were determined by multivariate modeling. RESULTS: The median age of patients (n = 115) was 80 (interquartile range: 77-84) years. The cohort comprised 46 women and 69 men; of which 98 are White, 11 Black, and 6 Asian. With 5 mg twice daily per labelling (n = 88), peak concentrations were higher in women: 248 ± 105 vs 174 ± 67 ng/mL in men (P < 0.001) and exceeded expected 95% range in 6 of 30 vs 0 of 55 men (P = 0.002). With 2.5 mg twice daily per label (n = 11), concentrations were <5 mg twice daily (peak: 136 ± 87 vs 201 ± 90 ng/mL, P = 0.026; trough: 65 ± 28 vs 109 ± 56 ng/mL, P < 0.001), but not different than 2.5 mg twice daily without reduction criteria (n = 13; peak: 132 ± 88; trough: 65 ± 31 ng/mL). Covariates associated with concentrations included sex, number of daily medications, and creatinine clearance. CONCLUSIONS: Older women had higher than expected peak apixaban concentrations, and 2.5 mg twice daily produced lower concentrations than standard dosing. Factors not currently included in dosing recommendations affected concentrations. The impact of apixaban concentrations on outcomes needs evaluation.

Patterns of dental antibiotic prescribing in 2017: Australia, England, United States, and British Columbia (Canada).

OBJECTIVE: Our objective was to compare patterns of dental antibiotic prescribing in Australia, England, and North America (United States and British Columbia, Canada). DESIGN: Population-level analysis of antibiotic prescription. SETTING: Outpatient prescribing by dentists in 2017. PARTICIPANTS: Patients receiving an antibiotic dispensed by an outpatient pharmacy. METHODS: Prescription-based rates adjusted by population were compared overall and by antibiotic class. Contingency tables assessed differences in the proportion of antibiotic class by country. RESULTS: In 2017, dentists in the United States had the highest antibiotic prescribing rate per 1,000 population and Australia had the lowest rate. The penicillin class, particularly amoxicillin, was the most frequently prescribed for all countries. The second most common agents prescribed were clindamycin in the United States and British Columbia (Canada) and metronidazole in Australia and England. Broad-spectrum agents, amoxicillin-clavulanic acid, and azithromycin were the highest in Australia and the United States, respectively. CONCLUSION: Extreme differences exist in antibiotics prescribed by dentists in Australia, England, the United States, and British Columbia. The United States had twice the antibiotic prescription rate of Australia and the most frequently prescribed antibiotic in the US was clindamycin. Significant opportunities exist for the global dental community to update their prescribing behavior relating to second-line agents for penicillin allergic patients and to contribute to international efforts addressing antibiotic resistance. Patient safety improvements will result from optimizing dental antibiotic prescribing, especially for antibiotics associated with resistance (broad-spectrum agents) or C. difficile (clindamycin). Dental antibiotic stewardship programs are urgently needed worldwide.

The association between physical health-related quality of life, physical functioning, and risk of contralateral breast cancer among older women.

BACKGROUND: Physical limitations prior to cancer diagnosis may lead to suboptimal health outcomes. Our objective was to evaluate the impacts of poor physical health-related quality of life (HRQOL) and physical functioning (PF) on the risk of contralateral breast cancer (CBC). METHODS: We performed a nested case-control study of women with invasive unilateral breast cancer (UBC) who did not receive prophylactic contralateral mastectomy using the Surveillance, Epidemiology and End Results Medicare Health Outcomes Survey data resource. Among 2938 women aged ≥ 65 years diagnosed with first stage I-III UBC between 1997 and 2011, we identified 100 subsequent CBC cases and 915 matched controls without CBC using incidence density sampling without replacement. Pre-diagnosis physical HRQOL and PF were determined using Medical Outcomes Trust Short Form-36 (SF-36)/Veterans Rand 12-Item Health Survey (VR-12) responses within 2 years prior to first UBC diagnosis. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression models. RESULTS: Cases and controls were similar with respect to comorbidities, stage, surgery, and radiation treatments, but differed by hormone receptor status (ER/PR-negative, 23% and 11%, respectively) of first UBC. Cases had modestly lower mean pre-diagnosis physical HRQOL (- 1.8) and PF (- 2.2) scores. In multivariable models, we observed an increased CBC risk associated with low physical HRQOL (lowest vs. highest quartile, OR = 1.8; 95% CI 0.8-4.3), but CIs included 1.0. Low PF was associated with a 2.7-fold (95% CI 1.1-6.7) increased CBC risk. CONCLUSIONS: Findings indicate that low physical HRQOL, specifically poor PF, is associated with CBC risk. Efforts to understand and minimize declines in PF post-breast cancer are well motivated.

Population-based recurrence rates among older women with HR-positive, HER2-negative early breast cancer: Clinical risk factors, frailty status, and differences by race.

BACKGROUND: Multiple independent risk factors are associated with the prognosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC), the most common BC subtype. This study describes U.S. population-based recurrence rates among older, resected women with HR+/HER2- early BC. METHODS: We conducted a retrospective cohort study of older women diagnosed with incident, invasive stages I-III HR+/HER2- BC who underwent surgery to remove the primary tumor using the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked Database (2007-2015). SEER records and administrative health claims data were used to ascertain patient and tumor-specific characteristics, treatment, and frailty status. Cumulative incidences of BC recurrence were estimated using a validated algorithm for administrative claims data. Multivariable Fine-Gray competing risk models estimated adjusted subdistribution hazards ratios and 95 % confidence intervals for associations with BC recurrence risk. RESULTS: Overall, 46,027 women age ≥65 years were included in our analysis. Over a median follow up of 7 years, 6531 women experienced BC recurrence with an estimated 3 and 5-year cumulative incidence rates of 10 % and 16 %, respectively. Higher 3- and 5-year cumulative incidences were observed in women with larger tumor size (5+ cm, 21 % and 28 %), lymph node involvement (4+ nodes, 27 % and 37 %), and with frail health status at diagnosis (13 % and 20 %). Independent of these clinical risk factors, Black, Hispanic and American Indian/Alaskan Native women had significantly increased BC recurrence risks. CONCLUSIONS: Rates of recurrence in HR+/HER2- early BC differs by several patient and clinical factors, including high-risk tumor characteristics. Racial differences in BC outcomes deserve continued attention from clinicians and policymakers.