Publications

BACKGROUND: Viridans group streptococci (VGS) are typically part of the commensal flora but can also cause severe invasive diseases such as infective endocarditis. There are limited data available showing antibiotic susceptibility over time for VGS.

OBJECTIVES: To evaluate antibiotic susceptibility trends in VGS over time.

METHODS: In vitro susceptibility patterns for 33 antibiotics were examined for Streptococcus mitis, Streptococcus oralis, and non-speciated VGS isolates from patients in Veterans Affairs (VA) Medical Centers in the United States between 2010 and 2020. Susceptibility determinations were made by the individual clinical microbiology laboratories and data were retrospectively collected from the VA Corporate Data Warehouse. Susceptibility trends were analysed using Poisson regression.

RESULTS: A total of 14 981 VGS isolates were included of which 19.5%, 0.7% and 79.8% were S. mitis, S. oralis and non-speciated VGS isolates, respectively. Cumulative susceptibility rates across all years were similar between species for ceftriaxone (range: 96.0% to 100%), clindamycin (81.3% to 84.5%), and vancomycin (99.7% to 100%). For penicillin, susceptibility rates were 71.0%, 80.9% and 86.3% for S. mitis, S. oralis and non-speciated isolates, respectively. From 2010 to 2020, susceptibility of non-speciated VGS isolates decreased for erythromycin (P = 0.0674), penicillin (P = 0.0835), and tetracycline (P = 0.0994); though the decrease was only significant for clindamycin (P = 0.0033). For S. mitis, a significant susceptibility rate decrease was observed for erythromycin (P = 0.0112).

CONCLUSIONS: Susceptibility rates for some clinically relevant antibiotics declined between 2010 and 2020. This worrisome trend highlights the need to improve antimicrobial stewardship efforts to limit unnecessary antibiotic use and preserve empirical treatment options.

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.

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.

A survey of Veterans' Affairs Medical Centers on control of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-producing CRE (CP-CRE) demonstrated that most facilities use VA guidelines but few screen for CRE/CP-CRE colonization regularly or regularly communicate CRE/CP-CRE status at patient transfer. Most respondents were knowledgeable about CRE guidelines but cited lack of adequate resources.

OBJECTIVE: To understand barriers and facilitators to evidence-based prescribing of antibiotics in the outpatient dental setting.

DESIGN: Semistructured interviews.

SETTING: Outpatient dental setting.

PARTICIPANTS: Dentists from 40 Veterans' Health Administration (VA) facilities across the United States.

METHODS: Dentists were identified based on their prescribing patterns and were recruited to participate in a semistructured interview on perceptions toward prescribing. All interviews were recorded, transcribed, and double-coded for analysis, with high reliability between coders. We identified general trends using the theoretical domains framework and mapped overarching themes onto the behavior change wheel to identify prospective interventions that improve evidence-based prescribing.

RESULTS: In total, 90 dentists participated in our study. The following barriers and facilitators to evidence-based prescribing emerged as impacts on a dentist's decision making on prescribing an antibiotic: access to resources, social influence of peers and other care providers, clinical judgment, beliefs about consequences, local features of the clinic setting, and beliefs about capabilities.

CONCLUSIONS: Findings from this work reveal the need to increase awareness of up-to-date antibiotic prescribing behaviors in dentistry and may inform the best antimicrobial stewardship interventions to support dentists' ongoing professional development and improve evidence-based prescribing.

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.

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.

PURPOSE: To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2022 in the United States, with a focus on the nonfederal hospital and clinic sectors.

METHODS: Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2022 were reviewed-including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, generics, COVID-19 pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2022 were based on a combination of quantitative analyses and expert opinion.

RESULTS: In 2021, overall pharmaceutical expenditures in the US grew 7.7% compared to 2020, for a total of $576.9 billion. Utilization (a 4.8% increase), price (a 1.9% increase) and new drugs (a 1.1% increase) drove this increase. Adalimumab was the top drug in terms of overall expenditures in 2021, followed by apixaban and dulaglutide. Drug expenditures were $39.6 billion (a 8.4% increase) and $105.0 billion (a 7.7% increase) in nonfederal hospitals and in clinics, respectively. In clinics and hospitals, new products and increased utilization growth drove growth, with decreasing prices for both sectors acting as an expense restraint. Several new drugs that are likely to influence spending are expected to be approved in 2022. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic.

CONCLUSION: For 2022, we expect overall prescription drug spending to rise by 4.0% to 6.0%, whereas in clinics and hospitals we anticipate increases of 7.0% to 9.0% and 3.0% to 5.0%, respectively, compared to 2021. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.

PURPOSE: We sought to compare trends in opioid purchasing between developed and developing economies to understand patterns of opioid consumption, and how they were impacted by the COVID-19 pandemic.

METHODS: We conducted a retrospective cross-sectional study of retail pharmacy opioid sales from 66 jurisdictions between July 2014 and August 2020. We measured monthly population-adjusted rate of opioid units purchased, stratified by development group and country, and used interventional time series analysis to assess the impact of the COVID-19 pandemic on rates of opioid purchasing among developed and developing economies separately.

RESULTS: Rates of opioid purchasing were generally higher among developed economies, although trends differed considerably by development group. Rates of opioid purchasing declined 23.8% (95% confidence interval [CI] -34.7% to 3.6%) in the 5 years prior to the pandemic in developed economies, but rose 15.2% (95% CI 4.6%-35.6%) among developing economies. In March 2020 there was a short-term increase in the rate of opioid purchases in both developing (10.9 units/1000 population increase; p < 0.0001) and developed (145.5 units/1000 population; p < 0.0001) economies, which was followed immediately by reduced opioid purchasing of a similar scale in April-May 2020 (-14.8 and -171.8 units/1000 population in developing and developed economies, respectively; p < 0.0001).

CONCLUSION: The COVID-19 pandemic led to disruptions in opioid purchasing around the world; although the specific impacts varied both between and among developed and developing economies. With global variation in opioid use, there is a need to monitor these trajectories to ensure the safety of opioid use, and adequate access to pain management globally.

STUDY OBJECTIVE: High prescribers of antibiotics and opioids are an important target for stewardship interventions. The goal of this study was to assess the association between high antibiotic and high opioid prescribing by provider type.

DESIGN: A national cross-sectional study.

SETTING: 2015-2017 Department of Veterans Affairs (VA) electronic health record data.

POPULATION: Prescribers were identified as dentists (2017: n = 1346) and medical providers (physicians n = 23,072; advanced practice providers [APP] n = 7705; and other providers [pharmacists/chiropractors] n = 3674) (2017: n = 34,451).

MEASUREMENTS: High prescribing was defined as being in the top 25% of visit-based rates of antibiotic or opioid prescribing (number of prescriptions/number of dental or medical visits). Multivariable random effects logistic regression with clustering by facility was used to assess the adjusted association between high antibiotic and opioid prescribing.

RESULTS: Medical providers prescribed 4,348,670 antibiotic and 10,256,706 opioid prescriptions; dentists prescribed 277,170 antibiotic and 124,103 opioid prescriptions. Among all high prescribers of antibiotics, 40% were also high prescribers of opioids as compared to 18% of those who were not high antibiotic prescribers (p < 0.0001). High prescribing of antibiotics was associated with high prescribing of opioids in medical providers (adjusted odds ratio [aOR] = 2.87, 95% confidence interval [CI] = 2.72-3.04) and dentists (aOR = 8.40, 95% CI 6.00-11.76). Older provider age, specific US geographic regions, and lower VA facility complexity and rurality were also associated with high opioid prescribing by medical providers. In dentists, younger provider age, male gender, specific regions of the United States, and lower number of dentists in a facility were associated with high opioid prescribing. At the facility level, high dental prescribers of antibiotics or opioids were not at the same facilities as high medical prescribers, respectively (p < 0.0001).

CONCLUSIONS: High antibiotic prescribing was associated with high opioid prescribing. Thus, stewardship interventions targeting both medication classes may have higher impact to efficiently reduce prescribing of medications with high public health impact. Provider-targeted interventions are needed to improve antibiotic and opioid prescribing in both dentists and medical providers.