Influence of Antibiotic Exposure Intensity on the Risk of Clostridioides difficile Infection.

BACKGROUND: Antibiotics are a strong risk factor for Clostridioides difficile infection (CDI), and CDI incidence is often measured as an important outcome metric for antimicrobial stewardship interventions aiming to reduce antibiotic use. However, risk of CDI from antibiotics varies by agent and dependent on the intensity (i.e., spectrum and duration) of antibiotic therapy. Thus, the impact of stewardship interventions on CDI incidence is variable, and understanding this risk requires a more granular measure of intensity of therapy than traditionally used measures like days of therapy (DOT). METHODS: We performed a retrospective cohort study to measure the independent association between intensity of antibiotic therapy, as measured by the antibiotic spectrum index (ASI), and hospital-associated CDI (HA-CDI) at a large academic medical center between January 2018 and March 2020. We constructed a marginal Poisson regression model to generate adjusted relative risks for a unit increase in ASI per antibiotic day. RESULTS: We included 35,457 inpatient encounters in our cohort. Sixty-eight percent of patients received at least one antibiotic. We identified 128 HA-CDI cases, which corresponds to an incidence rate of 4.1 cases per 10,000 patient-days. After adjusting for known confounders, each additional unit increase in ASI per antibiotic day is associated with 1.09 times the risk of HA-CDI (Relative Risk = 1.09, 95% Confidence Interval: 1.06 to 1.13). CONCLUSIONS: ASI was strongly associated with HA-CDI and could be a useful tool in evaluating the impact of antibiotic stewardship on HA-CDI rates, providing more granular information than the more commonly used days of therapy.

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.

Discrimination, Mediating Psychosocial or Economic Factors, and Antihypertensive Treatment: A 4-Way Decomposition Analysis in the Health and Retirement Study.

Untested psychosocial or economic factors mediate associations between perceived discrimination and suboptimal antihypertensive therapy. This study included 2 waves of data from Health and Retirement Study participants with self-reported hypertension (n = 8,557, 75% non-Hispanic White, 15% non-Hispanic Black, and 10% Hispanic/Latino) over 4 years (baselines of 2008 and 2010, United States). Our primary exposures were frequency of experiencing discrimination, in everyday life or across 7 lifetime circumstances. Candidate mediators were self-reported depressive symptoms, subjective social standing, and household wealth. We evaluated with causal mediation methods the interactive and mediating associations between each discrimination measure and reported antihypertensive use at the subsequent wave. In unmediated analyses, everyday (odds ratio (OR) = 0.86, 95% confidence interval (CI): 0.78, 0.95) and lifetime (OR = 0.91, 95% CI: 0.85, 0.98) discrimination were associated with a lower likelihood of antihypertensive use. Discrimination was associated with lower wealth, greater depressive symptoms, and decreased subjective social standing. Estimates for associations due to neither interaction nor mediation resembled unmediated associations for most discrimination-mediator combinations. Lifetime discrimination was indirectly associated with reduced antihypertensive use via depressive symptomatology (OR = 0.99, 95% CI: 0.98, 1.00). In conclusion, the impact of lifetime discrimination on the underuse of antihypertensive therapy appears partially mediated by depressive symptoms.

Clinical Outcomes of Oral Suspension versus Delayed-Release Tablet Formulations of Posaconazole for Prophylaxis of Invasive Fungal Infections.

Posaconazole is used for prophylaxis for invasive fungal infections (IFIs) among patients with hematologic malignancies. We compared the incidence of breakthrough IFIs and early discontinuation between patients receiving delayed-release tablet and oral suspension formulations of posaconazole. This was a retrospective cohort study of patients receiving posaconazole between 1 January 2010 and 30 June 2016. We defined probable or proven breakthrough IFIs using the European Organization for Research and Treatment of Cancer (EORTC) criteria. Overall, 547 patients received 860 courses of posaconazole (53% received the oral suspension and 48% received the tablet); primary indications for prophylaxis were acute myeloid leukemia (69%), graft-versus-host disease (18%), and myelodysplastic syndrome (3%). There were no significant differences in demographics or indications between patients receiving the different formulations. The incidence and incidence rate of probable or proven IFIs were 1.6% and 3.2 per 10,000 posaconazole days, respectively. There was no significant difference in the rate of IFIs between suspension courses (2.8 per 10,000 posaconazole days) and tablet courses (3.7 per 10,000 posaconazole days) (rate ratio = 0.8, 95% confidence interval [CI] = 0.3 to 2.3). Of the 14 proven or probable cases of IFI, 8/14 had posaconazole serum concentrations measured, and the concentrations in 7/8 were above 0.7 µg/ml. Posaconazole was discontinued early in 15.5% of courses; however, the frequency of discontinuation was also not significantly different between the tablet (16.5%) and oral suspension (14.6%) formulations (95% CI for difference = -0.13 to 0.06). In conclusion, the incidence of breakthrough IFIs was low among patients receiving posaconazole prophylaxis and not significantly different between patients receiving the tablet formulation and those receiving the oral suspension formulation.

Optimizing research methods used for the evaluation of antimicrobial stewardship programs.

Antimicrobial stewardship programs (ASPs) are an increasingly common intervention for optimizing antimicrobial therapy in healthcare settings. These programs aim to improve patient care and limit the emergence and spread of multidrug-resistant organisms by supporting prudent antimicrobial use. However, pressure from the current reimbursement climate necessitates that ASPs operate as cost-cutting programs rather than focus on patient outcomes. This has forced the research that is evaluating ASP interventions to concentrate heavily on economic outcomes. As the science of antimicrobial stewardship advances, it is essential that well-conducted evaluations, focused on patient and microbial outcomes, serve as the evidence base that directs optimal ASP intervention design and implementation. In this review, we provide guidance and recommendations for the design of studies to evaluate the impact of ASP interventions on patient and microbial outcomes.

Frequency of outpatient antibiotic prescription on discharge to hospice care.

The use of antibiotics is common in hospice care despite limited evidence that it improves symptoms or quality of life. Patients receiving antibiotics upon discharge from a hospital may be more likely to continue use following transition to hospice care despite a shift in the goals of care. We quantified the frequency and characteristics for receiving a prescription for antibiotics on discharge from acute care to hospice care. This was a cross-sectional study among adult inpatients (≥18 years old) discharged to hospice care from Oregon Health & Science University (OHSU) from 1 January 2010 to 31 December 2012. Data were collected from an electronic data repository and from the Department of Care Management. Among 62,792 discharges, 845 (1.3%) patients were discharged directly to hospice care (60.0% home and 40.0% inpatient). Most patients discharged to hospice were >65 years old (50.9%) and male (54.6%) and had stayed in the hospital for ≤7 days (56.6%). The prevalence of antibiotic prescription upon discharge to hospice was 21.1%. Among patients discharged with an antibiotic prescription, 70.8% had a documented infection during their index admission. Among documented infections, 40.3% were bloodstream infections, septicemia, or endocarditis, and 38.9% were pneumonia. Independent risk factors for receiving an antibiotic prescription were documented infection during the index admission (adjusted odds ratio [AOR]=7.00; 95% confidence interval [95% CI]=4.68 to 10.46), discharge to home hospice care (AOR=2.86; 95% CI=1.92 to 4.28), and having a cancer diagnosis (AOR=2.19; 95% CI=1.48 to 3.23). These data suggest that a high proportion of patients discharged from acute care to hospice care receive an antibiotic prescription upon discharge.

Variation in antibiotic susceptibility of uropathogens by age among ambulatory pediatric patients.

We compared uropathogen antibiotic susceptibility across age groups of ambulatory pediatric patients. For Escherichia coli (n=5,099) and other Gram-negative rods (n=626), significant differences (p<0.05) existed across age groups for ampicillin, cefazolin, and trimethoprim/sulfamethoxazole susceptibility. In E. coli, differences in trimethoprim/sulfamethoxazole susceptibility varied from 79% in children under 2 to 88% in ages 16-18 (p<0.001), while ampicillin susceptibility varied from 30% in children under 2 to 53% in ages 2-5 (p=0.015). Uropathogen susceptibility to common urinary anti-infectives may be lower in the youngest children. Further investigation into these differences is needed to facilitate appropriate and prudent treatment of urinary tract infections.

Use of electronic health record data to identify hospital-associated Clostridioides difficile infections: a validation study.

Background: Clinical research focused on the burden and impact of Clostridioides difficile infection (CDI) often relies upon accurate identification of cases using existing health record data. Use of diagnosis codes alone can lead to misclassification of cases. Our goal was to develop and validate a multi-component algorithm to identify hospital-associated CDI (HA-CDI) cases using electronic health record (EHR) data. Methods: We performed a validation study using a random sample of adult inpatients at a large academic hospital setting in Portland, Oregon from January 2018 to March 2020. We excluded patients with CDI on admission and those with short lengths of stay (< 4 days). We tested a multi-component algorithm to identify HA-CDI; case patients were required to have received an inpatient course of metronidazole, oral vancomycin, or fidaxomicin and have at least one of the following: a positive C. difficile laboratory test or the International Classification of Diseases, Tenth Revision (ICD-10) code for non-recurrent CDI. For a random sample of 80 algorithm-identified HA-CDI cases and 80 non-cases, we performed manual EHR review to identify gold standard of HA-CDI diagnosis. We then calculated overall percent accuracy, sensitivity, specificity, and positive and negative predictive value for the algorithm overall and for the individual components. Results: Our case definition algorithm identified HA-CDI cases with 94% accuracy (95% Confidence Interval (CI): 88% to 97%). We achieved 100% sensitivity (94% to 100%), 89% specificity (81% to 95%), 88% positive predictive value (78% to 94%), and 100% negative predictive value (95% to 100%). Requiring a positive C. difficile test as our gold standard further improved diagnostic performance (97% accuracy [93% to 99%], 93% PPV [85% to 98%]). Conclusions: Our algorithm accurately detected true HA-CDI cases from EHR data in our patient population. A multi-component algorithm performs better than any isolated component. Requiring a positive laboratory test for C. difficile strengthens diagnostic performance even further. Accurate detection could have important implications for CDI tracking and research.

Risk factors for oral infection and dry socket post-tooth extraction in medically complex patients in the absence of antibiotic prophylaxis: A case-control study.

INTRODUCTION: Dry socket and infection are complications of tooth extractions. The objective was to determine risk factors for post-extraction complications in patients without antibiotic prophylaxis stratified by early- and late-complications and complication type (oral infection and dry socket). METHODS: Retrospective, case (with complications)-control (without complications) study of patients (n = 708) who had ≥1 extraction performed at any Veterans Health Administration facility between 2015-2019 and were not prescribed an antibiotic 30 days pre-extraction. RESULTS: Early complication cases (n = 109) were more likely to be female [odds ratio (OR) = 2.06; 95% confidence interval (CI):1.05-4.01], younger (OR = 0.29; 95% CI:0.09-0.94 patients ≥ 80 years old, reference:18-44 years), Native American/Alaska Native (OR = 21.11; 95% CI:2.33-191.41) and have fewer teeth extracted (OR = 0.53 3+ teeth extracted; 95% CI:0.31-0.88, reference:1 tooth extracted). Late complication cases (n = 67) were more likely to have a bipolar diagnosis (OR = 2.98; 95% CI:1.04-8.57), history of implant placement (OR = 8.27; 95% CI:1.63-41.82), and history of past smoking (OR = 2.23; 95% CI:1.28-3.88). CONCLUSION: Predictors for post-extraction complications among patients who did not receive antibiotic prophylaxis were similar to prior work in cohorts who received prophylaxis. Unique factors identified in a medically complex population included being younger, Native American/Alaska Native, having mental health conditions, history of a dental implant, and fewer teeth extracted.

Utility of beta-lactam allergy assessment in patients receiving vancomycin for surgical prophylaxis.

Background: Beta-lactam antibiotics are first-line agents for most patients receiving antimicrobial prophylaxis in surgical procedures. Despite evidence showing low cross-reactivity between penicillins and cephalosporins, patients with beta-lactam allergies commonly receive vancomycin as an alternative to avoid allergic reaction. Methods: Adult patients receiving vancomycin for surgical prophylaxis with a reported beta-lactam allergy at our institution between August 2017 to July 2018 were retrospectively evaluated for potential eligibility for penicillin allergy testing and/or receipt of standard prophylaxis. Results: Among 830 patients who received vancomycin for surgical prophylaxis, 196 reported beta-lactam allergy and were included in the analysis. Approximately 40 % of surgeries were orthopedic. Of patients receiving vancomycin as first-line therapy, 189 (96.4 %) were potentially eligible for beta-lactam prophylaxis. Conclusions: Patients with beta-lactam allergies often qualify for receipt of a first-line antibiotic. An opportunity exists for improved allergy assessment as an antimicrobial stewardship intervention in surgical prophylaxis.

Use of electronic health record data to identify skin and soft tissue infections in primary care settings: a validation study.

BACKGROUND: Epidemiologic studies of skin and soft tissue infections (SSTIs) depend upon accurate case identification. Our objective was to evaluate the positive predictive value (PPV) of electronic medical record data for identification of SSTIs in a primary care setting. METHODS: A validation study was conducted among primary care outpatients in an academic healthcare system. Encounters during four non-consecutive months in 2010 were included if any of the following were present in the electronic health record: International Classification of Diseases, Ninth Revision (ICD-9) code for an SSTI, Current Procedural Terminology (CPT) code for incision and drainage, or a positive wound culture. Detailed chart review was performed to establish presence and type of SSTI. PPVs and 95% confidence intervals (CI) were calculated among all encounters, initial encounters, and cellulitis/abscess cases. RESULTS: Of the 731 encounters included, 514 (70.3%) were initial encounters and 448 (61.3%) were cellulitis/abscess cases. When the presence of an ICD-9 code, CPT code, or positive culture was used to identify SSTIs, 617 encounters were true positives, yielding a PPV of 84.4% [95% CI: 81.8-87.0%]. The PPV for using ICD-9 codes alone to identify SSTIs was 90.7% [95 % CI: 88.5-92.9%]. For encounters with cellulitis/abscess codes, the PPV was 91.5% [95% CI: 88.9-94.1%]. CONCLUSIONS: ICD-9 codes may be used to retrospectively identify SSTIs with a high PPV. Broadening SSTI case identification with microbiology data and CPT codes attenuates the PPV. Further work is needed to estimate the sensitivity of this method.

Sex- and age-specific trends in antibiotic resistance patterns of Escherichia coli urinary isolates from outpatients.

BACKGROUND: Urinary tract infections (UTIs) are one of the most common infections treated in ambulatory care settings, however the epidemiology differs by age and sex. The incidence of UTI is far greater in females than males, and infection in pediatric patients is more often due to anatomical abnormalities. The purpose of this research was to describe age- and sex-specific trends in antibiotic susceptibility to common urinary anti-infectives among urinary isolates of Escherichia coli from ambulatory primary care patients in a regional health maintenance organization. METHODS: Clinical microbiology data were collected for all urine cultures from patients with visits to primary care clinics in a regional health maintenance organization between 2005 and 2010. The first positive culture for E. coli tested for antibiotic susceptibilities per patient per year was included in the analysis dataset. The frequency of susceptibility to ampicillin, amoxicillin-clavulanate, ciprofloxacin, nitrofurantoin, and trimethoprim/sulfamethoxazole (TMP/SMX) was calculated for male and female patients. The Cochrane-Mantel-Haenzel test was used to test for differences in age-stratified susceptibility to each antibiotic between males and females. RESULTS: A total of 43,493 E. coli isolates from 34,539 unique patients were identified for study inclusion. After stratifying by age, E. coli susceptibility to ampicillin, amoxicillin-clavulanate, ciprofloxacin, and nitrofurantoin differed significantly between males and females. However, the magnitude of the differences was less than 10% for all strata except amoxicillin-clavulanate susceptibility in E. coli isolated from males age 18-64 compared to females of the same age. CONCLUSIONS: We did not observe clinically meaningful differences in antibiotic susceptibility to common urinary anti-infectives among E. coli isolated from males versus females. These data suggest that male sex alone should not be used as an indication for empiric use of second-line broad-spectrum antibiotic agents for the treatment of UTIs.

Reporting behaviors and perceptions toward the National Healthcare Safety Network antimicrobial use (AU) and antimicrobial resistance (AR) modules.

OBJECTIVES: To identify characteristics of US health systems and end users that report antimicrobial use and resistance (AUR) data, to determine how NHSN AUR data are used by hospitals and health systems and end users, and to identify barriers to AUR reporting. DESIGN: An anonymous survey was sent to Society of Infectious Diseases Pharmacists (SIDP) and Society for Healthcare Epidemiology of America (SHEA) Research Network members. METHODS: Data were collected via Survey Monkey from January 21 to February 21, 2020. Respondent and hospital data were analyzed using descriptive statistics. RESULTS: We received responses from 238 individuals across 43 US states. Respondents were primarily pharmacists (84%), from urban areas, (44%), from nonprofit medical centers (81%), and from hospitals with >250 beds (72%). Also, 62% reported data to the AU module and 19% reported data to the AR module. Use of software for local AU or AR tracking was associated with increased reporting to the AU module (19% vs 64%) and the AR module (2% vs 30%) (P < .001 each). Only 36% of those reporting data to the AU module used NHSN AUR data analysis tools regularly and only 9% reported data to the AR module regularly. Technical challenges and time and/or salary support were the most common barriers to AUR participation cited by all respondents. Among those not reporting AUR data, increased local expectations to report and better software solutions were the most commonly identified solutions to increase AUR reporting. CONCLUSIONS: Efforts to increase AUR reporting should focus on software solutions and salary support for data-entry activities. Increasing expectations to report may incentivize local resource allocation to improve AUR reporting rates.

Factors associated with dental implant loss/complications in the Veterans Health Administration, 2015-2019.

OBJECTIVES: Twelve percent of the U.S. population has a dental implant. Although rare, implant loss/complications can impact quality of life. This study evaluated indicators for implant loss/complications. METHODS: Veterans with dental implants placed between 2015 and 2019 were included. Implant loss/complications were defined as implant removal or peri-implant defect treatment within 90 days. Binomial logistic regression identified factors associated with implant loss/complications. RESULTS: From 2015 to 2019, 48,811 dental implants were placed in 38,246 Veterans. Implant loss/complications was identified for 202 (0.4%) implants. In adjusted analyses, Veterans aged 50-64 years (OR = 1.92 (95% confidence interval (CI): 1.06, 3.46)) and ≥65 (OR = 2.01 (95% CI: 1.14, 3.53)) were more likely to have implant loss/complications. History of oral infection, tooth location, and number of implants placed all significantly increased the odds of loss/complications. CONCLUSION: Dental implant loss/complications are rare outcomes. Older age, location of implant, and the number of implants placed during a visit were significant predictors of loss/complication.

General Perceptions and Knowledge of Antibiotic Resistance and Antibiotic Use Behavior: A Cross-Sectional Survey of US Adults.

This study aimed to assess understanding of antibiotic resistance and evaluate antibiotic use themes among the general public. In March 2018, respondents that were ≥21 years old and residing in the United States were recruited from ResearchMatch.org and surveyed to collect data on respondent expectations, knowledge, and opinions regarding prescribing antibiotics and antibiotic resistance. Content analysis was used to code open-ended definitions of antibiotic resistance into central themes. Chi-square tests were used to assess differences between the definitions of antibiotic resistance and antibiotic use. Among the 657 respondents, nearly all (99%) had taken an antibiotic previously. When asked to define antibiotic resistance, the definitions provided were inductively coded into six central themes: 35% bacteria adaptation, 22% misuse/overuse, 22% resistant bacteria, 10% antibiotic ineffectiveness, 7% body immunity, and 3% provided an incorrect definition with no consistent theme. Themes that were identified in respondent definitions of resistance significantly differed between those who reported having shared an antibiotic versus those who had not (p = 0.03). Public health campaigns remain a central component in the fight to combat antibiotic resistance. Future campaigns should address the public's understanding of antibiotic resistance and modifiable behaviors that may contribute to resistance.

Changes in antibiotic prescribing by dentists in the United States, 2012-2019.

OBJECTIVES: Dentists prescribe 10% of all outpatient antibiotics in the United States and are the top specialty prescriber. Data on current antibiotic prescribing trends are scarce. Therefore, we evaluated trends in antibiotic prescribing rates by dentists, and we further assessed whether these trends differed by agent, specialty, and by patient characteristics. DESIGN: Retrospective study of dental antibiotic prescribing included data from the IQVIA Longitudinal Prescription Data set from January 1, 2012 to December 31, 2019. METHODS: The change in the dentist prescribing rate and mean days' supply were evaluated using linear regression models. RESULTS: Dentists wrote >216 million antibiotic prescriptions between 2012 and 2019. The annual dental antibiotic prescribing rate remained steady over time (P = .5915). However, the dental prescribing rate (antibiotic prescriptions per 1,000 dentists) increased in the Northeast (by 1,313 antibiotics per 1,000 dentists per year), among oral and maxillofacial surgeons (n = 13,054), prosthodontists (n = 2,381), endodontists (n = 2,255), periodontists (n = 1,961), and for amoxicillin (n = 2,562; P < .04 for all). The mean days' supply significantly decreased over the study period by 0.023 days per 1,000 dentists per year (P < .001). CONCLUSIONS: From 2012 to 2019, dental prescribing rates for antibiotics remained unchanged, despite decreases in antibiotic prescribing nationally and changes in guidelines during the study period. However, mean days' supply decreased over time. Dental specialties, such as oral and maxillofacial surgeons, had the highest prescribing rate with increases over time. Antibiotic stewardship efforts to improve unnecessary prescribing by dentists and targeting dental specialists may decrease overall antibiotic prescribing rates by dentists.

Incidence and risk factors for clinically confirmed secondary bacterial infections in patients hospitalized for coronavirus disease 2019 (COVID-19).

OBJECTIVE: The true incidence and risk factors for secondary bacterial infections in coronavirus disease 2019 (COVID-19) remains poorly understood. Knowledge of risk factors for secondary infections in hospitalized patients with COVID-19 is necessary to optimally guide selective use of empiric antimicrobial therapy. DESIGN: Single-center retrospective cohort study of symptomatic inpatients admitted for COVID-19 from April 15, 2020, through June 30, 2021. SETTING: Academic quaternary-care referral center in Portland, Oregon. PATIENTS: The study included patients who were 18 years or older with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) PCR test up to 10 days prior to admission. METHODS: Secondary infections were identified based on clinical, radiographic, and microbiologic data. Logistic regression was used to identify risk factors for secondary infection. We also assessed mortality, length of stay, and empiric antibiotics among those with and without secondary infections. RESULTS: We identified 118 patients for inclusion; 31 (26.3%) had either culture-proven or possible secondary infections among hospitalized patients with COVID-19. Mortality was higher among patients with secondary infections (35.5%) compared to those without secondary infection (4.6%). Empiric antibiotic use on admission was high in both the secondary and no secondary infection groups at 71.0% and 48.3%, respectively. CONCLUSIONS: The incidence of secondary bacterial infection was moderate among hospitalized patients with COVID-19. However, a higher proportion of patients received empiric antibiotics regardless of an identifiable secondary infection. Transfer from an outside hospital, baseline immunosuppressant use, and corticosteroid treatment were independent risk factors for secondary infection. Additional studies are needed to validate risk factors and best guide antimicrobial stewardship efforts.

Characteristics of Prescription Drug Use Among Individuals With Multiple Sclerosis in the US Medicare Population.

Background: Few studies have characterized the full spectrum of prescription drug use for individuals with multiple sclerosis (MS). The objective of this study was to describe patterns and expenditures for disease-modifying therapies (DMTs) and other prescription drugs among Medicare beneficiaries with MS. Methods: Using Medicare claims data in 2014, we identified a cohort of Medicare beneficiaries with 12 months of continuous eligibility and 3 or more MS-related inpatient, outpatient, or prescription claims. We quantified the number, type, and costs of prescribed DMTs and other medications for MS-related symptoms. Medication costs were calculated according to whether beneficiaries received additional subsidies, which eliminate most out-of-pocket costs. Results: Of 43,283 Medicare beneficiaries identified with MS, 70% were DMT users. Most used self-administered DMTs (67%), and 3% used natalizumab; 93% received a supportive care medication. Among the 82% of individuals without subsidies, the annual median total and out-of-pocket DMT costs were $56,794 (interquartile range [IQR], $44,837-$62,038) and $4566 (IQR, $849-$5270), respectively. The most commonly used supportive care drugs were antidepressants (62%), opioid analgesics (50%), antispasticity drugs (47%), and anticonvulsants (46%). Annual median total and out-of-pocket costs for these drugs were $15,134 (IQR, $6571-$19,620) and $255 (IQR, $56-$877), respectively. Conclusions: Most Medicare beneficiaries with MS using DMTs face considerable out-of-pocket costs. Beneficiaries also used a significant number of medications potentially used for MS-related symptoms, although total and out-of-pocket costs were modest.

Infectious complications of probiotic use: A matched case-control study.

In this matched case-control study, we sought to determined the association between probiotic use and invasive infections caused by typical probiotic organisms. The odds of probiotic use in cases were 127 times the odds of probiotic use in controls (95% CI, 6.21-2600). Further research into these rare but severe complications is needed.

Association Between Pharmacy Benefit Restrictions and Disease-Modifying Therapy Use in the Medicare Part D Program.

Background and Objectives: To determine the association between Medicare Part D plan disease-modifying therapy (DMT) restrictiveness and adherence and outcomes among people with multiple sclerosis (MS). Methods: We used Medicare claims data from 2010 to 2014 to identify individuals with a full year enrollment (Parts A, B, and D), an MS diagnosis, and 1 or more self-administered DMT prescription. Plans were considered restrictive if all available DMTs required a prior authorization or step therapy restriction; otherwise they were considered permissive. We compared DMT adherence, defined as a medication possession ratio ≥80%, MS-related emergency department or inpatient admissions, and outpatient visits by Part D plan restrictiveness. We used multivariate regression models to control for patient demographics and comorbidities. Results: There were 37,713 Medicare beneficiaries with MS who were enrolled in either restrictive (n = 29,901) or permissive (n = 7812) Part D plans during the study period. Patients enrolled in restrictive plans were older (60 vs 58 years; p < 0.001), more likely to live in the south (38% vs 23%; p < 0.001), eligible through disability (67% vs 60%; p < 0.001), and more likely to have several chronic comorbid conditions. Patients enrolled in restrictive plans were less likely to be adherent to their DMT (54% vs 57%; p < 0.001; adjusted odds ratio [aOR] 0.92, 95% confidence interval [CI] 0.88-0.98) and had a higher rate of MS-related outpatient visits (1.7 vs 1.4 per year; p < 0.001; aRR 1.27, 95% CI 1.23-1.31). Discussion: Medicare beneficiaries with MS enrolled in restrictive Part D plans were less adherent to their DMT and had higher rates of MS-related outpatient visits.