The State of Use and Utility of Negative Controls in Pharmacoepidemiologic Studies.

Uses of real-world data in drug safety and effectiveness studies are often challenged by various sources of bias. We undertook a systematic search of the published literature through September 2020 to evaluate the state of use and utility of negative controls to address bias in pharmacoepidemiologic studies. Two reviewers independently evaluated study eligibility and abstracted data. Our search identified 184 eligible studies for inclusion. Cohort studies (115, 63%) and administrative data (114, 62%) were, respectively, the most common study design and data type used. Most studies used negative control outcomes (91, 50%), and for most studies the target source of bias was unmeasured confounding (93, 51%). We identified 4 utility domains of negative controls: 1) bias detection (149, 81%), 2) bias correction (16, 9%), 3) P-value calibration (8, 4%), and 4) performance assessment of different methods used in drug safety studies (31, 17%). The most popular methodologies used were the 95% confidence interval and P-value calibration. In addition, we identified 2 reference sets with structured steps to check the causality assumption of the negative control. While negative controls are powerful tools in bias detection, we found many studies lacked checking the underlying assumptions. This article is part of a Special Collection on Pharmacoepidemiology.

Benzonatate Safety and Effectiveness: A Systematic Review of the Literature.

OBJECTIVE: To review the available literature regarding the treatment effects and efficacy of benzonatate needed to better inform patients, providers, and regulators evaluating its role in modern medical therapies. DATA SOURCES: Comprehensive literature searches were conducted in PubMed, Embase (Elsevier), Cochrane Library, and Scopus for original research articles evaluating the effectiveness, tolerability, and safety profile of benzonatate from January 1956 through August 2022. STUDY SELECTION AND DATA EXTRACTION: The identified studies were screened for relevance and then assessed for inclusion through a full-text review, data extraction, and quality assessment by multiple reviewers using the online software Covidence. DATA SYNTHESIS: The selection process resulted in 37 articles consisting of 21 cohort studies, 5 experimental studies, and 11 case studies and series. Initial clinical studies exploring potential therapeutic benefits collected data from very small populations and limited clinical settings. Safety is primarily assessed in terms of toxicity due to overdose or inappropriate use. Quality assessment raised concerns for high degrees of biases primarily related to the limited sample size, data collection, generalizability, and study design. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review reveals substantial limitations within existing evidence pertaining to the safety and clinical effectiveness of benzonatate and thus, a need for large observational studies or randomized trials to better characterize its role and value in modern medical practice. CONCLUSIONS: Rising safety concerns should bring closer scrutiny upon the prescription of benzonatate whose approval is founded upon evidence that would not stand up to current regulatory review.

Optimizing therapeutic decision-making for off-label medicines use: A scoping review and consensus recommendations for improving practice and research.

PURPOSE: Off-label medicines use is a common and sometimes necessary practice in many populations, with important clinical, ethical and financial consequences, including potential unintended harm or lack of effectiveness. No internationally recognized guidelines exist to aid decision-makers in applying research evidence to inform off-label medicines use. We aimed to critically evaluate current evidence informing decision-making for off-label use and to develop consensus recommendations to improve future practice and research. METHODS: We conducted a scoping review to summarize the literature on available off-label use guidance, including types, extent and scientific rigor of evidence incorporated. Findings informed the development of consensus recommendations by an international multidisciplinary Expert Panel using a modified Delphi process. Our target audience includes clinicians, patients and caregivers, researchers, regulators, sponsors, health technology assessment bodies, payers and policy makers. RESULTS: We found 31 published guidance documents on therapeutic decision-making for off-label use. Of 20 guidances with general recommendations, only 35% detailed the types and quality of evidence needed and the processes for its evaluation to reach sound, ethical decisions about appropriate use. There was no globally recognized guidance. To optimize future therapeutic decision-making, we recommend: (1) seeking rigorous scientific evidence; (2) utilizing diverse expertise in evidence evaluation and synthesis; (3) using rigorous processes to formulate recommendations for appropriate use; (4) linking off-label use with timely conduct of clinically meaningful research (including real-world evidence) to address knowledge gaps quickly; and (5) fostering partnerships between clinical decision-makers, researchers, regulators, policy makers, and sponsors to facilitate cohesive implementation and evaluation of these recommendations. CONCLUSIONS: We provide comprehensive consensus recommendations to optimize therapeutic decision-making for off-label medicines use and concurrently drive clinically relevant research. Successful implementation requires appropriate funding and infrastructure support to engage necessary stakeholders and foster relevant partnerships, representing significant challenges that policy makers must urgently address.

Management of Iron Deficiency in Heart Failure: A Review of Evidence.

ABSTRACT: Iron deficiency is common in patients with heart failure and has been associated with worse outcomes, including increases in mortality, disease progression, and hospitalizations. As such, several studies have evaluated the role of iron supplementation in mitigating these risks. Evidence for the role of intravenous iron in improving exercise capacity, quality of life, and hospitalizations is promising, although the benefits of oral iron remain less clear. This review will evaluate the literature surrounding iron supplementation in heart failure and provide practical recommendations for its management.

Increasing student engagement using an Amazing Race-style competition.

BACKGROUND: Game-based learning is a successful strategy for teaching various concepts to students, from general orientations to more in-depth material. Pharmacy students in a first-year lab course were introduced to library and drug information resources through a lecture-style class in their first week of school, which was ineffective in terms of engagement. To combat this issue, the pharmacy liaison librarian advocated for moving this class session later in the semester and proposed a game-based activity to replace the lecture. CASE PRESENTATION: "The Amazing Race: Drug Information Edition" was inspired by a well-known TV competition that involves completing several stages (called "legs") of challenges to finish the race. The librarian developed questions designed to make students use various parts of the library website as well as two drug information databases. Students competed in teams, and the first three teams to complete the race were awarded small prizes. The race was first implemented in 2018, and modifications were made to the 2019 iteration based on student feedback. CONCLUSIONS: Despite several challenges, the race was well received by both the students and the course instructors and increased engagement with introductory library and drug information material. The activity has enhanced the librarian's relationship and collaboration with the course faculty and made a positive impression on the students.

A systematic review of best practices for the perioperative management of abdominal sacrocolpopexy.

PURPOSE: Enhanced recovery after surgery (ERAS) pathways have been shown to reduce surgical morbidity and length of stay across various procedures. Our objective was to systematically evaluate the literature for best practices of ERAS elements in abdominal sacrocolpopexy (ASC), to determine if there is sufficient evidence to create best practice guidelines for this procedure. MATERIALS AND METHODS: Following the preferred reporting items for systematic review and meta-analysis (PRISMA) statement, we performed a review using Pubmed, Embase, and Cochrane Library. Eligible articles contained ERAS components and postoperative outcomes of ASC published in English since 1997. Thirty-five full-text articles were selected for final qualitative analysis. RESULTS: Poor functional status before ASC was associated with a longer length of hospital stay. Laparoscopic ASC was associated with a shorter postoperative hospital stay, with no difference between laparoscopic and robotic approaches. Epidural analgesia in addition to spinal anesthesia lowered levels of pain throughout the postoperative stay in laparoscopic ASC. A multimodal bowel regimen shortened time to first bowel movement compared to a single agent regimen. Removing a Foley catheter may lead to sooner first spontaneous void but may result in higher rates of urinary retention and urinary tract infection. Studies investigating preoperative bowel preparation, preanesthesia medication, and multidose antimicrobial prophylaxis did not show significant benefit. CONCLUSIONS: Best practices for ASC can be developed based on current findings from the literature and extrapolation of evidence from other surgeries where ASC-specific elements are missing, with the ability to modify the pathways as new data become available.

Discrete Choice Experiments to Elicit Patient Preferences for the Treatment of Major Depressive Disorder: A Systematic Review.

BACKGROUND: Individual preferences for treatment options for major depressive disorder can impact therapeutic decision making, adherence, and ultimately outcomes. OBJECTIVES: This systematic review of discrete choice experiments (DCEs) on patient preferences for major depressive disorder treatment assessed the range of DCE applications in major depressive disorder to document patient stakeholder involvement in DCE development and to identify the relative importance of treatment attributes. METHODS: We searched MEDLINE via Ovid (1946-present), EMBASE (Elsevier interface), Cochrane Central Register of Controlled Trials (Wiley interface), and PsycINFO (EBSCO interface) databases on 29 May, 2024. Covidence software facilitated the review, which four members completed independently. The review was conducted in two phases: title and abstract and then a full-text review. We used an established quality reporting tool to evaluate selected articles. The Covidence extraction tool was adapted for this study. RESULTS: A total of 19 articles were included in this review. Most studies elicited preferences for depression treatment (63.2%) and care delivery (10.5%). Two assessed willingness to pay. Individuals prefer a combination of medicine and counseling over each treatment alone. Treatment efficacy, relapse prevention, and symptom relief were among the most important attributes. Individuals were willing to accept larger risks to achieve symptom improvement. Few studies examined preference heterogeneity with latent subgroups. CONCLUSIONS: Discrete choice experiments for major depressive disorder treatment preferences enable an assessment of trade-offs for first-line therapeutic options. Patient stakeholders are infrequently involved as collaborators in the DCE development. Few examined preference heterogeneity among subgroups.

Utility of fractional excretion of urea in acute kidney injury with comparison to fractional excretion of sodium: A systematic review and meta-analysis.

BACKGROUND: Differentiating between intrinsic and prerenal acute kidney injury (AKI) presents a challenge. Here, we assessed the performance of the fractional excretion of urea (FEUrea) and compared it to the fractional excretion of sodium (FENa) in distinguishing intrinsic from prerenal AKI. METHODS: A thorough search was conducted in several databases until January 16, 2024. We included studies evaluating FEUrea, with or without FENa, for differentiating AKI etiologies in adults. We assessed the methodological quality using the QUADAS-2 and QUADAS-C tools. We performed a meta-analysis using the bivariate random effects model, with subgroup analyses to explore the impact of diuretic therapy on FEUrea, and direct statistical comparisons between FEUrea and FENa involving the subgroups with and without diuretics. RESULTS: We included 11 studies with 1108 hospitalized patients. Among eight studies (915 patients) evaluating FEUrea >35% for distinguishing intrinsic from prerenal AKI, the pooled sensitivity and specificity were 66% (95% CI, 49%-79%) and 75% (95% CI, 60%-85%), respectively. In a subset of six studies (302 patients) comparing FEUrea at 35% to FENa at 1% in patients not receiving diuretics, there were no significant differences in sensitivity (77% versus 89%, P = 0.410) or specificity (80% versus 79%, P = 0.956). In four studies, 244 patients on diuretics, FEUrea demonstrated lower sensitivity (52% versus 92%, P < 0.001) but higher specificity (82% versus 44%, P < 0.001) compared to FENa for the diagnosis of intrinsic AKI. CONCLUSIONS: FEUrea has limited utility in differentiating intrinsic from prerenal AKI. FEUrea does not provide a superior alternative to FENa, even in patients receiving diuretics.

New onset or relapsing neuromyelitis optica temporally associated with SARS-CoV-2 infection and COVID-19 vaccination: a systematic review.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare chronic neuroinflammatory autoimmune condition. Since the onset of the COVID-19 pandemic, there have been reports of NMOSD clinical manifestations following both SARS-CoV-2 infections and COVID-19 vaccinations. Objective: This study aims to systematically review the published literature of NMOSD clinical manifestations associated with SARS-CoV-2 infections and COVID-19 vaccinations. Methods: A Boolean search of the medical literature was conducted between December 1, 2019 to September 1, 2022, utilizing Medline, Cochrane Library, Embase, Trip Database, Clinicaltrials.gov, Scopus, and Web of Science databases. Articles were collated and managed on Covidence® software. The authors independently appraised the articles for meeting study criteria and followed PRISMA guidelines. The literature search included all case reports and case series that met study criteria and involved NMOSD following either the SARS-CoV-2 infection or the COVID-19 vaccination. Results: A total of 702 articles were imported for screening. After removing 352 duplicates and 313 articles based on exclusion criteria, 34 articles were analyzed. A total of 41 cases were selected, including 15 patients that developed new onset NMOSD following a SARS-CoV-2 infection, 21 patients that developed de novo NMOSD following COVID-19 vaccination, 3 patients with known NMOSD that experienced a relapse following vaccination, and 2 patients with presumed Multiple Sclerosis (MS) that was unmasked as NMOSD post-vaccination. There was a female preponderance of 76% among all NMOSD cases. The median time interval between the initial SARS-CoV-2 infection symptoms and NMOSD symptom onset was 14 days (range 3-120 days) and the median interval between COVID-19 vaccination and onset of NMO symptoms was 10 days (range 1 to 97 days). Transverse myelitis was the most common neurological manifestation in all patient groups (27/41). Management encompassed acute treatments such as high dose intravenous methylprednisolone, plasmapheresis, and intravenous immunoglobulin (IVIG) and maintenance immunotherapies. The majority of patients experienced a favorable outcome with complete or partial recovery, but 3 patients died. Conclusion: This systematic review suggests that there is an association between NMOSD and SARS-CoV-2 infections and COVID-19 vaccinations. This association requires further study using quantitative epidemiological assessments in a large population to better quantify the risk.

Telehealth Palliative Care in Nursing Homes: A Scoping Review.

OBJECTIVES: Many adults older than 65 spend time in a nursing home (NH) at the end of life where specialist palliative care is limited. However, telehealth may improve access to palliative care services. A review of the literature was conducted to synthesize the evidence for telehealth palliative care in NHs to provide recommendations for practice, research, and policy. DESIGN: Joanna Briggs Institute guidance for scoping reviews, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews frameworks were used to guide this literature review. SETTINGS AND PARTICIPANTS: Reviewed articles focused on residents in NHs with telehealth palliative care interventionists operating remotely. Participants included NH residents, care partner(s), and NH staff/clinicians. METHODS: We searched Medline (Ovid), Embase (Elsevier), Cochrane Library (WileyOnline), Scopus (Elsevier), CINHAL (EBSCOhost), Trip PRO, and Dissertations & Theses Global (ProQuest) in June 2021, with an update in January 2022. We included observational and qualitative studies, clinical trials, quality improvement projects, and case and clinical reports that self-identified as telehealth palliative care for NH residents. RESULTS: The review yielded 11 eligible articles published in the United States and internationally from 2008 to 2020. Articles described live video as the preferred telehealth delivery modality with goals of care and physical aspects of care being most commonly addressed. Findings in the articles focused on 5 patient and family-centered outcomes: symptom management, quality of life, advance care planning, health care use, and evaluation of care. Consistent benefits of telehealth palliative care included increased documentation of goals of care and decrease in acute care use. Disadvantages included technological difficulties and increased NH financial burden. CONCLUSIONS AND IMPLICATIONS: Although limited in scope and quality, the current evidence for telehealth palliative care interventions shows promise for improving quality and outcomes of serious illness care in NHs. Future empirical studies should focus on intervention effectiveness, implementation outcomes (eg, managing technology), stakeholders' experience, and costs.

In too deep? A systematic literature review of fully-immersive virtual reality and cybersickness among older adults.

BACKGROUND: Virtual reality technology holds great promise in improving the health and well-being of older adults; however, this technology is associated with potential risks that may outweigh the benefits. The purpose of this systematic review is to synthesize and critique the existing literature on fully-immersive virtual reality interventions for older adults and the associated risk of cybersickness. METHODS: We searched eight databases for studies that utilized fully-immersive virtual reality, stated the population as older adults, provided outcomes related to cybersickness, and were written or translated into the English language. Our search generated 332 articles, 39 of which were selected for inclusion in this systematic synthesis and appraisal. RESULTS: We found that the majority of studies utilized a one-time session. The studies generally had weak sample generalizability and methodological design, but strong data collection and participant retention. The studies nearly all used the Simulator Sickness Questionnaire to measure cybersickness, but the scoring for the Simulator Sickness Questionnaire varied or was not mentioned. Most included studies reported only minor cybersickness among older adult participants. CONCLUSION: Researchers might conclude that the benefits of virtual reality interventions outweigh the risk of cybersickness in this population. Going forward, researchers should concentrate on the efficacy of virtual reality interventions among older adults, using larger samples and randomized controlled study design, along with measuring dosage effects.

AACP faculty affairs standing committee report of strategies for faculty self-advocacy and promotion.

OBJECTIVES: The 2020-2021 American Association of Colleges of Pharmacy Faculty Affairs Standing Committee (FASC) was charged with identifying how faculty can self-advocate and promote themselves in a social influence context. FINDINGS: The FASC identified social influence and persuasion theories and strategies that can be used by faculty to initiate self-advocacy discussions and collaborations. Social influence and persuasion theories can provide a framework for research and scholarship or for beginning discussions regarding self-advocacy. SUMMARY: This FASC report describes the Committee charge, background information, and an overview of social influence theories and how these theories can be applied in academic pharmacy. The report concludes with a summary of issues for follow-up to the Committee's work.

Systematic review and meta-analysis of the correlation between bispectral index (BIS) and clinical sedation scales: Toward defining the role of BIS in critically ill patients.

INTRODUCTION: The bispectral index (BIS) is an attractive approach for monitoring level of consciousness in critically ill patients, particularly during paralysis, when commonly used sedation scales cannot be used. OBJECTIVES: As a first step toward establishing the utility of BIS during paralysis, this review examines the strength of correlation between BIS and clinical sedation scales in a broad population of non-paralyzed, critically ill adults. METHODS: We included studies evaluating the strength of correlation between concurrent assessments of BIS and Richmond Agitation Sedation Scale (RASS), Ramsay Sedation Scale (RSS), or Sedation Agitation Scale (SAS) in critically ill adult patients. Studies involving assessment of depth sedation periperative or procedural time periods, and those reporting BIS and sedation scale assessments conducted >5 min apart or while neuromuscular blocking agents (NMBA) were administered, were excluded. Data were abstracted on sedation scale, correlation coefficients, setting, patient characteristics, and BIS assessment characteristics that could impact the quality of the studies. RESULTS: Twenty-four studies which enrolled 1235 patients met inclusion criteria. The correlation between BIS and RASS, RSS, and SAS overall was 0.68 (95% confidence interval, 0.61-0.74, Ƭ2  = 0.06 I2  = 71.26%). Subgroup analysis by sedation scale indicated that the correlation between BIS and RASS, RSS, and SAS were 0.66 (95% confidence interval 0.58-0.73, Ƭ2  = 0.01 I2  = 30.20%), 0.76 (95% confidence interval 0.69-0.82, Ƭ2  = 0.04 I2  = 67.15%), and 0.53 (95% confidence interval 0.42-0.63, Ƭ2  = 0.01 I2  = 26.59%), respectively. Factors associated with significant heterogeneity included comparator clinical sedation scale, neurologic injury, and the type of intensive care unit (ICU) population. CONCLUSIONS: BIS demonstrated moderate to strong correlation with clinical sedation scales in adult ICU patients, providing preliminary evidence for the validity of BIS as a measure of sedation intensity when clinical scales cannot be used. Future studies should determine whether BIS monitoring is safe and effective in improving outcomes in patients receiving NMBA treatment.

A Systematic Review of Cost-Effectiveness Analyses for Hepatocellular Carcinoma Treatment.

BACKGROUND: Hepatocellular carcinoma (HCC) is associated with significant financial burden for patients and payers. The objective of this study was to review economic models to identify, evaluate, and compare cost-effectiveness estimates for HCC treatments. METHODS: A systematic search of the PubMed, Embase, and Cochrane Library databases to identify economic evaluations was performed and studies that modeled treatments for HCC reporting costs and cost effectiveness were included. Risk of bias was assessed qualitatively, considering costing approach, reported study perspective, and funding received. Intervention costs were adjusted to 2021 US dollars for comparison. For studies reporting quality-adjusted life-years (QALYs), we conducted analyses stratified by comparison type to assess cost effectiveness at the time of the analysis. RESULTS: A total of 27 studies were included. Non-curative versus non-curative therapy comparisons were used in 20 (74.1%) studies, curative versus curative comparisons were used in 5 (18.5%) studies, and curative versus non-curative comparisons were used in 2 (7.4%) studies. Therapy effectiveness was estimated using a QALY measure in 20 (74.1%) studies, while 7 (25.9%) studies only assessed life-years gained (LYG). A health sector perspective was used in 26 (96.3%) of the evaluations, with only 1 study including costs beyond this perspective. Median intervention cost was $53,954 (range $4550-$4,760,835), with a median incremental cost of $6546 (range - $72,441 to $1,279,764). In cost-utility analyses, 11 (55%) studies found the intervention cost effective using a $100,000/QALY threshold at the time of the study, with an incremental cost-effectiveness ratio (ICER) ranging from - $1,176,091 to $1,152,440 when inflated to 2021 US dollars. CONCLUSION: The majority of HCC treatments were found to be cost effective, but with significant variation and with few studies considering indirect costs. Standards for value assessment for HCC treatments may help improve consistency and comparability.

Patient Centeredness in Hepatitis C Direct-Acting Antiviral Treatment Delivery to People Who Inject Drugs: A Scoping Review.

BACKGROUND AND OBJECTIVE: Patient-centered care (PCC) is crucial for value-based care. We aimed to assess PCC dimensions addressed in hepatitis C virus direct-acting antiviral treatment delivery to people who inject drugs. METHODS: We conducted a scoping review to identify the studies that described hepatitis C virus treatment delivery to people who inject drugs in the direct-acting antiviral treatment era. We analyzed the included studies against eight PCC dimensions: (1) access to care; (2) coordination and integration of care; (3) continuity and translation; (4) physical comfort; (5) information, education, and communication; (6) emotional support; (7) involvement of family and friends; and (8) respect for individual patient preferences, perceived needs, and values. Additionally, we assessed the use of patient-centered terminology and the recognition of PCC importance and its relevance to treatment outcomes. RESULTS: None of the identified 36 studies addressed all PCC dimensions (highest seven, lowest two). Our findings revealed that PCC dimensions are prioritized differently and addressed using different approaches and strategies. Studies that used PCC terminology referred to personalized activities, which does not imply comprehensive PCC. About one-third of the studies acknowledged the importance of patient centeredness and two-thirds recognized its relevance to treatment outcomes. CONCLUSIONS: Our findings suggest more engagement of people who inject drugs and comprehensive involvement of their families and friends in hepatitis C virus treatment journey, decisions, and outcomes. The recognition of PCC importance and its relevance to treatment outcomes in the analyzed studies emphasizes the need for more patient-centered hepatitis C virus treatment for people who inject drugs.

Risks and benefits of antioxidant dietary supplement use during cancer treatment: protocol for a scoping review.

INTRODUCTION: Antioxidant dietary supplements are used by many patients with cancer to reduce the side effects of chemotherapy and improve prognosis. While some research indicates oral antioxidant supplementation reduces side effects and improves patient survival, other studies suggest the use of antioxidant dietary supplements may interfere with chemotherapy and reduce its curative effects. There is a need to clarify the evidence base on the impact of dietary antioxidant supplementation during chemotherapy on both side effect and treatment efficacy outcomes. We will use a scoping review approach to identify what systematic review evidence exists regarding beneficial and harmful effects of dietary antioxidant supplements when used during cancer treatment. METHODS AND ANALYSIS: We will use Arksey & O'Malley and Joanna Briggs Institute methods for scoping reviews. We will systematically search PubMed, Embase, CINAHL, Scopus, Dissertations & Theses Global and the Cochrane Library from inception to October 2020. Systematic reviews of randomised controlled trials of oral dietary antioxidant supplements used by participants receiving curative chemotherapy, radiotherapy or other biological therapy for cancer will be eligible. Two reviewers will screen citations and full texts for inclusion and chart data on research questions from included reviews. Two reviewers will assess the overall confidence in systematic review results using A Measurement Tool to Assess Systematic Reviews-2 (AMSTAR-2), and summarised evidence will focus on reviews rated at high or moderate overall confidence. Tables will be used to map existing evidence and identify evidence gaps for safety and effectiveness outcomes. ETHICS AND DISSEMINATION: This scoping review does not require ethical approval as it is a secondary assessment of available literature. The results will be presented at conferences and submitted for publication in a peer-reviewed journal. We will also disseminate results to community and clinical stakeholders and involve them in developing subsequent research to address critical existing gaps in the evidence as identified by the scoping review.

A Comprehensive Review of Methods to Measure Oral Oncolytic Dose Intensity Using Retrospective Data.

BACKGROUND: Understanding the real-world use of oral oncolytics is essential to assess drug effectiveness. Retrospective analyses using medical and pharmacy claims data allow observation of drug use patterns and health outcomes. However, studies of medication adherence to oral oncolytics may not be sufficient in characterizing exposure because they typically measure refill frequency, not the administered dose or dose changes. Patients who appear fully adherent by traditional measures may be receiving different doses and experiencing differing effectiveness. Relative dose intensity (RDI) is a measure that has been used for intravenous drugs to capture the amount of a particular chemotherapeutic agent administered per unit of time (dose intensity), expressed as the fraction of the amount recommended in evidence-based guidelines. Such a measure would be useful for real-world studies of comparative effectiveness to characterize patient exposure to oral oncolytics. OBJECTIVE: To identify studies that used administrative claims data to measure real-world oral oncolytic dose intensity, RDI, or similar constructs. METHODS: Two health sciences librarians conducted a literature search (PubMed, January 1, 1809-February 6, 2018) including terms in each of the following concept areas: oncology drugs, dosage, and retrospective data sources. At least 2 reviewers scanned each title and abstract of publications retrieved from PubMed. Abstracts that indicated the study reported dose or related concepts and oral oncolytics using retrospective data sources were marked for full-text review. During full-text review, papers were excluded if they did not study oral oncolytics (i.e., only described intravenous chemotherapy); if they did not report drug dosage; or if the study was not retrospective. Resulting studies were included for full-text data extraction. RESULTS: Of the 1,640 publications returned from the search, 41 were marked for full-text review. Full-text review established that 17 studies addressed a concept related to dose of oral oncolytics using retrospective data. Twenty-four studies were excluded: 11 did not measure dose; 9 did not study oral oncolytics; and 4 were not retrospective studies. Among the 17 articles marked for extraction, 5 articles reported dose intensity or RDI using medical records or electronic health record (EHR) data. CONCLUSIONS: This study reveals not only the need for a claims-based measure of dose intensity for oral oncolytics, but also provides a basis for the development of such a measure based on previous EHR-based studies. While several claims data studies have characterized oral oncolytic dosing and duration, we found that no studies combined these dimensions into a single measure such as dose intensity. Methods using EHR data may be translatable to a claims data study. Future research is needed to develop and validate such measures. DISCLOSURES: Novartis Pharmaceuticals provided funding for this study and is a manufacturer of oral onalytics, which is under study in this article. Arcona and Zacker are employees of Novartis. Slejko reports grants from PhRMA, PhRMA Foundation, and Takeda Pharmaceuticals and consulting fees from Pfizer, outside the submitted work. Stuart reports consulting fees from the University of Maryland during the study. The other authors have nothing to disclose. The preliminary findings of this study were presented in a poster at AMCP Nexus 2018, October 22-25, 2018, in Orlando, FL.

Granulomatous inflammation masquerading as an infected urachal cyst.

Errors in urachal obliteration may result in 4 clinical anomalies: patent urachus, urachal cyst, urachal sinus, or vesicourachal diverticulum. Despite the fact that urachal cysts are one of the more common of these anomalies, most go undetected, presenting in the setting of infection. There are reports in the literature of cysts misdiagnosed as other inflammatory processes; however, the converse is reported with less frequency. We present the case of a 3-year-old girl who was admitted to our institution with a suspected urachal cyst. This was subsequently diagnosed as a granulomatous mass caused by the gram negative bacterium Bartonella.

Man with posterior fossa tumors 15 years apart.

A 48-year-old man with a history of hypertension, peripheral vascular disease and a 50-pack-year history of smoking presented with new onset vertigo, tinnitus, diplopia and ataxia in January 1978. CT scan showed a radiolucent defect in the left cerebellar hemisphere with a possible mural nodule. In ensuing months, he experienced worsening symptoms with a corresponding increase in lesion size on re-imaging. Months later, a left posterior fossa craniotomy was performed and revealed a single cystic lesion containing copious amounts of straw-colored fluid and a single mural nodule in the inferior portion of the cyst. Following resection, he was followed clinically until 1985 at which time follow-up was discontinued. He did well until January 1993 when he presented with progressively worsening episodic headaches and retro-orbital pressure. Subsequent MRIs of the brain and spine (February 1993, March 1993) showed multiple lesions along the neuraxis involving the superficial brain parenchyma, leptomeninges, and dura. Despite therapy, his condition progressively declined until he succumbed. A brain-only autopsy revealed numerous small tumor nodules involving the base of the brain over both frontal and temporal lobes, midbrain, pons, right optic nerve, pituitary fossa, and the base of the skull. Pathologic evaluation revealed metastatic hemangioblastoma. Metastatic hemangioblastoma is a rare entity, with only a few reported cases in the literature to date.