Optimizing large real-world data analysis with parquet files in R: A step-by-step tutorial.

PURPOSE: The use of open-source programming languages can facilitate open science practices in real-world evidence (RWE) studies. Real-world studies often rely on using big data, which makes using such languages complicated. We demonstrate an efficient approach that enables RWE researchers to use R to undertake RWE analysis tasks from cohort building to reporting. METHODS: Using the Merative Marketscan data (2017-2019), we developed an R function to transform the data into parquet format to be used in R. Then, we compared the differences in data size before and after transformation. We compared the performance of the transformed data in R to the original data in terms of numerical consistency and running times required to complete simple exploratory tasks. To show how the transformed databases can be used in practice, we conducted a simplified replication of an active comparator new user study from the literature. All codes are available on GitHub. RESULTS: Our approach exhibited high efficiency in data storage, as evidenced by the converted data size, which ranged from 10% to 43% of that of the original data files. The runtime of the exploratory tasks in R generally outperformed that of the original data with SAS. We showed, through example, how the converted data can be efficiently used to implement an RWE study. CONCLUSION: We demonstrate a free and efficient solution to facilitate the use of open-source programming languages with big real-world databases, which can facilitate the adoption of open science practices.

Adherence and persistence of HIV pre-exposure prophylaxis use in the United States.

PURPOSE: To describe medication adherence and persistence of HIV PrEP overall and compare between sex and age groups of commercially insured individuals in the United States. METHODS: We conducted a national retrospective cohort study of the Merative MarketScan Claims Database from 2011 to 2019 to describe adherence and persistence of PrEP overall and compared between sex and age groups. High adherence was defined as ≥80% of proportion of days covered and persistence was measured in days from initiation to the first day of a 60-day treatment gap. RESULTS: A total of 29 689 new PrEP users identified. Overall adherence was high (81.9%; 95% confidence interval [CI]: 81.5%-82.3%). Females were more adherent than males (adjusted odds ratio [aOR] 1.87; 95% CI: 1.50-2.34), while those ≥45-years were less adherent than individuals <45-years (aOR 0.87: 95% CI: 0.81-0.93). More than half of individuals discontinued therapy within the first year (median 238.0 days; interquartile range 99.0-507.0 days). Females were less persistent than males (hazard ratio [HR] 1.49; 95% CI: 1.34-1.65), and people ≥45-years old were more persistent (i.e., lower risk of discontinuation) than those <45-years (HR 0.43; 95% CI: 0.33-0.55). CONCLUSIONS: These findings show adherence to daily PrEP is high among commercially insured individuals but the majority still discontinue in the first year. Future research should investigate what factors influence PrEP discontinuation among this population and ways to reduce barriers to therapy maintenance to ensure the population-level benefits of PrEP treatment.

Fanconi Syndrome in Patients With Human Immunodeficiency Virus Treated With Tenofovir-Based Antiretroviral Therapy: A Systematic Literature Review.

OBJECTIVE: Several cases of Fanconi syndrome (FS), a severe form of nephrotoxicity, have been reported in patients with HIV on tenofovir-containing antiretroviral therapy. A systematic review of the published literature on tenofovir-related FS in patients with HIV was conducted. DATA SOURCES: PubMed and Embase were queried to identify articles in English published between January 2005 and June 2023, reporting tenofovir-related FS in adults with HIV. Preclinical studies, conference/poster abstracts, commentaries and responses, and review papers were excluded. STUDY SELECTION AND DATA EXTRACTION: Of the 256 articles screened, 57 met the inclusion criteria. These comprised 37 case reports, 11 case series, 1 cross-sectional study, 1 case-control study, 4 cohort studies, 1 single-arm open-label clinical trial, 1 sub-analysis of clinical trials, and 1 pooled analysis of clinical trials. DATA SYNTHESIS: Among 56 cases on which information was abstracted, median age at FS diagnosis was 50 years, 51.8% were men, and duration of tenofovir use ranged from 6 weeks to 11 years. Ritonavir was co-prescribed in almost half the cases. In observational and interventional studies, incidence of FS was low. Many studies reported resolution of FS symptoms after tenofovir discontinuation. All FS occurrences were identified in those on tenofovir disoproxil fumarate (TDF), except for one patient on tenofovir alafenamide (TAF). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Continuous monitoring of signs and symptoms of renal and bone toxicity is essential for patients with HIV on tenofovir-containing therapy. CONCLUSIONS: Occurrence of FS is low in patients with HIV treated with tenofovir-based regimens. Concomitant use of ritonavir may increase risk of FS. TAF may be a safer alternative than TDF in terms of nephrotoxicity.

Evaluating the use of methods to mitigate bias from non-transient medications in the case-crossover design: A systematic review.

PURPOSE: The case-crossover design is a self-controlled study design used to compare exposure immediately preceding an event occurrence with exposure in earlier control periods. The design is most suitable for transient exposures in order to avoid biases that can be problematic when using the case-crossover design for non-transient (i.e., chronic) exposures. Our goal was to conduct a systematic review of case-crossover studies and its variants (case-time-control and case-case-time-control) in order to compare design and analysis choices by medication type. METHODS: We conducted a systematic search to identify recent case-crossover, case-time-control, and case-case-time-control studies focused on medication exposures. Articles indexed in MEDLINE and EMBASE using these study designs that were published between January 2015 and December 2021 in the English language were identified. Reviews, methodological studies, commentaries, articles without medications as the exposure of interest, and articles with no available full text were excluded. Study characteristics including study design, outcome, risk window, control window, reporting of discordant pairs, and inclusion of sensitivity analyses were summarized overall and by medication type. We further evaluated the implementation of recommended methods to account for biases introduced by non-transient exposures among articles that used the case-crossover design on a non-transient exposure. RESULTS: Of the 2036 articles initially identified, 114 articles were included. The case-crossover was the most common study design (88%), followed by the case-time-control (17%), and case-case-time-control (3%). Fifty-three percent of the articles included only transient medications, 35% included only non-transient medications, and 12% included both. Across years, the proportion of case-crossover articles evaluating a non-transient medication ranged from 30% in 2018 to 69% in 2017. We found that 41% of the articles that evaluated a non-transient medication did not apply any of the recommended methods to account for biases and more than half of which were conducted by authors with no previous publication history of case-crossover studies. CONCLUSION: Using the case-crossover design to evaluate a non-transient medication remains common in pharmacoepidemiology. Researchers should apply appropriate design and analysis choices when opting to use a case-crossover design with non-transient medication exposures.

Patterns of prescription opioid use and opioid-related harms among adult patients with hematologic malignancies.

INTRODUCTION: Treatment advances for hematologic malignancies (HM) have dramatically improved life expectancy, necessitating greater focus on long-term cancer pain management. This study explored real-world patterns of opioid use among patients with HM. METHODS: This retrospective cohort study identified adults diagnosed with HM from January 1, 2013 through December 31, 2019 using the Truven MarketScan Commercial Claims and Encounters database. Across several HM types, we described rates of high-risk opioid use (based on Pharmacy Quality Alliance measures) and opioid-related harms, including incident opioid use disorder (OUD) diagnoses and opioid-related hospitalizations or emergency department (ED) visits. We used multivariable Cox regression to generate adjusted hazard ratios and 95% confidence intervals comparing the risk of opioid-related harms between patients with versus without high-risk opioid use. RESULTS: Our sample included 43,190 patients with HM. Median age at HM diagnosis was 54 years (interquartile range = 44-60). Most patients (61.9%) were diagnosed with lymphoma. Approximately half (49.2%) had an opioid dispensed in the follow-up period. Among all patients, 20.0% met criteria for high-risk opioid use, 0.9% had an OUD diagnosis, and 0.3% experienced an opioid-related hospitalization/ED visit in follow-up. High-risk opioid use increased the risk of an OUD diagnosis by 3.3 times (p < 0.0001) and an opioid-related hospitalization/ED visit 4.2 times (p < 0.0001). CONCLUSION: High-risk opioid use was prevalent among patients with HM and significantly increased the risk of opioid-related harms. However, rates of opioid-related harms were low. These findings highlight the importance of continually monitoring pain and opioid use throughout HM survivorship to provide safe, effective HM pain management.

Contextual factors affecting the implementation of drug checking for harm reduction: a scoping literature review from a North American perspective.

BACKGROUND: The opioid epidemic continues to be a significant cause of morbidity and mortality in the US. In 2020, 83% of opioid-related overdose deaths were due to synthetic opioids, such as fentanyl. Drug checking services have been widely implemented as a harm reduction intervention to facilitate the identification of substances in a drug sample. There is a need to inform decision-making on drug checking technologies and service implementation. This research aims to outline contextual considerations for the implementation of a drug checking service. METHODS: A scoping review was conducted using a structured search strategy in PubMed and EMBASE. Articles were independently screened by two reviewers, and included if they were primary literature and reported on an actionable consideration(s) for drug checking services. Data elements were extracted using a standardized form, and included study design, study population, drug checking technology utilized or discussed, and main findings. RESULTS: Twenty-nine articles were selected for inclusion, and four primary areas of consideration were identified: drug checking technologies, venue of a drug checking service, legality, and privacy. Technological considerations include the need for highly accurate, quantitative results which appeal to both populations of people with drug use disorder and recreational users. Accessibility of services was identified as an important factor that may be impacted by the location, integration with other services, how the service is provided (mobile vs. fixed), and the hours of operation. Maintaining plausible deniability and building trust were seen as important facilitators to service use and engagement. Issues surrounding legality were the most frequently cited barrier by patrons, including fear of criminalization, policing, and surveillance. Patrons and stakeholders identified a need for supportive policies that offer protections. Maintaining anonymity for patrons is crucial to addressing privacy-related barriers. CONCLUSION: This review highlights the need to understand the local population and climate for drug checking to implement a drug checking service successfully. Common themes identified in the literature included considerations related to the choice of technology, the type of venue, and the impact of legality and privacy. We intend to utilize these considerations in future research to help guide discussions with US-based stakeholders.

A qualitative assessment of key considerations for drug checking service implementation.

BACKGROUND: With many drug-related deaths driven by potent synthetic opioids tainting the illicit drug supply, drug checking services are becoming a key harm reduction strategy. Many drug checking technologies are available, ranging from fentanyl test strips to mass spectrometry. This study aimed to identify key considerations when implementing drug checking technologies and services to support harm reduction initiatives. METHODS: Key informant interviews were conducted with harm reduction stakeholders throughout Illinois. Participants included members of existing drug checking services and recovery centers. Interviews were recorded, transcribed, and coded by two researchers using the framework method. Findings were contextualized according to micro (client)-, meso (organization)-, and macro (policy)-level themes. RESULTS: Seven interviews were conducted with ten participants. Fourier transform infrared spectroscopy was consistently identified as a technology of choice given its accuracy, range of substance detection, portability, and usability. Recommendations included the use of confirmatory testing, which can help address the limitations of technologies and provide a mechanism to train technicians. Locations of drug checking services should maximize public health outreach and leverage existing harm reduction agencies and staff with lived experience, who are critical to developing trust and rapport with clients. Criminalization and loss of privacy were major concerns for clients using drug checking services. Additional issues included the need to raise awareness of the legitimacy of services through public support from governing bodies, and funding to ensure the sustainability of drug checking services. CONCLUSIONS: This research facilitated the identification of issues and recommendations from stakeholders around key considerations for the adoption of drug checking technologies, which not only included the cost and technical specifications of instrumentation, but also broader issues such as accessibility, privacy, and well-trained personnel trusted by clients of the service. Successful implementation of drug checking services requires knowledge of local needs and capacity and an in-depth understanding of the target population.

Pharmacists and Naloxone: Barriers to Dispensing and Effectiveness of an Educational Outreach Program.

BACKGROUND: The Illinois Naloxone Standing Order allows community pharmacists to dispense naloxone; however, this policy initiative may be underutilized. OBJECTIVE: Our study aims to characterize naloxone dispensing barriers, overall and by pharmacy type, make recommendations that can inform future policies to improve naloxone access, and evaluate outreach initiative effectiveness from academic detailers' perspectives. METHODS: We conducted a retrospective analysis of semistructured data collected as part of an educational outreach program targeting Illinois community pharmacists in 2021. Academic detailers conducted educational outreach visits across community pharmacy settings (i.e., primary pharmacy, grocery pharmacy, or independent pharmacy) to promote standing order use and discuss barriers pharmacists face when dispensing naloxone. Following each visit, detailers recorded visit characteristics, pharmacist-identified obstacles impacting naloxone dispensing, and visit effectiveness. RESULTS: Detailers performed in-person visits at 270 (78%) of 348 targeted sites. A lower proportion of independent pharmacies (61%) routinely stock naloxone than primary (95%, P < 0.001) or grocery (98%, P < 0.001) pharmacies. Among pharmacists at independent pharmacies, 43% indicated they were highly or extremely comfortable dispensing naloxone, a significantly lower proportion than pharmacists at grocery (79%, P < 0.001) or primary (68%, P < 0.001) pharmacies. The prevalence of salient barriers to naloxone dispensing was: cost/insurance issues (primary pharmacy = 38% vs. grocery pharmacy = 36% vs. independent pharmacy = 28%, P = 0.46), stigma (36% vs. 49% vs. 16%, P < 0.05), and lack of standing order enrollment (0% vs. 0% vs. 49%, P < 0.05). On average, detailers perceived visits as less useful to pharmacists working at independent pharmacies than those at primary or grocery pharmacies. CONCLUSIONS: Over 80% of pharmacists reported facing greater than one naloxone dispensing barrier. While cost/insurance issues appear ubiquitous, patient stigma-related factors were prevalent in primary and grocery pharmacies. Although many pharmacists are comfortable dispensing naloxone under the standing order, pharmacists at independent pharmacies are less comfortable, potentially secondary to lower standing order enrollment.

Time-Specific Differences in Stated Preferences for Health in the United States.

BACKGROUND: Changes over time in health state values from a societal perspective may be an important reason to consider updating societal value sets for preference-based measures of health. OBJECTIVE: The aim was to examine whether stated health preferences are different between 2002 and 2017, controlling for demographic changes in the United States. METHODS: Data from 2002 and 2017 US EQ-5D-3L valuation studies were combined. The primary analysis compared valuations of better-than-dead (BTD) states only, as both studies used the same time trade-off (TTO) method for these states. For worse-than-dead (WTD) states, the 2017 study used the lead-time TTO and the 2002 study used the conventional TTO, which necessitated transformation. Regression models were fitted to BTD values to estimate time-specific differences, adjusting for respondent characteristics. Secondary analyses examined models that fitted WTD values (using linear and nonlinear transformations of the 2002 data) and all values. RESULTS: The adjusted BTD-only model showed mean values were higher for 2017 compared with 2002 (ßY2017=0.05, P<0.001). WTD-only models showed negative changes over time but that were dependent on the transformation method (linear ßY2017=-0.72; nonlinear ßY2017=-0.35; both P<0.001). Using all values, 2017 mean valuations were lower using a linear transformation (ßY2017=-0.11; P<0.001) but did not differ with the nonlinear transformation. CONCLUSIONS: Individuals in 2017 are generally less willing to trade quantity for quality of life compared with 2002. This study provides evidence of time-specific differences in a society's preferences, suggesting that the era in which values were elicited may be an important reason to consider updating societal value sets.

Comparison of online and face-to-face valuation of the EQ-5D-5L using composite time trade-off.

OBJECTIVE: The aim of this study was to compare online, unsupervised and face-to-face (F2F), supervised valuation of EQ-5D-5L health states using composite time trade-off (cTTO) tasks. METHODS: The official EuroQol experimental design and valuation protocol for the EQ-5D-5L of 86 health states were implemented in interviewer-assisted, F2F and unsupervised, online studies. Validity of preferences was assessed using prevalence of inconsistent valuations and expected patterns of TTO values. Respondent task engagement was measured using number of trade-offs and time per task. Trading patterns such as better-than-dead only was compared between modes. Value sets were generated using linear regression with a random intercept (RILR). Value set characteristics such as range of scale and dimension ranking were evaluated between modes. RESULTS: Five hundred one online and 1,134 F2F respondents completed the surveys. Mean elicited TTO values were higher online than F2F when compared by health state severity. Compared to F2F, a larger proportion of online respondents did not assign the poorest EQ-5D-5L health state (i.e., 55555) the lowest TTO value ([Online] 41.3% [F2F] 12.2%) (p < 0.001). A higher percentage of online cTTO tasks were completed in 3 trade-offs or fewer ([Online] 15.8% [F2F] 3.7%), (p < 0.001). When modeled using the RILR, the F2F range of scale was larger than online ([Online] 0.600 [F2F] 1.307) and the respective dimension rankings differed. CONCLUSIONS: Compared to F2F data, TTO tasks conducted online had more inconsistencies and decreased engagement, which contributed to compromised data quality. This study illustrates the challenges of conducting online valuation studies using the TTO approach.

Secondary effects of an opioid-focused academic detailing program on non-opioid controlled substance prescribing in primary care.

Background: Educational outreach programs that focus on safe opioid prescribing and awareness of state prescription monitoring programs may modify clinicians' prescribing behavior. The objective of this study was to evaluate the secondary effects of an opioid-focused academic detailing (AD) program on non-opioid controlled substance prescribing in primary care. Methods: A quasi-experimental pre-post study of primary care clinicians exposed and unexposed to the AD program was conducted using data from the Illinois Prescription Monitoring Program from December 2017 to February 2019. Outcomes were mean monthly prescriptions for benzodiazepines (BZD), non-BZD sedative-hypnotics, and carisoprodol, per clinician. A difference-in-differences (DID) approach utilizing repeated-measures mixed-effects linear regression models was used to compare changes in outcomes six-months before and after the program. Results: Mean monthly BZD prescriptions declined in both groups of clinicians (AD-exposed n = 151; controls n = 399) after implementation of the AD program. Although the mean monthly number of BZD prescriptions decreased in both groups after the AD program, BZD prescribing in the AD-exposed group declined at a slower rate following the AD program (DID = 0.73; 95% CI: 0.14, 1.31). The AD-exposed group had a 0.06 (95% CI: -0.11, -0.01) lower rate of mean monthly carisoprodol prescriptions compared to the control group following the AD program. There was no change in the rate of mean monthly non-BZD sedative-hypnotic prescriptions between the two groups. Conclusions: The higher relative rate of BZD prescribing in the AD-exposed group compared to the control group following the AD program may be reflective of an unintended consequence of opioid-focused AD programs as clinicians learn to be cautious about opioid prescribing. Our findings may suggest the need for incorporation of targeted education on appropriate BZD prescribing into opioid-focused AD programs as a featured component. These findings warrant further consideration and investigation before large-scale implementation of opioid-focused educational outreach programs.

Targets of biologic disease-modifying antirheumatic drugs and risk of multiple myeloma.

Several commonly used immune-suppressing biologic drugs target proteins and cytokines involved in myeloma pathogenesis. Our objective was to determine whether targeted biologic disease-modifying antirheumatic drugs (DMARDs) are associated with risk of multiple myeloma (MM). We conducted a nested case-control study within a retrospective cohort of 56,886 commercially insured adults undergoing treatment for rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis between 2009 and 2015 using the Truven Health MarketScan Databases. MM cases (n = 287) were matched to up to 10 controls (n = 2,760) on age, sex and rheumatologic indication using incidence density sampling without replacement. Our exposures of interest were biologic DMARDs targeting tumor necrosis factor-alpha, interleukin 6, cytotoxic t-lymphocyte-associated protein-4 and depletion of B cells. Relative risks were estimated as adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression models. Cases and controls were similar with respect to use of prescription NSAIDs and concurrent conventional-synthetic DMARDs. Cases had slightly fewer etanercept users (4% vs. 7%) and slightly more tocilizumab users (1.4% vs. 0.4%). Compared to patients treated with only conventional-synthetic DMARDs, those receiving concomitant conventional-synthetic plus biologic DMARDs had lower risk of developing MM (OR = 0.48; 95% CI 0.30-0.88; p = 0.02). Risks differed by drug target with an inverse association observed with use of etanercept inhibiting tumor necrosis factor-alpha (OR = 0.55; 95% CI 0.30-1.02; p = 0.06) and a positive association with tocilizumab inhibiting interleukin-6 (OR = 4.33; 95% CI 1.33-14.19; p = 0.02) compared to biologic DMARD-naïve patients. Further investigation is warranted to understand the roles of drugs suppressing tumor necrosis factor-alpha and interleukin-6 in myeloma pathogenesis.

Impact of multimorbidity subgroups on the health care use of early pediatric cancer survivors.

BACKGROUND: Although pediatric cancer survivors in the United States are at an increased risk of developing chronic conditions, to the authors' knowledge there is limited information regarding the types and combinations of conditions they experience in the years immediately after the completion of cancer therapy. METHODS: An observational cohort study of early pediatric cancer survivors (children who were ≥2 years from the end of therapy and aged ≤18 years) was conducted using the Truven Health MarketScan (r) Commercial Claims and Encounters database (2009-2014). Latent class analysis was used to identify comorbidity groups among the subset with ≥2 conditions. Group-level health care use was compared with survivors without chronic conditions using multivariate regression. RESULTS: A total of 3687 early survivors were identified, of whom approximately 41.2% had no chronic conditions, 22.5% had 1 chronic condition, and 36.3% had ≥2 chronic conditions. Among those with ≥2 chronic conditions, 5 groups emerged: 1) general pediatric morbidity (35.4%); 2) central nervous system (CNS) (22.4%); 3) mental health conditions (22.2%); 4) endocrine (26.2%); and 5) CNS with endocrine (3.8%). The CNS group experienced the highest expenditures, at $17,964 more per year (95% CI, $1446-$34,482) compared with survivors without chronic conditions. The CNS group also had the highest odds of an emergency department visit (adjusted odds ratio, 1.71; 95% CI, 1.15-2.56). The endocrine group had the highest odds of hospitalization (odds ratio, 2.29; 95% CI, 1.24-4.22). CONCLUSIONS: Multimorbidity is common among pediatric cancer survivors. The current study identified 5 distinct comorbidity subgroups, all of which experienced high, yet differential, rates of health care use. The results of the current study highlight the complex health care needs of early survivors and provide evidence for the design of targeted survivorship services and interventions.

Practice change intentions after academic detailing align with subsequent opioid prescribing.

OBJECTIVE: Self-reported behavior change is used to evaluate the effectiveness of educational outreach interventions delivered to clinicians, such as academic detailing (AD). However, self-reported changes in behavior are often not corroborated with data on actual behavior change. To assess alignment between self-reported practice change intentions and actual opioid prescribing behavior among primary care clinicians after an AD intervention. METHODS: We used a difference-in-differences approach to compare pre-post changes in opioid prescribing using data from the Illinois Prescription Monitoring Program. An opioid-focused AD intervention was delivered to primary care clinicians from a large health system in the Chicago metropolitan area from June 2018 to August 2018. Immediately after the AD intervention, clinicians were administered a single-item self-reported practice change measure. Clinicians were categorized into 2 groups on the basis of their responses: (1) intention to change and (2) no-to-moderate intention to change. Outcomes were mean total opioid prescriptions and high-dose opioid prescriptions (≥ 90 morphine milligram equivalents) per clinician per month. Repeated measures linear regression models were used to compare changes in opioid prescribing outcomes between the 2 groups in the 6 months before and after the AD intervention. RESULTS: A total of 149 clinicians were included for analysis. An intention to change was reported by 72 clinicians and no-to-moderate intention to change was reported by 77 clinicians. In the 6 months after the AD intervention, there were 1.48 (95% CI -2.48 to -0.47) fewer total opioid prescriptions and 0.50 (-0.69 to -0.31) fewer high-dose opioid prescriptions per clinician per month in the intention to change group than in the no-to-moderate intention to change group. CONCLUSION: This study showed considerable alignment between self-reported practice change intentions and actual changes in opioid prescribing behavior. Future opioid-focused educational outreach interventions should consider using standardized single-item practice change measures as an immediate indicator of future behavior change.

Myelodysplastic syndrome and acute myeloid leukemia after receipt of granulocyte colony-stimulating factors in older patients with non-Hodgkin lymphoma.

BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs), which are used for the prevention of complications from chemotherapy-related neutropenia, are linked to the risk of developing second primary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The objective of this study was to examine the correlation between using a specific G-CSF agent and the risk of MDS/AML among older patients with non-Hodgkin lymphoma (NHL). METHODS: This was a retrospective cohort study of adults aged >65 years who were diagnosed with first primary NHL between 2001 and 2011. With data from the Surveillance, Epidemiology, and End Results-Medicare-linked database, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the risk of MDS/AML associated with the receipt of G-CSF(filgrastim and pegfilgrastim) in Cox proportional-hazards models, which were stratified according to treatment accounting for confounding by indication. RESULTS: Among 18,245 patients with NHL patients who had a median follow-up of 3.5 years, 56% received chemotherapy and/or immunotherapy, and G-CSF was most commonly used in those who received rituximab plus multiple chemotherapy regimens (77%). Subsequent MDS/AML diagnoses were identified in 666 patients (3.7%). A modest increased risk of MDS/AML was observed with the receipt of G-CSF (HR, 1.28; 95% CI, 1.01-1.62) and a trend was observed with increasing doses (Ptrend < .01). When specific agents were analyzed, an increased risk of MDS/AML was consistently observed with filgrastim (≥10 doses: HR, 1.67; 95% CI, 1.25-2.23), but not with pegfilgrastim (≥10 + doses: HR, 1.11; 95% CI, 0.84-1.45). CONCLUSIONS: A higher of MDS/AML was observed in patients with NHL risk among those who received G-CSF that was specific to the use of filgrastim (≥10 doses), but not pegfilgrastim. Neutropenia prophylaxis is an essential component of highly effective NHL treatment regimens. The differential risk related to the types of G-CSF agents used warrants further study given their increasing use and newly available, US Food and Drug Administration-approved, biosimilar products.

Use of Nonpalliative Medications Following Burdensome Health Care Transitions in Hospice Patients: A Matched Cohort Analysis.

BACKGROUND: Limited benefit medications (LBMs), those medications with questionable benefit at the end of life, are often recommended for discontinuation in hospice patients. Transitions in care are associated with inappropriate prescribing in older and terminally ill populations. OBJECTIVES: To evaluate the association between burdensome health care transitions and subsequent receipt of LBMs in older hospice patients. METHODS: We conducted a matched cohort analysis of patients admitted to hospice between 2008 and 2013 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. The prevalence of post-health care transition LBM use was assessed. Adjusted incidence rate ratios (IRRs) were estimated for the association between transitions and subsequent receipt of LBMs. RESULTS: In total, 17.9% of 7064 hospice patients received at least 1 LBM following their first burdensome health care transition. Posttransition continuation of a medication class used before hospice admission was most common for antidementia medications (14.2%) and antihypertensives (11.2%). Transitions were associated with a 33% increase in the risk of receiving at least 1 LBM [IRR, 1.33; 95% confidence interval (CI), 1.25-1.42], increasing to 56% when evaluating only hospitalization transitions (IRR, 1.56; 95% CI, 1.39-1.76). Medication classes more likely to be dispensed after a transition included antihyperlipidemics (IRR, 1.38; 95% CI, 1.13-1.70), antihypertensives (IRR, 1.28; 95% CI, 1.16-1.40), and proton-pump inhibitors (IRR, 1.40; 95% CI, 1.20-1.63). CONCLUSIONS: Burdensome health care transitions were associated with the receipt of nonpalliative medications in older hospice patients. Interventions aimed at improving provider communication and reducing fragmentation in care may help reduce unnecessary medication use in this vulnerable population.

Older Medicare Beneficiaries Frequently Continue Medications with Limited Benefit Following Hospice Admission.

BACKGROUND: The use of medications not relieving symptoms or maximizing quality of life should be minimized following hospice enrollment. OBJECTIVE: To evaluate the frequency of and predictive factors for continuation of medications with limited benefit after hospice admission among those admitted for cancer- and non-cancer-related causes. DESIGN: Cohort study using the Surveillance, Epidemiology and End Results-Medicare linked database. PATIENTS: Medicare Part D-enrolled beneficiaries 66 years and older who were admitted to and died under hospice care between January 1, 2008, and December 31, 2013 (N = 70,035). MAIN MEASURES: Patients were followed from hospice enrollment through death for Part D dispensing of limited benefit medications (LBMs) they had used in the 6 months prior to hospice admission, including anti-hyperlipidemics, anti-hypertensives, oral anti-diabetics, anti-platelets, anti-dementia medications, anti-osteoporotic medications, and proton pump inhibitors. The proportion of patients continuing an LBM after hospice admission was evaluated. Adjusted relative risks (RRs) were estimated for factors associated with LBM continuation. KEY RESULTS: Overall, 29.8% and 30.5% of patients admitted to hospice for a cancer- and non-cancer-related cause, respectively, continued at least one LBM after hospice admission. Anti-dementia medications were continued most frequently (29.3%) while anti-osteoporotic medications were continued least often (14.1%). Compared to home hospice, LBM continuation was greater in hospice patients residing in skilled nursing (RR 1.25, 95% CI 1.20-1.29), non-skilled nursing (RR 1.29, 95% CI 1.25-1.32), and assisted living facilities (RR 1.28, 95% CI 1.24-1.32). Patients with hospice stays ≥ 180 days were more likely to continue at least one LBM compared to those with stays of 1 week or less (RR 13.11, 95% CI 12.25-14.02). CONCLUSIONS: A substantial proportion of Medicare hospice beneficiaries continued to receive LBMs following hospice enrollment. Providers should evaluate the necessity of continuing non-palliative medications at the end of life through a careful, patient-centric consideration of their potential risks and benefits.

Increased risk of mycotic infections associated with sodium-glucose co-transporter 2 inhibitors: a prescription sequence symmetry analysis.

AIMS: To determine the risk of mycotic infections associated with the use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in a real-world setting. METHODS: We conducted a prescription sequence symmetry analysis using data from Truven Health MarketScan (2009-2015). We selected continuously enrolled patients newly initiating both an SGLT2i and an antifungal between 1 April 2013 and 31 December 2015 within time periods of 30, 60, 90, 180 or 365 days of each other. Adjusted sequence ratios (ASR) were calculated for each time period as the ratio of patients initiating SGLT2i first over those initiating an antifungal first adjusted for time trends in prescribing. Analyses were stratified by sex and type of SGLT2i. RESULTS: There were 23 276 patients who newly initiated both SGLT2i and an antifungal in our study period. These patients were further classified into those initiating the two drugs within 365 (n = 17 504), 180 (n = 11 873), 90 (n = 7697), 60 (n = 5856) or 30 (n = 3650) days of each other. Increased risks of mycotic infections were present across all time periods, with the strongest effect observed in the 90-day interval [ASR 1.53 (confidence interval, CI 1.43-1.60)]. Findings differed by sex [90-day ASR females: 1.65 (CI 1.56-1.74); males 1.25 (CI 1.14-1.36)] and by SGLT2i [90-day ASR canagliflozin 1.57 (CI 1.49-1.66); non-canagliflozin 1.42 (CI 1.31-1.55)]. CONCLUSION: Initiation of SGLT2i was associated with an increased risk for mycotic infections. Findings from this commercially insured population in the real world are consistent with evidence available from clinical trials.

Multimorbidity and healthcare utilization among early survivors of pediatric cancer.

Early survivors of pediatric cancer are at increased risk of experiencing chronic conditions; however, little is known about the morbidity burden in this population. In this observational cohort study of commercially insured pediatric cancer survivors in the United States (2009-2014), we find that 22.5% of survivors had one chronic condition, and 36.3% had multiple. Compared with survivors without chronic conditions, the presence of multiple conditions significantly increased the odds of an emergency department visit by 70% (odds ratios [OR], 1.7; 95% confidence interval [CI], 1.4-2.1) and of a hospitalization almost four-fold (OR, 3.8; 95% CI], 2.5-5.5). Findings are important for informing pediatric survivorship care plans in the years following completion of therapy.

Sodium-glucose co-transporter 2 inhibitors and the risk of fractures: A propensity score-matched cohort study.

PURPOSE: To determine the risk of fractures associated with sodium-glucose co-transporter 2 inhibitors (SGLT2i) compared with dipeptidyl peptidase-4 inhibitors (DPP4i). METHODS: We conducted a retrospective cohort study using data from the Truven Health MarketScan (2009-2015) databases. Our cohort included patients newly initiating treatment with SGLT2i or DPP-4i between 1 April 2013 and 31 March 2015 that were matched 1:1 using high dimensional propensity scores. Patients were followed up in an as-treated approach starting from initiation of treatment until the earliest of any fracture, treatment discontinuation, disenrollment, or end of data (31 December 2015). Risk of fractures was determined at any time during the follow-up, early in therapy (1-14 days of the follow-up), and later in therapy (15 days and beyond). Cox proportional hazards models were used to determine hazard ratios and robust 95% confidence intervals (95% CI). RESULTS: After matching, our cohort included 30 549 patients in each treatment group. Over a median follow-up of 219 days, there were 745 fractures overall. The most common site for fractures was the foot (32.7%). The effect estimates for fracture risk occurring at any time during follow-up, early in therapy, and later in therapy were HR 1.11 [95% CI 0.96-1.28], HR 1.82 [95% CI 0.99-3.32], and HR 1.07 [95% CI 0.92-1.24], respectively. CONCLUSION: There is a possible increase in risk for fractures early in therapy with SGLT2i. Beyond this initial period, SGLT2is had no apparent effect on the incidence of fractures.