Professional Fulfillment and Burnout in Fourth-Year Pharmacy Students and Risk Factors for the Future: A Mixed Methods Study.

OBJECTIVE: Many factors shape the professional identity of pharmacy students; however, little is known about the influence of well-being. Two aspects of well-being explored in this study include professional fulfillment and burnout. We describe the current levels of each among fourth-year pharmacy students, identify possible predictors, and uncover themes. METHODS: The Stanford Professional Fulfillment Index was used to measure professional fulfillment and burnout among students in the prior 2 weeks. Multivariable linear regressions were conducted to identify individual characteristics and activities as predictors of professional fulfillment and burnout. Upon completion of activities to foster personal wellness, student self-reflections were analyzed using thematic analysis to describe student-perceived barriers and facilitators of professional fulfillment and burnout. RESULTS: In total 54 students completed the Professional Fulfillment Index, wellness activities, and self-reflection. Having already completed the jurisprudence examination required for licensure and having a job upon graduation were statistically significantly associated with higher professional fulfillment scores. We identified that working in a non-pharmacy-related job, while completing practicums, was statistically significantly associated with higher work exhaustion scores. Themes uncovered from student self-reflections included a definition of wellness, how doing what you are supposed to be doing and working in a psychologically and physically safe environment contributes to professional fulfillment, and system-level factors leading to burnout. CONCLUSION: This study provides evidence of the importance of supporting pharmacy students in the completion of the steps to licensure, the value of exposure to a variety of pharmacist-related activities through experiential education, and well-being as foundational to professional identity.

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.

Association of Preterm Birth and Socioeconomic Status With Neonatal Brain Structure.

Importance: Preterm birth and socioeconomic status (SES) are associated with brain structure in childhood, but the relative contributions of each during the neonatal period are unknown. Objective: To investigate associations of birth gestational age (GA) and SES with neonatal brain morphology by testing 3 hypotheses: GA and SES are associated with brain morphology; associations between SES and brain morphology vary with GA; and associations between SES and brain structure and morphology depend on how SES is operationalized. Design, Setting, and Participants: This cohort study recruited participants from November 2016 to September 2021 at a single center in the United Kingdom. Participants were 170 extremely and very preterm infants and 91 full-term or near-term infants. Exclusion criteria were major congenital malformation, chromosomal abnormality, congenital infection, cystic periventricular leukomalacia, hemorrhagic parenchymal infarction, and posthemorrhagic ventricular dilatation. Exposures: Birth GA and SES, operationalized at the neighborhood level (using the Scottish Index of Multiple Deprivation), the family level (using parental education and occupation), and subjectively (World Health Organization Quality of Life measure). Main Outcomes and Measures: Brain volume (85 parcels) and 5 whole-brain cortical morphology measures (gyrification index, thickness, sulcal depth, curvature, surface area) at term-equivalent age (median [range] age, 40 weeks, 5 days [36 weeks, 2 days to 45 weeks, 6 days] and 42 weeks [38 weeks, 2 days to 46 weeks, 1 day] for preterm and full-term infants, respectively). Results: Participants were 170 extremely and very preterm infants (95 [55.9%] male; 4 of 166 [2.4%] Asian, 145 of 166 [87.3%] White) and 91 full-term or near-term infants (50 [54.9%] male; 3 of 86 [3.5%] Asian, 78 of 86 [90.7%] White infants) with median (range) birth GAs of 30 weeks, 0 days (22 weeks, 1 day, to 32 weeks, 6 days) and 39 weeks, 4 days (36 weeks, 3 days, to 42 weeks, 1 day), respectively. In fully adjusted models, birth GA was associated with a higher proportion of brain volumes (27 of 85 parcels [31.8%]; ß range, -0.20 to 0.24) than neighborhood-level SES (1 of 85 parcels [1.2%]; ß = 0.17 [95% CI, -0.16 to 0.50]) or family-level SES (maternal education: 4 of 85 parcels [4.7%]; ß range, 0.09 to 0.15; maternal occupation: 1 of 85 parcels [1.2%]; ß = 0.06 [95% CI, 0.02 to 0.11] respectively). There were interactions between GA and both family-level and subjective SES measures on regional brain volumes. Birth GA was associated with cortical surface area (ß = 0.10 [95% CI, 0.02 to 0.18]) and gyrification index (ß = 0.16 [95% CI, 0.07 to 0.25]); no SES measure was associated with cortical measures. Conclusions and Relevance: In this cohort study of UK infants, birth GA and SES were associated with neonatal brain morphology, but low GA had more widely distributed associations with neonatal brain structure than SES. Further work is warranted to elucidate the mechanisms underlying the association of both GA and SES with early brain development.

Immuno-epigenetic signature derived in saliva associates with the encephalopathy of prematurity and perinatal inflammatory disorders.

BACKGROUND: Preterm birth is closely associated with a phenotype that includes brain dysmaturation and neurocognitive impairment, commonly termed Encephalopathy of Prematurity (EoP), of which systemic inflammation is considered a key driver. DNA methylation (DNAm) signatures of inflammation from peripheral blood associate with poor brain imaging outcomes in adult cohorts. However, the robustness of DNAm inflammatory scores in infancy, their relation to comorbidities of preterm birth characterised by inflammation, neonatal neuroimaging metrics of EoP, and saliva cross-tissue applicability are unknown. METHODS: Using salivary DNAm from 258 neonates (n = 155 preterm, gestational age at birth 23.28 - 34.84 weeks, n = 103 term, gestational age at birth 37.00 - 42.14 weeks), we investigated the impact of a DNAm surrogate for C-reactive protein (DNAm CRP) on brain structure and other clinically defined inflammatory exposures. We assessed i) if DNAm CRP estimates varied between preterm infants at term equivalent age and term infants, ii) how DNAm CRP related to different types of inflammatory exposure (maternal, fetal and postnatal) and iii) whether elevated DNAm CRP associated with poorer measures of neonatal brain volume and white matter connectivity. RESULTS: Higher DNAm CRP was linked to preterm status (-0.0107 ± 0.0008, compared with -0.0118 ± 0.0006 among term infants; p < 0.001), as well as perinatal inflammatory diseases, including histologic chorioamnionitis, sepsis, bronchopulmonary dysplasia, and necrotising enterocolitis (OR range |2.00 | to |4.71|, p < 0.01). Preterm infants with higher DNAm CRP scores had lower brain volume in deep grey matter, white matter, and hippocampi and amygdalae (ß range |0.185| to |0.218|). No such associations were observed for term infants. Association magnitudes were largest for measures of white matter microstructure among preterms, where elevated epigenetic inflammation associated with poorer global measures of white matter integrity (ß range |0.206| to |0.371|), independent of other confounding exposures. CONCLUSIONS: Inflammatory-related DNAm captures the allostatic load of inflammatory burden in preterm infants. Such DNAm measures complement biological and clinical metrics when investigating the determinants of neurodevelopmental differences.

Moving beyond professionalism: Pharmacy students understanding of professionalism and professional identity.

INTRODUCTION: Professional identity is who we are in the context of our chosen profession, a complex and dynamic process. The purpose of this study was to describe pharmacy students' understanding of the terms professionalism and professional identity and the elements of formal and informal curricular activities that may contribute to professional identity formation. METHODS: This anonymous cross-sectional survey was administered to pharmacy students in years one through five at all 10 Canadian pharmacy schools with the help of local Canadian Association of Pharmacy Students and Interns representatives. Students were first asked to define professionalism and professional identity and then were provided with a definition of professional identity to support their statements as to what experiences were meaningful in its development. Both an inductive and deductive approach were used for thematic analysis of written responses alongside descriptive statistics. RESULTS: A total of 172 students responded. Most students were from the University of Alberta and were evenly distributed through years one through four of pharmacy. Key themes emerged of the traditional view of professionalism, expanding the six tenets defined by the American College of Clinical Pharmacy to include responsibility and accountability. Pharmacy students' definitions of professional identity more often included facets of professionalism, but when prompted acknowledged teaching related opportunities, professional development, and role-modelling as playing a key role in professional identity development. CONCLUSIONS: Most pharmacy students were unable to formally define professional identity; however when prompted they did understand what it was and which experiences nurtured its development.

Emotion regulation and cortisol response to the still-face procedure in preterm and full-term infants.

In infancy, stress responses and emotion regulation are often coupled. Both are impacted by prematurity, though their relationship to one another in the case of infants born preterm is not fully understood. We investigated emotion regulation behaviours, cortisol reactivity and recovery and coupling between emotion regulation and cortisol reactivity to and recovery from a stressor in preterm infants. 53 preterm and 67 full-term infants with mean (range) gestational age at birth 29+3 (24+0-31+6) and 39+3 (36+2-42+0) weeks respectively were exposed to a socio-emotional stressor, the still-face (SF) paradigm, at 9 months of age (corrected for prematurity). The duration of negative affect and self-comforting behaviours exhibited in response to the SF, coded from a 10-minute video-taped interaction, were compared between groups. Saliva was collected from a subset (20 preterm, 24 term infants) at three timepoints: pre-SF and 20- and 30-minutes post SF. Cortisol concentrations at each timepoint were compared between groups. Associations between behavioural measures and cortisol concentrations were explored. There was no significant difference in duration of self-comforting behaviour between preterm and term infants. Preterm infants spent a significantly smaller proportion of time in a negative affective state compared to term infants (0.18 vs 0.25 s, p = 0.03). Salivary cortisol concentration was significantly higher in the preterm compared to the term group 30 min post SF (2.85 vs 1.77 nmol/L, p = 0.009), though findings were no longer significant after adjusting for time of day of sampling and socioeconomic deprivation. After controlling for time of day, greater negative affect was correlated with higher cortisol concentration 30 min post SF in the full-term (r = 0.58, p = 0.004) but not the preterm group (r = -0.01, p > 0.05). Our findings suggest altered response to an acute stressor in preterm infants, manifesting as a muted emotional response, and a lack of coupling between endocrine and behavioural stress response. Replication studies in larger samples would help to further understand biological stress repose in preterm infants and its relationship to behaviour, time of day and deprivation.

The impact of the COVID-19 pandemic on pharmacy students' personal and professional learning.

INTRODUCTION: The COVID-19 pandemic impacted both healthcare delivery and the education of healthcare students, with a shift to remote delivery of coursework and assessment alongside the expansion of the scope of practice of Alberta pharmacists. The objective of this research was to understand how the learning of pharmacy students at the University of Alberta was impacted by the COVID-19 pandemic. METHODS: A cross-sectional survey was distributed to 397 pharmacy students in years one through three. Students responded to three short-answer reflection questions: (1) how has the COVID-19 pandemic situation affected your learning; (2) from a pharmacy and pharmacy school perspective, what have you learned since the COVID-19 pandemic began; and (3) from a personal perspective, what have you learned about yourself since the COVID-19 pandemic began? A thematic analysis was undertaken of students' responses to these reflection questions. RESULTS: A total of 53 students responded to the survey (response rate 13%). Two major themes were identified across all three reflection questions, with several subthemes: remote learning (learning environment, knowledge transfer, knowledge retention, assessment) and mental health (appreciation, stress, extroversion, motivation). Adaptability, routine, professional identity, and the role of the pharmacist were also identified as less prevalent themes. CONCLUSIONS: Pharmacy students' responses led to the identification of several themes related to their learning given the changes brought about by the COVID-19 pandemic. This increased understanding of student perceptions has the potential to improve the remote delivery of education, support increased university-wide mental health resourcing, and shape pharmacy curriculum development.

Thiazide Diuretic-Induced Change in Fasting Plasma Glucose: a Meta-analysis of Randomized Clinical Trials.

BACKGROUND: Prior meta-analyses measuring thiazide-induced glycemic change have demonstrated an increased risk of incident diabetes; however, this measure's definition has changed over time. AIM: To determine the magnitude of change in fasting plasma glucose (FPG) for thiazide diuretics. DATA SOURCES: A research librarian designed and conducted searches in Medline®, EMBASE, and EBM Reviews-Cochrane Central Register of Controlled Trials (inception through July 2018) and International Pharmaceutical Abstracts (inception to December 2014). STUDY SELECTION: Randomized, controlled trials comparing a thiazide or thiazide-like diuretic to any comparator reporting FPG were identified. Trials enrolling < 50 participants, those with a follow-up period of < 4 weeks, and conference abstracts were excluded. DATA EXTRACTION: Independent duplicate screening of citations and full-text articles, data extraction, and assessment of risk of bias was conducted. DATA SYNTHESIS: Ninety-five studies were included (N = 76,608 participants), with thiazides compared with placebo, beta-blockers, calcium channel blockers, renin-angiotensin-aldosterone-system inhibitors, potassium-sparing diuretic, and others alone or in combination. Thiazide diuretics marginally increased FPG (weighted mean difference 0.20 mmol/L (95% CI 0.15-0.25); I2 = 84%) (1 mmol/L = 18 mg/dL). Results did not change substantially when considering dose or duration, comparing thiazides with placebo or an active comparator, or using thiazides as monotherapy or combination therapy, even when combined with a potassium-correcting agent. CONCLUSION: Thiazide diuretics have a small and clinically unimportant impact on FPG.

Impact of preterm birth on brain development and long-term outcome: protocol for a cohort study in Scotland.

INTRODUCTION: Preterm birth is closely associated with altered brain development and is a leading cause of neurodevelopmental, cognitive and behavioural impairments across the life course. We aimed to investigate neuroanatomic variation and adverse outcomes associated with preterm birth by studying a cohort of preterm infants and controls born at term using brain MRI linked to biosamples and clinical, environmental and neuropsychological data. METHODS AND ANALYSIS: Theirworld Edinburgh Birth Cohort is a prospective longitudinal cohort study at the University of Edinburgh. We plan to recruit 300 infants born at <33 weeks of gestational age (GA) and 100 healthy control infants born after 37 weeks of GA. Multiple domains are assessed: maternal and infant clinical and demographic information; placental histology; immunoregulatory and trophic proteins in umbilical cord and neonatal blood; brain macrostructure and microstructure from structural and diffusion MRI (dMRI); DNA methylation; hypothalamic-pituitary-adrenal axis activity; social cognition, attention and processing speed from eye tracking during infancy and childhood; neurodevelopment; gut and respiratory microbiota; susceptibility to viral infections; and participant experience. Main analyses include creation of novel methods for extracting information from neonatal structural and dMRI, regression analyses of predictors of brain maldevelopment and neurocognitive outcome associated with preterm birth, and determination of the quantitative predictive performance of MRI and other early life factors for childhood outcome. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the National Research Ethics Service (NRES), South East Scotland Research Ethics Committee (NRES numbers 11/55/0061 and 13/SS/0143 (phase I) and 16/SS/0154 (phase II)), and NHS Lothian Research and Development (2016/0255). Results are disseminated through open access journals, scientific meetings, social media, newsletters anda study website (www.tebc.ed.ac.uk), and we engage with the University of Edinburgh public relations and media office to ensure maximum publicity and benefit.

Reversible alopecia areata: a little known side effect of leflunomide.

Leflunomide is a disease-modifying anti-rheumatic drug (DMARD) used in the management of rheumatoid arthritis (RA) and psoriatic arthritis. Commonly reported adverse effects include diarrhea, nausea, hepatotoxicity, hypertension, and transient global hair loss; however, additional side effects may be associated with the medication not reported in the monograph. We describe a rare case of reversible alopecia areata (AA) associated with the use of leflunomide and provide a literature review of three published similar cases. We use the Naranjo adverse drug reaction score to show the AA in our case is a "probable" side effect of leflunomide. Currently, AA is not listed as an adverse effect in the leflunomide product monograph. However, it would appear that based on our case and the three other reported cases, the likelihood of AA being an adverse effect of leflunomide is at least possible to probable.

What makes pharmacists successful? An investigation of personal characteristics.

OBJECTIVES: The primary objective of this study was to identify characteristics of pharmacists that contribute to their success. DESIGN: A working definition of success in pharmacy practice was derived from a scoping literature review and is based on the premise that successful pharmacists practice to full scope within the context of their practice setting. Semistructured individual interviews were conducted with selected pharmacists. Potential candidates were nominated by leading pharmacists in the field with the use of our prespecified definition of success. Lists from the nominators were compared, and pharmacists who appeared on more than 1 list were invited to participate. The interview tool was developed with the use of previous research on success in health care professions. SETTING AND PARTICIPANTS: Participants were 10 practicing pharmacists in a variety of locations (5 urban/5 rural) and practice settings (5 hospital/4 community/1 ambulatory care). OUTCOME MEASURES: Themes related to successful pharmacists practicing to full scope. RESULTS: Pharmacists meeting our definition of success were engaged in assessment and care planning, other expanded scope activities, and interpersonal activities and collaboration. The 10 interviewed pharmacists described motivation, critical thinking, emotional intelligence, core competencies, and work-life balance as significant contributors to their success. CONCLUSION: Several characteristics were identified as potentially related to success. These characteristics may be useful in pharmacists identifying areas for personal growth and development.

Admissions processes in North American pharmacy schools: To what extent are characteristics of practice success measured?

INTRODUCTION: The goal of preparing competent pharmacy practitioners starts with the admissions process, whereby skills and abilities can be screened to identify those individuals with a strong potential for success. This study sought to describe the admissions processes of top pharmacy schools in North America and identify the extent to which characteristics associated with professional success are measured. METHODS: An observational survey design was used to collect information to help characterize the admissions processes of 60 pharmacy schools. Online and centralized Pharmacy College Application Service data of admissions requirements were confirmed and further details were collected through a telephone or email cross-sectional survey. Data were analyzed using descriptive statistics. RESULTS: Online data indicate that every school (n = 60) requires prerequisite courses; 53 (88%) consider grade point average (GPA) and 45 (75%) consider the Pharmacy College Admission Test (PCAT). Most schools utilize interviews during admissions (94%), with 67% using a personal interview, 20% the Multiple Mini Interview (MMI), and 7% a combination of both. Of 60 schools contacted, 42% completed the survey. Most schools (92%) assess critical thinking and professional motivation; the personality traits of agreeableness and conscientiousness were considered by 83%. Personal interview was the most frequently cited method for assessing applicant characteristics. CONCLUSION: Current admissions practices in the top North American pharmacy schools are varied and continue to rely on traditional components including GPA, PCAT, and interviews. However, there is also a movement toward using standardized and validated measures of non-cognitive aspects potentially more predictive of success in pharmacy school and subsequent practice.

Patient Satisfaction and Costs of Multidisciplinary Models of Care in Rheumatology: a Review of the Recent Literature.

PURPOSE OF THE REVIEW: A number of novel models of care utilizing allied healthcare professionals, including nurses and pharmacists, have emerged as an alternate to rheumatologist specialist care to achieve disease outcomes in patients with inflammatory arthritis. We conducted a review of the literature for studies from the past 5 years that reported on measures of patient satisfaction and/or any health economic outcome in a model of care where the care providers had substantial, but not completely independent, responsibility. RECENT FINDINGS: Previous reviews have summarized the available evidence for collaborative models of care led by nurses (only), which demonstrate that patients with inflammatory arthritis achieve similar disease outcomes and feel well supported with their person-centered care. Patients are generally highly satisfied with the care provided in collaborative care models, in line with if not greater than that provided by rheumatologists. However, we identified substantial variability in direct costs and/or overall intervention costs and measures of health-related quality of life across the various countries and healthcare systems. Overall, nursing-led interventions likely cost more than do physician-led models of care in the short-term but may lead to greater quality of life, as demonstrated with a disease-specific measure.

Clinical effectiveness and safety of leflunomide in inflammatory arthritis: a report from the RAPPORT database with supporting patient survey.

Leflunomide is indicated for the treatment of adults with rheumatoid arthritis, yet is underutilized. Given the cost of biologic therapy, understanding real-life effectiveness, safety, and sustainability of leflunomide, particularly in patients who have failed methotrexate, would be of value. The primary objective was to assess the proportion of patients achieving clinically meaningful benefit following an adequate trial of leflunomide. A retrospective analysis of a cohort supplemented with patient self-reported data using a standardized questionnaire. Data were analyzed using descriptive statistics, with a database multivariate logistic regression analysis to determine predictors of leflunomide response. Of the cohort available (N = 2591), 1671 patients with confirmed leflunomide use were included in the retrospective analysis, of whom 249 were incident users. Low disease activity (DAS-28 < 3.2) was achieved or maintained by 20% of incident users, with 19% achieving a clinical response (DAS-28 decrease ≥1.2) at 3 months. Adverse effects (AE) were reported by 29% of incident users and after 1 year, 45% remained on leflunomide. Achievement of "minimal or no joint symptoms" was reported by 34% in the 661 analyzable survey responses (39% response rate). AE were reported by 55%, with nuisance (hair loss, nausea, stomach pain) AE and diarrhea being most common. Leflunomide was discontinued by 67% of responders within 1 year. An important proportion of patients, the majority of whom had previously failed methotrexate, achieved disease response with leflunomide with a low risk of serious adverse effects, suggesting that a trial of leflunomide may be a reasonable and cost-effective strategy prior to biologic therapy.

Self-reported use of natural health products among rheumatology patients: A cross-sectional survey.

OBJECTIVES: To describe the self-reported use of natural health products (NHPs) and identify characteristics that predict selected NHP use in rheumatology patients. METHODS: We conducted a cross-sectional survey of consecutive rheumatology patients in two major clinics in Edmonton, Alberta. Survey items included demographic data, rheumatologic diagnoses, prescribed medications, NHPs, and information regarding patients' use of NHPs. Selected NHPs of interest - defined to include joint-specific products, oils with putative joint benefits, and other non-vitamin, non-mineral products - were classified by 2 reviewers. The characteristics of selected NHP users and non-users were compared using chi-squared and ANOVA tests, followed by multivariable-adjusted logistic regression. RESULTS: 1063 patients completed the survey (response rate = 36%, mean age 53 [sd 15], 70% female). 36% of respondents reported using one or more of a wide range of selected NHPs (mean 1.8, range 1-9). The most common source of NHP recommendations for selected NHP users were physicians (42%). Significant predictors of selected NHP use were: being female (aOR 1.41, 95%CI [1.05-1.90], p = 0.02), having a post-secondary degree (aOR 1.60 [1.15-2.22], p = 0.005), and the number of non-rheumatic medications (aOR 1.08 [ 1.00-1.15], p = 0.03) and NSAIDs (aOR 1.32 [1.06, 1.63], p = 0.01). Similar findings were observed among only inflammatory arthritis patients. CONCLUSIONS: Our study confirms the frequent use of selected NHPs, possibly to mitigate persistent symptoms of rheumatologic illness. Rheumatologists appear to be trusted sources of advice and recommendations on NHP use and should provide balanced counselling for their patients.

Interaction Between Low-Dose Methotrexate and Nonsteroidal Anti-inflammatory Drugs, Penicillins, and Proton Pump Inhibitors.

OBJECTIVE: To review the potential drug interactions between low-dose methotrexate (LD-MTX) and nonsteroidal anti-inflammatory drugs (NSAIDs), penicillins, and proton-pump inhibitors (PPIs) given the disparity between interactions reported for high-dose and low-dose MTX to help guide clinicians. DATA SOURCES: A literature search was performed in MEDLINE (1946 to September 2016), EMBASE (1974 to September 2016), and International Pharmaceutical Abstracts (1970 to January 2015) to identify reports describing potential drug interactions between LD-MTX and NSAIDS, penicillins, or PPIs. Reference lists of included articles were reviewed to find additional eligible articles. STUDY SELECTION AND DATA EXTRACTION: All English-language observational, randomized, and pharmacokinetic (PK) studies assessing LD-MTX interactions in humans were analyzed to determine clinical relevance in making recommendations to clinicians. Clinical case reports were assigned a Drug Interaction Probability Scale score. DATA SYNTHESIS: A total of 32 articles were included (28 with NSAIDs, 3 with penicillins, and 2 with PPIs [1 including both PPI and NSAID]). Although there are some PK data to describe increased LD-MTX concentrations when NSAIDs are used concomitantly, the clinical relevance remains unclear. Based on the limited data on LD-MTX with penicillins and PPIs, no clinically meaningful interaction was identified. CONCLUSION: Given the available evidence, the clinical importance of the interaction between LD-MTX and NSAIDs, penicillins, and PPIs cannot be substantiated. Health care providers should assess the benefit and risk of LD-MTX regardless of concomitant drug use, including factors known to predispose patients to MTX toxicity, and continue to monitor clinical and laboratory parameters per guideline recommendations.