Evaluation of adverse drug reaction formatting in drug information mobile phone applications.

OBJECTIVE: To evaluate the differences in presentation (formatting) of adverse drug reaction (ADR) information within drug monographs in commonly used drug information (DI) mobile device applications. METHODS: A cross-sectional analysis of ADR formatting of twenty commonly prescribed oral medications within seven DI mobile applications was performed. Databases were assessed for ADR information, including presence of placebo comparisons, severity of ADR, onset of ADR, formatting of ADRs in percentile (quantitative) format or qualitative format, whether references were used to cite information, and whether ADRs are grouped by organ system. Data was collected by two study investigators and discrepancies were resolved via consensus. RESULTS: The seven DI mobile applications varied significantly on every analyzed ADR variable with the exception of ADR onset, which was absent in all databases. Significant differences were found for variables known to impact clinical judgment such as placebo comparisons and qualitative versus quantitative formatting. Placebo comparisons were most common among monographs in Lexicomp (30%) but were absent among monographs within other applications. Quantitative information was commonly used in most databases but was absent in Epocrates. Qualitative formatting was present in all Epocrates and Micromedex applications but absent in the majority of other applications. Substantial variations were also found in severity and grouping information. CONCLUSION: Substantial variation in ADR formatting exists among the most common DI mobile applications. These differences may translate into alternative interpretations of medical information and thus impact clinical judgment. Health care librarians and clinicians should consider ADR formatting when choosing between DI applications.

Deviant Dosing: A Post hoc Analysis of Pharmacist Characteristics Related to Renal Dosing Decisions.

BACKGROUND: A recent study demonstrated that pharmacists presented with multiple estimating equations deviated from recommended dosing guidance more often than pharmacists who were presented with a single estimate on clinical vignettes. OBJECTIVES: To identify characteristics associated with an increased tendency to deviate from approved recommendations. METHODS: Participant data were split into 2 cohorts: pharmacists who chose a dose that was inconsistent with dosing recommendations on at least 1 of the 4 vignettes and pharmacists who did not deviate on a single case. Bivariate analysis of demographic- and practice-related variables were conducted between groups using the χ2, Mann-Whitney U, or Student t-test for nominal, ordinal, and continuous variables, respectively. Statistically different covariates between groups (P < 0.05) were assessed using multivariable linear regression. RESULTS: Survey data from 154 inpatient pharmacists, 71 of whom deviated on at least 1 clinical vignette, were analyzed. On univariate analysis, deviator pharmacists were more likely to have completed postgraduate residency training (68% vs 41%; P < 0.05) and board certification (39% vs 20%; P < 0.05). Deviator pharmacists were also more likely to have been presented with multiple renal estimates as opposed to a single estimate and had differing renal dosing practices at baseline (P < 0.05). Following multivariable regression, residency training, mismatched baseline renal practices, and multiple renal estimates remained independent predictors (P < 0.05) of dosing deviation. CONCLUSION AND RELEVANCE: Higher clinical training, practice variation, and multiple renal estimates may affect renal dosing practices. Prospective, statistically powered studies are needed to verify these hypotheses.

The Impact of Multiple Renal Estimates on Pharmacist Dosing Recommendations: A Randomized Trial.

BACKGROUND: Numerous equations are used for estimation of renal function, and many electronic medical records report multiple clearance estimates to assist with drug dosing. It is unknown whether the presence of multiple clearance estimates affects clinical decision-making. OBJECTIVE: To determine whether the presence of multiple renal clearance estimates affects pharmacist drug dosing decisions. METHODS: A randomized trial in the form of an electronic survey including 4 clinical vignettes was delivered to hospital pharmacists. Vignettes consisted of a patient presenting with an acute pulmonary embolism requiring enoxaparin therapy. Pharmacists were randomized to receive a single estimate of renal function or multiple estimates for all vignettes. The primary outcome was deviation from approved recommendations on at least 1 vignette. The χ2 test was used to detect differences in deviation rates between groups. Logistic regression was performed to adjust for the effects of potentially confounding variables. RESULTS: A total of 154 studies were completed (73 in the multiple-estimate group and 81 in the single-estimate group). Pharmacists presented with multiple renal estimates were significantly more likely to deviate from recommended dosing regimens than pharmacists presented with a single estimate (54.7% vs 38.2%; P = 0.04). The results were driven primarily by the 2 vignettes that included discordance among Cockcroft-Gault equation creatinine clearance estimates. Logistic regression identified multiple estimates as the only independent predictor of deviation (P = 0.04). CONCLUSION AND RELEVANCE: Pharmacists provided with a single renal clearance estimate were more likely to adhere to approved dosing recommendations than pharmacists provided with multiple estimates.

Evaluation of adverse drug reaction formatting in drug information databases.

OBJECTIVE: The research evaluated the differences in formatting of adverse drug reaction (ADR) information in drug monographs in commonly used drug information (DI) databases. METHODS: A cross-sectional analysis of formatting of ADR information for twenty commonly prescribed oral medications in seven commonly used DI databases was performed. Databases were assessed for presentation of ADR information, including presence of placebo comparisons, severity of ADR, onset of ADR, formatting of ADRs in percentile (quantitative) format or qualitative format, whether references were used to cite information, whether ADRs are grouped by organ system, and word count of the ADR section. Data were collected by two study investigators and discrepancies were resolved via consensus. Chi-square analyses and one-way analysis of variance (ANOVA) were used to evaluate for mean group differences in categorical and continuous data, respectively. RESULTS: The seven DI databases varied significantly on each analyzed ADR variable, including variables known to impact interpretation such as placebo comparisons and qualitative versus quantitative formatting. Placebo comparisons were most common among monographs in Micromedex In-Depth Answers (70%) but were absent among monographs in Epocrates, Lexicomp, and Micromedex. Quantitative information was commonly used in most databases but was absent in Epocrates. Average word counts were higher in Clinical Pharmacology and Micromedex In-Depth answers compared to other databases. CONCLUSION: Substantial variation in ADR formatting exists between the most common DI databases. These differences may translate into alternative interpretations of medical information and, thus, impact clinical judgment. Further studies are needed to assess whether these differences impact clinical practice.

Prophylactic unfractionated heparin and hemorrhage in neurocritically ill underweight patients: A case series and review of the literature.

PURPOSE: Three cases of major bleeding associated with thromboprophylactic unfractionated heparin (UFH) therapy in underweight neurocritically ill patients are reported. SUMMARY: Three underweight patients (body mass index of <18.5 kg/m2) were treated in the intensive care unit with major bleeds associated with UFH thromboprophylaxis. Two of the patients, a 76-year-old female and a 56-year-old female, had hemorrhages on presentation; the third patient, a 29-year-old male, developed bleeding during his admission. All 3 patients had past medical histories consisting of acute neurologic conditions within 6 weeks of presentation, including subdural hematoma, subarachnoid hemorrhage, and obstructive hydrocephalus secondary to a brain mass. All hemorrhages developed following the receipt of prophylactic UFH at doses of 5,000 units every 8 to 12 hours, which translated to high weight-based dosages (>300 units/kg/d). Additionally, hemorrhages were associated with prolonged activated partial thromboplastin time, which declined following heparin discontinuation. The major bleeds following UFH administration included an acute on chronic subdural hematoma, acute rectus sheath hematoma, and cerebellar hematoma. Stabilization of the subdural hematoma was achieved without the use of protamine and the patient was discharged in stable condition. The other 2 patients expired secondary to their hemorrhagic events. Naranjo nomogram scores for the patients indicated that heparin was the probable cause of bleed in 2 cases and a possible cause in 1 case. CONCLUSION: Three major hemorrhages developed following the administration of UFH. Underweight patients with neurologic injury may require increased clinical vigilance, reduced doses, and pharmacodynamic monitoring to improve safety outcomes associated with thromboprophylaxis.

Clearance Confusion: An Exploratory Analysis of Inpatient Dosing Discordances Between Renal Estimating Equations.

BACKGROUND: Numerous equations exist for estimating renal clearance for drug dosing, and discordance rates may be as high as 40% in certain populations. However, the populations and types of equations used in these studies may not be generalizable to broader pharmacy practice. OBJECTIVES: To determine the dosing discordance rate between Cockcroft-Gault (C-G), Chronic Kidney Disease Epidemiology (CKD-EPI), and Modification of Diet in Renal Disease (MDRD) equations in a community hospital population. METHODS: This was a cross-sectional analysis of inpatients who had documented renal function assessment over a 6-month period. Renal estimation was calculated using 5 equations (MDRD, CKD-EPI, and 3 C-G variants). Differences between equations were assessed using mean bias, dosing discordance, and agreement (κ statistic). Patients with acute kidney injury and those requiring renal replacement therapy were excluded. RESULTS: A total of 466 patients were eligible for inclusion. Dosing discordance was evident between C-G variants and both MDRD and CKD-EPI equations in greater than 20% of patients. Agreement was highest between MDRD and CKD-EPI (κ = 0.93) and lowest between MDRD and C-G calculated using ideal body weight (κ = 0.33). The majority of discordant instances led to higher dosing recommendations when using MDRD and CKD-EPI equations compared with C-G variants. Dosing discordance exceeded 18% between the different C-G variants, with the highest discordance (36%) observed between total body weight and ideal body weight variants. CONCLUSION AND RELEVANCE: Dosing discordance between renal estimating equations is widespread. Practitioners and institutions should be aware of these differences when dosing medications and implementing renal dosing policies.

Evaluation of a multidisciplinary approach to reduce internal medicine readmissions using a readmission prediction index.

PURPOSE: Readmission prediction indices are used to stratify patients by the risk of hospital readmission. We describe the integration of a 30-day hospital readmission prediction index into the electronic medical record (EMR) and its impact on pharmacist interventions during transitions of care (TOC). METHODS: A retrospective cohort study was conducted to compare 30-day readmission rates between adult internal medicine inpatients admitted by a multidisciplinary team providing TOC services (the TOC group) and those who received usual care (the control group). Interventions by a pharmacist serving on the TOC team were guided by an EMR-integrated readmission index, with patients at the highest risk for readmission receiving targeted pharmacist interventions. Inpatient encounters (n = 374) during the 5-month study period were retrospectively identified. Chi-square and Mann-Whitney U tests were performed to analyze differences in nominal and nonparametric continuous variables, respectively. Logistic regression was performed to identify variables associated with 30-day readmissions. The log-rank test was used to analyze hazard ratios for readmission outcomes in the 2 cohorts. RESULTS: Thirty-day readmission rates did not differ significantly in the TOC group and the control group (20.9% vs 18.3%, P = 0.52). However, patients who received additional direct pharmacist interventions, as guided by use of a hospital readmission index, had a lower 30-day readmission rate than patients who did not (11.4% vs 21.7%, P = 0.04). The readmission index score was significantly associated with the likelihood of 30-day readmission (odds ratio for readmission, 1.25; 95% confidence interval, 1.16-1.34; P < 0.01). The difference in unadjusted log-rank scores at 30 days with and without pharmacist intervention was not significant (P = 0.05). A mean of 4.5 medication changes were identified per medication reconciliation performed by the TOC pharmacist. CONCLUSION: A multidisciplinary TOC team approach did not reduce the 30-day readmission rate on an internal medicine service. However, patients who received additional direct pharmacist interventions guided by a readmission prediction index had a reduced readmission rate.

Adverse drug reactions in drug information databases: does presentation affect interpretation?

OBJECTIVE: Formatting of adverse drug reaction (ADR) information differs among drug information (DI) resources and may impact clinical decision-making. The objective of this study was to determine whether ADR formatting impacts adverse event interpretation by pharmacy practitioners and students. METHODS: Participants were randomized to receive ADR information in a comparative quantitative (CQUANT), noncomparative quantitative (NQUANT), or noncomparative qualitative (NQUAL) format to interpret 3 clinical vignettes. Vignettes involved patients presenting with adverse events that varied in the extent to which they were associated with a medication. The primary outcome was interpretation of the likelihood of medication-induced adverse events on a 10-point Likert scale. Lower scoring on likelihood (i.e., ADR deemed unlikely) reflected more appropriate interpretation. Linear regression was performed to analyze the effects of ADR information format on the primary outcome. RESULTS: A total of 108 participants completed the study (39 students and 69 pharmacists). Overall, the CQUANT group had the lowest average likelihood compared to NQUAL (4.0 versus 5.4; p<0.01) and NQUANT (4.0 versus 4.9; p=0.016) groups. There was no difference between NQUAL and NQUANT groups (5.4 versus 4.9; p=0.14). In the final model, at least 2 years of postgraduate training (-1.1; 95% CI: -1.8 to -0.3; p<0.01) and CQUANT formatting (-1.3; 95% CI: -0.9 to -1.7; p<0.01) were associated with reduced likelihood. CONCLUSIONS: Formatting impacts pharmacists' and pharmacy students' interpretation of ADR information. CQUANT formatting and at least two years of postgraduate training improved interpretation of adverse events.

Therapeutic Enoxaparin in the Morbidly Obese Patient: A Case Report and Review of the Literature.

Enoxaparin is a low molecular weight heparin commonly used in the treatment of venous thromboembolisms (VTEs); however, evidence on optimal empiric dosing recommendations are lacking in patients with morbid obesity. Utilization of an absolute dose cap, anti-Xa monitoring, and reduced empiric dosing are among the techniques used in this population. We describe a case of a morbidly obese man (body-mass index, BMI: 68.2 kg/m2, total body weight: 236 kg) who required therapeutic enoxaparin for suspected pulmonary embolism (PE) and critical limb ischemia as a bridge therapy during warfarin initiation. An initial empiric dose of 200 mg Q12 hours (0.85 mg/kg) resulted in an anti-Xa level of 1.01 IU/mL following the fifth dose, and no dose modification was deemed necessary. He experienced no adverse effects from treatment. This report adds to a growing body of evidence illustrating the need for reduced empiric weight-based doses of enoxaparin in the morbidly obese population and raises the question of whether dose capping is an appropriate practice in the clinical setting of morbidly obese patients with acute VTE.

Development of an iterative validation process for a 30-day hospital readmission prediction index.

PURPOSE: A study was conducted to determine if an iterative validation process could maintain or improve the discriminative and predictive capabilities of a 30-day hospital readmission prediction index over 2.5 years. METHODS: Patient admissions were retrospectively identified using the electronic medical record. The receiver operating characteristic curve was used to assess model discrimination. Prediction index specificity, sensitivity, and positive and negative predictive values were also assessed. A rolling iterative validation process was developed in which patient admissions were divided into 3-month cohorts. Each cohort was analyzed individually and then included into the cumulative patient cohort and analyzed again. RESULTS: From 121,277 patient visits, an iterative validation approach maintained the discrimination (0.71 to 0.72), predictive validity, and overall accuracy (80.9% to 81.7%) of the 30-day readmission prediction index over 2.5 years. Index sensitivity and negative predictive value increased from baseline while specificity and positive predictive value remained largely unchanged. None of the assessed index parameters diminished or became less useful over the course of the study. CONCLUSION: An internal iterative validation process based on frequentist statistics maintained the discriminative ability and accuracy of a readmission index over 2.5 years despite numerous changes in the variables associated with readmission in the patient population.

Efficacy of Capsaicin for the Treatment of Cannabinoid Hyperemesis Syndrome: A Systematic Review.

Objective: Cannabinoid hyperemesis syndrome (CHS) is characterized by cyclic vomiting, abdominal pain, and alleviation of symptoms via hot showers in chronic cannabinoid users. Capsaicin is recommended as a reasonable first-line treatment approach for CHS despite limited clinical evidence regarding its use. The objective of this study is to systematically review the efficacy data for capsaicin in CHS. Data Sources: A literature search using keywords related to cannabinoids, emesis, and capsaicin was performed in MEDLINE, CINAHL, and EMBASE from inception through March 31, 2019. Study Selection and Data Extraction: Studies and published abstracts in which capsaicin was used for CHS and clinical outcomes were reported were eligible for inclusion. Data Synthesis: A total of 241 articles were screened, of which 5 full-text articles and 6 conference abstracts were included. Full-text case reports (n = 3) and case series (n = 2) found capsaicin to be effective in a total of 18 patients. Published abstracts were in the form of case reports (n = 1), case series (n = 3), and retrospective cohort studies (n = 2). Relevance to Patient Care and Clinical Practice: Capsaicin use was described as beneficial in all case series and case reports; however, both retrospective cohort studies were unable to find a significant benefit for capsaicin on primary outcomes (emergency department length of stay). Conclusion: Current data for capsaicin efficacy in CHS is of low methodological quality. However, the limited data on alternative antiemetic therapies and capsaicin's favorable risk-benefit profile make it a reasonable adjunctive treatment option.

Pharmacotherapy in Acutely Anemic Jehovah's Witnesses: An Evidence-Based Review.

OBJECTIVE: To determine the pharmacological treatment methods available to anemic Jehovah's Witnesses (JW). DATA SOURCES: MEDLINE and PubMed were searched from inception through February 2018 using the search terms Jehovah's Witnesses, treatment, erythropoietin, hemoglobin-based oxygen carrier, Sanguinate, Hemopure, bleeding, and anemia. STUDY SELECTION AND DATA EXTRACTION: All clinical trials, cohort studies, case-control studies, and observational trials involving pharmacotherapy in anemic JW patients were evaluated. Case reports and bibliographies were also analyzed for inclusion. DATA SYNTHESIS: Two studies involving the use of erythropoietin (EPO) and one study involving recombinant factor VIIa were included. Information was also included from other pharmacotherapeutic modalities that had case report data only. Current published evidence is limited with regard to evidence-based management of JW patients. High-dose EPO, intravenous iron supplementation, and hemostatic agents have demonstrated good clinical outcomes in case reports. EPO doses as high as 40 000 units daily have been advocated by some experts; however, pharmacokinetic studies do not support dose-dependent effects. Hemoglobin-based oxygen carriers (HBOCs) are currently not Food and Drug Administration approved. They are available through expanded access programs and may represent a lifesaving modality in the setting of severe anemia. CONCLUSIONS: There are currently not enough data to make definitive recommendations on the use of pharmacological agents to treat severe anemia in the JW population. Further evidence utilizing EPO and HBOCs will be beneficial to guide therapy.

Biologic-Induced Infections in Inflammatory Bowel Disease: The TNF-α Antagonists.

OBJECTIVE: To review the mechanism and association of infectious risk among the tumor-necrosis factor α (TNF-α) antagonists used in inflammatory bowel disease. DATA SOURCES: A PubMed literature search was performed using the following search terms: infliximab, adalimumab, certolizumab, golimumab, inflammatory bowel disease, crohn's, ulcerative colitis, adverse effects, adverse events, safety, and infection. STUDY SELECTION AND DATA EXTRACTION: Meta-analyses and cohort studies with outcomes pertaining to quantitative infectious risk were reviewed. Case reports and case series describing association between TNF-α inhibitors and infection were also reviewed. DATA SYNTHESIS: A total of 7 recent meta-analyses of randomized trials demonstrate inconclusive association of infection with TNF-α antagonists. Registry data suggest that medications carry an independent risk of opportunistic infections. Risk factors for infection include older age, malnutrition, diabetes, and possibly combination therapy. Reported infections vary widely but include intracellular and granulomatous bacteria, viruses, and fungi. CONCLUSION: TNF-α antagonists are associated with an increased risk of opportunistic infection, although this risk has not been demonstrated conclusively in randomized controlled trials. Knowledge of concomitant risk factors, mechanism of infectious risk, and available treatment options can improve patient care in the clinical setting.

New direct-acting antivirals in hepatitis C therapy: a review of sofosbuvir, ledipasvir, daclatasvir, simeprevir, paritaprevir, ombitasvir and dasabuvir.

Hepatitis C is a chronic infection associated with considerable morbidity and mortality. In recent years, there has been a shift in treatment paradigm with the discovery and approval of agents that target specific proteins vital for hepatitis C replication. The NS3/4A inhibitors simeprevir and paritaprevir, the NS5A inhibitors ombitasvir, ledipasvir, and daclatasvir, and the NS5B inhibitors sofosbuvir and dasabuvir have been newly FDA approved and incorporated as first-line agents into the latest IDSA-AASLD guidelines for Hepatitis C treatment. Used in combination, these agents produce higher rates of sustained virologic response and less adverse effects than historical options, along with limited rates of resistance. Pertinent clinical data, pharmacology, and pharmacokinetics are reviewed for these new direct acting antiviral agents.