Brian Odle

Probable etoposide interaction with Echinacea.

ABSTRACT Echinacea is an herbal supplement commonly used as an immune system stimulant to prevent infections, such as the common cold or flu. Echinacea has been documented as a cyctochrome P450 (CYP) 3A4 inhibitor in vitro, but no formal studies have been conducted in humans. Etoposide is a cytotoxic, topoisomerase II inhibitor, chemotherapeutic agent used in the treatment of lung cancer. Etoposide is primarily metabolized by CYP 3A4. We report the first possible drug–herbal interaction between Echinacea and etoposide. A 61-year-old gentleman newly diagnosed with nonsmall cell lung cancer began concurrent chemoradiation with cisplatin and etoposide. He was admitted to the hospital on day 8 of his first cycle and found to be thrombocytopenic. His platelet count eventually reached a nadir of 16 × 103/L, requiring platelet transfusion support. Upon admission, it was discovered he was taking Echinacea, which was discontinued. He received his next cycle of chemotherapy without taking Echinacea. His platelet count decreased to a nadir of 44 × 103/L, but he did not require platelet transfusions. Echinacea likely contributed to this patients profound thrombocytopenia and should be avoided in patients receiving etoposide and possibly other chemotherapeutic drugs that are CYP 3A4 substrates.

Potential Toxicity of Caffeine when Used as a Dietary Supplement for Weight Loss

ABSTRACT Background: Caffeine is added to dietary supplements to increase energy and suppress appetite. Many people take dietary supplements for weight loss. Patients may be unaware that supplements can contain caffeine, even if caffeine is not listed as an ingredient. Commonly used herbal dietary supplement ingredients, such as guarana, are natural sources of caffeine. Objective: To describe a case of possible caffeine-induced seizure in a patient taking an over-the-counter weight loss supplement. Case Report: A previously healthy 38-year-old female experienced blurring of vision and a new onset grand mal seizure. The patient had a two-month history of taking the dietary supplement, Zantrex - 3™. Zantrex - 3™ is advertised as a weight loss supplement which may provide rapid weight loss and extreme energy in one “power packed pill.” Conclusions/Summary: After discontinuation of Zantrex - 3™, the patient experienced no further seizure activity. Outpatient follow up at 2 and 6 weeks was noncontributory with follow up MRI and EEG both within normal limits.

Comparison of Postoperative Bleeding in Total Hip and Knee Arthroplasty Patients Receiving Rivaroxaban or Enoxaparin

Background: The Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism (RECORD) 1 to 4 trials compared rivaroxaban 10 mg daily with commonly used doses of enoxaparin and demonstrated similar rates of VTE and bleeding. Objective: To evaluate bleeding events between patients who received enoxaparin or rivaroxaban for prevention of venous thromboembolism (VTE) following total hip arthroplasty (THA) or total knee arthroplasty (TKA). Methods: Retrospective cohort that compared patients undergoing THA and TKA who received enoxaparin (enoxaparin) with those who received rivaroxaban (rivaroxaban) and also with those who received enoxaparin in the RECORD 1 to 4 trials (enoxaparin RECORD). The primary outcome was any postoperative bleeding, defined as a composite of major and clinically relevant nonmajor bleeding based on the definitions in the RECORD 1 to 4 trials. Results: There was a lower rate of any postoperative bleeding (2.2% vs 6.8%, P = 0.004) in patients who received enoxaparin compared with rivaroxaban, and bleeding rates between the enoxaparin group and the enoxaparin RECORD groups were similar (2.2% vs 2.5%, P = 0.085). Major bleeding in the enoxaparin group (0.2%) was not significantly different from that in the rivaroxaban group (1.4%, P = 0.12) or the RECORD group (0.2%, P = 0.93). Clinically relevant nonmajor bleeding was also lower in the enoxaparin group compared with the rivaroxaban group (2.0% vs 5.5%, P = 0.012). Conclusions: The use of enoxaparin for VTE prophylaxis following THA and TKA was associated with a lower rate of the primary outcome (any postoperative bleeding) compared with the use of rivaroxaban in a similar cohort of patients.

Retrospective Evaluation of Postoperative Bleeding Events in Patients Receiving Rivaroxaban After Undergoing Total Hip and Total Knee Arthroplasty: Comparison with Clinical Trial Data.

Although data from the Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism (RECORD) 1–4 trials have shown a similar postoperative bleeding risk between rivaroxban and enoxaparin in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA), anecdotal observations from local institutions have suggested that postoperative bleeding rates seemed higher in patients who received rivaroxaban than those reported in the RECORD trials. Thus, the objective of this pilot study was to assess postoperative bleeding events observed in clinical practice in patients receiving rivaroxaban after undergoing THA and TKA and to compare their results with those published in the RECORD trials.

Development and evaluation of the Medication-based Index of physical Function (MedIP)

Background the development of an objective and comprehensive drug-based index of physical function for older adults has the potential to more accurately predict fall risk. Design the index was developed using 862 adults (ages 57-85) from the National Social Life, Health, and Aging Project (NSHAP) Wave 1 study. The index was evaluated in 70 adults (ages 51-88) from a rehabilitation study of dizziness and balance. Methods the prevalence among 601 drugs for 1,694 side effects was used with fall history to determine the magnitude of each side effects contribution towards physical function. This information was used to calculate a Medication-based Index of Physical function (MedIP) score for each individual based on his or her medication profile. The MedIP was compared to the timed up and go (TUG) test as well as drug counts using receiver operating characteristic (ROC) analysis. The associations between various indices of physical function and MedIP were calculated. Results within the NSHAP data set, the MedIP was better than drug counts or TUG at predicting falls based on ROC analysis. Using scores above and below the cutpoint, the MedIP was a significant predictor of falls (OR = 2.61 [95% CI 1.83, 3.64]; P < 0.001). Using an external data set, it was shown that the MedIP was significantly correlated with fall number (P = 0.044), composite physical function (P = 0.026) and preferred gait speed (P = 0.043). Conclusion the MedIP has the potential to become a useful tool in the healthcare and fall prevention of older individuals.

Coltsfoot as a Potential Cause of Deep Vein Thrombosis and Pulmonary Embolism in a Patient also Consuming Kava and Blue Vervain

ABSTRACT Objective: To report a case of deep vein thrombosis (DVT) with symptomatic pulmonary embolism (PE) possibly associated with the use of coltsfoot, kava, or blue vervain. Case Summary: A 27-year-old white male presented with leg pain and swelling, tachycardia, and pleuritic chest pain. He had no significant medical history. A medication history revealed extensive herbal medication use including: coltsfoot, passionflower, red poppy flower petals, wild lettuce, blue lily flowers, wild dagga flowers, Diviners Three Burning Blend® (comprised of salvia divinorum, blue lily, and wild dagga), kava–kava, St. Johns Wort, blue vervain, and Dreamers Blend® (comprised of Calea zacatechichi, vervain, Entada rheedii, wild lettuce, and Eschscholzia californica). Lower extremity Doppler ultrasound and computed topography (CT) of the chest revealed DVT and PE. A hypercoagulable work-up was negative. The patient was treated with enoxaparin and warfarin and was discharged home. Discussion: While no distinct agent can be identified as a sole cause of this venous thromboembolic event, coltsfoot could potentially affect coagulation through its effect on vascular endothelial cells as they regulate nitric oxide. Nitric oxide is a known mediator of platelet activity and coagulation, particularly in the pulmonary vasculature. Kava and vervain have estrogenic properties. Conclusions: Of the medications consumed by this self-proclaimed “herbalist,” coltsfoot is a potential cause of venous thromboembolic disease (VTE).

Comparison of Postoperative Bleeding in Total Hip and Knee Arthroplasty Patients Receiving Rivaroxaban, Enoxaparin, or Aspirin for Thromboprophylaxis:

Background: Guidelines recommend the use of multiple pharmacologic agents and/or mechanical compressive devices for prevention of venous thromboembolism, but preference for any specific agent is no longer given in regard to safety or efficacy. Objective: To compare postoperative bleeding rates in patients receiving enoxaparin, rivaroxaban, or aspirin for thromboprophylaxis after undergoing elective total hip arthroplasty or total knee arthroplasty. Methods: This retrospective cohort analysis evaluated patients who received thromboprophylaxis with either enoxaparin, rivaroxaban, or aspirin. All data were collected from the electronic medical record. The primary outcome was any postoperative bleeding. Results: A total of 1244 patients were included with 366 in the aspirin, 438 in the enoxaparin, and 440 in the rivaroxaban arms. Those who received aspirin or enoxaparin were less likely to experience any bleeding compared to those patients who received rivaroxaban (P < .05). There was also a lower rate of major bleeding in these groups, but the differences were not significant. Conclusions: Aspirin and enoxaparin conferred similar bleeding risks, and both exhibited less bleeding than patients who received rivaroxaban.

Visual biofeedback training reduces quantitative drugs index scores associated with fall risk

ObjectiveDrugs increase fall risk and decrease performance on balance and mobility tests. Conversely, whether biofeedback training to reduce fall risk also decreases scores on a published drug-based fall risk index has not been documented. Forty-eight community-dwelling older adults underwent either treadmill gait training plus visual feedback (+VFB), or walked on a treadmill without feedback. The Quantitative Drug Index (QDI) was derived from each participant’s drug list and is based upon all cause drug-associated fall risk. Analysis of covariance assessed changes in the QDI during the study, and data is presented as mean ± standard error of the mean.ResultsThe QDI scores decreased significantly (p = 0.031) for participants receiving treadmill gait training +VFB (− 0.259 ± 0.207), compared to participants who walked on the treadmill without VFB (0.463 ± 0.246). Changes in participants QDI scores were dependent in part upon their age, which was a significant covariate (p = 0.007). These preliminary results demonstrate that rehabilitation to reduce fall risk may also decrease use of drugs associated with falls. Determination of which drugs or drug classes that contribute to the reduction in QDI scores for participants receiving treadmill gait training +VFB, compared to treadmill walking only, will require a larger participant investigation.Trial Registration ISRNCT01690611, ClinicalTrials.gov #366151-1, initial 9/24/2012, completed 4/21/2016

New antibiotics – old problems

Over the past year, the antibiotic pipeline has been relatively fruitful in comparison to years past; however, the introduction of these agents to market has not been without some unanticipated challenges. These challenges include resistance, cost, dosing and administration issues. The most recently approved antimicrobials include Avycaz (ceftazidime-avibactam) February 2015, Zerbaxa (ceftolozane-tazobactam) December 2014, Orbactiv (oritavancin) August 2014, Sivextro (tedizolid) June 2014 and Dalvance (dalbavancin) May 2014. The need for new antimicrobials with activity against multidrug-resistant Gram-negative organisms has been a point of emphasis for drug development due to the introduction of more difficult to inhibit ß-lactamases, such as NDM-1 and KPC. Interestingly, Winkler and colleagues tested frozen isolates from 10 years ago to ceftazidime–avibactam and found a certain percentage displayed resistance without prior exposure. This finding suggests that the introduction of these agents is not necessarily a panacea and only serves to reinforce the importance of continued stewardship. In comparison, the Grampositive agents to date have not had reports of resistance, although resistance is likely certain with increased use. While most of the focus in regard to cost of new drug therapies has recently been fixated on direct-acting antivirals in the treatment of hepatitis C, cost has also become a significant barrier when considering these new antimicrobials for addition to hospital formularies. Ceftolozane– tazobactam has an average daily cost of

Intravenous and Inhaled Antimicrobials at Home in Cystic Fibrosis Patients

249 compared to ceftazidime–avibactam, which is significantly costlier at