Pain Management Stewardship Programs, Part I: A Review of Legislative and Regulatory Changes.

Background: Opioid use is classified as an epidemic by many due to the impact of these medications on society. Federal and state laws for prescribing and dispensing opioids have changed rapidly in a short period of time to hopefully balance proper pain control with their use. Pharmacy directors must be informed of these rapid changes to effectively work as part of any opioid stewardship team. Objective: The objective of this study was to provide foundational leadership guidance to pharmacy directors on current opioid legislation, literature, and best practices to assist in improving opioid use. Methods: A review of the literature from 2003 to the present was conducted along with collating important up to date resources and other publications that provide foundational information to help support a comprehensive management of opioid use. A summary of these data has been collated into an easy to use table and summarized throughout this article. Conclusion: The information provided in this article helps to properly inform pharmacy leaders to the resources available to improve the prescribing, dispensing, and monitoring of opioids and alternatives.

Risk factors for venous thromboembolism in patients with chronic liver disease.

BACKGROUND: Pharmacologic prophylaxis for venous thromboembolism (VTE) in patients with chronic liver disease (CLD) presents a unique challenge because of coagulopathies associated with the disease. When evaluating whether these patients require VTE prophylaxis upon hospitalization, it would be advantageous if risk factors for the development of VTE in this population were known. OBJECTIVE: To evaluate risk factors associated with the development of VTE in patients with CLD. METHODS: A retrospective case-control study was conducted. Patients admitted to the University of Kentucky Chandler Hospital from October 2006 to July 2010 with a diagnosis of CLD and VTE were matched in a 1:3 fashion with CLD patients without VTE. The primary objective was to determine whether there were significant differences in laboratory values between the 2 groups. RESULTS: During this time, 27 patients with CLD (1.0%) were diagnosed with VTE. These patients had significantly lower median aspartate aminotransferase (AST) (47 vs 70 U/L, p = 0.04), alanine transaminase (ALT) (24.5 vs 36 U/L, p = 0.02), albumin (2.1 vs 2.4 g/dL, p = 0.02) and hematocrit (Hct) (28.3% vs 32%, p = 0.03) values compared to the control patients. Patients with albumin lower than 1.9 g/dL had a 5.1 times greater risk of VTE compared to patients with albumin of 2.8 g/dL and higher (OR 5.14, 95% CI 1.05-25.2). CONCLUSIONS: Patients with CLD who developed VTE had significantly lower AST, ALT, albumin, and Hct compared to those of control patients. Studies are necessary to further examine the significance of this finding.

Evaluation of a clinical scoring scale to direct early appropriate therapy in heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a serious adverse effect associated with heparin therapy. Current laboratory confirmation for immune mediated HIT often results in false positives and unnecessary treatment, exposing individuals to possible complications. As a result, clinical evaluation has been recommended in conjunction with laboratory testing. We hypothesize that utilization of a clinical scoring scale, the 4T's, will result in the initial appropriate therapy for suspected HIT. METHODS: This is a retrospective chart review of 108 patients who underwent ELISA testing for HIT at a university hospital. The 4T's scale was applied, stratifying individuals into low, intermediate, and high-risk categories. Each risk score was compared to the ELISA results to determine if the 4T's can predict the diagnosis of HIT and result in appropriate management. ELISA optical density scores as well as incidence of adverse events were also compared among risk categories. STUDY RESULTS: Individuals with low risk correlate with a negative ELISA compared to intermediate and high-risk individuals (p = 0.01 and p<0.01) and also were significantly more likely to predict institution of appropriate therapy (p<0.01). Median optical density scores were 0.184 (0.046-2.116), 0.226 (0.067-1.887), and 0.476 (0.096-1.309) for low, intermediate, and high 4T scores. Major adverse events include thrombosis and bleeding. CONCLUSIONS: Individuals with low risk were more likely to receive initial, appropriate therapy and were also significantly more likely to have a negative ELISA test result. Individuals with low risk determined by the 4T score therefore may have therapy and serologic testing for HIT withheld.

Effects of a pharmacist-to-dose computerized request on promptness of antimicrobial therapy.

OBJECTIVES: To examine the effects of computerized requests for pharmacist-to-dose (PTD), an advanced clinical decision support tool for dosing guidance, on antimicrobial therapy with vancomycin and aminoglycosides, describe PTD request utilization, and identify factors that may prolong this process. DESIGN: A retrospective review was conducted of patients hospitalized from Jan 2004 to Jun 2006 with suspected pneumonia who received vancomycin, tobramycin, or gentamicin via PTD (study) or routine provider order entry (control). MEASUREMENTS: The primary endpoint was time to pharmacist completion of PTD request. Secondary data points included medication turn-around times for first doses of vancomycin or aminoglycosides and for first doses of any antibiotic, dose adjustment for renal dysfunction, medication errors, and time of order entry. Multivariate analysis was conducted to identify predictors of total time to pharmacist verification and time to administration of first doses of vancomycin or aminoglycosides. RESULTS: Median time for pharmacist completion of PTD requests was 29 minutes. Delays were noted in the study group (n = 49) by comparison with the control group (n = 48) for median time to first dose of vancomycin or aminoglycoside (185 vs. 138 min, p = 0.45) and for any antibiotic (134 vs. 118 min, p = 0.42), respectively. Fewer medication errors were reported in the study group (5 vs. 18 errors, p = 0.002). In a multivariate model, PTD was not significantly predictive of time to pharmacy verification or medication turn-around time. CONCLUSIONS: Pharmacists completed pharmacist-to-dose consultations for dosing guidance of vancomycin and aminoglycosides within a median of 30 minutes. Implementation of a computerized request for clinical pharmacists to provide medication-related clinical decision support increased medication turn-around time of vancomycin and aminoglycosides and reduced medication errors. Consultation of clinical pharmacists by computerized request for initial antibiotic dosing of medications with narrow therapeutic windows is an option for medication-related clinical decision support but providers should be aware that consultation may delay medication turn-around time.

Effects of hyperglycemia on the development of new-onset diabetes after liver transplantation.

CONTEXT: New-onset diabetes after transplantation (NODAT) has been associated with cardiovascular and thrombotic complications, acute rejection, and infection in transplant recipients. NODAT in kidney transplantation is well described; however, data are lacking in liver transplant recipients. OBJECTIVE: To evaluate the incidence of new-onset diabetes within 6 months postoperatively in adult liver transplant recipients. DESIGN, PARTICIPANTS, SETTING, AND INTERVENTIONS: Patients who underwent a liver transplantation at our institution between January 2004 and December 2005 were retrospectively evaluated. NODAT was defined according to the diagnostic criteria of the American Diabetes Association/World Health Organization, persistent hyperglycemia (serum glucose > or = 200 mg/dL occurring 2 weeks after initial steroid induction and persisting for more than 2 weeks), or the need for hypoglycemic agents upon discharge. MAIN OUTCOMES: Incidence of NODAT within 6 months after transplantation in patients with poor glycemic control within the first 2 weeks after transplantation, acute rejection episodes, infections, hospital readmissions, and cardiovascular and thrombotic events. RESULTS: Forty-five patients were evaluated. Within the first 6 months after transplantation, NODAT developed in 11 (24%). Acute rejection, infection, hospital readmissions, cardiovascular events, and thrombotic events did not differ between the groups. CONCLUSION: Elevated fasting levels of blood glucose during the first 2 weeks after liver transplantation may be associated with an increased incidence of NODAT and may have predictive value. More studies are needed to determine the effects of recognition and treatment of hyperglycemia in recent transplant recipients.

Fondaparinux as a treatment option for heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication that can occur after exposure to heparin products. Because patients with HIT are at increased risk for thrombosis, anticoagulation is warranted. The direct thrombin inhibitors lepirudin and argatroban are approved by the United States Food and Drug Administration (FDA) for this indication. Bivalirudin, another direct thrombin inhibitor, is approved for use in patients with HIT who must undergo percutaneous coronary intervention. The synthetic pentasaccharide fondaparinux lacks FDA approval for treating patients with HIT; however, a few published reports describe its use. Furthermore, various small-scale, in vitro studies have demonstrated a lack of cross-reactivity between fondaparinux and HIT antibodies. Large, in vivo comparison trials must be performed before fondaparinux can become a standard treatment option in the setting of HIT.

Clinical utility of a continuous intravenous infusion of valproic acid in pediatric patients.

STUDY OBJECTIVE: To describe the dose-concentration relationship of a continuous intravenous infusion of valproic acid (VPA) in pediatric patients when a dosing protocol is used. DESIGN: Retrospective and concurrent chart review. SETTING: Tertiary care, 473-bed, academic medical center with a 120-bed, dedicated children's hospital. PATIENTS: Twenty-six pediatric patients (< 18 yrs old) who received VPA according to the protocol for continuous intravenous infusions between January 1, 2004, and March 31, 2006, identified by using a pharmacy order-entry system. MEASUREMENTS AND MAIN RESULTS: Patient demographics, VPA treatment regimens, clinical responses, and safety data were recorded and analyzed. Median patient age was 8.5 years (range 1.4-16 yrs). Approximately two thirds received VPA for seizures, and one third for migraines. Patients were given a mean +/- SD VPA loading dose of 28.5 +/- 5.2 mg/kg followed by a continuous infusion rate of 1 +/- 0.2 mg/kg/hour. Mean +/- SD serum concentration measured 4.5 +/- 1.6 hours after the loading dose was 83.3 +/- 22.8 microg/ml. Steady-state concentration at 23.3 +/- 3.0 hours after the start of the continuous infusion was 80.0 +/- 26.0 microg/ml. Postload and steady-state serum concentrations were within the target concentration of 50-100 microg/ml in 77% and 69% of patients, respectively. On further analysis, when the target range was expanded to 50-125 microg/ml (125 microg/ml was deemed acceptable if no adverse effects were noted), 89% and 92% of patients, respectively, had postload and steady-state VPA serum concentrations within this range. The response rate was excellent, with nearly 85% of patients achieving a complete or partial response to therapy. Adverse effects were generally mild and uncommon. CONCLUSIONS: The continuous-infusion protocol permitted rapid intravenous loading of VPA in pediatric patients while minimizing adverse events and achieving concentrations in the upper region of the therapeutic range.

Pharmacy resident participation in cardiopulmonary resuscitation events.

PURPOSE: An electronically administered cross-sectional survey was conducted to establish the rate of pharmacy resident participation in cardiopulmonary resuscitation (CPR) events at pharmacy residency programs throughout the United States and Puerto Rico. METHODS: A 46-item questionnaire was developed and sent by e-mail to pharmacy residency program directors. The recipients were given one month to complete the survey. Responses were screened for duplicate answers, and the most complete survey was included in the analysis. The survey dealt with residency program demographics and sought information about required life-support certifications for pharmacy personnel, institution-specific training methods for medical emergencies employed by pharmacy departments, responsibilities of pharmacy personnel who respond to CPR events, and evaluation methods used to assess resident performance in CPR events. RESULTS: A total of 745 pharmacy residency directors were surveyed. Responses were received from 190 residency program directors, which represented 221 residency programs. The three most common residency program settings were community (not-for- profit) hospitals, college and university hospitals, and government hospitals. Thirty percent of respondents required pharmacy resident response to CPR events, while 38% made this opportunity optional. In 85% of programs that required or offered resident response to CPR events, there was a formal CPR team. The three primary roles fulfilled by pharmacists in medical emergencies were provision of drug information, drug admixture, and documentation; pharmacy resident duties mirrored these roles. CONCLUSION: Pharmacy resident response to CPR events was required in approximately 30% of responding pharmacy residency programs. Various methods were used in educating, assessing, and evaluating pharmacy residents in this role.

An institutional process to improve inpatient glycemic control.

Many institutions are evaluating their inpatient patterns of care for patients with diabetes mellitus and hyperglycemia, based upon compelling evidence that strict glycemic control improves outcomes in a variety of hospital settings. In 2005, a multidisciplinary task force was established at the University of Kentucky Chandler Medical Center in Lexington, Kentucky, to guide a process to improve the quality and safety of inpatients with hyperglycemia. This article describes the stepwise process including an examination of our procedures, adoption of standards, and establishment of common protocols and procedures. Successful implementation of the protocols was preceded by extensive educational efforts. Refinement of the protocols based on early experience and feedback from staff has resulted in improvements in glycemic parameters and less reliance on sliding scale insulin regimens.

Drug selection in a patient with a history of hypersensitivity reactions: a practical approach for the orthopedist.

Drug allergies are specific to characteristics of the medication's chemical structure.

Use of Continuous Renal Replacement Therapy for Removal of Dabigatran in a Patient in Need of Emergent Surgery.

Purpose. To report the ability to remove serum dabigatran using continuous renal replacement therapy (CRRT) in a patient with life-threatening bleeding. Summary. A 77-year-old female with history of atrial fibrillation who takes dabigatran for stroke prevention presented with abdominal pain. Patient was found to have bleeding and possible mesenteric ischemia and was taken to the operating room and had continued bleeding postoperatively. CRRT was initiated for the removal of any remaining dabigatran, with serum dabigatran levels collected to evaluate removal of dabigatran with CRRT. This patient had an increased dabigatran level prior to intervention, which decreased to an undetectable level after use of CRRT. Greater than 80% of the drug was removed due to 4 hours of CRRT and residual kidney function. Reversal of dabigatran is an area of current research with recent FDA approval of idarucizumab for use. Conclusion. Bleeding may occur as a result of the use of dabigatran and change in patient's clinical condition. Use of CRRT may be an option in removing serum dabigatran in the case of a life-threatening bleed.

Effect of nesiritide versus milrinone in the treatment of acute decompensated heart failure.

The use of nesiritide in the improvement of patient hemodynamics, decreased length of stay (LOS), and rehospitalization is discussed. Nesiritide is a useful agent for the treatment of the acutely decompensated heart failure patient. Previous trials suggest that the use of nesiritide results in improved outcomes as compared with other agents. To date, there are no data comparing nesiritide to milrinone in the treatment of the acutely decompensated heart failure patient. Fifty-five patients admitted to the heart failure service were identified retrospectively; 29 received nesiritide and 26 received milrinone. Baseline characteristics, hemodynamic data, and LOS data were collected. Primary outcomes were the overall LOS, intensive care LOS, and readmission within 30 days of discharge. Other outcomes included duration of vasoactive agents used, overall diuresis, and total cost of therapy. Baseline hemodynamic data were similar between groups. Patients in the milrinone group had an overall LOS of 8.2 days compared to 7 days in the nesiritide group (p = NS). LOS in the intensive care unit was 5.9 days in the milrinone group compared with 3.9 days in the nesiritide group (p = 0.007). Readmission at 30 days was 28% in the milrinone group compared with 16% in the nesiritide group (p = NS). Infusion time was shorter in the nesiritide group, 50 versus 117 hours (p = 0.001). Cost of therapy (cost of bed, supplies, and drug) was $398 less per patient receiving nesiritide. The use of nesiritide led to improvement in patient hemodynamics and resulted in a trend toward decreases in LOS and rehospitalization. Total cost of therapy was lower in the nesiritide group as compared to those patients treated with milrinone.

Gas discharge visualization evaluation of ultramolecular doses of homeopathic medicines under blinded, controlled conditions.

OBJECTIVES: To determine the feasibility of using a computerized biophysical method, gas discharge visualization (GDV), to differentiate ultramolecular doses of homeopathic remedies from solvent controls and from each other. DESIGN: Blinded, randomized assessment of four split samples each of 30c potencies of three homeopathic remedies from different kingdoms, for example, Natrum muriaticum (mineral), Pulsatilla (plant), and Lachesis (animal), dissolved in a 20% alcohol-water solvent versus two different control solutions (that is, solvent with untreated lactose/sucrose pellets and unsuccussed solvent alone). PROCEDURES: GDV measurements, involving application of a brief electrical impulse at four different voltage levels, were performed over 10 successive images on each of 10 drops from each bottle (total 400 images per test solution per voltage). The dependent variables were the quantified image characteristics of the liquid drops (form coefficient, area, and brightness) from the resultant burst of electron-ion emission and optical radiation in the visual and ultraviolet ranges. RESULTS: The procedure generated measurable images at the two highest voltage levels. At 17 kV, the remedies exhibited overall lower image parameter values compared with solvents (significant for Pulsatilla and Lachesis), as well as differences from solvents in fluctuations over repeated images (exposures to the same voltage). At 24 kV, other patterns emerged, with individual remedies showing higher or lower image parameters compared with other remedies and the solvent controls. CONCLUSIONS: GDV technology may provide an electromagnetic probe into the properties of homeopathic remedies as distinguished from solvent controls. However, the present findings also highlight the need for additional research to evaluate factors that may affect reproducibility of results.

Strength of vital force in classical homeopathy: bio-psycho-social-spiritual correlates within a complex systems context.

OBJECTIVE: To explore associations between a global rating for the classical homeopathic construct of vital force and clinician and patient ratings on previously validated bio-psycho-social-spiritual questionnaires. METHODS: Sixty-two (62) community-recruited patients with fibromyalgia (FM) were assessed at baseline prior to a clinical trial of individualized homeopathy. Two homeopaths jointly performed case-taking interviews. A conventional medical provider independently evaluated patients with a standardized history and physical examination. Homeopaths rated each patient's vital force (five-point Likert scale, with 1 = very weak to 5 = very strong). Homeopaths and the conventional medical provider rated their Clinical Global Impression (CGI) of the severity of illness (1 = normal; 7 = among the most extremely ill). Patients completed self-rating scales on pain, global health, mood, quality of life, coping style, health locus of control, multidimensional well-being, spirituality, sense of coherence, positive states of mind, and social desirability. RESULTS: Greater vital force ratings (mean 2.9 standard deviation [SD] 0.6) correlated moderately (p < or = 0.005) with less severe CGI illness ratings by the homeopaths (r =-0.59), decreased patient-rated mental confusion (r =-0.43), higher vigor (r = 0.38), and greater positive states of mind (r = 0.36). Vital force also showed correlations (p < 0.05) with lower CGI ratings by the conventional medical provider (r =-0.32), better selfrated quality of life (r = 0.33), lesser fatigue (r =-0.31), better global health (r = 0.29), greater sense of coherence (r = 0.28), powerful-others health locus of control (r = 0.27), increased emotional well-being (r = 0.27), and higher social desirability (r = 0.27), but not with age, pain, or illness duration. CONCLUSION: Homeopathic vital force ratings reflect better perceived mental function, energy, and positive dimensions of the individual, beyond absence of disease.

Individual differences in response to randomly assigned active individualized homeopathic and placebo treatment in fibromyalgia: implications of a double-blinded optional crossover design.

OBJECTIVE: To assess individual difference characteristics of subgroups of patients with fibromyalgia (FM) patients with respect to the decision to stay in or switch from randomly-assigned verum or placebo treatment during an optional crossover phase of a double-blinded homeopathy study. DESIGN: Double-blinded, randomized, placebo-controlled, optional crossover clinical trial. PARTICIPANTS: Fifty-three (53) community-recruited patients with FM entered the optional crossover phase. INTERVENTION: Two homeopaths jointly selected an individualized homeopathic remedy for all patients. The pharmacy dispensed either verum LM remedy or indistinguishable placebo in accord with randomized assignment for 4 months and the patient's optional crossover decision for an additional 2 months. OUTCOME MEASURES: Patients completed a battery of baseline state/trait questionnaires, including mood, childhood neglect and abuse, and trait absorption. They rated global health (whole person-centered) and tender point pain on physical examination (disease-specific) at baseline, 3 months, and 6 months. RESULTS: Rates of optional crossover from verum to placebo or placebo to verum were comparable (p = 0.6; 31%, and 41%, respectively). The switch subgroups had greater baseline psychologic issues (emotional neglect in placebo-switch; depression and anger in verum-switch). The verum-stay subgroup scored highest on treatment helpfulness and included all six exceptional responders who fell, prior to crossover, into the top terciles for improvement in both global health and pain. Patients staying in their randomly assigned groups, active or placebo (n = 34), scored significantly higher in trait absorption than did those who switched groups (n = 19). CONCLUSION: Individual difference factors may predict better and poorer responders with FM to specific and nonspecific effects of homeopathic and placebo treatment.

Electroencephalographic cordance patterns distinguish exceptional clinical responders with fibromyalgia to individualized homeopathic medicines.

OBJECTIVES: To characterize initial central nervous system responses to olfactory administration of homeopathic remedies as biomarkers for subsequently exceptional, simillimum-like clinical outcomes at a systemic level (i.e., both locally and globally). DESIGN: Double-blinded, randomized, placebo-controlled clinical trial. SETTING: A private homeopathic clinic in Phoenix, AZ, and a university laboratory in Tucson, AZ. PATIENTS: Sixty-two (62) persons with physician-confirmed fibromyalgia (FM) (mean age, 49 years; 94% women) enrolled; 53 completed the 3-month assessment visit. Exceptional responders (n = 6, 23% of active treatment group; none on placebo) were those with improvements in the top one-third for both tender point pain and global health ratings after 3 months. INTERVENTION: Patients took daily oral doses of treatment solution in LM (1/50,000 dilution) potency (active group received individualized remedy; placebo group received plain solvent). Dependent measures: Baseline and 3-month difference scores for initial prefrontal electroencephalographic alpha frequency cordance (EEG-C, a correlate of functional brain activity) during 16 pairs of randomized, double-blinded bottle sniffs (treatment minus control solutions). RESULTS: Exceptional responders versus other patients exhibited significantly more negative initial EEG-C difference scores at prefrontal sites. Right prefrontal cordance findings correlated with subsequently reduced pain (r = 0.85, p = 0.03), better global health (r =-0.73, p = 0.10), and trait absorption (genetically determined ability to focus attention selectively and fully) (r = 0.91, p = 0.012). CONCLUSIONS: These observations suggest prefrontal EEG-C as an early biomarker of individualized homeopathic medicine effects in patients with FM who later exhibit exceptional outcomes. Prefrontal cortex controls executive function, including ability to redirect attention. Interactions between executive function, absorption, and the simillimum remedy could facilitate exceptional responses.

Biofield detection: role of bioenergy awareness training and individual differences in absorption.

OBJECTIVE: To measure health care providers' capacity to detect biofields before and after bioenergy awareness training in relation to individual differences in the personality trait of absorption. METHODS: Twenty-seven (27) physicians, psychologists, and nurses participated in a 5-day intensive bioenergy healing training course with Rev. Rosalyn Bruyere. The course was part of the Associate Fellows Program in the Program in Integrative Medicine at the University of Arizona. Blindfolded participants received a 24-trial hand biofield detection test (HBDT) pretraining and post-training. The experimenter placed his or her dominant hand a few inches above the participant's left or right hand for 30-second trials. After each trial, the participant guessed which hand was being tested. Blocks contained two right- and two left-hand trials in different orders. Participants filled out Tellegen's Absorption Scale, a measure of the capacity to focus attention in tasks. RESULTS: Percent HBDT accuracy for the entire sample was 50.8% (standard deviation [SD] = 12.24) at pretraining (50% is chance); accuracy increased to 55.5% (SD = 12.38) at post-training (t = p = 2.08, p < 0.05). Pretraining absorption (mean = 23.9; SD = 5.52) was significantly correlated with degree of detection accuracy increase (r = 0.42, n = 22, p < 0.05). High absorption (mean = 28.2 n = 11) participants increased to 58.3% compared to 52.7% for low absorption (mean = 19.2 n = 11) participants. CONCLUSION: The findings support claims of energy healers that (1) training can improve bioenergy awareness, and (2) there are substantial individual differences in response to training.

Preventing the harm of a closer look: contrast-induced nephropathy in adults.

Contrast media is administered to many patients in hospitals nationwide. Although the use of contrast and dyes is widespread and has a well accepted use among the medical profession, contrast-induced nephropathy can be a common and potentially harmful complication. Identifying patients at risk, attempting to minimize risk, and using preventative strategies should be priorities to decrease the harmful effects that are associated with the administration of contrast media. This article provides a general overview of contrast-induced nephropathy and a brief review of the risk factors and prophylactic treatment.