An International, Multicenter Evaluation of Comprehensive Medication Management by Pharmacists in ICU Recovery Centers.

BACKGROUND: Post-intensive care syndrome (PICS) is defined as a new or worsening impairment in physical, cognitive, or mental health following critical illness. Intensive care unit recovery centers (ICU-RC) are one means to treat patients who have PICS. The purpose of this study is to describe the role of pharmacists in ICU-RCs. RESEARCH QUESTION: What is the number and type of medication interventions made by a pharmacist at an ICU-RC at 12 different centers? STUDY DESIGN AND METHODS: This prospective, observational study was conducted in 12 intensive care units (ICUs)/ICU-RCs between September 2019 and July 2021. A full medication review was conducted by a pharmacist on patients seen at the ICU-RC. RESULTS: 507 patients were referred to the ICU-RC. Of these patients, 474 attended the ICU-RC and 472 had a full medication review performed by a pharmacist. Baseline demographic and hospital course data were obtained from the electronic health record and at the ICU-RC appointment. Pharmacy interventions were made in 397 (84%) patients. The median number of pharmacy interventions per patient was 2 (interquartile range [IQR] = 1,3). Medications were stopped and started in 124 (26%) and 91 (19%) patients, respectively. The number of patients that had a dose decreased and a dose increased was 51 (11%) and 43 (9%), respectively. There was no difference in the median total number of medications that the patient was prescribed at the start and end of the patient visit (10, IQR = 5, 15). Adverse drug event (ADE) preventive measures were implemented in 115 (24%) patients. ADE events were identified in 69 (15%) patients. Medication interactions were identified in 30 (6%) patients. INTERPRETATION: A pharmacist plays an integral role in an ICU-RC resulting in the identification, prevention, and treatment of medication-related problems. This paper should serve as a call to action on the importance of the inclusion of a pharmacist in ICU-RC clinics.

An Electronic Decision Support Intervention Reduces Readmissions for Patients With Cirrhosis.

INTRODUCTION: Rifaximin use in combination with lactulose is associated with a decreased risk of overt hepatic encephalopathy (HE). METHODS: We prospectively evaluated the impact of an interruptive electronic medical record alert to indicate rifaximin for patients with cirrhosis and HE on lactulose. RESULTS: The intervention was associated increased rifaximin utilization, particularly for nongastroenterology and hospitalist services odds ratio 1.20 95% confidence interval (1.09-1.31). For patients with HE, the intervention was associated with a lower readmission risk-adjusted subdistribution hazard ratio 0.63 95% confidence interval (0.48-0.82). DISCUSSION: An interruptive alert in the electronic ordering system was associated with a lower risk of readmissions.

Medication Changes and Diagnosis of New Chronic Illnesses in COVID-19 Intensive Care Unit Survivors.

BACKGROUND: Currently, there is limited literature on the impact of the COVID-19 infection on medications and medical conditions in COVID-19 intensive care unit (ICU) survivors. Our study is, to our knowledge, the first multicenter study to describe the prevalence of new medical conditions and medication changes at hospital discharge in COVID-19 ICU survivors. OBJECTIVE: To determine the number of medical conditions and medications at hospital admission compared to at hospital discharge in COVID-19 ICU survivors. METHODS: Retrospective multicenter observational study (7 ICUs) evaluated new medical conditions and medication changes at hospital discharge in patients with COVID-19 infection admitted to an ICU between March 1, 2020, to March 1, 2021. Patient and hospital characteristics, baseline and hospital discharge medication and medical conditions, ICU and hospital length of stay, and Charlson comorbidity index were collected. Descriptive statistics were used to describe patient characteristics and number and type of medical conditions and medications. Paired t-test was used to compare number of medical conditions and medications from hospital discharge to admission. RESULTS: Of the 973 COVID-19 ICU survivors, 67.4% had at least one new medical condition and 88.2% had at least one medication change. Median number of medical conditions (increased from 3 to 4, P < .0001) and medications (increased from 5 to 8, P < .0001) increased from admission to discharge. Most common new medical conditions at discharge were pulmonary disorders, venous thromboembolism, psychiatric disorders, infection, and diabetes. Most common therapeutic categories associated with medication change were cardiology, gastroenterology, pain, hematology, and endocrinology. CONCLUSION AND RELEVANCE: Our study found that the number of medical conditions and medications increased from hospital admission to discharge. Our results provide additional data to help guide providers on using targeted approaches to manage medications and diseases in COVID-19 ICU survivors after hospital discharge.

The impact of the COVID-19 pandemic on medical conditions and medication adherence in people with chronic diseases.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has drastically disrupted primary health care and pharmacy services, posing a challenge in people with chronic diseases who receive routine care. Currently, there exists limited literature on the indirect impact of the pandemic on chronic disease management, particularly related to accessibility to medications and health care resources. OBJECTIVES: To determine the prevalence of medical- and medication-related problems reported by people with chronic diseases during the pandemic. The secondary objective was to identify the barriers and contributing factors related to these medical- and medication-related problems. METHODS: The anonymous and voluntary, Web-based survey was filled out by interested adult respondents with chronic disease(s) across Michigan between September 1, 2020, and January 1, 2021. The primary outcome included self-reported medical- and medication-related problems during the pandemic. Secondary outcomes included potential risk factors for medical- and medication-related problems. Descriptive statistics was used to describe respondents' demographics, chronic disease characteristics, medication adherence, medical- and medication-related problems, and COVID-19-related factors. The multivariable Firth logistic regression was used to analyze correlations between potential risk factors associated with medical- and medication-related problems. RESULTS: A total of 1103 respondents completed the survey and were included in the analysis. Approximately, 51% of respondents reported a medication-related problem with 19.6% reported problems obtaining medication(s) and 31.7% reported forgetting or not taking their medication(s). The top reason for problems obtaining medication(s) was doctor's office being closed for in-person visit(s). In addition, of all responses, more than half reported worsening symptoms of their chronic disease(s) during the pandemic especially with psychiatric disorders (79.5%) and inflammatory bowel disease (60%). Respondents with a significantly higher risk of medication-related problems included those who were younger, were female, and had psychiatric disorder(s), diabetes, arthritis, or lupus, and respondents with a significantly higher risk of medical-related problems included those with multiple chronic diseases, psychiatric disorder(s), and heart failure. CONCLUSION: Understanding the consequences of the pandemic, such as medical- and medication-related problems, in this population is critical to improving health care accessibility and resources through potential outpatient pharmacy services during this and future pandemics.

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.

Pharmacists' Perceptions on Their Role, Activities, Facilitators, and Barriers to Practicing in a Post-Intensive Care Recovery Clinic.

Background: Complex medication regimen changes burden intensive care unit (ICU) survivors and their caregivers during the transition to home. Intensive care unit recovery clinics are a prime setting for pharmacists to address patients' and their caregivers' medication-related needs. The purpose of this study was to describe ICU recovery clinic pharmacists' activities, roles, and perceived barriers and facilitators to practicing in ICU recovery clinics across different institutions. Methods: An expert panel of ICU recovery clinic pharmacists completed a 15-item survey. Survey items addressed the pharmacists' years in practice, education and training, activities performed, their perceptions of facilitators and barriers to practicing in an ICU recovery clinic setting, and general ICU recovery clinic characteristics. Descriptive statistics were used. Results: Nine ICU recovery clinic pharmacists participated. The average number of years in practice was 16.5 years (SD = 13.5, range = 2-38). All pharmacists practiced in an interprofessional ICU recovery clinic affiliated with an academic medical center. Seven (78%) pharmacists always performed medication reconciliation and a comprehensive medication review in each patient visit. Need for medication education was the most prevalent item found in patient comprehensive medication reviews. The main facilitators for pharmacists' successful participation in an ICU recovery clinic were incorporation into clinic workflow, support from other health care providers, and adequate space to see patients. The ICU recovery clinic pharmacists perceived the top barriers to be lack of dedicated time and inadequate billing for services. Conclusions: The ICU recovery clinic pharmacists address ICU survivors' medication needs by providing direct patient care in the clinic. Strategies to mitigate pharmacists' barriers to practicing in ICU recovery clinics, such as lack of dedicated time and adequate billing for pharmacist services, warrant a multifaceted solution, potentially including advocacy and policy work by national pharmacy professional organizations.

Daclatasvir: A NS5A Replication Complex Inhibitor for Hepatitis C Infection.

OBJECTIVES: To review the pharmacology, efficacy, and safety of daclatasvir in the treatment of patients with chronic hepatitis C virus (HCV) infection. DATA SOURCES: A literature search through EMBASE and PubMed was conducted (January 1966 to August 2015) using the terms BMS-790052, daclatasvir, and hepatitis C. References from retrieved articles were reviewed for any additional material. Additionally, the new drug application and prescribing information were retrieved. STUDY SELECTION/DATA EXTRACTION: The literature search was limited to human studies published in English. Phase 1, 2, and 3 studies describing the pharmacology, pharmacokinetics, efficacy, and safety of daclatasvir for HCV were identified. DATA SYNTHESIS: Daclatasvir, a nonstructural 5A protein inhibitor, combined with sofosbuvir, is indicated for adult patients with chronic HCV genotype 3 regardless of treatment or cirrhosis status. The phase III ALLY-3 trial (n = 152) demonstrated that daclatasvir taken once daily with sofosbuvir for 12 weeks was effective at achieving sustained virological response (SVR) rates in treatment-naïve (97%) and treatment-experienced (94%) patients without cirrhosis. Patients with cirrhosis had significantly lower SVR rates (58 and 69%, respectively). The most common adverse drug events associated with daclatasvir and sofosbuvir in ALLY-3 were headache (20%), fatigue (19%), and nausea (12%). CONCLUSIONS: Daclatasvir, when combined with sofosbuvir, is an effective agent to treat HCV genotype 3, with SVR rates above 90% for patients without cirrhosis who are treatment naïve or experienced. SVR rates for treatment-naïve or -experienced patients with cirrhosis are not as robust (58%-69%).

Ledipasvir-sofosbuvir: interferon-/ribavirin-free regimen for chronic hepatitis C virus infection.

OBJECTIVES: To review the pharmacology, efficacy, and safety of ledipasvir-sofosbuvir for the treatment of chronic hepatitis C virus (HCV). DATA SOURCES: A literature search through clinicaltrials.gov, EMBASE, and PubMed was conducted (January 1966 to October 2014) using the terms ledipasvir, sofosbuvir, GS-5885, and GS-7977. References from retrieved articles and abstracts presented at recent meetings were reviewed for any additional material. The prescribing information was also reviewed. STUDY SELECTION/DATA EXTRACTION: Phase 1, 2, and 3 human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of ledipasvir and sofosbuvir for HCV were identified. DATA SYNTHESIS: Ledipasvir-sofosbuvir, a fixed-dose combination (FDC) tablet inhibiting nonstructural (NS) 5A and 5B proteins, without peginterferon and ribavirin is indicated for adult patients with genotype 1 HCV infection who are treatment naïve or experienced, with or without cirrhosis. Pivotal trials (n = 1952) have demonstrated that once-daily administration of ledipasvir-sofosbuvir for 12 or 24 weeks is effective at achieving sustained virological response (SVR) rates (94%-99%) in treatment-naïve patients (12 weeks), treatment-experienced patients without cirrhosis (12 weeks), and treatment-experienced patients with cirrhosis (24 weeks). Treatment-naïve patients without cirrhosis and baseline viral levels of less than 6 million IU/mL may be considered for 8 weeks of treatment. The most common adverse drug events (ADEs) associated with ledipasvir-sofosbuvir include headache, fatigue, insomnia, nausea, and diarrhea. CONCLUSIONS: Ledipasvir-sofosbuvir is the first interferon- and ribavirin-free FDC agent that has SVR rates much greater than 94%, with minimal ADEs, for the treatment of chronic HCV genotype 1 in naïve and treatment-experienced patients.

Vedolizumab: an α4ß7 integrin inhibitor for inflammatory bowel diseases.

OBJECTIVES: To review the pharmacology, efficacy, and safety of vedolizumab in the treatment of patients with ulcerative colitis (UC) and Crohn's disease (CD). DATA SOURCES: A literature search through clinicialtrials.gov, EMBASE and MEDLINE was conducted (January 1966-June 2014) using the terms vedolizumab and MLN0002. References from retrieved articles were reviewed for any additional material. Additionally, the prescribing information was retrieved. STUDY SELECTION/DATA EXTRACTION: Phase 1, 2, and 3 human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of vedolizumab were identified. DATA SYNTHESIS: Vedolizumab, an α4ß7 integrin inhibitor, was recently approved for adult patients with moderate to severe active UC or CD who are refractory or intolerant to standard therapies or who are dependent on corticosteroids. Trial data have demonstrated that vedolizumab 300 mg at weeks 0, 2, and 6 followed by every 8 weeks is effective at inducing and maintaining clinical response and remission, improving mucosal appearance, and achieving corticosteroid-free remission in patients with UC. This regimen is also effective at achieving clinical response, remission, and corticosteroid-free remission in patients with CD. Patients treated with vedolizumab, unadjusted for exposure, reported experiencing nasopharyngitis, headache, nausea, arthralgias, pyrexia, upper-respiratory-tract infections, fatigue, and cough. CONCLUSIONS: Vedolizumab is an effective agent at inducing and maintaining remission in patients with UC or CD. Vedolizumab is generally well tolerated and has not been associated with progressive multifocal leukoencephalopathy.

Incidence and Management of Rash in Telaprevir-Treated Patients.

BACKGROUND: Telaprevir-induced rash is a common, therapy-limiting adverse drug event (ADE) for patients with hepatitis c virus (HCV) infection. Given the similarity between telaprevir and simeprevir, real-world management of rash during treatment with an NS3/4A protease inhibitor and its implications are important. OBJECTIVE: The objectives of this study were to determine the incidence of rash in telaprevir-treated patients, its management, and the impact on sustained virological response and to identify any risk factors for rash development. METHOD: This was a retrospective study of adult patients who were treated with telaprevir in a hepatology clinic from July 1, 2011, to August 31, 2012. Pertinent information on demographics, past medical history, medications, laboratory data, outcomes of rash, other ADEs related to treatment, and physician grading of rash were collected. RESULT: Of 159 patients included, 44% (70/159) developed rash, and 4% (7/159) discontinued therapy because of rash. Median number of days until rash did not differ between patients who continued and discontinued therapy (25 vs 45, respectively; P = 0.88). Patients who developed rash were more likely to have lower actual body weight (ABW) or body mass index (BMI; P ≤ 0.01). No significant difference in rash development when drug-allergy history was considered was found. Most patients who continued telaprevir were prescribed topical corticosteroids (93.7%) and cetirizine (41.3%). Patients who discontinued therapy were more likely to be evaluated by dermatology (P = 0.002), prescribed oral corticosteroids (P = 0.02), hydroxyzine (P = 0.001), and topical triamcinolone (P = 0.01). CONCLUSION: ABW and BMI appear to be related to rash development. This finding may have implications in the treatment of HCV with simeprevir, given its similarity to telaprevir.

Identification of Patient Safety Threats in a Post-Intensive Care Clinic.

The extent to which postintensive care unit (ICU) clinics may improve patient safety for those discharged after receiving intensive care remains unclear. This observational cohort study conducted at an academic, tertiary care medical center used qualitative survey data analyzed via conventional content analysis to describe patient safety threats encountered in the post-ICU clinic. For 83 included patients, safety threats were identified for 60 patients resulting in 96 separate safety threats. These were categorized into 7 themes: medication errors (27%); inadequate medical follow-up (25%); inadequate patient support (16%); high-risk behaviors (5%); medical complications (5%); equipment/supplies failures (4%); and other (18%). Of the 96 safety threats, 41% were preventable, 27% ameliorable, and 32% were neither preventable nor ameliorable. Nearly 3 out of 4 patients within a post-ICU clinic had an identifiable safety threat. Medication errors and delayed medical follow-up were the most common safety threats identified; most were either preventable or ameliorable.

Combination therapy for the treatment and prevention of hepatic encephalopathy.

OBJECTIVE: To evaluate the efficacy and safety of combination therapy for the treatment and prevention of hepatic encephalopathy (HE). DATA SOURCES: A PubMed MEDLINE search was conducted (1947-June 2012) using the key terms lactulose, lactitol, nonabsorbable disaccharide, metronidazole, rifaximin, neomycin, probiotics, and hepatic encephalopathy. Searches were limited to include articles published in English. STUDY SELECTION AND DATA EXTRACTION: Study selection included published trials, case reports, and case series of humans with HE who were treated with combination therapy of rifaximin, lactulose, lactitol, metronidazole, neomycin, and/or probiotics. DATA SYNTHESIS: Only 6 studies that evaluated the benefits of combination drug therapy in the treatment or prevention of HE were available for review. Four studies addressed the treatment of HE, 2 found no significant difference between lactulose/neomycin versus placebo or rifaximin/lactulose, 1 assessed the use of rifaximin/lactulose without a control group, and the fourth found no significant difference between lactulose/probiotics versus either drug alone, although each group showed improvement from baseline. In the 2 prevention trials, both of which stemmed from the same data, the combination of rifaximin/lactulose was superior to lactulose alone, showing significant improvement in mental status, blood ammonia levels, and health-related quality of life and reductions in HE recurrence and hospitalization. Currently, there are no available clinical studies evaluating dual antibiotic therapy, metronidazole with nonabsorbable disaccharides, or antibiotics with probiotics. CONCLUSIONS: The evidence evaluating the use of combination therapy for the treatment of HE does not support its widespread use. The combination of rifaximin and lactulose may be considered in the treatment of HE and in patients refractory to monotherapy. The combination of rifaximin and lactulose should be considered for the prevention of HE, especially after the second episode of HE recurrence.

Changing patterns of the prevalence of burnout and secondary traumatic stress in health-system pharmacists throughout the COVID-19 pandemic.

Introduction: The demands posed during the coronavirus disease 2019 (COVID-19) pandemic have led to greater stress and frustration, which in turn can fuel exhaustion, cynicism, secondary traumatic stress (STS), and burnout. More evidence is needed regarding the prevalence of burnout and STS throughout the pandemic. Objectives: The aim of this study was to describe the changing pattern of the prevalence of burnout and STS in health-system pharmacists throughout the pandemic (early to 20 months into the pandemic). Methods: A cross-sectional, listserv-based online survey was conducted in health-system pharmacists. The survey was administered between April and May 2020 (early group) and again between October and December 2021 (20-month group). The survey questionnaire included demographics, employment characteristics, COVID-19-related questions, survey of respondent's perceptions of prevalence and severity of burnout, and Professional Quality of Life Scale (ProQOL) which assessed compassion satisfaction and fatigue (burnout and STS). Results: A total of 1126 health-system pharmacists completed the survey (484 in the early group and 642 in the 20-month group). Based on respondents' self-rating of burnout, significantly more respondents reported feeling burned out in the 20-month group vs the early group (69% vs 47.7%; P < .001). Based on ProQOL, significantly more respondents were identified with moderate-high likelihood of burnout (83.8% vs 65.3%; P < .001) and moderate-high probability of STS (63.2% vs 51.4%; P < .001) in the 20-month group vs the early group. Approximately 99% of respondents in both groups were identified with moderate-high probability of compassion satisfaction. Conclusion: Twenty months into the COVID-19 pandemic, almost 83% of health-system pharmacist respondents were identified with burnout, 63% with STS, and 99% with compassion satisfaction. These rates are significantly higher compared with rates early in the pandemic. Unfortunately, the development of burnout and STS in these pharmacists may lead to several work-related consequences (eg, increase risk of medical errors); therefore, further studies are critical to develop and assess effective interventions to address the long-term effects of the pandemic and well-being of health-system pharmacists.

Burnout and secondary traumatic stress in health-system pharmacists during the COVID-19 pandemic.

PURPOSE: To describe the prevalence of burnout and secondary traumatic stress (STS) in health-system pharmacists during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A cross-sectional, professional pharmacy organization listserver-based online survey of a target group of health-system pharmacists across the United States was conducted. The survey was sent out through professional organization listservers and was anonymous and voluntary. The survey questionnaire included items regarding demographics and employment characteristics, COVID-19-related questions, a survey of respondents' perceptions of the prevalence and severity of burnout, and the Professional Quality of Life Scale (ProQOL). The ProQOL assessed respondents for compassion satisfaction (subcategorized as burnout and STS) and compassion fatigue. Descriptive statistics was used to assess the prevalence of burnout and STS. RESULTS: Four hundred eighty-four health-system pharmacists completed the survey. Based on respondents' self-ratings of burnout, 47% were identified as having current burnout and 81% as having a history of burnout. Based on ProQOL scoring, 65.3% of respondents were identified as having a moderate or high likelihood of burnout, which was a prevalence higher than that indicated by respondents' self-ratings. Additionally, 51.4% of respondents were identified as having a moderate or high probability of STS and 99.4% as having a moderate or high probability of compassion satisfaction. CONCLUSION: The survey found that over half of health-system pharmacists were affected with burnout, half with STS, and all with compassion satisfaction during the COVID-19 pandemic. Unfortunately, the development of burnout and STS in these health-system pharmacists may lead to several work-related consequences (eg, increase risk of medical errors, depression); therefore, addressing burnout and STS is crucial. Further studies of the consequences of burnout and STS during the COVID-19 pandemic are needed.

Evaluation of a specialty hepatitis C virus telephone pharmacy service.

PURPOSE: Direct-acting antivirals (DAAs) used to treat hepatitis C virus (HCV) infection are associated with significant drug-drug interactions (DDIs). Pharmacists are well positioned to identify and mitigate these DDIs. Data to guide assessment of the impact of HCV specialty pharmacy services on identifying and addressing DDIs with DAAs are lacking. The overall purpose of the study described here was to determine the incidence and severity of DDIs identified by specialty pharmacists among patients treated with DAAs prior to and 1 month into therapy. METHODS: An observational, retrospective study was conducted to evaluate the impact of specialty pharmacy services in mitigating DDIs associated with use of DAAs. Adult patients with HCV infection (n = 200) who received DAAs and were enrolled with a specialty pharmacy service over a 1-year period were included. Endpoints included number, severity, and type of DDIs and DDIs per patient at baseline and 1 month into therapy, pharmacists' interventions, and safety and clinical outcomes. RESULTS: Fifty-nine percent of patients had at least 1 DDI. A total of 170 DDIs were identified (137 at baseline and 33 at 1-month follow-up), and the mean number of DDIs per patient significantly decreased from baseline to 1-month follow-up (from 1.38 to 0.16, P < 0.0001). The rate of "potentially clinically significant" or "critical" interactions was significantly lower at 1-month follow-up vs baseline assessment (69.6% vs 81.7%, P < 0.0001). The most commonly identified DDIs involved acid suppressive medications (49.6% and 66.6% of DDIs at baseline and follow-up assessment, respectively) and cardiovascular medications (26.2% and 21.2%, respectively). Total number of DDI interventions was 131, with an acceptance rate of 85%. Most common intervention was patient education and monitoring. CONCLUSION: Approximately 60% of patients had DDIs with DAAs. Implementing HCV specialty pharmacy services significantly decreased DDIs while maintaining SVR12.

Eltrombopag: a novel oral thrombopoietin receptor agonist.

OBJECTIVE: To review the pharmacology and pharmacokinetics and evaluate the safety and efficacy of eltrombopag for the treatment of chronic immune (idiopathic) thrombocytopenic purpura (ITP) and thrombocytopenia associated with hepatitis C virus (HCV) cirrhosis. DATA SOURCES: A Cochrane Controlled Trial Register, clinicaltrials.gov, EMBASE, and MEDLINE search was performed (January 1966-March 2010) using the key terms eltrombopag and SB-497115-GR. Searches were limited to published English-language studies in humans and a reference review of the pertinent literature was conducted. STUDY SELECTION AND DATA EXTRACTION: Published pharmacokinetic data and safety and efficacy trials, case reports, and case series on the use of eltrombopag were selected for inclusion. DATA SYNTHESIS: Eltrombopag is a novel second-generation thrombopoietin receptor agonist that was approved by the Food and Drug Administration for the treatment of chronic ITP in patients who had an insufficient response to corticosteroids, intravenous immune globulin, or splenectomy. Eltrombopag has been shown to be superior to placebo in increasing platelet counts, with more patients achieving counts >50 x 10(3)/microL. One study has also shown eltrombopag to be effective in the treatment of thrombocytopenia associated with HCV cirrhosis. Eltrombopag has a boxed warning related to risk of hepatotoxicity, with criteria for discontinuation in patients with elevated liver enzyme levels or clinical signs of liver damage. As such, close monitoring of laboratory parameters is required, and patients must be registered with the PROMACTA CARES program. CONCLUSIONS: Eltrombopag is effective in increasing platelet counts in patients with chronic ITP and in patients with HCV cirrhosis. In the treatment of ITP, eltrombopag has been studied only for short durations and is more expensive than first-line oral corticosteroids; therefore, it should be considered a second-line agent. More studies are needed to identify a place in therapy for eltrombopag in the treatment of thrombocytopenia associated with HCV cirrhosis.

Continuous infusion of pantoprazole with octreotide does not improve management of variceal hemorrhage.

STUDY OBJECTIVE: To assess the effect of a prolonged continuous infusion of pantoprazole on patient outcomes when the drug was combined with standard octreotide therapy in patients with variceal hemorrhage. DESIGN: Retrospective cohort study. SETTING: Large academic hospital. Patients. One hundred thirty adults who received treatment for a documented variceal hemorrhage; 53 patients received standard octreotide therapy plus a prolonged continuous infusion of pantoprazole (continuous-infusion group) and 77 patients received either octreotide alone, octreotide with a short-term (<24 hrs) infusion of pantoprazole, or octreotide with intermittent acid suppression (control group). MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was the number of units of packed red blood cells transfused during hospitalization. Baseline characteristics between the treatment groups were similar. The duration of therapy for variceal hemorrhage was significantly longer in the continuous-infusion group than in the control group. Transfusion requirements for packed red blood cells (mean+/-SD 6.4+/-6.5 vs 5.8+/-6.6 units, p=0.66) and platelets (8.8+/-15.1 vs 5.1+/-11.9 units, p=0.13) were similar for the continuous-infusion group versus the control group. The continuous-infusion group, however, received significantly more units of fresh-frozen plasma than the control group (6.1+/-10.6 vs 2.9+/-6.2 units, p=0.05). There was no significant difference in mortality rate between groups. CONCLUSION: Prolonged continuous infusions of pantoprazole with octreotide seemed to offer no additional benefit compared with octreotide plus short-term infusions of pantoprazole or intermittent acid suppression in the management of acute variceal hemorrhage. Prospective studies should be conducted to evaluate the role of continuously infused proton pump inhibitors in this setting before their use can be advocated.

Clinical outcomes and pharmacists' acceptance of a community hospital's anticoagulation management service utilizing decentralized clinical staff pharmacists.

BACKGROUND: In 2008, the Joint Commission released an updated National Patient Safety Goals document that requires institutions to implement practices that reduce the likelihood of patient harm associated with use of anticoagulation therapy. One of the expectations associated with this goal was that each organization would establish an anticoagulant management program. To our knowledge, few data exist to describe the implementation and assessment of anticoagulation programs in smaller, nonteaching community hospitals using decentralized pharmacists in an integrated practice model. OBJECTIVE: To compare the performance of a protocol-driven anticoagulation management service led by decentralized pharmacists in a nonteaching community hospital with that of usual medical care provided by hospitalist physicians before this program was implemented. Based on these results, as well as a pharmacist satisfaction survey, evaluate the service and identify barriers to expansion. METHODS: We conducted a retrospective cohort study comparing 50 consecutive patients who were starting warfarin for the first time beginning in November 2003 with 50 patients managed by hospitalist physicians prior to November 2002 (the time of program implementation). RESULTS: There were no significant differences between groups with regard to time in therapeutic range once therapeutic, length of stay, international normalized ratios (INRs) greater than 3.5, or INRs less than 2. Patients in the pharmacy management group had significantly fewer drug interactions with antimicrobials than did the usual medical care group. Although time to therapeutic range was longer in the pharmacy protocol group, there were fewer patients with INRs greater than 3.5, although this did not reach statistical significance. CONCLUSIONS: The efficacy of the pharmacist-led anticoagulation management service was no different from that of usual medical care. Patient safety appeared improved, in part due to more careful initial dose selection based on patient-specific factors. Although this program was accepted by pharmacists, time limitations were perceived to be a major barrier to quality care and expansion of the service.

Amino Acid requirements in critically ill patients with acute kidney injury treated with continuous renal replacement therapy.

Acute kidney injury in critically ill patients is often a complication of an underlying condition such as organ failure, sepsis, or drug therapy. In these patients, stress-induced hypercatabolism results in loss of body cell mass. Unless nutrition support is provided, malnutrition and negative nitrogen balance may ensue. Because of metabolic, fluid, and electrolyte abnormalities, optimization of nutrition to patients with acute kidney injury presents a challenge to the clinician. In patients treated with conventional intermittent hemodialysis, achieving adequate amino acid intake can be limited by azotemia and fluid restriction. With the use of continuous renal replacement therapy (CRRT), however, better control of azotemia and liberalization of fluid intake allow amino acid intake to be maximized to support the patient's metabolic needs. High amino acid doses up to 2.5 g/kg/day in patients treated with CRRT improved nitrogen balance. However, to our knowledge, no studies have correlated increased amino acid intake with improved outcomes in critically ill patients with acute kidney injury. Data from large, prospective, randomized, controlled trials are needed to optimize the dosing of amino acids in critically ill patients with acute kidney injury who are treated with CRRT and to study the safety of high doses and their effects on patient morbidity and survival.