Real-world use of inhaled nitric oxide therapy in patients with COVID-19 and mild-to-moderate acute respiratory distress syndrome.

Background: Inhaled nitric oxide (iNO) has been studied in patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 when it may be too late to impact disease course. This article aims to describe real-world iNO use and outcomes in patients with COVID-19 with mild-to-moderate ARDS in the United States. Methods: This was a retrospective medical chart review study that included patients who were ≥18 years old, hospitalized for COVID-19, met the Berlin ARDS definition, received iNO for ≥24 hours continuously during hospitalization, and had a partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (P/F ratio) of >100 to ≤300 mmHg at iNO initiation. Outcomes included oxygenation parameters, physician-rated Clinical Global Impression-Improvement (CGI-I) scale scores, and adverse events. Response to iNO was defined as >20% improvement in P/F ratio. Results: Thirty-seven patients at six sites were included. A P/F ratio of ≤100 was the most common reason for exclusion (n=146; 83% of excluded patients). The mean P/F ratio (SD) increased from 136.7 (34.4) at baseline to 140.3 (53.2) at 48 hours and 151.8 (50.0) at 72 hours after iNO initiation. The response rate was 62% (n=23). During hospitalization, no patient experienced adverse events, including methemoglobinaemia, airway injury, or worsening pulmonary oedema associated with iNO. At discharge, 54.0% (n=20) of patients improved or remained stable according to the CGI-I. Conclusion: In patients hospitalized with COVID-19 and mild-to-moderate ARDS, iNO was associated with improvement in the P/F ratio with no reported toxicity. This study provides additional evidence supporting a favourable benefit-risk profile for iNO in the treatment of mild-to-moderate ARDS in patients with COVID-19 infection.

Treatment patterns and outcomes among nontransplant newly diagnosed multiple myeloma patients in Spain.

Aim: To describe treatment patterns and outcomes in nontransplant newly diagnosed multiple myeloma (NDMM) patients in Spain. Methods: This retrospective study included two cohorts of NDMM patients diagnosed between 1 January 2012 to 31 December 2013 and 1 April 2016 to 31 March 2017. Results: Among 113 patients, proteasome inhibitor (PI) + alkylator combinations (49%) and PI-based regimens without an alkylator (30%) were the most common first-line (1L) therapies. Use of PI + immunomodulatory drug-based regimens increased between the cohorts; PI-based regimens without an alkylator/immunomodulatory drug decreased. Use of 1L oral regimens was low but increased over time; use of maintenance therapy was low across both periods. Median 1L duration of treatment was 6.9 months. Conclusion: Short 1L duration of treatment and low use of 1L oral regimens and maintenance therapy highlight unmet needs in NDMM.

Lay abstract This study describes treatment patterns and outcomes in newly diagnosed multiple myeloma (NDMM) patients in Spain who were not candidates for transplant. The study looked at two patient groups: patients diagnosed between 1 January 2012 and 31 December 2013 and those diagnosed between 1 April 2016 and 31 March 2017. Among the 113 patients considered, the most common first-line therapies were proteasome inhibitor (PI) + alkylator combinations (49%) and PI-based regimens without an alkylator (30%). We saw increased use of PI with immunomodulators (which arm the immune system to battle disease) and decreased use of PI-based regimens without an alkylator or immunomodulator. First-line use of oral regimens was low but increased over time. The median length of first-line treatment for both groups combined was 6.9 months. Finding low use of first-line oral regimens and maintenance therapy and a short duration of first-line treatment, our study highlights the unmet needs that exist in NDMM patients who are not transplant candidates in Spain.

Cost-Utility of All-Oral Direct-Acting Antiviral Regimens for the Treatment of Genotype 1 Chronic Hepatitis C Virus-Infected Patients in Hong Kong.

BACKGROUND: Direct-acting antivirals (DAAs) are entering the hepatitis C virus (HCV) treatment landscape in Hong Kong, prompting the need for cost-effectiveness evaluations of these interventions to enable optimal use of healthcare resources. AIMS: This study aimed to compare the cost-effectiveness of DAAs to standard-of-care pegylated interferon plus ribavirin (RBV) in treatment-naïve patients without significant liver fibrosis and to compare different DAAs in patients who are treatment-experienced and/or have advanced liver disease. METHODS: A Markov model was constructed to evaluate cost-effectiveness over a lifetime time horizon from the payer perspective. The target population was treatment-naïve and treatment-experienced HCV genotype 1 patients, stratified by degree of liver fibrosis. The model consists of 16 health states encompassing METAVIR fibrosis score (F0-F4), treatment success or failure, decompensated cirrhosis, hepatocellular carcinoma, liver transplant, and liver-related death. The proportions of patients achieving sustained virologic response were obtained from clinical trials. Other inputs were obtained from published and local data. The primary outcome was incremental cost-utility ratio for each DAA versus pegylated interferon + ribavirin and among different DAAs. RESULTS: In treatment-naïve F0-2 HCV patients, all DAAs were cost-effective in genotype 1a and daclatasvir + asunaprevir, elbasvir/grazoprevir, ledipasvir/sofosbuvir, and glecaprevir/pibrentasvir were cost-effective compared to pegylated interferon + ribavirin in genotype 1b. In genotypes 1a and 1b, treatment-experienced patients, and F3-4 patients, elbasvir/grazoprevir was the least costly DAA and economically dominant over most other DAAs. CONCLUSIONS: DAAs can be a cost-effective option for the treatment of genotype 1 HCV patients in Hong Kong, and elbasvir/grazoprevir is cost-effective.

Economic and Humanistic Burden of Cervical Cancer in the United States: Results from a Nationally Representative Survey.

Objective: To measure the economic and humanistic burden of cervical cancer in the United States. Materials and Methods: This was a retrospective analysis of Medical Expenditure Panel Survey data (2006-2015). Cervical cancer cases were identified using International Classification of Diseases, Ninth Revision, Clinical Modification code "180" or clinical classification software code "26". The control group included women without any cancer diagnosis. Study outcomes included health care resource use (institutional inpatient and outpatient, emergency room, and physician office visits), costs, limitations in activities of daily living, and quality of life (general health status, 12-Item Short Form Health Survey [SF-12] physical and mental component summary [MCS], EuroQol-5D and Short-Form Six-Dimension health utility, and Patient Health Questionnaire-2 depression severity). Generalized linear models, controlling for sociodemographic and clinical covariates, were conducted to compare outcomes between cases and controls. Results: The analytic cohort included 275,246 cervical cancer cases and 146,061,609 noncancer controls. Cases were significantly older (mean age [years]: 42.03 vs. 36.98) and had a higher Charlson comorbidity burden (mean score: 1.06 vs. 0.46) versus controls. Multivariate analyses suggested that compared to controls, cancer cases had significantly higher costs: institutional outpatient ($1,610 vs. $502), physician visit ($2,422 vs. $1,321), and total health care ($10,031 vs. $4,913). Cases were 1.99 (odds ratio [OR]: 1.991; 95% confidence interval [CI]: 1.23-3.22) and 2.56 (OR: 2.562; 95% CI: 1.78-3.68) times as likely to report activity limitations and poor general health versus controls. Cervical cancer patients had significantly lower SF-12 physical and MCS score, health utility, and higher depression severity. Conclusions: Cervical cancer is associated with significant economic burden, activity limitations, and quality of life impairment among ambulatory women in the United States.

Economic impact model of delayed inhibitor development in patients with hemophilia a receiving emicizumab for the prevention of bleeding events.

Aims: Cumulative exogenous factor VIII (FVIII) exposure is an important predictor of developing neutralizing antibodies (inhibitors) to FVIII in patients with persons with hemophilia A (PwHA). The aim of this study was to model the costs of emicizumab versus FVIII prophylaxis and total treatment costs for patients with severe HA.Materials and Methods: An Excel-based decision model was developed to calculate cumulative costs in PwHA over a 20-year time horizon from the US payer perspective. The model considered persons with severe HA beginning at age 12 months with no prior FVIII exposure and initiating prophylaxis with emicizumab or FVIII. PwHA could develop inhibitors on accumulation of 20 FVIII exposure days. PwHA with inhibitors replaced FVIII with bypassing agents until inhibitors resolved spontaneously, following immune tolerance induction (ITI), or at the end of the time horizon. The primary model outcome was the difference in emicizumab versus FVIII treatment costs in 2019 USD. Sensitivity analyses were performed to test the robustness of results.Results: Total incremental cost over 20 years was -$1,945,480 (emicizumab arm, $4,919,058; FVIII arm, $6,864,538). Prophylaxis costs (emicizumab arm, $4,096,105; FVIII arm, $6,290,919) comprised the majority of costs in both groups, followed by breakthrough bleed treatment for the FVIII arm ($342,652) and ITI costs for the emicizumab arm ($733,671). Higher costs in the FVIII group reflected earlier inhibitor development (FVIII, 4 months; emicizumab, 162 months) and switch to bypassing agents.Limitations: The model design reflects a simplified treatment pathway for patients with severe HA who initiate FVIII or emicizumab prophylaxis. In the absence of clinical data, a key conservative assumption of the model is that patients receiving emicizumab and FVIII prophylaxis have the same risk of developing inhibitors.Conclusions: This study suggests that prophylaxis with emicizumab results in cost savings compared to FVIII prophylaxis in HA.

Projected impact of elbasvir/grazoprevir in patients with hepatitis C virus genotype 1 and chronic kidney disease in Vietnam.

BACKGROUND: Hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients with chronic kidney disease (CKD). The objective of this study was to predict the impact of EBR/GZR on the incidence of liver and kidney related complications compared with no treatment (NoTx) and pegylated interferon plus ribavirin (pegIFN/RBV) in patients with CKD stage 4/5 in Vietnam. METHODS: We developed a mathematical model of the natural history of chronic HCV, CKD, and liver disease. Efficacy of EBR/GZR and pegIFN/RBV were derived from the C-SURFER trial and a meta-analysis, respectively. We calculated lifetime cumulative morbidity and mortality rates, including incidence of decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and life expectancy. RESULTS: Estimated lifetime incidence of DC was significantly reduced in patients receiving EBR/GZR (3.47%) compared to NoTx (18.14%) and pegIFN/RBV (9.01%). Estimated incidence of HCC was 1.02%, 21.64%, and 8.90%, and 1.02% in patients receiving EBR/GZR, NoTx, and pegIFN/RBV. EBR/GZR was estimated to extend life expectancy by 4.2 and 2.0 years compared with NoTx and pegIFN/RBV. CONCLUSIONS: Our model predicted that EBR/GZR will significantly reduce the incidence of liver-related complications and prolong life in patients with chronic HCV GT1 infection and CKD compared with NoTx or pegIFN/RBV.

Brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma who are Ineligible for autologous stem cell transplant: A Germany and United Kingdom retrospective study.

OBJECTIVE: Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate licensed for the treatment of relapsed/refractory Hodgkin lymphoma (rrHL) following autologous stem cell transplant (ASCT) or at least two prior therapies when ASCT or multiagent chemotherapy is not an option. The objective of this study was to describe real-world outcomes with BV in patients with rrHL considered ASCT ineligible or who refuse ASCT. METHODS: This was a retrospective medical chart review study that enrolled patients ≥18 years old who were initially diagnosed with HL between January 1, 2008 and June 30, 2014, considered ASCT ineligible, and treated in routine care with BV for progressive disease after multidrug chemotherapy regimens. Clinical outcomes included best response to treatment, progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: A total of 136 patients were included, with a median age of 70 years at initial HL diagnosis. The most common reasons for ASCT ineligibility were comorbidities (74%) and age (57%). Overall response rate was 74%, and PFS and OS were 15.1 and 17.8 months, respectively. Peripheral neuropathy was observed in 9.6% of patients. CONCLUSION: The results of this study provide real-world evidence on the feasibility and effectiveness of BV in elderly or frail ASCT-ineligible patients with rrHL in a real-world setting.

Epidemiology and outcome of invasive fungal infections and methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and complicated skin and soft tissue infections (cSSTI) in Lebanon and Saudi Arabia.

The objectives of this retrospective medical chart review study were to document the inpatient incidence, treatment, and clinical outcomes associated with invasive fungal infections (IFI) due to Candida and Aspergillus species, Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and MRSA complicated skin and soft tissue infections (cSSTI) in the Middle East. This study evaluated 2011-2012 data from 5 hospitals in Saudi Arabia and Lebanon with a combined total of 207,498 discharges. Hospital medical chart data were abstracted for a random sample of patients with each infection type (102 patients - IFI, 93 patients - MRSA pneumonia, and 87 patients-MRSA cSSTI). Descriptive analysis found that incidence of IFI (per 1000 hospital discharges) was higher than MRSA cSSTI and MRSA pneumonia (IFI: 1.95 and 2.57; MRSA cSSTI: 2.01 and 0.48; and MRSA pneumonia 0.59 and 0.55 for Saudi Arabia and Lebanon, respectively). Median time from hospital admission to diagnosis and from admission to initiation of active therapy were 6 and 7 days, respectively, in IFI patients; median time from admission to diagnosis was 2days for both MRSA pneumonia and cSSTI, with a median of 4 and 2days from admission to MRSA-active antibiotic start, respectively. The mean hospital LOS was 32.4days for IFI, 32.4days for MRSA pneumonia and 26.3days for MRSA cSSTI. Inpatient mortality was higher for IFI (42%) and MRSA pneumonia (30%) than for MRSA cSSTI (8%). At discharge, 33% of patients with IFI and 27% and 9% of patients with MRSA pneumonia and cSSTI, respectively, were considered to have failed therapy. In conclusion, there is a significant burden of these serious infections in the Middle East, as well as opportunity for hospitals to improve the delivery of patient care for difficult-to-treat infections by promoting expedited diagnosis and initiation of appropriate antimicrobial therapy.

Peripheral nerve blocks in the management of postoperative pain: challenges and opportunities.

Peripheral nerve blocks (PNBs) are increasingly used as a component of multimodal analgesia and may be administered as a single injection (sPNB) or continuous infusion via a perineural catheter (cPNB). We undertook a qualitative review focusing on sPNB and cPNB with regard to benefits, risks, and opportunities for optimizing patient care. Meta-analyses of randomized controlled trials have shown superior pain control and reductions in opioid consumption in patients receiving PNB compared with those receiving intravenous opioids in a variety of upper and lower extremity surgical procedures. cPNB has also been associated with a reduction in time to discharge readiness compared with sPNB. Risks of PNB, regardless of technique or block location, include vascular puncture and bleeding, nerve damage, and local anesthetic systemic toxicity. Site-specific complications include quadriceps weakness in patients receiving femoral nerve block, and pleural puncture or neuraxial blockade in patients receiving interscalene block. The major limitation of sPNB is the short (12-24 hours) duration of action. cPNB may be complicated by catheter obstruction, migration, and leakage of local anesthetic as well as accidental removal of catheters. Potential infectious complications of catheters, although rare, include local inflammation and infection. Other considerations for ambulatory cPNB include appropriate patient selection, education, and need for 24/7 availability of a health care provider to address any complications. The ideal PNB technique would have a duration of action that is sufficiently long to address the most intense period of postsurgical pain; should be associated with minimal risk of infection, neurologic complications, bleeding, and local anesthetic systemic toxicity; and should be easy to perform, convenient for patients, and easy to manage in the postoperative period.

Addressing innovative off-label medication use at an academic medical center.

PURPOSE: A large hospital's systematic and evidence-based approach to adjudicating, monitoring, and ensuring the safety of off-label medication use is described. SUMMARY: In 2003 the University of Pittsburgh Medical Center (UPMC)-Presbyterian implemented a policy that created a formal process for the systematic evaluation of formulary requests and drug-utilization patterns indicating or suggesting off-label use. Explicit criteria were developed for differentiating "innovative off-label use" (i.e., use based on a reasonable rationale yet lacking definitive scientific support in the form of fully published randomized controlled trials) from medication use more appropriately classified as clinical research. The UPMC-Presbyterian policy also outlined a process for the development, implementation, and evaluation of guidelines on innovative off-label use, including the collection of efficacy and safety outcomes. As of October 2012, 31 proposals for off-label medication use had been evaluated by the medical center's pharmacy and therapeutics committee and formulary subcommittee. Thirteen requests resulted in a determination of innovative off-label use and the development of prescribing guidelines, and 10 prompted the extension of an agent's current formulary status; in 6 cases, proposed off-label uses were determined to constitute clinical research. In some instances, innovative off-label medication use generated safety and outcomes data that led to changes in local standards of care. An algorithm to guide decision-making with regard to requests and proposals for off-label medication use is provided. CONCLUSION: The UPMC-Presbyterian experience indicates that off-label medication use can be effectively managed using evidence-based principles and peer review mechanisms.

Early risk factors for persistent anemia after kidney transplantation.

STUDY OBJECTIVE: To identify predictors of persistent posttransplant anemia that appear within the first week after kidney transplantation in order to determine the high-risk patients who might receive the most benefit from erythropoiesis-stimulating agents. STUDY DESIGN: Retrospective cohort study. SETTING: University-affiliated hospital and outpatient clinic. PATIENTS: One hundred sixty-four adult kidney transplant recipients (January 1, 2002-June 30, 2007) with anemia on posttransplant day 7 who were followed at the clinic for at least 2 months after transplantation. MEASUREMENTS AND MAIN RESULTS: Data from deidentified electronic medical records of the kidney transplant recipients were collected and included demographic characteristics, primary cause of renal failure, pertinent laboratory data, and donor information. To detect early predictors of persistent anemia, patients with persistent posttransplant anemia, defined as a hemoglobin level below 11 g/dl for 2 months (day 60) after transplantation, were compared with those who had nonpersistent posttransplant anemia, defined as a hemoglobin level below 11 g/dl on day 7 but 11 g/dl or greater on day 60. Of the 164 patients classified as having anemia on posttransplant day 7, 39 (23.8%) had persistent posttransplant anemia on day 60. In univariate analyses, hemoglobin level of 9 g/dl or below on day 7, donor age younger than 10 years, and female sex were variables associated with increased risk of persistent posttransplant anemia. In a multivariate analysis, donor age younger than 10 years was the most significant predictor of persistent posttransplant anemia, followed by hemoglobin level of 9 g/dl or below. CONCLUSION: Patients receiving transplants from donors younger than 10 years and those with hemoglobin levels of 9 g/dl or below on postoperative day 7 were found to be at highest risk for persistent posttransplant anemia and may receive the most benefit from early initiation of erythropoiesis-stimulating agent therapy. In most of the kidney transplant recipients, posttransplant anemia resolved without the use of these agents.

Influence of medications and diagnoses on fall risk in psychiatric inpatients.

PURPOSE: The influence of medications and diagnoses on fall risk in psychiatric inpatients was evaluated. METHODS: In this retrospective case-control study, psychiatric inpatients age 18 years or older with a documented fall that was reported served as study cases. These patients were matched to control patients from the same hospital (1:1) by admission year, sex, and age. Psychiatric diagnoses evaluated included major depressive disorder, schizophrenia or schizoaffective disorder, bipolar disorder, Alzheimer's disease and dementia, anxiety or neurosis, delirium, personality disorder, and obsessive-compulsive disorder. Medications assessed as independent variables were conventional antipsychotics, atypical antipsychotics, selective serotonin-reuptake inhibitors, tricyclic antidepressants, atypical antidepressants, monoamine oxidase inhibitors, lithium, anticonvulsants, benzodiazepines, nonbenzodiazepine sleep aids, Alzheimer's disease medications, antihistamines, antiarrhythmics, antihypertensives, benign prostatic hyperplasia medications, oral hypoglycemic agents, histamine H(2)-receptor blockers, laxatives and stool softeners, muscle relaxants, nonsteroidal antiinflammatory drugs, opioids, Parkinson's disease medications, and overactive bladder medications. Univariate logistic regression models were developed for each risk factor to determine its impact on fall risk. RESULTS: A total of 774 patient cases were matched with controls. Most falls occurred on the second day of hospitalization. Medications associated with a higher risk of falls were alpha-blockers, nonbenzodiazepine sleep aids, benzodiazepines, H(2)-blockers, lithium, antipsychotics, atypical antidepressants, anticonvulsants, and laxatives and stool softeners. Patients with a diagnosis of dementia and Alzheimer's disease also had an increased risk of falling. CONCLUSION: Alpha-blockers, nonbenzodiazepine sleep aids, benzodiazepines, H(2)-blockers, lithium, atypical antipsychotics, atypical antidepressants, anticonvulsants and mood stabilizers, conventional anti-psychotics, laxatives and stool softeners, and dementia and Alzheimer's disease were significant predictors of inpatient falls in a psychiatric population.

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.

Effect of drug information request templates on pharmacy student compliance with the modified systematic approach to answering drug information questions.

BACKGROUND: The modified systematic approach to answering drug information questions is a technique used in drug information practice and in teaching pharmacy students to effectively provide drug information. Drug information request templates were developed to prompt students and other trainees to ask appropriate background questions and perform an effective search. OBJECTIVE: An evaluation was conducted to determine whether use of drug information templates by fourth-year pharmacy students during their drug information experiential rotation improved compliance with the modified systematic approach. METHODS: Fifty documented drug information requests, including 25 prior to template implementation (August 2005-August 2006) and 25 after template implementation (August 2007-August 2008), were randomly selected for evaluation. Each question was evaluated for completeness of background information obtained, categorization and identification of the ultimate question, completeness of references searched, and formulation of a concise response and an evidence-based recommendation. RESULTS: Background information was complete in 16% of pre-template questions and 92% of post-template questions (p < 0.001). Eighty-four percent of pre-template questions and 96% of post-template questions were appropriately categorized (p = 0.349). The requestor's ultimate question was clearly identified in 68% of pretemplate questions and 92% of post-template questions (p = 0.074). All necessary references were searched in 36% of pre-template questions and 88% of post-template questions (p < 0.001). A concise response was documented in 80% of pretemplate questions and 92% of post-template questions (p = 0.417). In questions determined to require a specific recommendation among the pre-template (n = 20) and post-template groups (n = 14), a clear and evidence-based recommendation was described in 40% (p = 0.038) and 79% (p = 0.038), respectively. CONCLUSIONS: Use of drug information request templates improves students' compliance with the modified systematic approach, most notably in obtaining background information and searching necessary references including primary literature.

Instructor satisfaction with a technology-based resource for diabetes education.

OBJECTIVES: To evaluate instructor use patterns and satisfaction with DM Educate, a comprehensive, Web-based diabetes course. METHODS: Instructors completed a post-course survey instrument to assess their use of course materials and components, as well as satisfaction with the course content, design, and technology utilized, and to solicit their suggestions for additional content areas. RESULTS: Thirty-eight percent of respondents utilized DM Educate as a standalone elective and 62% had integrated materials into existing courses. The pharmacotherapy module was the most utilized at 91% and slide sets were the most utilized course components at 63%. All instructors stated that they would use the course again the following year. Suggestions for improvement included incorporation of more active-learning activities and patient cases. CONCLUSION: Instructors' were highly satisfied with the course materials and technology used by DM Educate, a Web-based diabetes education course, and indicated they were able to customize the course materials both to establish new courses and supplement existing courses. All instructors planned to use the course again.

Use of lipid emulsion to reverse local anesthetic-induced toxicity.

OBJECTIVE: To evaluate the use of lipid emulsion for reversal of local anesthetic-induced toxicity. DATA SOURCES: Literature was accessed through PubMed and OVID (1966-May 2007) using the search terms lipid emulsion and local anesthetic. Reference lists were consulted to identify additional publications. STUDY SELECTION AND DATA EXTRACTION: All articles published in English were evaluated for inclusion. Publications describing the use of lipid emulsion for reversal of local anesthetic in either humans or animals were included. DATA SYNTHESIS: It has been suggested that lipid emulsion (Intralipid) may reverse local anesthetic toxicity by extracting lipophilic local anesthetics from aqueous plasma or tissues or by counteracting local anesthetic inhibition of myocardial fatty acid oxygenation. Studies in rats and dogs have shown that lipid emulsion is effective in resuscitating animals who are asystolic after the administration of intravenous bupivacaine. Three case reports support the use of lipid emulsion to reverse systemic toxicity, including seizures, electrocardiogram abnormalities, and cardiac arrest, resulting from the administration of levobupivacaine, ropivacaine, bupivacaine, or mepivacaine. The regimens used in these cases consisted of bolus doses of 1.2-2 mL/kg followed by continuous infusions of 0.25-0.5 mL/kg/min. All of the patients recovered fully with no neurologic sequelae. CONCLUSIONS: Literature describing animal studies and human case reports suggests that lipid emulsion is effective in the reversal of local anesthetic toxicity. The potential risks of administering the relatively high doses of this agent are uncertain, and the optimal dose has not been established. In light of these uncertainties, it is appropriate to administer lipid emulsion only after advanced cardiac life support has failed and prior to cardiopulmonary bypass.

Evaluation of conflicting literature and application to formulary decisions.

PURPOSE: Guidelines were developed for grading the quality, quantity, and consistency of drug literature in support of formulary recommendations. METHODS: Four developmental steps were taken to create a comprehensive literature evaluation system. The first step identified the attributes of a body of literature that were most reflective of its applicability to patient care. The next step defined each domain (quality, quantity, consistency), as determined by the Agency of Healthcare Research and Quality (AHRQ), in terms of the specific qualities to be assessed; a value was assigned to those qualities. Also, a literature search was conducted to identify strategies for evaluating bodies of literature employed in published assessment tools. Following the analysis of previously published systems, which were evaluated with respect to their inclusion of the AHRQ-identified domains, the next step was the development of specific domains and definitions to get a composite grade (with "better" evidence earning more points) for formulary recommendations. The final step was the creation of a system that aggregated the final score for the recommendation. The recommendation was categorized according to quality, quantity, and consistency of supporting evidence, and the total number of points was calculated and the recommendation given letter and numerical grades. RESULTS: The guidelines that were developed allow the user to accurately, consistently, and easily determine the strength of recommendations for a body of literature that may be conflicting. The addition of criteria for quantity and consistency to previously-published grading systems has made the guidelines more objective. CONCLUSION: A system that accounts for the quality, quantity, and consistency of drug literature was developed to assist in making formulary decisions.

Effect of long-term tacrolimus immunosuppression on renal function in liver transplant recipients.

STUDY OBJECTIVES: To describe changes in renal function occurring after long-term treatment with tacrolimus in clinically stable liver transplant recipients, and to identify risk factors for a clinically significant decline in renal function in these patients. DESIGN: Retrospective cohort study. Setting. University medical center. Patients. Four hundred thirty-two patients aged 18 years or older who underwent liver transplantation between January 1, 1996, and December 31, 2000, and received tacrolimus as part of their immunosuppressive treatment regimen. MEASUREMENTS AND MAIN RESULTS: Six hundred patients were identified from an electronic records review. Those who received multiorgan transplants, were not receiving their first liver transplant, or died during the hospitalization were excluded from the study. Outcomes measured were change in mean glomerular filtration rate (GFR) up to 5 years after transplantation, and proportion of patients with a decline in GFR of 30% or greater from baseline to the last recorded serum creatinine level. Covariates that affected this decline were identified using a logistic regression model. Patients were followed for a mean +/- SD of 3.7 +/- 2.0 years. Mean GFR showed a statistically significant decline from baseline to end of follow-up (67.7 +/- 25.6 vs 58.4 +/- 26.5 ml/min/1.73 m(2), p<0.001). The GFR declined by 30% or more in 154 (35.6%) patients. Increasing age (odds ratio [OR] = 1.03, p=0.020), female sex (OR = 1.92, p=0.006), higher baseline GFR (OR = 1.03, p<0.001), and diagnosis of diabetes mellitus (OR = 1.74, p=0.059) were identified as predictors of this outcome. CONCLUSION: After the acute posttransplantation period, liver transplant recipients given long-term treatment with tacrolimus experienced only small changes in GFR over time. Patients with diabetes and women had the highest risk of experiencing a clinically significant decline in renal function.

Impact of nonsteroidal antiinflammatory drugs on the cardioprotective effects of aspirin.

OBJECTIVE: To examine the evidence of a pharmacodynamic interaction between aspirin and nonsteroidal antiinflammatory drugs (NSAIDs); specifically, to determine whether a deleterious relationship exists with respect to the cardioprotective effects of aspirin. DATA SOURCES: Primary articles were identified by a MEDLINE search (1966-May 2004). Search terms included aspirin, nonsteroidal antiinflammatory drug, drug interaction, mortality, myocardial infarction, and stroke. STUDY SELECTION AND DATA EXTRACTION: All prospective and retrospective studies conducted in human subjects and investigating the potential interaction between aspirin and NSAIDs were included. DATA SYNTHESIS: Several controlled pharmacodynamic studies indicate that the sustained inhibition of cyclooxygenase activity by aspirin is blunted in the presence of some NSAIDs. While these data are fairly consistent, they are limited in that they rely on surrogate markers and not clinical outcomes. Observational studies have shown conflicting results regarding the effect of combination NSAID and aspirin therapy on mortality risk and incidence of myocardial infarction. CONCLUSIONS: Pharmacodynamic data indicating an interaction between aspirin and NSAIDs have not translated to a consistent clinical effect in observational studies. In the absence of a randomized, controlled, clinical outcomes study, there is insufficient evidence to dictate a change in therapy.

Atomoxetine: the first nonstimulant for the management of attention-deficit/hyperactivity disorder.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety, drug interactions, dosage and administration, and place in therapy of atomoxetine in the treatment of attention-deficit/hyperactivity disorder (ADHD) are reviewed. SUMMARY: Atomoxetine is a methylphenoxy-benzenepropanamine derivative with antidepressant activity and is thought to enhance noradrenergic function via selective inhibition of the presynaptic norepinephrine transporter. Atomoxetine is rapidly absorbed from the gastrointestinal tract, reaching peak levels in 1.83 hours in pediatric patients and 1-1.5 hours in adults. The clinical efficacy of atomoxetine in the treatment of ADHD has been evaluated in six published clinical trials of children and adolescents and two studies enrolling only adults. Clinical trial data indicate that atomoxetine is safe and well tolerated for the treatment of ADHD; however, safety data about long-term use (greater than one year) are unavailable. Adverse events reported in clinical trials were mainly mild to moderate and transient in nature. Recommended dosing of atomoxetine is weight based, and dosages should be adjusted to a target dosage of 1.2 mg/kg/day in children and adolescents weighing 70 kg or less and to 80 mg/day in children and adolescents weighing over 70 kg and adults. While current guidelines from the American Academy of Pediatrics recommend stimulants and behavior modification as first-line therapy for the management of ADHD, atomoxetine offers those patients who do not respond to or cannot tolerate one or more stimulants an alternative treatment option. CONCLUSION: Atomoxetine, the first non-stimulant approved for the management of ADHD in children, adolescents, and adults, provides patients who have not responded to or cannot tolerate one or more stimulants an alternative treatment option.