Delayed Onset of Central Diabetes Insipidus With Ketamine Sedation: A Report of 2 Cases.

Ketamine is being prescribed with greater frequency due to an emphasis on multimodal analgesia. With increasing use, uncommon adverse effects associated with ketamine are likely to surface. Limited reports of transient central diabetes insipidus (DI) occurring early after initiation (ie, within 10 hours) of ketamine have been reported. We present 2 cases of delayed onset (32 hours or more after initiation), ketamine-induced, transient central DI in patients cannulated for venovenous extracorporeal membranous oxygenation. No other causes of central DI were determined based upon physical examination or laboratory data, and both patients responded to treatment with desmopressin/vasopressin. The Naranjo adverse drug reaction probability scale noted a probable causation for each case. These cases demonstrate the possibility of a rare but serious complication of ketamine. Improvement after discontinuation of ketamine and administration of desmopressin/vasopressin appear to support a drug-effect association.

Associated Mortality of Liberal Fluid Administration in Sepsis.

Fluid resuscitation, to restore intravascular volume and improve oxygen delivery, is a crucial step in early resuscitation efforts of patients with sepsis or septic shock. The 2016 Surviving Sepsis Campaign guidelines suggest the use of dynamic versus static measures of fluid responsiveness and fluid resuscitation with at least 30 mL/kg of intravenous crystalloid within the first 3 hours followed by fluid administration if hemodynamic factors continue to improve. Despite these recommendations, risks to this practice may exist as multiple studies have demonstrated an association between a positive fluid balance and/or administration of large fluid volume and increase in mortality. These studies are limited by variations in their methodologic design; therefore, cause and effect cannot yet be determined. Future multicenter, randomized, controlled studies that evaluate fluid balance and fluid volume need to be conducted to clarify the role of fluid administration to patients with sepsis to maximize benefits and minimize risk.

Defibrotide: An Oligonucleotide for Sinusoidal Obstruction Syndrome.

OBJECTIVE: To review the efficacy and safety of defibrotide as well as its pharmacology, mechanism of action, pharmacokinetics (PK), drug-drug interactions, dosing, cost considerations, and place in therapy. DATA SOURCES: A PubMed search was performed through August 2017 using the terms defibrotide, oligonucleotide, hepatic veno-occlusive disease (VOD), sinusoidal obstruction syndrome (SOS), and hematopoietic cell transplantation (HCT). Other data sources were from references of identified studies, review articles, and conference abstracts plus manufacturer product labeling and website, the Food and Drug Administration website, and clinicaltrials.gov. STUDY SELECTION AND DATA EXTRACTION: English-language trials that examined defibrotide's pharmacodynamics, mechanism, PK, efficacy, safety, dosing, and cost-effectiveness were included. DATA SYNTHESIS: Trials have confirmed the safety and efficacy of defibrotide for treatment of VOD/SOS in adult and pediatric HCT patients, with complete response rates and day +100 overall survival rates ranging from 25.5% to 76% and 35% to 64%, respectively. The British Committee for Standards in Haematology/British Society for Blood and Marrow Transplantation Guidelines recommend defibrotide prophylaxis in pediatric and adult HCT patients with risk factors for VOD/SOS; however, its prophylactic use in the United States is controversial. Although there are efficacy data to support this strategy, cost-effectiveness data have not shown it to be cost-effective. Defibrotide has manageable toxicities, with low rates of grade 3 to 4 adverse effects. CONCLUSIONS: Defibrotide is the first medication approved in the United States for the treatment of adults and children with hepatic VOD/SOS, with renal or pulmonary dysfunction following HCT. Data evaluating defibrotide for VOD/SOS prevention are conflicting and have not shown cost-effectiveness.

Pimavanserin: A Novel Antipsychotic for Parkinson's Disease Psychosis.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of pimavanserin for the treatment of hallucinations and delusions of Parkinson's disease psychosis (PDP). DATA SOURCES: A comprehensive PubMed search (1966 to January 2017) was conducted using the search terms Parkinson's disease psychosis, hallucinations, delusions, pimavanserin, and ACP-103. Additional data were obtained from references of identified articles, governmental sources, manufacturer product labeling and website, and Clinicaltrials.gov. STUDY SELECTION AND DATA EXTRACTION: All English-language trials evaluating pimavanserin in PDP were included. Data from review articles were included if relevant to clinical practice. One phase II and 3 phase III trials are discussed. DATA SYNTHESIS: Pimavanserin was approved in April 2016 for the treatment of delusions and hallucinations of PDP. One phase II and 2 phase III trials reported no difference for primary outcomes when pimavanserin was compared with placebo. The pivotal phase III ACP-103-020 trial adapted a scale to target more specific symptoms prevalent in PDP and showed that least-squares mean differences of the total PD-adapted Scale for the Assessment of Positive Symptoms score were significantly improved for pimavanserin-treated patients as compared with placebo-treated patients (difference = -3.06; 95% CI [-4.91 to -1.20]; P = 0.0014]). Pimavanserin's adverse effect profile includes urinary tract infections, falls, peripheral edema, hallucinations, confusion, nausea, and headaches. CONCLUSION: Pimavanserin is a novel 5-HT2A inverse agonist that has shown promising results for managing hallucinations and delusions in patients with PDP without worsening motor effects or orthostasis. Yet its high cost and specialty pharmacy access may limit use in clinical practice.

Talimogene Laherparepvec: An Oncolytic Virus Therapy for Melanoma.

OBJECTIVE: To review the efficacy and safety of talimogene laherparepvec (T-VEC) as well as its pharmacology, pharmacokinetics, drug-drug interactions, handling procedures, cost considerations, and place in therapy. DATA SOURCES: Searches of PubMed (1966 to February 2017) and Cochrane Library (1999 to February 2017) were conducted using the terms talimogene laherparepvec, T-VEC, OncoVEX, immunotherapy, melanoma, and oncolytic virus. Additional information was determined from bibliographies, manufacturer product labeling and website, meeting abstracts, Food and Drug Administration website, and clinicaltrials.gov. STUDY SELECTION AND DATA EXTRACTION: A total of 79 English-language publications were identified. Articles that assessed T-VEC's pharmacokinetics, pharmacodynamics, mechanism, dosing, safety, and efficacy were included as well as narrative reviews that provided practical information. DATA SYNTHESIS: Clinical trials have confirmed the safety and efficacy of T-VEC as monotherapy for the treatment of advanced melanoma, with an overall response rate (ORR) of 26%. Relative to granulocyte-macrophage colony-stimulating factor, T-VEC significantly increased durable response rate (DRR; 16.3% vs 2.1%, P < 0.001); however, median overall survival was not improved (23.3 vs 18.9 months, P = 0.051). Phase 1b trials have combined T-VEC and immunotherapies with promising results. T-VEC's adverse effects are generally considered mild to moderate in severity. CONCLUSION: T-VEC is the first approved oncolytic virus for local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in melanoma recurrent after initial surgery. T-VEC improves ORR and DRR as a single agent, shows promise in combination therapy, and is well tolerated. Ongoing trials will determine if T-VEC has a role in early treatment or in combination therapy for melanoma or other malignancies.

Cangrelor Bridge Therapy for Gastroduodenal Biopsy.

Dual antiplatelet therapy (DAPT) is the key for secondary prevention of acute coronary syndromes and percutaneous coronary intervention with stent placement. Premature discontinuation of DAPT can result in an increase in cardiac ischemic events and death. If early interruption of DAPT for urgent procedures or surgery is necessary, then ischemic and bleed risks must be balanced with bridging therapy. To date, no medications have a Food and Drug Administration indication for antiplatelet bridge therapy. We present a case of a woman with a history of gastrointestinal bleeding on DAPT for a drug-eluting stent who received cangrelor as bridge therapy prior to gastroduodenal biopsy.

Emerging role of ivabradine for rate control in atrial fibrillation.

Control of ventricular rate is recommended for patients with paroxysmal, persistent, or permanent atrial fibrillation (AF). Existing rate-control options, including beta-blockers, nondihydropyridine calcium channel blockers, and digoxin, are limited by adverse hemodynamic effects and their ability to attain target heart rate (HR). Ivabradine, a novel HR-controlling agent, decreases HR through deceleration of conduction through If ('funny') channels, and is approved for HR reduction in heart failure patients with ejection fraction less than 35% and elevated HR, despite optimal pharmacological treatment. Because If channels were thought to be expressed solely in sinoatrial (SA) nodal tissue, ivabradine was not investigated in heart failure patients with concomitant AF. Subsequent identification of hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4), the primary gene responsible for If current expression throughout the myocardium, stimulated interest in the potential role of ivabradine for ventricular rate control in AF. Preclinical studies of ivabradine in animal models with induced AF demonstrated a reduction in HR, with no significant worsening of QT interval or mean arterial pressure. Preliminary human data suggest that ivabradine provides HR reduction without associated hemodynamic complications in patients with AF. Questions remain regarding efficacy, safety, optimal dosing, and length of therapy in these patients. Prospective, randomized studies are needed to determine if ivabradine has a role as a rate-control treatment in patients with AF.

Dinutuximab: An Anti-GD2 Monoclonal Antibody for High-Risk Neuroblastoma.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, and formulary considerations for dinutuximab. DATA SOURCES: MEDLINE was searched (1964 to January 2016) using the terms ch14.18, dinutuximab, immunotherapy, and neuroblastoma. Other information was identified from package insert, Biologics License Application, abstracts, news releases, and ClinicalTrials.gov. STUDY SELECTION AND DATA EXTRACTION: Identified English-language articles were reviewed. Selected studies included phase I through III. DATA SYNTHESIS: High-risk neuroblastoma is primarily a childhood cancer with 5-year survival rates of 40% to 50%. Treatment for high-risk neuroblastoma includes induction chemotherapy, surgery, myeloablative chemotherapy with autologous hematopoietic stem cell transplant, and radiation therapy. For patients achieving clinical remission, limited treatments exist for preventing relapse. Dinutuximab is a chimeric, human-murine, anti-GD2 monoclonal antibody approved in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), aldesleukin (interleukin-2 [IL-2]), and isotretinoin (13-cis-retinoic acid [RA]) for maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy. In phase III trials, dinutuximab increased 2-year event-free survival and overall survival when compared to standard treatment. Severe adverse effects of dinutuximab include pain, hypersensitivity reactions, capillary leak syndrome, and hypotension. CONCLUSIONS: Dinutuximab is the first anti-GD2 monoclonal antibody approved in combination with GM-CSF, IL-2, and RA for maintenance treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to first-line multiagent, multimodality therapy. Ongoing research will determine if dinutuximab could be used earlier in treatment, in nonresponders to initial therapies, in combination with chemotherapy, or in other cancers.

Intravenous Lidocaine as an Adjuvant for Pain Associated with Sickle Cell Disease.

The objectives of this study were to evaluate the efficacy and safety of adjuvant intravenous (IV) lidocaine in adults with sickle cell disease (SCD). This was a retrospective review. Adults with SCD receiving at least one IV lidocaine infusion from 2004 to 2014 were included. Patient demographics, lidocaine treatment parameters, pain scores, pain medications, and adverse effects were recorded. Eleven patients were identified, yielding 15 IV lidocaine trials. Clinical improvement in pain scores from pre-lidocaine challenge to 24 hours post-lidocaine challenge, defined by ≥ 20% reduction in pain scores, was achieved in 53.3% (8 of 15) of IV lidocaine challenges. Of the 8 clinically successful trials, the mean reduction in morphine dose equivalents (MDE) from 24 hours pre-lidocaine challenge to 24 hours post-lidocaine challenge was 32.2%. Additionally, clinically successful trials had a mean initial and a maximum dose of 1 mg/kg/h (range: 0.5-2.7 mg/kg/h) and 1.3 mg/kg/h (range: 0.5-1.9 mg/kg/h), respectively. On average, these patients underwent 3 dose titrations (range: 1-8) and received lidocaine infusions for 4.4 days (range: 2-8 days). Two patients experienced disorientation and dizziness. The authors conclude that adjuvant IV lidocaine provided pain relief and a mean reduction in MDE during sickle cell pain crisis. These results provide preliminary insight into the use of IV lidocaine for treating pain in patients with SCD, although prospective studies are needed to determine efficacy, dosing, and tolerability of IV lidocaine in this patient population.

Vedolizumab: an α4ß7 integrin antagonist for ulcerative colitis and Crohn's disease.

Ulcerative colitis (UC) and Crohn's disease (CD) are chronic, relapsing inflammatory bowel diseases associated with significant morbidity. Conventional therapies for these diseases include corticosteroids, aminosalicylates, immunomodulators, and monoclonal antibodies. Over the years tumor necrosis factor (TNF)-α antagonists alone or in combination with other therapies have emerged as the cornerstone of treatment for induction and maintenance of remission of moderate to severe UC and CD. Unfortunately, some patients with moderate to severe UC and CD are unable to attain or maintain remission with TNF-α antagonist treatment. Vedolizumab, a humanized monoclonal antibody, is the first integrin receptor antagonist approved that selectively antagonizes α4ß7 gastrointestinal integrin receptors. US Food and Drug Administration approval is for treatment of patients with moderate to severe active UC and CD who have inadequate response with, lost response to, or are intolerant to a TNF-α antagonist or an immunomodulator; or have inadequate response with, are intolerant to, or demonstrate dependence on corticosteroids. When administered according to approved dosing in patients with moderate to severe CD and UC, vedolizumab induces clinical response rates up to 31.4% and 47.1% at week 6, and clinical remission rates up to 39% and 41.8% at week 52, respectively. Serious adverse events reported with vedolizumab include serious infections, malignancies, and anaphylaxis. Since vedolizumab is gastrointestinal selective, to date, it has not shown evidence of causing progressive multifocal leukoencephalopathy; however, postmarketing studies monitoring for this adverse effect are ongoing. Further assessment of vedolizumab earlier in the course of these diseases and in combination with other therapies is warranted.

High On-Treatment Platelet Reactivity Associated With Prasugrel.

Objective: To report a case of high on-treatment platelet reactivity (HTPR) with prasugrel maintenance therapy despite adequate initial platelet response to a loading dose. Case Summary: A 51-year-old woman presented to the emergency department complaining of chest pain. She was diagnosed with acute-on-chronic systolic heart failure and non-ST-elevated myocardial infarction (MI). She had a previous MI with bare metal stent placement and was taking aspirin and prasugrel 10 mg daily. Once admitted, a P2Y12 assay revealed HTPR (331 PRU); therefore, prasugrel was reloaded (60 mg). The next day a P2Y12 assay showed adequate platelet reactivity inhibition (118 PRU), so prasugrel 10 mg daily was continued in the hospital and on discharge. Seventeen days after discharge she was readmitted for possible ischemia. On day 3 of admission, a P2Y12 assay revealed HTPR (278 PRU); subsequently, prasugrel was discontinued and ticagrelor started. After 3 doses of ticagrelor, a P2Y12 assay was 97 PRU, so ticagrelor was continued. Five months have passed since discharge. The patient continues to take ticagrelor and has had no further cardiac events. Discussion: HTPR indicates hypo- or nonresponsiveness for antiplatelet agents and may result in serious adverse events. HTPR has rarely been reported with prasugrel or ticagrelor. An objective causality assessment of our case revealed a probable association between HTPR and prasugrel. Conclusion: Patient education and recognition of signs and symptoms associated with prasugrel HTPR may prevent morbidity and mortality from treatment failure. Additional research may determine incidence, risk factors, and optimal management of HTPR with prasugrel.

Ado-trastuzumab emtansine: a HER2-positive targeted antibody-drug conjugate.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, adverse effects, drug-drug interactions, dosage and administration, and formulary considerations for ado-trastuzumab emtansine. DATA SOURCES: Sources of information were identified through a PubMed search (1966 to June 2014) using the key terms ado-trastuzumab emtansine, trastuzumab-DM1, trastuzumab-MCC-DM1, and T-DM1. Other information was obtained from clinicaltrials.gov, product labeling, and press releases. STUDY SELECTION AND DATA EXTRACTION: All English-language clinical trials and abstracts evaluating ado-trastuzumab emtansine in humans were reviewed for inclusion. DATA SYNTHESIS: Overexpression or amplification of human epidermal growth factor receptor 2 (HER2) occurs in approximately 20% of breast cancers and is associated with more aggressive tumors and poorer prognosis in the absence of treatment. Although effective therapies for the initial management of HER2-positive metastatic breast cancer (MBC) exist, many patients will experience disease progression. Most second-line therapies are associated with either significant toxicities or limited improvements in overall survival (OS). Ado-trastuzumab emtansine is a HER2-positive directed antibody drug conjugate (ADC) approved in February 2013. In phase III clinical trials comparing the efficacy and safety of ado-trastuzumab emtansine with lapatinib-capecitabine or physician's choice, ado-trastuzumab emtansine had a better tolerability profile and improved progression-free survival compared with lapatinib-capecitabine or physician's choice and increased OS compared with lapatinib-capecitabine. CONCLUSION: Ado-trastuzumab emtansine is a novel ADC effective for HER2-positive MBC in patients previously treated with trastuzumab, lapatinib, and a taxane. Further studies will determine its use in the adjuvant and neoadjuvant setting and in combination with pertuzumab.

Serotonin-norepinephrine reuptake inhibitors for the management of chemotherapy-induced peripheral neuropathy.

OBJECTIVE: To review the literature evaluating serotonin-norepinephrine reuptake inhibitors (SNRIs) for chemotherapy-induced peripheral neuropathy (CIPN). DATA SOURCES: A PubMed search (1966-January 2014) was performed using the key terms serotonin-norepinephrine reuptake inhibitor, desvenlafaxine, duloxetine, milnacipran, venlafaxine, chemotherapy, and peripheral neuropathy. Bibliographies of select articles were examined for additional references and abstracts. STUDY SELECTION AND DATA EXTRACTION: Case reports and clinical trials published in English and conducted in humans were identified. All reports and trials evaluating a SNRI for the treatment of CIPN were included; 4 case reports, 1 open-label study, and 2 randomized controlled trials were identified for review. DATA SYNTHESIS: At present, no medications are approved for the treatment for CIPN. Emerging evidence suggests that venlafaxine and duloxetine may be effective for treating CIPN. Results of select trials report that these medications not only decrease pain but also relieve symptoms of numbness and tingling and improve the functional status and quality of life of patients suffering from CIPN. CONCLUSIONS: Evidence to support venlafaxine and duloxetine for the treatment of CIPN from oxaliplatin- or paclitaxel-based regimens is promising. Unfortunately, direct comparisons between venlafaxine and duloxetine do not exist, so definitive conclusions about which agent is preferred cannot be made. However, the breadth of data with duloxetine is larger, suggesting that it may be prudent to consider duloxetine first when choosing a SNRI for CIPN treatment. More robust trials are needed to establish their optimal place in therapy with regard to patient population, timing of therapy, dosing, and treatment duration.

Booster and higher antigen doses of inactivated influenza vaccine in HIV-infected patients.

OBJECTIVE: To review the literature regarding booster or higher doses of influenza antigen for increasing immunogenicity of inactivated influenza vaccine (IIV) in HIV-infected patients. DATA SOURCES: MEDLINE (1966 to September 2013) was searched using the terms immunize, influenza, vaccine, and HIV or AIDS in combination with two-dose, booster-dose, increased antigen, or high-dose. One trial of booster dosing with standard doses (SDs) of IIV, trivalent (IIV3); 2 trials of booster dosing with intermediate doses (ID) of H1N1 IIV or IIV3; and 1 trial of high-dose (HD) IIV3 were identified. STUDY SELECTION AND DATA EXTRACTION: Trials administering 2-dose, booster-dose, or increased antigen of influenza vaccine to patients with HIV were reviewed. Because adjuvanted IIV is not available and IIV, quadrivalent was recently approved in the United States, studies evaluating these vaccines were excluded. DATA SYNTHESIS: HIV-infected individuals are at high risk for influenza-related complications; however, vaccination with SD IIV may not confer optimal protection. It has been postulated that booster or higher doses of influenza antigen may lead to increased immunogenicity. When ID and SD or ID with boosters were evaluated in HIV-infected patients, significant increases in surrogate markers for influenza protection were not achieved. However, HD IIV3 did result in significant increases in seroprotective antibody levels, though 'clinical' influenza was not evaluated. CONCLUSIONS: Currently, evidence is insufficient to reach conclusions about the efficacy of booster dosing, ID, or HD influenza vaccine in HIV-infected patients. Trials evaluating booster or higher-antigen doses of IIV for 'clinical' influenza are necessary before routinely recommending for HIV-infected patients.

Angiotensin-converting enzyme inhibitors for intermittent claudication associated with peripheral arterial disease.

OBJECTIVE: To review published literature regarding the effectiveness of angiotensin-converting enzyme (ACE) inhibitors for managing intermittent claudication (IC) associated with peripheral arterial disease (PAD). DATA SOURCES: A search of MEDLINE/PubMed (1966-July 2013) using the MeSH terms intermittent claudication and angiotensin-converting enzyme inhibitors was conducted. Limits included articles written in English with human participants. Additional data were identified through bibliographic reviews. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were evaluated. Clinical trials and meta-analyses were included if they evaluated the efficacy of ACE inhibitors for improving functional capacity of patients with PAD with IC. In all, 9 clinical trials and 1 meta-analysis were identified and included for review. ACE inhibitors evaluated in the studies were captopril, lisinopril, perindopril, quinapril, and ramipril. DATA SYNTHESIS: Current medications approved for treating the symptoms and improving function in PAD with IC have limited efficacy. It has been suggested that ACE inhibitors may be effective in PAD with IC. Though data evaluating ACE inhibitors as a class in this patient population are conflicting, results of the largest and longest trial reported that ramipril increases maximum walking time and pain-free walking time and improves quality of life in patients with PAD with IC. CONCLUSIONS: ACE inhibitors may provide some relief of IC symptoms when used in patients with PAD. The greatest functional benefit has been seen with ramipril; it is unknown whether other agents in the class would show similar results. Well-controlled and designed studies with sufficient power and using diverse patient populations are needed.

Brentuximab vedotin: a CD30-directed antibody-cytotoxic drug conjugate.

Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL), which is a subtype of non-Hodgkin lymphoma, are relatively uncommon lymphoproliferative types of cancer. These malignancies are highly curable with initial treatment. Nonetheless, some patients are refractory to or relapse after first- and second-line therapies, and outcomes for these patients are less promising. Brentuximab vedotin is a CD30-directed antibody-cytotoxic drug conjugate that has demonstrated efficacy in response rates (objective response rates and complete response) when given to patients with refractory or relapsed HL and sALCL. Although not compared directly in clinical trials, the response rates with brentuximab vedotin are higher than those of several current treatments for refractory or relapsed HL and sALCL. Adverse effects associated with brentuximab vedotin are considered manageable. Nonetheless, several serious adverse effects (e.g., neutropenia, peripheral sensory neuropathy, tumor lysis syndrome, Stevens-Johnson syndrome, and progressive multifocal leukoencephalopathy, resulting in death) have been reported with its use. Despite a lack of survival and patient reported outcome data, the United States Food and Drug Administration (FDA) granted accelerated approval to brentuximab vedotin for the treatment of HL after failure of autologous stem cell transplantation or at least two combination chemotherapy regimens, and for sALCL after failure of at least one combination chemotherapy regimen. With this approval, brentuximab vedotin is the first FDA-approved agent for the treatment of HL in over three decades and the first agent specifically indicated to treat sALCL. Results of ongoing prospective trials should determine if brentuximab vedotin has a survival benefit when compared directly with standard treatment and if brentuximab vedotin is safe and efficacious when given earlier in the disease process, or when used with other chemotherapy for the treatment of HL and sALCL or other CD30-positive malignancies.

Tiotropium for adults with inadequately controlled persistent asthma.

OBJECTIVE: To review the literature evaluating the efficacy and steroid-sparing effect of tiotropium for inadequately controlled persistent asthma in adults. DATA SOURCES: Information was obtained through a search of MEDLINE/PubMed (1966-October 2012), using the terms asthma and tiotropium. A further review of reference citations was performed to identify other relevant articles. STUDY SELECTION AND DATA EXTRACTION: English-language case reports and clinical trials were reviewed. Publications evaluating the efficacy and steroid-sparing effect of tiotropium in adults with inadequately controlled persistent asthma were included in the review. One case report and 5 clinical trials met our criteria. DATA SYNTHESIS: The ultimate goal for asthma management is to maintain disease control by preventing acute exacerbations while avoiding adverse medication effects. Inhaled corticosteroids (ICS) are part of all preferred maintenance regimens for persistent asthma. Unfortunately, persistent asthma remains inadequately controlled in some patients and concerns about serious adverse effects with long-term high-dose ICS treatment exist. Interest in the use of tiotropium to control asthma symptoms and reduce steroid requirements in inadequately controlled persistent asthma is emerging. Results of several trials indicate that tiotropium improves pulmonary function markers and reduces corticosteroid requirements. Moreover, the largest and longest published trial not only showed improvements in pulmonary function tests but also a reduction in corticosteroid use and an increase in the time to first exacerbation. CONCLUSIONS: Although tiotropium use in treatment of persistent asthma appears to be promising, more robust clinical trials are needed to assess whether improved pulmonary function tests as well as a decrease in asthma exacerbations and corticosteroid requirements translate into improvements in quality of life. Additionally, the optimal patient population, long-term efficacy, and safety of tiotropium when delivered by various methods need to be determined before it can be recommended over current alternative asthma therapies.

Antibiogram compliance in University HealthSystem Consortium participating hospitals with Clinical and Laboratory Standards Institute guidelines.

PURPOSE: The degree of compliance with antibiogram guidance among University HealthSystem Consortium (UHC) hospitals was analyzed. METHODS: The UHC Pharmacy Council Pharmacy Practice Advancement Committee conducted a survey to evaluate hospital policies regarding the generation, reporting, and utilization of antibiograms among UHC hospitals. The survey was distributed via a UHC online survey tool to pharmacy directors at 237 UHC hospitals. Responses were collected from April 13 to May 14, 2010. RESULTS: Of the 237 hospitals to which surveys were sent, 49 hospitals (21%) from 28 states submitted survey responses. Forty-eight hospitals reported that they routinely generated antibiograms, and 36 reported that they adopted all or most of the standards recommended by the 2009 guidelines on antibiograms published by the Clinical and Laboratory Standards Institute (CLSI). The compliance rates to the four key CLSI recommendations were as follows: 98% reported data at least annually, 89% eliminated duplicate isolates, 83% did not include surveillance isolates, and 64% required at least 30 isolates for each reported species. Thirty-eight hospitals had an antimicrobial stewardship program; 35 of them formally reviewed antibiograms and 19 implemented new programs based on the antibiogram data. In 16 hospitals, formulary changes were made as a consequence of antibiogram results. In 30 hospitals, pharmacists had significant involvement in compiling, reviewing, and reporting antibiograms. CONCLUSION: Among respondents from 47 UHC hospitals, the compliance rates to four key CLSI recommendations for antibiograms ranged from 64% to 98%. Respondents from 30 hospitals reported significant involvement of pharmacists in compiling, reviewing, and reporting antibiograms.

Intravenous ketamine for treatment-resistant major depressive disorder.

OBJECTIVE: To evaluate the literature regarding the efficacy and safety of intravenous ketamine for treatment-resistant major depressive disorder (MDD). DATA SOURCES: A MEDLINE search (1966-September 2011) was performed using the terms treatment-resistant depression and ketamine. The search was restricted to articles published in English and reporting on use of ketamine in humans. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data search were evaluated. Data were eligible for inclusion if they were primary literature and evaluated the efficacy of ketamine for depressive symptoms in treatment-resistant MDD. One case report, 3 case series, 3 open-label trials, and 1 randomized crossover trial were included. DATA SYNTHESIS: Several medications are available for treatment-resistant MDD; however, they are often limited by a slow onset of therapeutic effect and tolerability. It has been suggested that ketamine, a rapid-acting, N-methyl-D-aspartate glutamate receptor antagonist, may have antidepressant effects. Case reports, case series, and select trials evaluating ketamine use for depressive symptoms in treatment-resistant MDD have demonstrated a rapid effect for reductions of scores on a number of depression scales; however, its sustainability effect remains unknown. Several studies reported a large or moderate to large effect size for ketamine. Additionally, these studies showed that ketamine use in this patient population is associated with relatively well-tolerated adverse effects. CONCLUSIONS: Ketamine for treatment-resistant MDD requires further evaluation before it can be considered a viable treatment option.

Colchicine for the primary prevention of the postpericardiotomy syndrome.

OBJECTIVE: To review literature regarding the safety and efficacy of colchicine for the primary prevention of the postpericardiotomy syndrome (PPS). DATA SOURCES: Searches of MEDLINE (1966-April 2011) and Cochrane Database (1993-April 2011) were conducted. Key search terms included postpericardiotomy syndrome, postcardiac injury syndrome, and colchicine. Limits were set for articles written in English with human subjects. Additional data were identified through bibliographic reviews. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were evaluated. All primary data were eligible for inclusion if they evaluated the safety and/or efficacy of colchicine for the primary prevention of PPS. Two prospective trials were identified and included for review. DATA SYNTHESIS: PPS occurs in 10-40% of patients who undergo cardiac surgery and is associated with significant morbidity. Effective medications used for the treatment of PPS include nonsteroidal antiinflammatory drugs or corticosteroids. Unfortunately, effective drug therapy for the primary prevention of PPS does not exist. Colchicine, an antiinflammatory agent with possible immunopathic antifibroblast properties, has shown benefit in the treatment and secondary prevention of pericarditis; thus, its use for primary prevention of PPS has been investigated. Limited data evaluating colchicine for the primary prevention of PPS have been published. However, results of the largest, well-designed trial showed positive efficacy outcomes for colchicine reducing the incidence of PPS with minimal adverse effects. CONCLUSIONS: At this time, there are not sufficient data to recommend colchicine as routine therapy for the primary prevention of PPS in patients undergoing cardiac surgery. Large clinical trials need to be conducted.