Space Radiation and Plasma Effects on Satellites and Aviation: Quantities and Metrics for Tracking Performance of Space Weather Environment Models.

The Community Coordinated Modeling Center has been leading community-wide space science and space weather model validation projects for many years. These efforts have been broadened and extended via the newly launched International Forum for Space Weather Modeling Capabilities Assessment (https://ccmc.gsfc.nasa.gov/assessment/). Its objective is to track space weather models' progress and performance over time, a capability that is critically needed in space weather operations and different user communities in general. The Space Radiation and Plasma Effects Working Team of the aforementioned International Forum works on one of the many focused evaluation topics and deals with five different subtopics (https://ccmc.gsfc.nasa.gov/assessment/topics/radiation-all.php) and varieties of particle populations: Surface Charging from tens of eV to 50-keV electrons and internal charging due to energetic electrons from hundreds keV to several MeVs. Single-event effects from solar energetic particles and galactic cosmic rays (several MeV to TeV), total dose due to accumulation of doses from electrons (>100 keV) and protons (>1 MeV) in a broad energy range, and radiation effects from solar energetic particles and galactic cosmic rays at aviation altitudes. A unique aspect of the Space Radiation and Plasma Effects focus area is that it bridges the space environments, engineering, and user communities. The intent of the paper is to provide an overview of the current status and to suggest a guide for how to best validate space environment models for operational/engineering use, which includes selection of essential space environment and effect quantities and appropriate metrics.

Engaging in Collaborative Research: Focus on the Pharmacy Practitioner.

Research offers an opportunity for investigators to explore unanswered questions, highlight best practices, and engage in collaboration. Clinical research can engage health care professionals to identify treatments or procedures to enhance patient care, quality of life, and outcomes. Research may also include experiences in a unique practice site or teaching methodology of trainees, staff, or patients. The goal of research is to improve individual patient care via dissemination of knowledge through publications. This article aims to highlight the importance of pharmacist-led research in the academic or community medical center and the need for resident-based research and mentorship for the integration of collaborative research and achievement of organizational goals.

High-Dose Sedation and Analgesia During Extracorporeal Membrane Oxygenation: A Focus on the Adjunctive Use of Ketamine.

Use of ketamine in patients requiring extracorporeal membrane oxygenation (ECMO) has rarely been reported, and the optimal dosing strategy remains unclear. A patient admitted with hypoxic respiratory failure required ECMO in addition to continuous infusion of low-dose ketamine following titration of opioid and sedative medications to high doses. After initiation of ketamine, infusion rates of opioids and/or sedatives were maintained or decreased. Recorded Richmond Agitation-Sedation Scale (RASS) scores were -4 to -5 and documented pain scores were 0. No adverse effects were reported while receiving low-dose ketamine. This case illustrates that use of low-dose ketamine infusion may be a useful adjunctive agent in patients receiving ECMO and high-dose opioid and sedative medications.

The use of activated recombinant factor VII in a patient with fulminant hepatic failure requiring placement of an intracranial pressure monitor.

OBJECTIVE: To evaluate the use of recombinant activated factor VII (rFVIIa) in a patient with fulminant hepatic failure (FHF) requiring placement of an intracranial pressure monitor. CASE SUMMARY: A 21-year-old female with no significant medical history was admitted to an outside hospital with elevated results of liver function tests. Subsequently, the patient was diagnosed with autoimmune hepatitis. Systemic corticosteroids were started, but her condition continued to decompensate. She was transferred to our tertiary care facility 5 days after initial presentation. The liver function test results remained elevated (eg, total bilirubin 27 mg/dL), and international normalized ratio (INR) was 3.57. The medical team decided to place an intracranial pressure monitor, with the neurosurgery team's goal being an INR less than 1.5 before placement of the monitor. After multiple units of fresh frozen plasma (FFP) failed to lower the patient's INR, rFVIIa 40 µg/kg was administered. A rapid decrease of the INR allowed the neurosurgery team to perform the procedure without complications. DISCUSSION: The use of rFVIIa allowed for decrease of this patient's INR after multiple units of FFP had failed to correct it. The utility of INR as a marker of coagulopathy in fulminant hepatic failure has been debated, but it is currently used as the standard laboratory test prior to invasive procedures, as in the case presented here. CONCLUSIONS: The use of rFVIIa for rapid decrease of INR in a patient with FHF prior to an invasive procedure was safe and efficacious. When considering the use of rFVIIa, clinicians should be aware of the risk of thrombosis. In our experience, and in the limited literature on the matter, rFVIIa 40 µg/kg appears to be an appropriate dose for decrease of the INR. Further studies are needed to confirm this finding.

Clinical usefulness of recombinant activated factor VII in patients with liver failure undergoing invasive procedures.

OBJECTIVE: To evaluate the use of recombinant activated factor VII (rFVIIa) in patients with liver failure undergoing invasive procedures. METHODS: An OVID/MEDLINE and PubMed search (1997-June 2011) was performed to identify literature on the use of rFVIIa to reduce bleeding risk in patients with liver failure undergoing invasive procedures. STUDY SELECTION AND DATA EXTRACTION: English-language data evaluating the efficacy of rFVIIa to reverse coagulopathies prior to invasive procedures in patients with liver disease were included. DATA SYNTHESIS: Following administration of rFVIIa, prothrombin time (PT) and international normalized ratio (INR) response is within 30 minutes. Doses ranging from 20 to 120 µg/kg have been studied, with a reduction in PT seen in a dose-dependent manner. One study in patients with no bleeding administered 5, 20, and 80 µg/kg sequentially during a 24-day period. All doses provided reversal of prolonged PT within 10 minutes, and the duration was dose-dependent. In a study of 15 patients with fulminant liver failure, requiring intracranial pressure monitor placement, a rFVIIa dose of 40 µg/kg was compared to fresh frozen plasma. In patients who received rFVIIa, the PT and INR normalized, compared to none of the patients in the fresh frozen plasma group. CONCLUSIONS: Retrospective and prospective data demonstrate that rFVIIa effectively reverses elevated PT and INR, reducing the risk of bleeding and safely facilitating invasive procedures. Based on available data, a dose of 20-40 µg/kg 30 minutes prior to an invasive procedure should be considered in patients with acute or chronic liver failure at risk for bleeding complications. A major limitation of rFVIIa use is the high cost of therapy. A prospective, randomized trial could help determine the appropriate dose of rFVIIa, timing of dose in relationship to procedure, and usefulness of subsequent doses.

Terlipressin in hepatorenal syndrome.

OBJECTIVE: To compare the pharmacology, dosing, and adverse reactions of vasopressin and terlipressin for the treatment of hepatorenal syndrome (HRS) and assess the efficacy of the investigational drug terlipressin for HRS. DATA SOURCES: Articles evaluating prospective studies for vasopressin and terlipressin were discussed after being identified through PubMed (1966-November 2010), International Pharmaceutical Abstracts (1970-November 2010), and EMBASE (1985-November 2010) with combinations of the following terms: vasopressin, terlipressin, and hepatorenal syndrome. In addition, reference citations from publications identified were reviewed. Thirteen studies were identified for terlipressin, along with 4 meta-analyses and 1 case report. For vasopressin, 2 studies were identified. STUDY SELECTION AND DATA EXTRACTION: Prospective clinical studies directly comparing terlipressin and vasopressin were evaluated, as well as prospective clinical studies and meta-analyses for terlipressin in HRS. DATA SYNTHESIS: No randomized, placebo-controlled trials using vasopressin for the treatment of type I HRS have been published, and 4 randomized studies involving 197 patients provide the most current outcome data for use of terlipressin in HRS. Terlipressin differs significantly from vasopressin with regard to its pharmacology, dosing, and adverse drug reaction profile. There is a paucity of data on vasopressin for HRS. CONCLUSIONS: No definitive recommendations can be made for the use of terlipressin for this indication until further, well-conducted studies are performed.

Efficacy of short-course, low-dose corticosteroid therapy for acute pulmonary sarcoidosis exacerbations.

BACKGROUND: Although corticosteroids are the drug of choice for acute exacerbations of pulmonary sarcoidosis, the dose and duration of therapy is not standardized. We reviewed the short-term treatment outcome (median duration = 21 days) of 36 patients with acute exacerbations of pulmonary sarcoidosis using low-dose corticosteroid therapy (20 mg or less of daily prednisone equivalent). To the best of our knowledge, this is the shortest period of time over which the treatment of pulmonary sarcoidosis with corticosteroids has been assessed. METHODS: Patients were identified retrospectively from an institution-approved database. Patient symptoms and spirometry were obtained from chart review. Additional clinical data were obtained from chart and database review. RESULTS: Follow-up visits occurred a median of 21 days after the date of the exacerbation (mean 25 +/- 3 standard error of mean). The average prednisone dose was 19 mg +/- 0.4 standard error of mean. Patients had significant improvement in spirometry on this low-dose treatment regimen by the time of their short-term follow-up (forced vital capacity percent predicted improved from 68 to 82 [P < 0.0001] and was not significantly different from baseline; forced expiratory volume in 1 second percent predicted improved from 57 to 72 [P < 0.0001] and was not significantly different from baseline). Pulmonary symptoms also improved. CONCLUSIONS: Treatment of acute exacerbations of pulmonary sarcoidosis with 20 mg prednisone for a median of 21 days improved spirometry back to baseline and improved clinical symptoms. These data suggest that this corticosteroid dose can be safely used initially, and an attempt at tapering can be considered within the first month.

Relationships between colleges of pharmacy and academic medical centers.

PURPOSE: The nature of the relationships between academic medical centers and colleges of pharmacy, particularly in respect to experiential education, was studied. METHODS: A 22-item questionnaire was developed to assess the extent and type of student experiences academic medical centers offered, the presence of a contractual agreement, satisfaction level, role of pharmacy staff and residents, and perceived value of the relationship. The questionnaire was distributed electronically to pharmacy directors at 90 University HealthSystem Consortium (UHC) academic medical centers, with subsequent responses analyzed with descriptive statistics. RESULTS: The response rate was 52% (n = 47), representing a broad geographic distribution of UHC members. All academic medical centers reported having a relationship with at least one college of pharmacy. The mean number of academic affiliations for each respondent was 2.4. The majority of medical centers were satisfied with these relationships. All academic medical centers provided fourth-year pharmacy student clerkship training, with 20% and 27% offering experiential activities for second- and third-year students, respectively. Compensation from colleges of pharmacy for practice-based education was typically directed to the pharmacy department, with a mean of $500 per rotation. The majority of medical centers also trained pharmacy residents, with 62% of these engaging the residents in student experiential education. The most common motivations for offering student experiential education were fulfilling professional responsibility, developing future employees, and financial compensation. CONCLUSION: While relationships between academic medical centers and colleges of pharmacy were generally positive, the growing need for early experiential education sites, increased class sizes, and shortage of qualified preceptors necessitate a reexamination of the relationships to ensure that they continue to benefit both parties.

Common problems in critically ill obstetric patients, with an emphasis on pharmacotherapy.

Pharmacological treatment of critically ill obstetric patients can be especially challenging due to the complexity of caring for 2 patients, with a paucity of research to support practice. This review will provide practitioners with primary recommendations for management of the critical illnesses most commonly encountered in pregnancy and will discuss the scientific and clinical merit of these recommendations.

Evaluation of an intensive insulin protocol for septic patients in a medical intensive care unit.

OBJECTIVE: Intensive insulin therapy to normalize blood glucose may improve outcome in intensive care unit patients. We prospectively evaluated the implementation of an intensive insulin protocol in medical intensive care patients to identify and overcome obstacles that this complex therapy creates. DESIGN: This prospective, quality assessment study was designed to establish a standard protocol for glucose control in critically ill patients. SETTING: The study took place in the medical intensive care unit at the Medical University of South Carolina, a tertiary care center. PATIENTS: Patients diagnosed with sepsis and two consecutive blood glucose measurements of >120 mg/dL were included in the study. INTERVENTIONS: The protocol, targeting blood glucose of 80-120 mg/dL, was a multidisciplinary initiative involving extensive education of house staff before subject enrollment. Based on predefined criteria, patients were monitored daily for glycemic control, inclusion criteria, and protocol adherence. Protocol improvements were assessed at 6 and 12 months via nursing surveys. MEASUREMENTS AND MAIN RESULTS: Seventy patients receiving insulin infusion for >8 hrs were included in data analysis, accounting for 4,920 glucose readings. Eighty-six hypoglycemic events were recorded, with the number of events decreasing from 7.6% to 0.3% by the final version of the protocol. Average duration on protocol was 6 days, and average time to target range was 5.4 hrs. Identifiable causes of hypoglycemia and survey results led to four protocol revisions by study completion. CONCLUSIONS: In comparison to studies suggesting that normoglycemia is an easily achievable goal, our protocol often recorded glucose values <80 mg/dL, although values <60 mg/dL were rare and usually due to protocol violations. In the interval before automated glucose-sensing insulin infusion devices become available for the intensive care unit, the current protocol is available to assist others in achieving target glucose levels shown to improve mortality rate in an intensive care unit population.

Treatment of sarcoidosis with infliximab.

BACKGROUND/OBJECTIVES: Many patients with sarcoidosis are unable to tolerate corticosteroids or alternative therapeutic agents due to side effects or have disease refractory to these agents. We report our experience using infliximab to treat such patients. METHODS: A group of patients in whom traditional sarcoidosis therapy failed, either due to drug failure or intolerable side effects, were prescribed infliximab. Their charts were retrospectively reviewed. RESULTS: Ten patients receiving infliximab were reviewed. Nine of the 10 patients reported a symptomatic improvement with therapy, and all 10 demonstrated objective evidence of improvement. A drug reaction developed in one patient after several months of therapy, oral candidiasis developed in one patient, and angioimmunoblastic lymphoma developed in another patient. The corticosteroid dose was reduced in five of the six patients who were receiving corticosteroids at the time of infliximab therapy. CONCLUSION: Infliximab appears to be an effective, safe treatment for patients with refractory sarcoidosis, including such manifestations as lupus pernio, uveitis, hepatic sarcoidosis, and neurosarcoidosis. Infliximab appears to be steroid sparing. Patients receiving the drug should be screened for latent tuberculosis and lymphoproliferative disorders.

Intravenous ethanol for the treatment of alcohol withdrawal syndrome in critically ill patients.

Critically ill patients with alcoholism are at greater risk of morbidity and mortality from alcohol withdrawal syndrome than are patients without alcoholism. Benzodiazepines are considered the drugs of choice for the prevention and treatment of alcohol withdrawal syndrome, but some studies have suggested that intravenous ethanol may be as effective as those agents, as well as being less sedating. We evaluated the evidence regarding the use of intravenous ethanol for the prevention and treatment of alcohol withdrawal syndrome in critically ill patients in order to determine its role in this patient population. Because of the paucity of well-designed clinical trials, and because of intravenous ethanol's questionable efficacy, inconsistent pharmacokinetic profile, and relatively narrow therapeutic index, routine use of this drug is not recommended in critically ill patients who have alcohol withdrawal syndrome or are at risk for it.

Fatality related to a 30-g venlafaxine overdose.

A 30-g venlafaxine overdose resulted in death for a 39-year-old woman whose 43-day clinical course was highlighted by refractory hypotension and the resulting complications of bowel ischemia and perforation. Her venlafaxine and O-desmethylvenlafaxine levels, analyzed by high-performance liquid chromatography one day after ingestion, were 21.82 mg/L (therapeutic range 0.1-0.5 mg/L) and 3.33 mg/L (0.2-0.4 mg/L), respectively. These levels remained elevated for over 7 days. Postulated explanations for these extended elevated levels were saturation of drug metabolism, decreased drug metabolism, and existence of a genetic polymorphism. Our patient's venlafaxine overdose produced a wide variety of clinical challenges, to include seizures, tachycardia, decreased level of consciousness, refractory hypotension, and bowel dysmotility. In addition, this case augments the growing body of literature that suggests that venlafaxine may be fatal in overdose situations.

Treatment of corticosteroid-resistant neurosarcoidosis with a short-course cyclophosphamide regimen.

BACKGROUND/OBJECTIVES: Many patients with neurosarcoidosis have disease that is refractory to corticosteroids or they are unable to tolerate high-dose corticosteroids because of detrimental side effects. We examined a short-course, pulse-dose regimen using cyclophosphamide to treat such patients. METHODS: We identified a population of patients with neurosarcoidosis refractory to standard therapy with corticosteroids. Patients who were unable to tolerate corticosteroid therapy due to side effects were also included. Alternative therapy for these patients was initiated using i.v. cyclophosphamide. RESULTS: Seven patients were identified for treatment with our cyclophosphamide regimen. The mean duration of therapy was 5.4 months. Four of the seven patients reported symptomatic improvement on therapy, and all seven patients demonstrated objective improvement in either MRI or cerebrospinal fluid abnormalities. Mean corticosteroid dose of the group was reduced from 42 mg/d before therapy to 18 mg/d after therapy. Relapse of neurologic symptoms was noted in one patient after the completion of therapy. One patient acquired an opportunistic infection, and a second patient required hospitalization for a central venous catheter infection. CONCLUSION: Short-course cyclophosphamide appears to be a reasonable, steroid-sparing treatment option for patients with corticosteroid-refractory neurosarcoidosis.