Annals of Pharmacotherapy

Previous studies have evaluated the impact of oral magnesium on blood pressure; however, they used magnesium salts with low bioavailability, had methodological issues, and showed differing results.

To evaluate the long-term blood pressure–lowering ability of oral magnesium L-lactate versus placebo in patients with implanted cardioverter defibrillators (ICDs).

In this double-blind, 24-week trial, 50 patients with ICDs were randomized to receive magnesium L-lactate (6 tablets daily, supplying a total of 504 mg of elemental magnesium daily) or matching placebo for at least 12 weeks. Baseline intracellular and serum magnesium concentrations were determined. The primary efficacy endpoint was the mean sitting systolic blood pressure at 24 weeks.

In 50 patients who completed at least 12 weeks of follow-up, 86% of patients, regardless of randomization, had a baseline intracellular magnesium deficiency, but no patients had a serum magnesium deficiency. At 12 weeks, magnesium L-lactate significantly reduced systolic blood pressure compared with placebo (117.7 ± 11.8 vs 126.3 ± 16.7 mm Hg, respectively; p = 0.04). In the 45 patients who continued in the study through the 24-week time period, the systolic blood pressure reduction was maintained, but statistical significance was lost (118.1 ± 14.1 vs 125.5 ± 17.2 mm Hg, respectively; p = 0.13). Magnesium L-lactate did not impact diastolic blood pressure at either time period (p ≥ 0.75 for both). Patients with a documented history of hypertension at baseline showed similar qualitative results to the primary analysis.

A large number of subjects with ICDs have an intracellular magnesium deficiency not captured through serum magnesium determination. The use of magnesium L-lactate in patients with an ICD results in significant improvement in systolic blood pressure at 12 weeks, which may be maintained through 24 weeks.

Bisphosphonate (BP)-related gastrointestinal (Gl) adverse events can lead to discontinuation of osteoporosis treatment. Irritation of the GI tract related to BPs may be worsened by more frequent administration.

To compare the number of women who experienced severe GI events within 3 months of starling once-monthly oral ibandronate with those starting once-weekly oral BP (alendronate or risedronate).

In a retrospective database study design, eligible women with a new prescription for monthly ibandronate were propensity-matched to women with a new weekly BP prescription. Patients had continuous health plan enrollment for 6 months prior to the index date and for 3 months after the index date. Women with previous intravenous BP treatment, Paget's disease, or oral BP treatment within the 6-month preindex period were excluded. Severe GI events (including acute events involving perforation or bleeding/perforation) within 3 months of treatment initiation were identified by ICD-9 and Current Procedural Terminology codes. A post hoc analysis assessed treatment discontinuation after severe GI events. GI-related healthcare utilization rates and costs were also compared,

Of the 8608 patients per group, 45 (0.52%) who were receiving monthly ibandronate and 70 (0.81%) of those receiving weekly BP treatment experienced a severe GI event. Ibandronate patients had a 36% reduction in the risk of severe GI events compared with weekly BP users (OR 0.64, 95% CI 0.44 to 0.93). Significantly more women receiving a weekly BP discontinued treatment after a severe GI event compared with those receiving ibandronate (100% vs 55.6%: p< 0.001). Most healthcare utilization outcomes were not significantly different between the 2 groups; outpatient visits were significantly higher for ibandronate (p = 0.02). Costs were not significantly different between the 2 groups.

Patients receiving monthly ibandronate therapy had a significantly reduced risk of severe GI events compared with those receiving weekly BP treatment. In addition, patients receiving a weekly BP were more likely to discontinue treatment after a severe GI event.

Contemporary studies document the outcomes of unfractionated heparin (UFH), enoxaparin, fondaparinux, and bivalirudin in patients with non–ST-elevation acute coronary syndrome (NSTE-ACS). It remains unclear which anticoagulant regimen is the most cost-effective.

To perform a cost-effectiveness analysis comparing 4 anticoagulant regimens in NSTE-ACS.

A decision analysis was conducted from a healthcare provider perspective. Data sources included the SYNERGY, OASIS-5, and ACUITY trials, including 2 subgroup analyses. A decision tree model was created incorporating the outcomes associated with 4 antithrombotic approaches: UFH with eptifibatide, enoxaparin with eptifibatide, bivalirudin alone, and fondaparinux with eptifibatide. The percentage of eptifibatide use in each arm was consistent with clinical trials. Probabilities of complications (eg, myocardial infarction, revascularization, major/minor bleeding at 30 days) were calculated. Costs were assigned to each outcome, incorporating the cost associated with diagnosis-related group and/or current procedural terminology codes, drug acquisition, and red blood cell infusions. Multiple sensitivity analyses were performed.

The base case analysis showed bivalirudin monotherapy to be the least costly regimen ($1131 per average course), and it dominated enoxaparin plus eptifibatide ($1609) and UFH plus eptifibatide ($1739) in cost-effectiveness. The total average cost of fondaparinux with eptifibatide ($1184) was higher than bivalirudin alone, but the combination was more effective, resulting in an incremental cost of $2569 per each additional patient treated without complication. Sensitivity analyses showed the model's results to be sensitive to drug acquisition cost and complication probabilities. Probabilistic sensitivity analyses favored neither bivalirudin nor fondaparinux; however, when 2 or more vials of bivalirudin were necessary, bivalirudin was no longer a cost-effactive alternative.

Bivalirudin is the least costly agent in moderate- to high-risk NSTE-ACS patients managed with an early invasive approach, if its use is consistent with the ACUITY trial. Fondaparinux is the preferred agent in patients undergoing a conservative treatment strategy.

Energy drinks are frequently purported to improve cognitive function and concentration. However, the cardiovascular effects of these drinks have not been adequately studied.

To determine the cardiac effects of a commercially available, multicomponent energy drink in healthy volunteers.

Fifteen healthy adults were Included in this prospective study. Individuals who had chronic medical conditions, ware on chronic medication, or were pregnant or breast-feeding were excluded. Subjects abstained from caffeine for 48 hours prior to and during the study. In the morning on Day 1 of the study, while subjects were in a fasted state, baseline blood pressure (BP), heart rate (HR), and electrocardiographic (ECG) parameters were measured. Participants then consumed 500 mL (2 cans) of an energy drink and measurements were repeated 30 minutes, 1 hour, 2 hours, 3 hours, and 4 hours later. Participants then drank 500 mL of energy drink daily for the next 5 days. Day 1 protocol was repeated on Day 7.

On Days 1 and 7, maximum mean systolic BP (SBP), HR, and QTc interval occurred at 4 hours. Maximum diastolic BP (DBP) occurred at 2 hours on Days 1 and 7. Within 4 hours of energy drink consumption, on Days 1 and 7, respectively, SBP increased by 7.9% (p = 0.006) and 9.6% (p < 0.001), HR increased by 7.8% (p = 0.009) and 11.0% (p < 0,001). and QTc interval increased by 2.4% (p = 0.368) and 5.0% (p = 0.052), DBP increased by 7.0% < p = 0.046) and 7.8% (p = 0.063) within 2 hours of energy drink consumption on Days 1 and 7, respectively.

Although no significant ECG changes were observed, HR increased 5–7 beats/min and SBP increased 10 mm Hg after energy drink consumption.

Medication Therapy Management (MTM) is a voluntary patient participation program mandated for Medicare Part D sponsors by the Centers for Medicare and Medicaid Services for chronically ill beneficiaries with high medication costs/utilization.

To assess the impact of an MTM program on mortality, healthcare utilization, and prescription medication costs and to quantify drug-related problems (DRPs) identified during MTM.

This nonrandomized controlled study was conducted among beneficiaries who were targeted for MTM in 2006. The MTM intervention was designed to identify potential DRPs, educate the patient/caregiver about appropriate medication use, and ensure that the patient was appropriately integrated into clinical services. Data were collected from administrative databases and manual chart abstractions. Study outcomes included all-cause death (primary outcome), hospitalization, and emergency department (ED) visit rates and medication cost changes in the 180 days following MTM targeting and quantification of DRPs. Multivariate logistic regression was used to adjust the outcomes for baseline risk and other potential confounders. A mock MTM intervention was performed for beneficiaries who declined MTM and died, were hospitalized, and/or made an ED visit.

A total of 459 opt-in and 336 opt-out beneficiaries who agreed and declined, respectively, to receive MTM were included in the analysis. Beneficiaries who opted in were less likely to die compared with beneficiaries who opted out (adjusted OR [AOR] 0.5; 95% CI 0.3 to 0.9) but were more likely to have had a hospitalization (AOR 1.4; 95% CI 1.1 to 2.0) and an increase in medication costs (AOR 1.4; 95% CI 1.1 to 1.9) during follow-up. There was no difference in ED visit rates. At least one DRP was identified in more than 83% of beneficiaries in both groups, with the most common DRP being drug–drug interaction.

Our investigation supports the use of MTM, with its increased coordination of information between healthcare providers and patients, since it may impact mortality positively in a population of high-risk Medicare beneficiaries.

In 2006. the Center for Medicare & Medicaid Services incorporated the requirement for a Medication Therapy Management Program (MTMP) for individuals with Part D coverage to ensure that drug regimens provide optimal therapeutic outcomes through improved medication use, thereby reducing adverse drug events.

To evaluate the effectiveness of an MTMP implemented for Medicare Advantage Prescription Drug members enrolled with Health Alliance Plan (HAP) during 2006 and 2007.

Patient eligibility for MTMP was searched electronically. Clinical pharmacists researched medication histories and adherence and, through telephone contact, ascertained the patients' healthcare goals and needs. A patient-centered pharmacotherapy plan was created and implemented collaboratively with the patient's physician(s). To ensure that therapy goals were met, pharmacists performed follow-up interventions. Clinical outcomes and cost savings were compared for MTMP enrollees versus those declining enrollment.

Average enrollment rate for the MTMP was 20% for 2006 and 2007. Nearly 60% of interventions involved changing therapy to improve efficacy and greater than 40% involved changing therapy to improve safety. Analysis of 2006 data revealed an overall improvement in electronically measurable clinical outcomes for MTMP enrollees versus individuals who declined enrollment, including a trend toward improved adherence to drug therapy for heart failure, insulin use, and a significant reduction in gastrointestinal bleeds (p = 0.001). Cost-savings analysis indicated a greater reduction in total prescription per member per month costs ($PMPM) of 17.2% for MTMP enrollees versus a 7% reduction for those who declined MTMP (p = 0.001). Patients who enrolled into the 2006 MTMP also saw a sustained positive effect in lowered $PMPM for prescription drugs in 2007.

The HAP MTMP, conducted through telephone contacts, produced positive trends in improving clinical outcomes, reductions in pharmacy costs, and sustained pharmacy cost savings for patients who enrolled in the MTMP compared with patients who declined enrollment.

In 2008, the Joint Commission released an updated National Patient Safety Goals document that requires institutions to implement practices that reduce the likelihood of patient harm associated with use of anticoagulation therapy. One of the expectations associated with this goal was that each organization would establish an anticoagulant management program. To our knowledge, few data exist to describe the implementation and assessment of anticoagulation programs in smaller, nonteaching community hospitals using decentralized pharmacists in an integrated practice model.

To compare the performance of a protocol-driven anticoagulation management service led by decentralized pharmacists in a nonteaching community hospital with that of usual medical care provided by hospitalist physicians before this program was implemented. Based on these results, as well as a pharmacist satisfaction survey, evaluate the service and identify barriers to expansion.

We conducted a retrospective cohort study comparing 50 consecutive patients who were starting warfarin for the first time beginning in November 2003 with 50 patients managed by hospitalist physicians prior to November 2002 (the time of program implementation).

There were no significant differences between groups with regard to time in therapeutic range once therapeutic, length of stay, international normalized ratios (INRs) greater than 3.5, or INRs less than 2. Patients in the pharmacy management group had significantly fewer drug interactions with antimicrobials than did the usual medical care group. Although time to therapeutic range was longer in the pharmacy protocol group, there were fewer patients with INRs greater than 3.5, although this did not reach statistical significance.

The efficacy of the pharmacist-led anticoagulation management service was no different from that of usual medical care. Patient safety appeared improved, in part due to more careful initial dose selection based on patient-specific factors. Although this program was accepted by pharmacists, time limitations were perceived to be a major barrier to quality care and expansion of the service.

Continuous insulin infusions have become a standard of care in many intensive care units (ICUs); however, methods for transitioning patients from continuous infusions to other insulin therapies have not been extensively evaluated.

To determine the most effective method for transitioning ICU patients from continuous insulin infusions to subcutaneous insulin therapy.

A searchable pharmacy database at the University of North Carolina Hospitals was used to retrospectively identify adults admitted to the neurosurgery ICU and prescribed a continuous insulin infusion between May 2007 and February 2008, All patients were transitioned to subcutaneous insulin upon floor transfer. Patients were stratified according to the dose of subcutaneous insulin as a percentage of their prior 24-hour continuous insulin requirement and then analyzed on the rate of achievement of goal blood glucose values (80–150 mg/dL) within the first 48 hours after transition.

A total of 769 blood glucose values from 79 patients were recorded during the study. Data analysis demonstrated significantly lower median blood glucose values with the use of subcutaneous insulin doses that were 60–70% of insulin infusion requirements when compared with all other groups. For patients without a history of diabetes mellitus, the use of a subcutaneous dose that was 60–70% of the insulin infusion requirement resulted in a significantly greater percentage of patients within the target range compared with other groups (78%; p < 0.05). For those with a history of diabetes, subcutaneous doses higher than 70% of the insulin infusion requirement yielded the most frequent achievement of target values, although there was substantial variability within this group. No significant difference was noted in the incidence of hypoglycemia (blood glucose <80 mg/dL) between groups, although the frequency of hypoglycemia was almost twice as high in the group with diabetes as in those without it (4.2% vs 2.2%).

Methods currently used to transition patients off insulin infusions vary widely. Initial data suggest that utilizing 60–70% of the 24-hour insulin infusion requirement as a subcutaneous dose would result in blood glucose values of 80–150 mg/dL 70% of the time. Further study is necessary to adequately assess the optimal insulin infusion transition protocol for critically ill patients to ensure both safety and efficacy.

Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder that is common among combat veterans and may lead to very poor sleep and disturbing nightmares.

To examine the safety and effectiveness of topiramate as add-on therapy for the management of combat-related PTSD and to examine the effects of topiramate on sleep and alcohol consumption.

We conducted an 8-week open-label pilot study of topiramate (or male combat veterans (N = 43) with PTSD, with analysis of veterans who completed the protocol. Psychometric, sleep, and alcohol consumption assessments were conducted at baseline and at week 8.

Twenty-nine subjects completed the 8-week study. Significant reductions in Clinician Administered PTSD Scale scores were observed at the 8-week endpoint (from 86,3 ± 21.1 to 67.1 ± 25.1; p < 0.01). Decreases were seen in both Stanford Sleepiness Scale scores (from 10.5 ± 0.72 to 9.0 ± 0.58; p = 0.08) and Mississippi PTSD scores (from 120.4 ± 6.5 to 111.5 ± 20.9; p = 0.08), but the extent of the changes did not attain statistical significance for either scale. There was a significant reduction in the proportion of patients with nightmares (from 100% to 62%; p < 0.001) and patients who experienced anxiety that interfered with falling asleep (from 90% to 62%; p < 0.05). The proportion of patients with high-risk drinking patterns also decreased (from 31% to 14%). Two serious adverse events were reported during the study: an increase in tow back pain and an episode of acute confusion.

When used in addition to other empiric therapy, topiramate may be effective at reducing general symptoms of combat-related PTSD and reducing high-risk alcohol intake and nightmares. Further randomized controlled trials of topiramate for the treatment of combat-related PTSD are warranted.

Pharmacists are increasingly acknowledging their responsibility to inform and counsel patients. However, it is unclear how these tasks are implemented and whether patients' needs are being fulfilled.

To examine patients' perceptions of information received at the start of selective serotonin-reuptake inhibitor (SSRI) treatment, aiming to identify (1) information needs and (2) the potential role of the community pharmacist as information provider.

A qualitative descriptive study comprising semi-structured telephone interviews was carried out with patients who had recently started a new course of SSRI treatment. Patients were recruited through 6 Dutch community pharmacies. The interviews were guided by the following topics: type of information obtained, unmet information needs, preferred information provider, and the role of the pharmacist.

Forty-one patients took part in an interview. Information needs varied widely among patients; overall, patients felt that they would benefit from information tailored to their needs. Many patients required more concrete and practical information on adverse effects and delayed onset of action than was provided. In addition, an explanation of the term dependency in the context of SSRI use and a discussion of the necessity for use and believed harms of long-term treatment were important to patients. Regardless of patients' needs, the role of the pharmacist was generally perceived as limited, and patients identified several pharmacy-related barriers to improved communication, including the timing of information (mainly restricted to first-time dispensing), lack of time and privacy, lack of empathy and a protocol-driven way of providing information, and inexperience of pharmacy technicians.

Patients starting treatment with antidepressants may benefit from information tailored to their personal needs. Along with the prescribing physician, community pharmacists could have an important role in informing and counseling patients.

Written materials are commonly used to communicate pharmacy-relevant information to patients. However, they are often composed at a level that limits comprehension, mitigating a well-intended effect.

To (1) use the cloze procedure (a test designed to assess reading comprehension) to evaluate an individual's understanding of a pharmacy-relevant educational pamphlet; (2) compare results of the cloze procedure with the reading comprehension component of the Short Test of Functional Health Literacy in Adults (S-TOFHLA); and (3) use results to demonstrate rewriting of the educational pamphlet.

The cloze procedure was applied to a pharmacy-relevant educational pamphlet describing safe medication practices. A total of 162 subjects were recruited from university faculty, staff, and students; a local adult literacy center; and community senior centers. Subjects completed a background interview, the S-TOFHLA. and cloze procedure for the pharmacy-relevant educational pamphlet. S-TOFHLA and cloze procedure scores were described and compared. Cloze procedure responses were used to demonstrate revision of the pamphlet RESULTS: Of the 154 subjects analyzed, mean ± SD age was 56.5 ± 20.4 years. Subjects were predominantly white (93.5%), female (71.4%). and college graduates (42.2%). Mean score on the S-TOFHLA was 92.1%. A majority (95.5%, 147/154) of subjects demonstrated adequate functional health literacy. In contrast, mean score on the cloze procedure was 53.3%. Internal consistencies of the S-TOFHLA and the cloze procedure were 0.92 and 0.90, respectively. Scores on the cloze procedure and the S-TOFHLA were highly correlated (r = 0.71, p < 0.001), Performance on the cloze procedure indicated that 55.2% of subjects required supplemental teaching.

In this highly educated, health-literate sample, a majority did not understand the pharmacy-relevant educational pamphlet despite adequate performance on a standard measure of health literacy. The cloze procedure can be used to assess comprehension of educational materials, solicit feedback from intended users, and guide the revision of educational materials.

To evaluate the pharmacodynamic properties, efficacy, safety, and clinical application of insulin glulisine, a rapid-acting insulin analog, in the treatment of diabetes mellitus in ambulatory and hospitalized patients.

Searches were performed with the headings glulisine, insulin analog, [LysB3, GluB29] insulin, insulin glulisine, rDNA insulin, rapid-acting insulin, SoloStar, safety, efficacy, pharmacodynamics, and cost analysts within MEDLINE and PubMed, American Diabetes Association (ADA), the Food and Drug Administration (FDA), and Sanofi-aventis Pharmaceuticals (1990–August 2008).

Phase 1, Phase 2, Phase 3, and postmarketing trials examining the efficacy and safety of glulisine in type 1 or type 2 diabetes were reviewed. Studies published as abstracts and the manufacturer's product information supplemented data absent from clinical trials.

Insulin glulisine is a rapid-acting insulin with relative equivalence in efficacy and safety to other short- and rapid-acting insulins. Glulisine's onset of action of 20 minutes and 4-hour duration of action allow for bolus administration 15–20 minutes prior to or up to 20 minutes after meals. Clinical trials have demonstrated the safety and efficacy in adults with type 1 or type 2 diabetes. Several studies indicated a statistically significant decrease of hemoglobin A_1C (A1C) with glulisine compared with regular insulin (0.10 decrease); however, no difference in A1C control was found compared with insulin aspart or lispro, Significant adverse effects appear to be limited to localized and systemic allergic reactions and hypoglycemia.

Insulin glulisine is a safe and effective rapid-acting insulin analog for the treatment of adults with diabetes. Clinical benefit over other short- and rapid-acting insulin products is not established. Addition of insulin glulisine to a formulary should be based on institution-specific availability and cost differences between glulisine, lispro, and aspart in the absence of superiority of clinical efficacy or safety and data beyond 26 weeks.

To review the pharmacology, pharmacokinetics, efficacy, and safety of the prodrug lisdexamfetamine for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adults and describe its potential place in therapy.

Primary literature published between January 1, 1990, and August 1, 2008, was selected from PubMed using the search key words lisdexamfetamine, Vyvanse, and NRP104. References of selected publications were also reviewed. Posters and abstracts of research presented at national meetings were reviewed when available. The product labeling for Vyvanse was also used.

Preference was given to published, randomized, and controlled research describing the pharmacokinetics, efficacy, and safety of lisdexamfetamine. Noncontrolled studies, postmarketing reports, and poster presentations were considered secondly. All published studies were included.

Lisdexamfetamine is a prodrug of dextroamphetamine covatently bound to Hysine, which is activated during first-pass metabolism. The unique pharmacokinetic profile owing to lisdexamfetamine's prodrug design and rate-limited enzymatic biotransformation allows for once-daily dosing with a duration of activity of approximately 12 hours. Lisdexamfetamine has been proven to reduce the symptoms of ADHD both in children aged 6–12 years and adults aged 18–55 years, decreasing ADHD rating scale scores by approximately 27 and 19 points, respectively. Adverse effects with an incidence greater than 10% during preclinical trials included appetite suppression, insomnia, and headache. Lisdexamfetamine's unique pharmacokinetic properties may provide additional safety with regard to reducing abuse potential. As with other central nervous system (CNS) stimulants, concerns regarding sudden cardiac death and adverse effects on growth also apply to lisdexamfetamine.

Lisdexamfetamine provides another amphetamine-based CNS stimulant option for treatment of children and adults with ADHD. However, its use may be limited by a lack of significant differentiation when compared with cunently used stimulants and a lack of evidence to support its use in adolescents.

Continuity of care is important for the delivery of quality health care. Despite the abundance of research on this concept in the medical and nursing literature, there is a lack of consensus on its definition. As pharmacists have moved beyond their historical product-centered practice, a source of patient-centered research on continuity of care for practice application is required.

To determine the scope of research in which pharmacists were directly involved in patients' continuity of care and to examine how the phrase continuity of care was defined and applied in practice.

A working definition of continuity of care and a tool for relevance quality assessment of search articles were developed. MEDLINE, International Pharmaceutical Abstracts, EMBASE, and the Cochrane Collaboration evidence-based medicine reviews and bibliographies were searched (1996–March 2008). Reporting clarity was assessed by the Consolidated Standards of Reporting Trials checklist and outcomes were grouped by economic, clinical, and/or humanistic classification.

The search yielded 21 clinical and randomized controlled trials, including 11 pharmacist-only and 10 multidisciplinary studies. A broad range of research topics was identified and detailed analysis provided ready reference for considerations of research replication or practice application. Studies revealed a range of research aims, settings, subject characteristics, attrition rates and group sizes, interventions, measurement tools, outcomes, and definitions of continuity of care. Research focused on patients with depression (n = 4), cardiovascular disease {n = 4), diabetes (n = 2), and dyslipidemia (n = 1); specific drugs included non–tricyclic antidepressants, cardiovascular drugs, and benzodiazepines. From the proposed endpoints of economic cost (n = 6) and clinical (n = 14) and humanistic (n = 16) outcomes, 15 studies reported statistically significant results.

Medication management at primary, secondary, and tertiary levels of care indicated an expanded role and collaboration of pharmacists in continuity of care. However, the exclusion of disadvantaged patients in 19 studies is at odds with continuity of care for these patients, who may have been the most in need for the same reason that they were excluded.

To review studies evaluating the use of midodrine and octreotide in hemodynamic complications of cirrhosis, including ascites and hepatorenal syndrome.

Searches of MEDLINE (1966–September 2008) and EMBASE (1974–September 2008) were conducted using the terms midodrine, octreotide, hepatorenal syndrome, ascites, cirrhosis, and paracentesis-induced circulatory dysfunction. Literature review was limited to English-language, human studies.

Studies identified from data sources were considered for review. Studies were excluded if primary therapy involved any of the following: transjugular intrahepatic portosystemic shunt procedure, medications other than midodrine or octreotide, or patients included for treatment or prevention of portal hypertension and/or variceal bleeding. Pharmacokinetic/pharmacodynamic studies and studies using retrospective data collection were excluded. Seven studies were included in this review.

Midodrine and octreotide in combination or alone have shown conflicting results for systemic and renal hemodynamics and renal function in patients with cirrhosis-related complications. Patients with ascites being treated with midodrine, alone or in combination with octreotide, showed significant changes in systemic hemodynamics, without a correlating change in renal perfusion. Studies comparing the use of midodrine with use of albumin for the prevention of paracentesis-induced circulatory dysfunction (PICD) showed no incidence of PICD in either treatment group. In hepatorenal syndrome, patients using midodrine with octreotide showed significant changes in systemic hemodynamics and improvements in renal perfusion. This regimen's effect on survival is yet to be determined,

Available evidence shows inconsistent results for the effectiveness and safety of midodrine and octreotide use in cirrhotic patients. Because of the contradictory results, longer treatment duration and increased number of study participants are necessary to determine the proper use of midodrine and octreotide in these patients.

Effective written consumer medicines information is essential to support safe and effective medicine taking, but the wording and layout of currently provided materials do not meet patients' needs.

To identify principles from the wider discipline of information design for use by health professionals when developing or assessing written drug information for patients.

Six experts in information design nominated texts on best practice in information design applicable to consumer medicines information. A content analysis identified key principles that were tabulated to bring out key themes.

Six texts that met the Inclusion criteria, were Identified, and content analysis indentified 4 themes: words, type, lines, and layout. Within these main themes, there were 24 subthemes. Selected principles relating to these subthemes were: use short familiar words, short sentences, and short headings that stand out from the text; use a conversational tone of voice, addressing the reader as “you”; use a large type size while retaining sufficient white space; use bullet points to organize lists; use unjustified text (ragged right) and bold, lower-case text for emphasis. Pictures or graphics do not necessarily improve a document.

Applying the good information design principles identified to written consumer medicines information could support health professionals when developing and assessing drug information for patients.

To evaluate the use of immediate-release quetiapine for the treatment of insomnia.

Pre-MEDLINE and MEDLINE were searched (1966 to October 2008) using the terms quetiapine, sleep, insomnia, and antipsychotics.

All studies and case reports evaluating insomnia as a primary endpoint were reviewed.

The role of quetiapine for improving sleep in various patient populations is uncertain. Quetiapine has moderately sedative properties, and closes used in treatment of insomnia have ranged from 12.5 to 800 mg. Results of clinical trials and observations in case studies have revealed possible beneficial effects of quetiapine on several subjective and objective sleep parameters. In most studies, significant improvements in sleep were found in areas of total sleep time, sleep efficiency, and subjective sleep scores. However, some of these results may not be clinically significant. Also, quetiapine has been found to have adverse effects such as periodic leg movements, akathisia, and metabolic complications. Additionally, changes in rapid eye movement (REM) and percentage of REM sleep have been noted in different populations and need further study. Despite quetiapine's sedative properties, current data do not appear to support its use as first-line treatment for sleep complications. However, it may be useful for treatment of insomnia in patients with psychiatric disorders (eg, bipolar, schizophrenia) who do not respond to primary or secondary treatments.

Further studies are needed to define the placement, dose, and adverse effects of quetiapine for the treatment of sleep problems.

To evaluate the efficacy and safety of various treatment options for osteopenia and osteoporosis secondary to cancer treatment in pediatric patients undergoing cancer therapy.

A systematic search of PubMed (1949–November 2008) and international Pharmaceutical Abstracts (to November 2008) was conducted using the following search terms: osteoporosis, osteopenia, pediatrics, cancer, neoplasms, chemotherapy, bisphosphonates, calcium, vitamin D, calcitonin, and physical therapy.

All prospective studies that evaluated various osteoporosis treatment options in pediatric patients undergoing chemotherapy were included. Results from studies evaluating bisphosphonates and other treatments in children with osteoporosis due to other causes were also included if important safety and efficacy data were provided. Most commonly reported primary efficacy endpoints included comparisons of bone density parameters measured before and after treatment.

Four clinical studies and 2 case reports describing treatment with bisphosphonates, specifically alendronate and Pamidronate, for osteoporosis or osteopenia in pediatric cancer patients were identified. Results from the trials showed that these medications were efficacious in reducing bone mineral density loss during cancer therapy and were well tolerated in this special population. Primary efficacy endpoints included improvements in Z-scores measured by dual-energy X-ray absorptiometry scans. The most commonly reported adverse effects included hypocalcemia, mild stomach upset, and infusion-related hyperpyrexia. Four additional clinical trials involving the treatment of osteoporosis or osteopenia in children and adolescents who developed bone degeneration after chronic steroid therapy are also included. In these trials, treatment options such as calcitonin, and calcium and vitamin D supplementation were also shown to be beneficial.

The clinical trials published to date are limited to only a few conducted in small populations of patients diagnosed with lymphoblastic leukemia or non–Hodgkin's lymphoma. However, alendronate and Pamidronate both appeared to be effective options in improving bone mineral density scores with minimal adverse effects.

To review the efficacy and safety of modafinil in the treatment of cancer-related fatigue (CRF).

Literature was accessed via MEDLINE (1950–week 3, November 2008), International Pharmaceutical Abstracts, and Google Scholar using the terms modafinil, cancer, and fatigue. Reference citations from articles identified were reviewed.

All English-language publications identified were analyzed for significance. Studies relevant to the objective were used, including 2 prospective open-label studies, one randomized double-blind, dose-controlled trial with an open-label extension, and one Phase 3 randomized, placebo-controlled, double-blind trial.

Fatigue is a nearly universal adverse effect of cancer and its treatment that is unrelated to physical exertion, is not relieved by sleep or rest, and negatively affects quality of life. Modafinil is a central nervous system stimulant with minimal toxicity and a low propensity for abuse. Clinical data demonstrate that modafinil significantly reduces fatigue in patients who have received cancer treatment or are currently undergoing chemotherapy. Additional benefits include improvement in cognitive function, mood, general activity, walking ability, normal work ability, relations with other people, and enjoyment of life. Limitations of the available data include open-label design in 3 of the 4 studies; the absence of numerical results of fatigue assessments in the abstract of 1 trial, preventing the determination of clinical significance; and the full inclusion/exclusion criteria, which were not included in the published abstracts. These limitations leave readers without a clear picture of the study populations. Finally, different patient populations at different points in treatment with varying durations of therapy were used, which makes extrapolation of data to the general population challenging.

Further randomized placebo-controlled trials are necessary to amass evidence for the effective and safe use of modafinil for CRF; however, if traditional therapies have failed or are intolerable, modafinil can be considered a treatment option.

Ginkgo biloba is one of the most popular herbal supplements in the world. The supplement has been shown to induce the enzymatic activity of CYP2C19, the main cytochrome P450 isozyme involved in voriconazole metabolism. Because this enzyme exhibits genetic polymorphism, the inductive effect was expected to be modulated by the CYP2C19 metabolizer status.

To examine the possible effects of Ginkgo biloba as an inducer of CYP2C19 on single-dose pharmacokinetics of voriconazole in Chinese volunteers genotyped as either CVP2C19 extensive or poor metabolizers.

Fourteen healthy, nonsmoking volunteers–7 CYP2C19 extensive metabolizers (2C19*1/2C19*1) and 7 poor metabolizers (2C19*2/2C19*2)–were selected to participate in this study. Pharmacokinetics of oral voriconazole 200 mg after administration of Ginkgo biloba 120 mg twice daily for 12 days were determined for up to 24 hours by liquid chromatography–electrospray tandem mass spectrometry in a 2-phase randomized crossover study with 4-week washout between phases.

For extensive metabolizers, the median value for voriconazole area under the plasma concentration–time curve from zero to infinity (AUC_0-00) was 5.17 μg•h/mL after administration of voriconazole alone and 4.28 μg•/mL after voriconazole with Ginkgo biloba (p > 0.05). The other pharmacokinetic parameters of voriconazole such as AUC_0-24, time to reach maximum concentration, half-life, and apparent clearance also did not change significantly for extensive metabolizers in the presence of Ginkgo biloba. Pharmacokinetic parameters followed a similar pattern for poor metabolizers.

The results suggest that 12 days of treatment with Ginkgo biloba did not significantly alter the single-dose pharmacokinetics of voriconazole in either CYP2C19 extensive or poor metabolizers. Therefore, the pharmacokinetic interactions between voriconazole and Ginkgo biloba may have limited clinical significance.

Patients are exposed to a broad range of drug information (DI) sources; among them is the Internet, which has been increasingly used over the years, especially by adolescents.

To identify patients' needs and common sources of DI: examine the differences in use of DI sources among groups, by age and sex; and better understand patients' use of the Internet as a source of DI.

A quota sample of 201 outpatients from National University Hospital in Singapore was surveyed. A questionnaire was developed to examine patients' needs for and common sources of DI as well as their experience with and attitudes toward using the Internet as a DI source.

Physicians (83.1%) and pharmacists (57.7%) were reported to be the most commonly used sources of DI regarding prescription drugs (n = 201), whereas pharmacists (40.9%) and relatives or friends (40.9%) were the most commonly reported sources for information about nonprescription drugs (n = 149). Respondents most commonly sought DI about adverse effects (72.6%), dosing (54.7%), and indications (54.2%). Among Internet users, people aged 31–50 years were more likely than those in other age groups to search the Internet for DI (p < 0.001). The Internet was considered to be a convenient source with a broad range of information; however, patients faced both the inability to find needed information and uncertainty about information reliability when searching (or DI on the Internet.

Pharmacists play an important role in counseling patients about prescription and nonprescription drugs. There is a need to educate patients on how to locate and evaluate DI on the Internet.

To report a case of fatal intracranial bleeding possibly due to an interaction between warfarin and inactivated influenza vaccination.

A 64-year-old white male was admitted to the hospital after becoming unresponsive. The family reported a 2-day history of bleeding from the patient's rectum prior to admission. He had no recent changes in medical conditions or medication regimen, which included warfarin for stroke prophylaxis secondary to atrial fibrillation. The patient had received an inactivated influenza vaccine 4½ weeks prior to presentation, at which time his international normalized ratio (INR) was 2.0. Upon admission, the patient's INR was greater than 15: INR values over the previous 6 months had been relatively stable {range 1.4–4.7). A noncontrast computed tomography scan of the head showed a large parenchymal hemorrhagic infarction involving the left temporal, parietal, and occipital lobes. In the emergency department, the patient received a nitroglycerin infusion to maintain systolic blood pressure In the range of 140–160 mm Hg as well as an infusion of 4 units of fresh frozen plasma and 10 mg of vitamin K. Following a neurosurgery evaluation, it was determined that nothing meaningful could be done to alter the patient's outcome positivefy, and he died approximately 17 hours after admission.

To date, most reports of concomitant warfarin therapy and influenza vaccination indicate no significant change in average anticoagulation parameters. However, there are reports of individuals who may have experienced increased anticoagulation following influenza vaccination. The reason for these increases is unknown, but may involve only certain components of the vaccine, which is altered almost annually. Our patient's significant INR elevation, after being relatively stable for at least 6 months, was thought to be due to an interaction between warfarin and the influenza vaccination. The Horn Drug Interaction Probability Scale indicated a possible interaction between warfarin and the influenza vaccination.

Considering the outcome in our patient, as well as outcomes in other individuals who have experienced an increased INR in a similar scenario, it appears justified to implement more frequent INR evaluations during the 4–6 weeks following influenza vaccination.

To report the occurrence of fatal acute liver failure following addition of levothyroxine to a regimen of sunitinib and acetaminophen.

A 57-year-old woman who started sunitinib treatment for relapsed metastatic gastrointestinal stromal tumor after imatinib failure had disease stabilization and normal livar function through 8 cycles of sunitinib 50 mg/day for 4 weeks, followed by 2 weeks off treatment. Her continuing medications included acetaminophen approximately 4.5 g/wk, as well as standard medications for asthma. In cycle 8, she received oral levothyroxine 50–150 pg/day for approximately 30 days to control hypothyroidism before beginning cycle 9 of sunitinib. On day 4 of cycle 9, she was hospitalized with progressively rising circulating liver enzyme levels. She died 4 days postadmission despite discontinuation of sunitinib and initiation of Intensive supportive treatment. At autopsy, her liver showed severe centrliobular necrosis with moderate-to-severe steatosis and minimal parenchymal invasion by the neoplasm. Viral stains were negative.

Hepatic failure has been reported rarely in patients receiving sunitinib. Autopsy results excluded neoplastic disease progression and viral infection in the etiology of the event, and the patient may have died of the combined interaction of sunitinib, acetaminophen, and levothyroxine. Although sunitinib was not more than a possible hepatotoxin (Roussel Uclaf Causality Assessment Method) and may even have been hepatoprotective over a 48-week period against chronic intake of acetaminophen (probable hepatotoxin) by producing regional hypothyroidism within the liver, it is hypothesized that correction of the putative hepatic hypothyroidism with oral levothyroxine (possible hepatotoxin) and reinitiation of sunitinib treatment may have triggered hepatic necrosis.

Acetaminophen should be used with particular caution in patients receiving sunitinib. In sunitinib-treated patients who also require levothyroxine therapy, increased caution in restarting subsequent sunitinib treatment and discontinuation of acetaminophen, if possible, is advisable. Further evaluation of this potential interaction is warranted.

To report a case of calcineurin-induced pain syndrome (CIPS) in a child undergoing his second hematopoietic stem cell transplant (HSCT).

A 6.1-year-old child received cyclosporine and methotrexate for acute graft-versus-host disease (aGVHD) prophylaxis after his first HSCT for acute myeloblastic leukemia. Amlodipine was given for the treatment of hypertension. Symptoms of CIPS were not observed. After the second HSCT at the age of 6.7 years, the child received cyclosporine (target trough whole blood cyclosporine concentration range 150–200 μg/L). starting on day −3, and mycophenolate mofetil for aGVHD prophylaxis. With the first cyclosporine dose, the patient complained of leg pain that was most severe during the cyclosporine infusion. Analgesic agents and a change from intravenous to oral administration of cyclosporine were Ineffective In controlling the pain. Magnetic resonance imaging findings on day 10 showed periosteal soft tissue changes and mild bone marrow edema of the femora and tibiae. Tacrolimus was substituted for cyclosporine on day 20; on day 21 amlodipine was initiated to manage hypertension. Trough whole blood tacrolimus concentrations ranged from 1.7 to 6.2 μg/L. Pain was reduced in seventy by day 29 and completely resolved once tacrolimus was discontinued on day 42. In this case, CIPS was considered to be probably associated with cyclosporine according to the Naranjo probability scale.

CIPS is hypothesized to result from calcineurin-induced vascular changes that disturb bone perfusion and permeability, leading to intraosseous vasoconstriction and bone manow edema. In our patient, symptoms were most acute during the infusion, when whole blood cyclosporine concentrations were likely to be the highest. Our patient's symptoms were resolved when tacrolimus was substituted for cyclosporine and amlodipine was initiated.

interventions aimed at reducing pain associated with CIPS may include the initiation of calcium-channel blocker therapy and conversion to an alternative calcineurin inhibitor.

To report a case of angioedema likely associated with amlodipine administration in a patient with a right thalamic hemorrhagic stroke.

A 50-year-old female experienced angioedema during hospitalization for s right thalamic hemorrhagic stroke. She had no past history of angioedema and all of her medications were assessed for risk of angioedema. After careful evaluation, case reports linking calcium channel blockers (CCBs) and angioedema led to further examination of amlodipine as a cause. Amlodipine therapy had been initiated 24 hours prior to the development of angioedema, which then resolved 72 hours after discontinuation of the drug. In total, the patient experienced oropharyngeal swelling for 10 days.

In determining a cause for the patient's angioedema we eliminated genetic, allergic, physically induced, thyroid autoimmune disease-associated, and medication-induced causes. Three case reports describing 7 patients have linked the CCBs verapamil, diltiazem, and nifedipine with angioedema. The onset and resolution of symptoms in our patient were very similar to those seen in other case reports. Application of the Naranjo probability scale found a probable link between amlodipine and angioedema.

Although few reports of CCB-induced angioedema exisi, to our knowledge, this is the first reported case to suggest a link between angioedema and amlodipine therapy. Clinicians should consider amlodipine as a potential cause of angioedema.

To report and discuss a case of anaphylaxis in a young, healthy white male taking celecoxib for intermittent lower back pain.

A healthy 27-year-old man with a documented history of anaphylaxis to penicillins and macrolides presented to the emergency department (ED) in anaphylactic shock after ingesting a 200-mg capsule of celecoxib and a cup of orange juice. The patient had been taking celecoxib over the past 6 months, for 1-2 weeks at a time, for low back pain secondary to a pilonidal cyst and an L5/S1 bulging disc. The day of admission was the seventh day of the most recent course of twice-daily celecoxib. The patient initially self-treated the reaction with diphenhydramine and subcutaneous epinephrine that he had at home due to his history of drug- and bee sting-induced anaphylaxis; neither intervention improved his symptoms, He became profoundly diaphoretic and developed systemic swelling, shortness of breath, bradycardia, and hypotension. Emergency medical services transported the patient to the ED, where he was treated appropriately and the symptoms resolved. However, 4 hours later, at time of discharge from the ED, the symptoms recurred. He was admitted to the intensive care unit and monitored for 3 days. Supportive care, steroids, and histamine blockade provided resolution of the symptoms. Cardiac workup was initiated because of the recunence and severity of bradycardia and hypotension; results of the workup were unremarkable. The patient was discharged in stable condition.

This case demonstrates rare anaphylaxis to celecoxib in a patient who had previously taken the drug and who had documented tolerance to sulfonamide antibiotics. Despite this history, our patient developed type V immunoglobulin E-mediated anaphylaxis secondary to the sulfonamide component of celecoxib. This reaction was considered probable according to the Naranjo probability scale. A review of published case reports and related atlergy literature for celecoxib allergenicity revealed that such reactions are rare. This is the first case report with great detail of a patient with anaphylaxis to celecoxib after having previously tolerated the medication.

Celecoxib can produce an anaphylactic reaction in patients who have previously tolerated sulfonamide antibiotics and who have previously tolerated celecoxib. This case also reviews the potentially biphasic presentation of anaphylaxis. Clinicians need to be aware of this biphasic anaphylactic response to ensure optimal duration of evaluation.

To report a case of acute encephalopathy associated with ingestion of gemifloxacin, a fluoroquinolone.

A 67-year-old woman presented to the emergency department with an acute alteration in mental status. Twenty-four hours earlier she had taken one 320-mg tablet of her husband's gemifloxacirt prescription to treat symptoms of a mild upper respiratory infection. During her initial evaluation at our institution, the woman was dysphasia, unable to follow commands, and agitated, suggesting encephalopathy. A thorough diagnostic investigation did not reveal any structural, metabolic, or infectious etiology. Her mental status returned to normal within 2 days without any definitive treatment.

Fluoroquinolone-associated neurotoxicity may manifest as encephalopathy, seizures, confusion, or toxic psychosis. To date, none of these adverse effects, specifically encephalopathy, has been reported with gemifloxacin. An objective causality assessment revealed that encephalopathy was probably associated with gemifloxacin use. Seizures, either convulsive or nonconvulsive, may have contributed to our patient's presentation, but she denied seizures prior to this event and did not suffer a seizure in the 18 months following her discharge, However, her second electroencephalograph revealed an underlying predisposition to seizures, which gemifioxacin may have unmasked.

This report illustrates that severe central nervous system adverse effects associated with some fluoroquinolones may also occur with gemifloxacin. Gemifloxacin and other fluoroquinolones should be considered in the etiologic evaluation of patients with acute encephalopathy.

To report a case of neuroleptic malignant syndrome (NMS) secondary to quetiapine in which the patient developed extrapyramidal symptoms (EPS).

A 34-year-old male with a history of severe brain damage, mental retardation, and seizures was admitted to the hospital with changes in mental status, development of tremors, and a temperature of 39.9 °C. Initial differentia) diagnoses included seizure, aspiration, stroke, and infection. Once these were excluded, NMS was considered. The patient exhibited other characteristics of NMS during hospitalization, including lead pipe rigidity, tachycardia, and high creatine kinase level (up to 12,654 IU/L). Drug therapy on presentation included quetiapine 200 mg 3 times per day, guanfacine 2 mg/day. carbamazepine 400 mg every 12 hours, valproic acid 500 mg twice daily, and lorazepam 2 mg (unknown schedule). He reportedly had received these medications for at least a month before admission. On hospital day 2, quetiapine was discontinued. The patient received traditional treatment (or NMS, which included bromocriptine, dantrolene, intravenous fluids, and supportive care. The NMS resolved in 7 days.

In cases of NMS, clinicians previously believed that the risk for developing severe adverse effects such as EPS was lower with atypical versus typical antipsychotics. We identified 13 cases of NMS secondary to quetiapine in the literature via a search of MEDLINE/PubMed (1950–2008), and Iowa Drug Information Service (1966–2008). Seventy-five percent of previous reports of NMS secondary to quetiapine had reactions that included EPS, Common patient characteristics in our report and others included male sex, history of mental retardation, and treatment modalities used in NMS. Unique characteristics in this case included length of therapy without dosage change or titration and no known history of drug-related EPS. The Naranjo probability scale indicated a probable relationship between the development of NMS and quetiapine.

NMS with associated EPS has been previously associated with quetiapine. Clinicians should be aware that NMS with EPS can occur with quetiapine at steady state doses without recent dosage adjustments or titration.