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Background There are limited options for the treatment of behavioral and psychological symptoms of dementia (BPSD). Objective Evaluate the efficacy and safety of using atypical antipsychotics for BPSD among patients residing in long-term care. Setting Long term care community facility in the United States. Methods Retrospective observational study of patients residing in a long-term care facility with a diagnosis of dementia not trauma-induced with documented BPSD treated with an atypical antipsychotic for at least 2 weeks. Paper medical records were reviewed from January 1, 1990 until March 23, 2010. Main outcome measure Behavioral/psychological efficacy outcomes were documented beginning 2 weeks after atypical antipsychotic therapy was initiated and safety outcomes were documented from the time of atypical antipsychotic initiation, until the last documentation available. Efficacy and safety outcomes were documented as part of routine clinical practice based on the responsible clinician. Results A total of 85 distinct atypical antipsychotic treatment periods for 73 unique patients were included. Nearly 50% of patients continued atypical antipsychotic treatment for at least 1 year and 5.6% of treatments were discontinued due to an adverse event. Patients’ behavioral/psychological outcomes improved for 52 (61%) treatments, remained stable for 17 (20%) treatments, and worsened for 16 (19%) treatments. Adverse events were reported by 57% of patients, with the most common adverse events being metabolic, fall related, and extrapyramidal symptoms. The odds ratio for an adverse event was 1.08 (p = 0.03) for every 90 day increase in duration of treatment. Conclusion In patients who reside in a long-term care setting, atypical antipsychotic treatment improved BPSD, but also increased the potential risk of adverse events.

Objectives To evaluate dosing alert appropriateness, categorize orders with alerts, and compare the appropriateness of alerts due to customized and non-customized dose ranges at a pediatric hospital. Methods This was a retrospective analysis of medication orders causing dosing alerts. Orders for outpatient prescriptions, patients ≥18 years of age, and research protocols were excluded. Patient medical records were reviewed and ordered doses compared with a widely used pediatric reference (Lexi-Comp) and institutional recommendations. The alerted orders were categorized and the occurrence of appropriate alerts was compared. Results There were 47 181 inpatient orders during the studied period; 1935 orders caused 3774 dosing alerts for 369 medications in 573 patients (median age 6.1 years). All alerted orders had an alert overridden by the prescriber. The majority (86.2%) of alerted orders inappropriately caused alerts; 58.0% were justifiable doses and 28.2% were within Lexi-Comp. However, 13.8% of alerted orders appropriately caused alerts; 8.0% were incorrect doses and 5.8% had no dosing recommendations available. Appropriately alerted orders occurred in 19.7% of alerted orders due to customized ranges compared to 12.8% due to non-customized ranges (p=0.002). Preterm and term neonates, infants, and children (2–5 years) had higher proportions of inappropriate alerts compared to appropriate alerts (all p

Background: Irritable bowel syndrome (IBS) is a complex syndrome that is difficult to manage. Here we present the evidence supporting medication treatments for specific IBS symptoms, discuss evidence-based management of IBS with medications including dose regimens and adverse effects and review progress on research for new IBS treatments. Summary: Currently, there is evidence to support improvements in specific IBS symptoms following treatment with loperamide, psyllium, bran, lubiprostone, linaclotide, amitriptyline, trimipramine, desipramine, citalopram, fluoxetine, paroxetine, dicyclomine, peppermint oil, rifaximin, ketotifen, pregabalin, gabapentin and octreotide and there are many new medications being investigated for the treatment of IBS. Key Message: Of the medications with demonstrated improvements for IBS symptoms, rifaximin, lubiprostone, linaclotide, fiber supplementation and peppermint oil have the most reliable evidence supporting their use for the treatment of IBS. Onset of efficacy for the various medications has been noted to be as early as 6 days after initiation; however, the efficacy of most medications was not assessed prospectively at predefined periods. Additional studies of currently available and new medications are ongoing and are needed to better define their place in therapy and expand therapeutic options for the treatment of IBS. The most promising new medications for IBS include a variety of novel pharmacologic approaches, most notably the dual μ-opioid receptor agonist and δ-opioid antagonist, JNJ-27018966.

Purpose The use of intermittent i.v. sildenafil dosing in three patients with pulmonary hypertension (PH) and limited venous access is reported. Summary One preterm infant with PH in addition to bronchopulmonary dysplasia and two full-term neonates with PH after congenital diaphragmatic hernia repairs were successfully treated for PH with adjunctive intermittent i.v. sildenafil. sildenafil dosages ranged from 0.4 to 2 mg/kg every six hours. Infusion periods ranged from one to three hours. The longer infusion periods were used to minimize the risk of hypotension during infusion, with continued efficacy assessment between dosing intervals by monitoring ongoing oxygenation saturation trends and oxygen requirements when the drug was not infusing. Treatment duration ranged from 5 to 50 days. Decreases or fluctuations in systemic blood pressure were noted at the beginning of treatment, but minimal interventions were required to maintain blood pressure, which generally increased during extended treatment. Fraction of inspired oxygen requirements were decreased or remained stable during each patient’s first dose, and the need for respiratory support decreased over time, with improvements in oxygenation and prevention of continual life-threatening desaturation episodes. PH eventually resolved in each patient, based on improvements in serial echocardiographic studies with decreased requirements for inhaled nitric oxide, oxygen, and mechanical ventilation. All three patients required weaning from sildenafil treatment, suggesting a potential for rebound respiratory insufficiency with abrupt discontinuation of sildenafil. Conclusion Intermittent i.v. sildenafil dosing provided a well-tolerated, practical, and potentially effective treatment for PH in three patients when enteral intake was undesirable and when there was a need to conserve available venous access.

The purpose of this study was to identify and characterize adverse drug events (ADEs) in a primary care setting using an electronic health record (EHR). This prospective, observational study enrolled patients with any medication change who were seen at an outpatient internal medicine clinic. Patients were evaluated for ADEs by EHR review and telephone interview. ADEs were independently assessed for causality, severity, preventability, and ameliorability by a physician and a pharmacist using a grading instrument. There were 1368 unique medication changes for 701 individuals who completed the study (1.95 changes per person). Of the 226 suspected ADEs, 68 (58%) were deemed to be “definite” or “probable” following causality assessment; 21% were preventable and 40% ameliorable. Only 2 ADEs were serious or life-threatening. Compared with prior reports, ADEs in primary care have decreased in frequency and severity, yet the occurrence of preventable and ameliorable ADEs has increased.

The lack of commercially available liquid dosage forms for pediatric patients prompted this study. The objectives of our study were to determine the stability of zonisamide, amitriptyline, and glycopyrrolate in extemporaneously prepared oral suspensions in plastic prescription bottles. One group of suspensions was prepared in OraPlus:OraSweet (1:1) for each drug and stored either under refrigeration (4°C) or at room temperature (25°C). A second group of suspensions were compounded in 1% methylcellulose:simple syrup at a 1:10 proportion for zonisamide, amitriptyline, and glycopyrrolate; these suspensions were stored at either under refrigeration (4°C) or at room temperature (25°C). The drug concentrations were measured by the stability-indicating high-performance liquid chromatographic methods. The mean concentration of zonisamide (10 mg/mL) remained above 95% of the original concentration for 91 days in each group of suspensions at both 4°C and 25°C. The mean concentration of amitriptyline (20 mg/mL) was above 95% for 91 days in the suspensions containing OraPlus/ OraSweet at both 4°C and 25°C. However, in the suspensions containing methylcellulose:simple syrup, the mean concentration of amitriptyline was about 95% for 42 days at 4°C and 28 days at 25°C. The mean concentration of glycopyrrolate (0.2 mg/mL) was above 95% in each group of suspensions during the 14-day study period. These data indicate that zonisamide, amitriptyline, and glycopyrrolate can be prepared extemporaneously as suspensions and stored in plastic prescription bottles for varying periods at 4°C and 25°C for use in pediatric patients.

Asthma is a frequent comorbidity in hospitalized children and adults. Patients with a history of asthma may have no breathing complaints or abnormal chest exam findings to trigger care for this comorbidity during hospitalization. Consequently, this may lead to a potential missed opportunity to discuss asthma as a comorbidity and ongoing issue to ensure its optimal management at home. Our goal is to raise awareness that such patient encounters may represent opportunities for health care professionals to optimize asthma management. Despite focusing on the present illness and limited time availability, asthma care may be improved in a time-efficient manner in these patients.

Extemporaneously prepared liquid dosage forms are needed to administer required medications in infants and young children. The goal of this study was to evaluate the stability of levothyroxine, doxycycline, hydrocortisone, and pravastatin in extemporaneously prepared suspensions stored in plastic prescription bottles under refrigeration and room temperature. Levothyroxine (25 mcg/mL), doxycycline (5 mg/mL), hydrocortisone (2 mg/mL), and pravastatin (10 mg/mL) were each prepared in two groups of suspensions. All of these suspensions were stored in plastic prescription bottles under refrigeration and at room temperature. Levothyroxine was stable for two weeks at 4°C but only one week at 25°C in both suspensions. Doxycycline was stable for two weeks in both suspensions at 4°C and 25°C. Hydrocortisone was stable for the entire two-week study period in both suspensions at both 4°C and 25°C. Pravastatin was stable for the one-week study period in both suspensions at both 4°C and 25°C. These results can be used to offer age-appropriate extemporaneously prepared medications to infants and young children when no suitable commercially available liquid formulations are available.

Background and objective Accurate and informed prescribing is essential to ensure the safe and effective use of medications in pediatric patients. Computerized clinical decision support (CCDS) functionalities have been embedded into computerized physician order entry systems with the aim of ensuring accurate and informed medication prescribing. Owing to a lack of comprehensive analysis of the existing literature, this review was undertaken to analyze the effect of CCDS implementation on medication prescribing and use in pediatrics. Materials and methods A literature search was performed using keywords in PubMed to identify research studies with outcomes related to the implementation of medication-related CCDS functionalities. Results and discussion Various CCDS functionalities have been implemented in pediatric patients leading to different results. Medication dosing calculators have decreased calculation errors. Alert-based CCDS functionalities, such as duplicate therapy and medication allergy checking, may generate excessive alerts. Medication interaction CCDS has been minimally studied in pediatrics. Medication dosing support has decreased adverse drug events, but has also been associated with high override rates. Use of medication order sets have improved guideline adherence. Guideline-based treatment recommendations generated by CCDS functionalities have had variable influence on appropriate medication use, with few studies available demonstrating improved patient outcomes due to CCDS use. Conclusion Although certain medication-related CCDS functionalities have shown benefit in medication prescribing for pediatric patients, others have resulted in high override rates and inconsistent or unknown impact on patient care. Further studies analyzing the effect of individual CCDS functionalities on safe and effective prescribing and medication use are required.

Objective To assess potential associations between joblessness and oral anti-diabetic (OAD) medication adherence in US diabetic working-age adults. Study Design A retrospective longitudinal panel design used pooled 2001-2007 Medical Expenditure Panel Survey (MEPS) data forming a nationally representative sample of diabetic individuals, ages 24-59 years. Pregnancy, seasonal job status, retired persons, a student designation, and those prescribed insulin were excluded. Adherence was measured using the proportion of days covered (PDC). A PDC ≥0.80 was classified as adherent. Descriptive statistics and multivariate regression analysis accounting for the MEPS' complex survey design were conducted. Results There were 2256 individuals (means: age 48.3 years [SD 8.15], body mass index 31.1 [SD 0.30], Charlson Comorbidity Index 0.37 [SD 0.79]) who met study criteria. Thirty-four percent were jobless at the first interview round and 29% remained jobless all 5 interview rounds during the 2-year panel period. Reasons cited for joblessness included: waiting to start a new job (73%) and unable to work due to illness or disability (20%). Negligible proportions cited staying home to care for family members or maternity leave as reasons for joblessness. Proportionately, more individuals were nonadherent (55%, SE 0.006). Joblessness was associated with a 16% significant reduction in the PDC (β −15.9, P P = 0.002), while holding all other variables constant. Conclusions The results indicate that jobless working-age individuals with diabetes were significantly less likely to adhere to OAD medication than employed individuals.

Background Perinatal depression may further complicate the health of women with human immunodeficiency virus (HIV) infection. Diagnosis and subsequent treatment of depressive symptoms may significantly improve the health of mother and newborn. Objective We sought to examine the association between race and perinatal depression among a sample of low-income women with HIV infection. Methods This retrospective cohort study used data from a multi-state Medicaid administrative claims database to study HIV-infected perinatal women between 2003 and 2007. Multivariate regression analysis was used to study the objective. Results The overall prevalence of perinatal depression in the sample (n = 650) was 27.8%. Black women had significantly lower odds of experiencing perinatal depression (odds ratio 0.328; 95% confidence interval 0.225-0.479) compared with non-black women. Non-black women showed significantly higher comorbidity severity scores than black women (0.356 vs. 0.220, P = .035). Conclusions This study found that non-black women may be more vulnerable to perinatal depression. Improved health care provider vigilance for depressive symptoms among low-income, HIV-infected women of all races during the perinatal period is warranted.

Racial disparities exist in many aspects of HIV/AIDS. Comorbid depression adds to the complexity of disease management. However, prior research does not clearly show an association between race and antiretroviral therapy (ART) adherence, or depression and adherence. It is also not known whether the co-existence of depression modifies any racial differences that may exist.To examine racial differences in ART adherence and whether the presence of comorbid depression moderates these differences among Medicaid-enrolled HIV-infected patients.Retrospective cohort study.Multi-state Medicaid database (Thomson Reuters MarketScan®).Data for 7,034 HIV-infected patients with at least two months of antiretroviral drug claims between 2003 and 2007 were assessed.Antiretroviral therapy adherence (90 % days covered) were measured for a 12-month period. The main independent variables of interest were race and depression. Other covariates included patient variables, clinical variables (comorbidity and disease severity), and therapy-related variables.In this study sample, over 66 % of patients were of black race, and almost 50 % experienced depression during the study period. A significantly higher portion of non-black patients were able to achieve optimal adherence (≥90 %) compared to black patients (38.6 % vs. 28.7 %, p 0.001). In fact, black patients had nearly 30 % decreased odds of being optimally adherent to antiretroviral drugs compared to non-black patients (OR = 0.70, 95 % CI: 0.63-0.78), and was unchanged regard less of whether the patient had depression. Antidepressant treatment nearly doubled the odds of optimal ART adherence among patients with depression (OR = 1.92, 95 % CI: 1.12-3.29).Black race was significantly associated with worse ART adherence, which was not modified by the presence of depression. Under-diagnosis and under-treatment of depression may hinder ART adherence among HIV-infected patients of all races.

Purpose As members of the future pharmacy workforce, newly practicing pharmacists will be directly involved in key changes in practice. The purpose of this study is to (a) determine the desirability of core health-system pharmacist responsibilities among new practitioners, (b) assess new practitioner satisfaction about the current state of practice, and (c) evaluate the willingness of newly practicing pharmacists to change practice. Results Results from this study indicate new practitioners have a greater preference for clinical, direct patient care activities compared with traditional operational functions. There is a disparity between new practitioner preferences and current practice opportunities. Respondents were satisfied with pharmacy practice at their institution (86%), yet less satisfied (56%) with the current state of health-system pharmacy practice in the United States. Satisfaction with practice at respondents' institutions was significantly associated with region, with respondents from the Great Lakes region significantly more satisfied than respondents from the Eastern, Western, and Southeastern regions ( P = .02). Respondents with postgraduate training had 2.3 times higher odds of being satisfied than those without postgraduate training ( P = .02). Survey respondents indicated a general willingness to accept change. When these results were compared to director of pharmacy responses from a 2008 survey, differences were identified between new practitioner preferences and practice availability. Conclusion New practitioners tend to prefer clinical functions with greater direct patient contact and are satisfied with pharmacy practice. New practitioners are willing to accept change and, therefore, will be integral to developing and implementing practice models. These findings will help the profession move forward in developing practice models that address new practitioner skills, attitudes, and opinions, successfully building the future vision of pharmacy practice.

A residency requirement has been proposed as a prerequisite for all pharmacists providing direct patient care. This editorial explores the basis for requiring a residency, direct patient care offered by pharmacists with or without a residency, needs to increase interprofessional team–based health care, importance of distinguishing levels of pharmacy practice, role of pharmacy technicians, availability of residency positions, and future of pharmacy residencies. All PharmD graduates should be able to provide a certain level of direct patient care, including medication therapy management services, without completing a residency, and residency programs should be offered for complex levels of direct patient care in all practice settings.

Summary What is known and Objective: The complexity and diversity of irritable bowel syndrome’s (IBS) presentation make treatment difficult. Although there are reviews and guidelines for treating IBS, they focus on the efficacy of medications for IBS symptoms using high-priority endpoints, leaving those of lower priority largely unreported. Therefore, the aim of this review is to provide a comprehensive evidence-based review of the efficacy of medications to treat IBS symptoms, reported by IBS subtype, including secondary symptom endpoints that are often underreported. Methods: A review of PubMed for articles published through December 2009 using the keywords: ‘irritable bowel syndrome’, ‘therapeutics’, ‘antidiarrhoeals’, ‘laxatives’, ‘loperamide’, ‘dietary fibre’, ‘psyllium’, ‘calcium polycarbophil’, ‘bulking agents’, ‘lubiprostone’, ‘antidepressant agents, tricyclics’ and its representative entities, ‘serotonin reuptake inhibitors’ and its representative entities, ‘dicyclomine’, hyoscyamine’, ‘peppermint oil’, ‘parasympatholytics’ and its representative entities, ‘rifaximin’, ‘pregabalin’, ‘gabapentin’, ‘clonidine’, ‘octreotide’, ‘atropine’ and ‘probiotics’ is provided. Placebo-controlled trials were evaluated for the strength of evidence supporting the efficacy of each medication for explicit IBS symptoms. The efficacy of each medication for the symptoms of abdominal pain, bloating, stool form, mucus, urgency, feeling of incomplete evacuation, flatulence, frequency, or borborgymi and overall symptoms are reported by IBS subtype. Results and Discussion: The literature search identified 58 placebo-controlled trials of the efficacy of medications for treating IBS symptoms, which were critically evaluated and reported. The available studies suggest improvement in various IBS symptoms with loperamide, fibre supplements, lubiprostone, tricyclic antidepressants (TCAs), selective serotonin receptor inhibitors (SSRIs), antispasmotics, rifaximin, pregabalin, gabapentin, clonidine, octreotide and probiotic treatments. What is new and Conclusion: This review is the first to compile the available evidence on the efficacy of the various pharmacological treatments for IBS on the basis of IBS subtype and specific symptoms. This evidence is limited and more well-designed studies are required to better inform therapeutic decision-making in the management of this difficult syndrome.

The purpose of this retrospective cohort study was to examine the impact of the type of health plan (capitated vs. fee for service [FFS]) on outcomes (medication adherence and health care service utilization) in type 2 diabetes Medicaid enrollees. Subjects were 8581 Medicaid enrollees with type 2 diabetes who newly started oral pharmacotherapy and were followed for 6 months before and 12 months after the index antidiabetic medication to collect data on medication adherence and health care service utilization. Multiple log-linear regression analysis was used to predict medication adherence while negative binomial regressions were used to examine health care service utilization. Medication adherence was found to be significantly lower for patients in capitated plans (5%, P < 0.05). Moreover, patients in capitated plans were associated with 14% more hospitalizations and 16% increased odds of emergency room visits, but 27% fewer outpatient visits compared to those in FFS plans (all P < 0.05). Although Medicaid programs use capitated managed care plans primarily as a cost-containment strategy, these plans may not be cost-effective for the long-term management of chronic conditions such as diabetes.

I am honored and grateful to be chosen as the 2009 Richard Helms Award recipient. This recognition has a special meaning since it carries the name of an individual who has contributed so much to pediatric pharmacy through innovative practice, education and research, especially in the area of parenteral nutrition, as well as mentoring numerous outstanding students, residents, fellows and colleagues over the years. This award is also particularly meaningful because I am able to share this recognition with many of my former fellows and students who are here today. Furthermore, this recognition is an honor because it is coming from the Pediatric Pharmacy Advocacy Group (PPAG) and its members who are dedicated to the improvement of the lives of pediatric patients. It has been a privilege for me to be actively involved in pediatric pharmacy practice, teaching, research and service activities over the past 30 years. I discovered the rewards of patient care, teaching and research during my education and training, and thus pursued an academic position which could combine all of these functions. In 1977, Ohio State University recruited the first group of fulltime clinical faculty and Children’s

BackgroundInadequacies in mental health care coverage remain an enormous problem in the United States. Barriers include scarcity of accessible mental health care professionals. Use of a mental health mobile app incorporating social cognitive theory may help improve confidence in coping skills and improve anxiety and depression. Sinasprite is a mobile app that recruited users via self-referral and clinician referral. Users completed questionnaires to obtain demographic and medical histories. At baseline and 6-week follow-up, users completed the Patient Health Questionnaire 8 (PHQ-8), General Anxiety Disorder 7-Item (GAD-7), and the Coping Self-Efficacy Scale (CSE). It is unknown how self-directed use of a mobile app improves confidence in coping skills and its effects on self-reported depression and anxiety. ObjectiveThe objective of this study was to evaluate the Sinasprite database to assess self-directed engagement and how use of this mobile app impacted self-reported confidence in coping skills and severity of depression and anxiety. MethodsThis retrospective longitudinal study involved users recruited via clinician referral and self-referral through social media and news media. Questionnaires were used to record demographic, medical, and prescription medication histories. Mental health status was assessed via PHQ-8, GAD-7, and CSE questionnaires. A deidentified dataset reporting mobile app use data was provided to investigators. Individuals with verifiable usage data and at least one completed questionnaire at 6 weeks of use were included. Mann–Whitney U and Kruskal-Wallis tests were used to assess whether demographic data and psychotherapy were related to baseline questionnaire scores and usage. A Spearman rho (ρ) test was used to assess the relationship between improvement in the CSE and GAD-7 and PHQ-8 questionnaires. Changes in mental health status were assessed using Wilcoxon signed-rank test. A mixed-effects repeated-measures linear regression model assessed the main effects of time, concomitant counseling, and psychotropic prescription medication use on mental health status. ResultsThirty-four users were eligible for inclusion in the analysis. Users were predominantly female, white, married, and college educated. At baseline, 35% (12/34) of respondents reported the use of individual/group counseling, and 38% (19/34) reported using prescription medications for their mental health. The median user completed 5.7 (interquartile range 2.7-14.1) trackable activities per week. Statistically significant improvements using a Wilcoxon signed-ranked test were observed in the PHQ-8 (P

Allergic rhinitis (AR) affects a large percentage of paediatric patients. With the wide array of available agents, it has become a challenge to choose the most appropriate treatment for patients. Second-generation antihistamines have become increasingly popular because of their comparable efficacy and lower incidence of adverse effects relative to their first-generation counterparts, and the safety and efficacy of this drug class are established in the adult population. Data on the use of the second-generation antihistamines oral cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, and the leukotriene receptor antagonist montelukast as well as azelastine nasal spray in infants and children are evaluated in this review. These agents have been found to be relatively safe and effective in reducing symptoms associated with AR in children. Alternative dosage forms such as liquids or oral disintegrating tablets are available for most agents, allowing ease of administration to most young children and infants; however, limited data are available regarding use in infants for most agents, except desloratadine, cetirizine and montelukast. Unlike their predecessors, such as astemizole and terfenadine, the newer second-generation antihistamines and montelukast appear to be well tolerated, with absence of cardiotoxicities. Comparative studies are limited to cetirizine versus ketotifen, oxatomide and/or montelukast. Although second-generation antihistamines and montelukast are deemed relatively safe for use in paediatric patients, there are some noteworthy drug interactions to consider when selecting an agent. Given the wide variety of available agents for treatment of AR in paediatric patients, the safety and efficacy data available for specific age groups, type of AR, dosage form availability and cost should be considered when selecting treatment for AR in infants and children.

Dexmedetomidine is being used off-label as an adjunctive agent for sedation and analgesia in pediatric patients in the critical care unit and for sedation during non-invasive procedures in radiology. It also has a potential role as part of anesthesia care to prevent emergence delirium and postanesthesia shivering. Dexmedetomidine is currently approved by the US FDA for sedation only in adults undergoing mechanical ventilation for24 hours. Pediatric experiences in the literature are in the form of small studies and case reports. In patients sedated for mechanical ventilation and/or opioid/benzodiazepine withdrawal, the loading dose ranged from 0.5 to 1 microg/kg and was usually administered over 10 minutes, although not all patients received loading doses. This patient group also received a continuous infusion at rates ranging from 0.2 to 2 microg/kg/h, with higher rates used in burn patients and those with withdrawal followingor =24 hours of opioid/benzodiazepine infusion. The dexmedetomidine dosage used for anesthesia and sedation during non-invasive procedures, such as radiologic studies, ranged from a loading dose of 1-2 microg/kg followed by a continuous infusion at 0.5-1.14 microg/kg/h, with most patients spontaneously breathing. For invasive procedures, such as awake craniotomy or cardiac catheterization, dosage ranged from a loading dose of 0.15 to 1 microg/kg followed by a continuous infusion at 0.1-2 microg/kg/h. Adverse hemodynamic and respiratory effects were minimal; the agent was well tolerated in most patients. The efficacy of dexmedetomidine varied depending on the clinical situation: efficacy was greatest during non-invasive procedures, such as magnetic resonance imaging (MRI), and lowest during invasive procedures, such as cardiac catheterization. Dexmedetomidine may be useful in pediatric patients for sedation in a variety of clinical situations. The literature suggests potential use of dexmedetomidine as an adjunctive agent to other sedatives during mechanical ventilation and opioid/benzodiazepine withdrawal. In addition, because of its minimal respiratory effects, dexmedetomidine has also been used as a single agent for sedation during non-invasive procedures such as MRI. However, additional studies in pediatric patients are warranted to further evaluate its safety and efficacy in all age ranges.

To report a case of serotonin syndrome associated with a single, 50 mg dose of sertraline in a child and discuss the findings in context with previous relevant literature involving other selective serotonin reuptake inhibitors used in children.A nine-year old male with chronic behavioral problems was prescribed oral sertraline 50 mg daily. After the first dose, the patient presented with abdominal pain, seizure-like activity, and change in mental status. He was admitted to a tertiary-care pediatric hospital and was treated for serotonin syndrome. Laboratory findings of elevated creatine kinase and serum creatinine were consistent with rhabdomyolysis as result of continued hypertonicity. Sertraline was discontinued and treatment with lorazepam and cyproheptadine was initiated. Clinical status, creatine kinase, and serum creatinine improved over 5 days of hospitalization. The Adverse Drug Reaction Probability Scale by Naranjo et al was applied to assess causality. The scale indicated the association of a single dose of sertraline and serotonin syndrome as "probable."To our knowledge this is the first reported case of serotonin syndrome associated with a single dose of sertraline in a child using a validated causality scale. The sertraline 50 mg dose given to the child was higher than usual recommended initial doses (25 mg). This potential adverse reaction should be considered when selecting antidepressant therapy for children.

OBJECTIVES This study examined trends in physician-prescribing of medications for children with sleep difficulties in outpatient settings in the US. Additionally, we explored the incidence of physician prescribing patterns of medications with high abuse potential for children with sleep difficulties. METHODS A cross-sectional study was conducted on patients aged < or =17 years with sleep difficulties from 1993-2004 using data from the National Ambulatory Medical Care Survey (NAMCS). Office visits were considered related to sleep difficulties if relevant ICD-9 codes were recorded and if sleep difficulties were reported as the reason for the visits. Medications were retrieved using the NAMCS drug codes, and all analyses were weighted to determine national estimates. RESULTS During 1993 to 2004, approximately 18.6 million visits occurred for sleep related difficulty in children. The highest percentage of visits were by school-aged children (6 to 12 years). Pediatricians saw 35% of patients, psychiatrists saw 24%, and general/family practice physicians saw 13% of the patients. Eighty-one percent of visits among children with sleep difficulties resulted in a prescription for a medication. Many of these medications prescribed lack FDA approved labeling to assure their effectiveness and safety in this population. CONCLUSION The findings of this study suggest that physicians frequently prescribed medications for sleep difficulties in children in US outpatient settings. Of particular concern is prescribing of many unapproved medications for this population.

BACKGROUND Diphenhydramine is frequently used in children, but the consequences of single unintended dose exposures in young children are unknown. METHODS We evaluated 2000-2001 American Association of Poison Control Centers-Toxic Exposure Surveillance data on children exposed to diphenhydramine ingestions. RESULTS Nine hundred twenty-six cases met the inclusion criteria; 49.1% were men, mean age was 29.7 +/- 13.0 months (range, 1-72 months). Approximately 85% of unintentional exposures occurred in 1- to 3-year-old children. The mean dose ingested was 6.4 +/- 6.1 mg/kg (median, 4.6 mg/kg). Thirty-two percent of patients were symptomatic: minor (29.4%), moderate (2.9%), and severe (0.11%). There was no relationship between dose and symptom severity. Diphenhydramine dose ingestion of 7.5 mg/kg or greater was not a predictor of severity (P = 0.47) CONCLUSIONS The relationship between ingested dose and severity of symptoms was insignificant.

Study Objectives:New pharmacotherapeutic treatment options are available to treat patients with 1 or more insomnia symptoms. However, these new Pharmaceuticals are subject to a variety of managed-c...

To report a case of hepatitis associated with atomoxetine hydrochloride use and to describe the previously-unpublished severe cases of this syndrome.An eight-year-old female with attention deficient hyperactive disorder (ADHD) was treated with atomoxetine hydrochloride. She complained of increased abdominal pain and occasional emesis; her transaminases and bilirubin were markedly elevated. She was admitted to a tertiary-care pediatric hospital and treated for drug-induced hepatitis. Atomoxetine was discontinued and supportive care was instituted. A liver biopsy showed hepatitis with moderate piecemeal necrosis. Clinical status and liver function tests improved over 13 days of hospitalization.To our knowledge this is the first published severe case of atomoxetine-induced hepatitis. The International Organization of Medical Science Diagnostic Scale and the Adverse Drug Reaction Probability Scale by Naranjo et al. were applied to assess causality. Both scales indicated the association of atomoxetine and hepatitis as "probable;" a positive rechallenge would have made this association "definitive." This potential serious adverse reaction should be considered in children receiving atomoxetine therapy.

Despite national recommendations for treatment of constipation, prescribing patterns for treatment are inconsistent, and health care utilization has increased.To identify patterns in pharmacologic and nonpharmacologic treatment of constipation and associations between treatment and other variables across age groups.This was a retrospective cross-sectional study that used the National Ambulatory Medical Care Survey (NAMCS) to compare prescribing from 2000 to 2004 and from 2005 to 2009. Treatment patterns for constipation, irritable bowel syndrome-related constipation (IBS-C), and opioid-induced constipation were considered.From 2000 to 2009, there were 89.6 million office visits related to constipation: 63.4 million for constipation alone, 28.2 million for IBS-C alone, and 3.7 million for opioid-induced constipation. For constipation, there was an overall decrease in the prescription of combination therapy (17% vs. 11%, P less than 0.05); an increase in the prescription of medication monotherapy (21% vs. 29%, P less than 0.05); decreases in the use of lubricants (9% vs. 2%, P less than 0.05) and saline (7% vs. 1%, P less than 0.001) among patients aged less than 18 years; a decrease in combination therapy (31% vs. 17%, P less than 0.05); and age group differences in the prescription of specific medications. For IBS-C and opioid-induced constipation, there were no changes in major treatment category or specific medication. Age, gender, race, ethnicity, payer source, physician specialty, and region were all found to be associated with treatment choice.Health care utilization for constipation increased, and prescribing patterns shifted significantly from 2000 to 2009 for constipation and IBS-C. Patterns in treatment were significantly influenced by many factors, including age, gender, and race. Changes in treatment categories over time included a decrease in combination therapy for patients aged less than 18 years and an increase in medication monotherapy for all ages, which are in contrast to national recommendations.

A population pharmacokinetic study was conducted in 74 hypertensive children (mean age 10.4 +/- 4.4 years [mean +/- SD]) receiving amlodipine (mean dose 0.17 +/- 0.13 mg/kg/d) chronically. Multiple blood samples were obtained from each subject to characterize amlodipine pharmacokinetics. Plasma amlodipine concentrations were determined by liquid chromatography/mass spectrophotometry with multiple-reaction monitoring detection. Population pharmacokinetic analysis was performed using NONMEM. Amlodipine concentrations were similar in subjects dosed either once or twice daily. Amlodipine pharmacokinetics were well described by a 1-compartment model with first-order absorption and elimination. For a subject at the population median weight (45 kg), predicted apparent clearances (CL/F) were 23.7 L/h for males and 17.6 L/h for females, and the apparent volume of distribution (V/F) was 25.1 L/kg. Dosing frequency did not appear to affect amlodipine concentrations in children. Weight-adjusted CL/F and V/F of amlodipine in younger children were significantly greater than in older children, suggesting a need for higher doses when treating young children with amlodipine.

Purpose. The stability of sildenafil citrate 2.5 mg/mL in two extemporaneously prepared oral suspensions stored at 4 and 25 °C was studied. Methods. Thirty 25-mg tablets of sildenafil citrate were ground to powder, and the powder was combined with a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of methylcellulose 1% and Simple Syrup, NF, to produce two 2.5-mg/mL suspensions. Five plastic bottles of each suspension were stored in amber plastic prescription bottles at 4 or 25 °C. Samples were collected on days 0, 7, 14, 28, 42, 56, 70, and 91 for analysis of sildenafil content by high-performance liquid chromatography; pH was also measured. Samples were visually observed against black and white backgrounds. Results. The mean concentration of sildenafil citrate exceeded 98% of the initial concentration in all samples at both temperatures throughout the 91-day study period. No changes in pH, odor, or physical appearance were observed. Conclusion. Sildenafil citrate 2.5 mg/mL in two extemporaneously compounded oral suspensions was stable for 91 days in plastic prescription bottles at 4 and 25 °C.

Costs and patients' adherence related to biologics are important factors to consider while making informed decisions regarding therapy with biologics in psoriasis management.To examine predictors of adherence related to biologics, total health care costs, and service utilization among psoriasis patients.This was a longitudinal cohort study of psoriasis patients (65 years old) enrolled in North Carolina Medicaid who were prescribed biologics (alefacept, efalizumab, and etanercept). Patients' medication adherence, health care costs, and service utilization patterns in the pre- and post-biologics period were examined.Adherence to biologics was significantly higher compared with the other psoriasis medications (0.66 vs 0.39; p0.001). Prescription costs were significantly higher in the post-biologics period (3796.77 US dollars vs 11,706.32 US dollars; p0.001). However, total health care costs in the post-biologics period did not differ significantly from the pre-biologics period (14,662.22 US dollars vs 16,156.10 US dollars; p0.05). Patients' adherence and health care costs did not differ significantly across the biologics. After controlling for other variables, patients had a significantly lower number of hospitalizations in the post-biologics period (p0.001).Although costs associated with prescriptions for biologics were higher, total health care costs did not differ significantly in the post-biologics period. Biologics had a better adherence rate compared with other psoriasis medications.

Atomoxetine hydrochloride, a selective norepinephrine reuptake inhibitor was FDA approved for patients with attention-deficit/hyperactivity disorder. Little is known about adverse drug reactions of atomoxetine following an overdose among children. The objective of our study was to evaluate the type of atomoxetine adverse drug reactions in relation to dose.We evaluated children exposed to atomoxetine reported to a poison center from January-December 2004.Sixty-four cases met all inclusion criteria. Twenty-one patients had an adverse drug reaction (15 at dosage range 0.52-6.25 mg/kg): agitation, headache, erythema, rash, elevated blood pressure and heart rate, nausea, emesis, and lethargy. In 51 patients, weights were known: group 1 (n = 43) received higher than maximum recommended doses1.4 mg/kg and group 2 (n = 8) receivedor = 1.4 mg/kg. There were no differences in adverse drug reactions in group 1 versus 2. Eight patients were admitted to a healthcare facility and all were discharged without any sequelae. Hypertension occurred in 3 of 9 patients for whom blood pressure was recorded.At the doses reported, adverse drug reactions did not correlate with atomoxetine dose. Hypertension may occur in some patients following atomoxetine overdose.

Purpose. The development, implementation, and outcomes assessment of an innovative pharmacist-managed ambulatory care and community pharmacy practice clinic are described. Summary. The Clinical Partners Program at The Ohio State University (OSU) provides an active learning environment for students and residents, offers a patient-focused practice model based on pharmaceutical care principles, and serves as an arena for applied research in pharmacy practice. The program offers multiple services, including anticoagulation management, diabetes self-management, cholesterol management, hepatitis C education, herbal product and dietary supplement consultations, medication management, smoking cessation, and wellness. The practice is currently staffed by two faculty members from the college of pharmacy, with a 0.8 full-time-equivalent (FTE) pharmacist and a 0.65 FTE community pharmacy resident. It has served as a training site for 17 pharmacy residents, 28 bachelor of science (B.S.) in pharmacy students, 30 post-B.S. doctor of pharmacy (Pharm.D.) students, and 132 entry-level Pharm.D. students at various levels of training. The most successful methods of reimbursement for programs have been contracted services with OSU Managed Health Care Systems, Inc., which serves OSU faculty and staff and fee-for-service billing, charged directly to non-OSU patients. Numerous studies have shown that Clinical Partners has consistently demonstrated improved therapeutic outcomes over those achieved in traditional practice. Faculty are exploring outreach services, including the development of advanced practice community sites for the college, establishing patient care services within physician offices, and providing disease management services for self-insured employers. Conclusion. The Clinical Partners Program has improved patient care and provided education and training opportunities for pharmacy students and residents.

Objective To evaluate medication adherence, medication safety, health care utilization, and health outcomes among patients enrolled in a subsidized prescription program. Design Cross-sectional study. Setting Conducted as part of the Prescription Access program, a subsidized prescription program serving indigent patients residing in Franklin County, Ohio. Patients Patients qualifying for enrollment in the program were uninsured and had a household income of 200% or less of federal poverty level. Approximately 5% of the 2,500 patients (mean age, 70.6 years) enrolled in the program were systematically selected from a computer-generated patient enrollment report. Intervention Telephone interviews conducted by a pharmacist or advanced student pharmacist between January and September 2002. Main Outcome Measures: Patterns of medication use and safety, level of health care utilization, and health outcomes. Results A total of 104 patients reported taking a mean (± SD) of 6.7 ± 3.8 medications. A total of 72 (69%) patients reported taking their medications correctly, and 90 (87%) reported finishing their medication course as prescribed. Medication refills were obtained by 75 (72%) patients, but of these patients, only 55 (73%) indicated that they obtained their refills on time. Adverse effects occurred in 25 (24%) patients, and 2 patients reported an allergic reaction. A total of 51 (49%) patients made unscheduled visits to their primary care physician, another health care facility, an emergency department, and/or were admitted to a hospital. Unscheduled visits occurred more often among nonadherent patients (59%) than adherent patients (44%), but not significantly so. In addition, 82 (79%) patients reported an improvement in health-related quality of life (QOL); 90 (87%) had a means of transportation to obtain medications; and 93 (89%) indicated that they would have to skip medications or give up necessities, if they were not enrolled in a subsidized prescription program. Conclusion An improvement in self-reported QOL and a high rate of medication adherence demonstrate support for the benefits of this and similar subsidized prescription drug programs. A high rate of additional health care utilization, especially among nonadherent patients, indicates an area for further analysis, program revisions, and/or patient education.

The literature concerning the efficacy and safety of ketamine for conscious sedation during procedures in pediatric emergency departments was reviewed. Data were obtained from the Guidelines for Monitoring and Management of Pediatric Patients During and After Sedation for Diagnostic and Therapeutic Procedures developed by the American Academy of Pediatrics Committee on Drugs, and from a MEDLINE search (January 1966-July 2004). Search terms were conscious sedation, ketamine, and emergency department; articles relevant to pediatric age group were selected. Clinical end points were efficacy and adverse effects associated with ketamine. Ketamine was effective for conscious sedation in 89-100% of patients in various studies using intravenous, intramuscular, or oral routes of administration. The efficacy of ketamine was similar to or greater than that of other drugs, such as midazolam and the combination of meperidine, promethazine, and chlorpromazine. The main adverse effects of ketamine were emesis, recovery agitation, and emergence phenomena. Ketamine appears to be an effective and well-tolerated agent for conscious sedation in pediatric patients. Overall physician and parent satisfaction with the administration of this agent for conscious sedation was high.

Background Patient weight and family history are significant risk factors for the development of hypertension in children. Multiple genetic factors have been identified in primary (essential) hypertension in adults; however, the delineation of genetic factors in the separate populations of children with primary or secondary hypertension are not well understood. Heritability is the proportion of observed variation in a particular trait that can be attributed to an inherited genetic factor in contrast to environmental factors. In the consideration of hypertension, heritability can be assessed in terms of an underlying continuous gradient of the liability for developing hypertension. With this assumption it is possible to compute heritability using hypertension incidence among relatives and described by Falconer. Heritability values range from 0 (no genetic contribution) to 1 (complete genetic contribution). The aim of this study was to determine the genetic contribution to primary and secondary hypertension in a pediatric population through heritability analysis. Methods This was a retrospective case-control analysis of medical records of children ( n = 276) followed in the Pediatric Nephrology Clinic over a 4-year period from 1999 to 2002. There were 192 children and adolescents with primary hypertension (124 male, 68 female, age 0 to 21 years) and 84 children and adolescents with secondary hypertension (46 male, 38 female, age 0 to 21 years). Each hypertensive group served as the control for the other. Estimates of heritability were made using Falconer’s method 2. 11 The model assumes independence between the environment and genetic factors and that the joint distribution of liabilities between parent and child are normally distributed. Problems can arise from computing heritability due to dominance within loci, correlations between nongenetic familial effects, or the presence of a major gene. Results Of the children and adolescents with primary hypertension, 49% had parents with primary hypertension; and of the children and adolescents with secondary hypertension, 24% had parents with primary hypertension. Of the children and adolescents with primary hypertension, 10% had parents with secondary hypertension; and of the children and adolescents with secondary hypertension, 46% had parents with secondary hypertension. The estimated heritability for primary hypertension was 0.84 (SE = 0.21). The estimated heritability for secondary hypertension was 1.14 (SE = 0.21). As the value was >1, this indicates that the fit of the liability model is poor and that a few genes, or even one major gene, were significantly involved in the causes of secondary hypertension in the children and adolescents studied. Conclusions The results suggest that primary and secondary hypertension do not share the same type of genetic profile. Primary hypertension in children and adolescents is likely due to a large number of additive contributions of genes, although a highly correlated environmental component can not be excluded. The continuous liability model is inappropriate for secondary hypertension because the estimate was substantially greater than one. This study supports the model that secondary hypertension in children and adolescents may be related to just a few genes.

OBJECTIVE: To review the safety and efficacy of selective serotonin-reuptake inhibitors (SSRIs) for the treatment of depression in adults with HIV. DATA SOURCES: We searched Pre-MEDLINE and MEDLINE (1966-May 2004) using terms including generic names of antidepressants and antiretrovirals, depression, HIV, and acquired immunodeficiency syndrome. All English-language articles were included in this review. DATA SYNTHESIS: SSRIs may be effective and better tolerated than tricyclic antidepressants in HIV-positive adults. SSRIs did not appear to affect CD4+ cell counts. CONCLUSIONS: Controlled trials comparing SSRIs are lacking; thus, it is difficult to determine whether one SSRI is more efficacious than another. It appears that most SSRIs may be used in HIV-positive adults. If drug-drug interactions are a concern, sertraline, citalopram, and possibly escitalopram may be considered.

Objectives Based on the content of the article, you will be able to: 1. Identify the two drugs in EMLA and the youngest pediatric age for its approved use. 2. List the procedures for which EMLA has been used to control pain in infants. 3. Describe the efficacy of EMLA vs. other agents in treating pain. 4. Discuss the potential adverse effects of EMLA in infants. See page 48 for instructions.

Summary Purpose: The pharmacokinetics of gabapentin in paediatric patients with uncontrolled seizures was studied. Methods: Thirteen paediatric patients (mean age: 9·4 years) with uncontrolled partial seizures were included. Patients received gabapentin orally until doses were individualized to 9·6–39·8 mg/kg/day. Blood samples were obtained just prior to the dose and over 8 h after gabapentin was administered in the fasting state. The plasma concentration of gabapentin was measured by a high-performance liquid chromatography assay. Pharmacokinetic parameters for gabapentin were determined by non-compartment methods using multivariate regression analysis. Results: Data from nine patients were suitable for pharmacokinetic analysis. The Cmax from 0·9 to 5·8 μg/mL (mean: 2·6 ± 1·7 μg/mL) and Tmax from 0·5 to 2·0 h (mean: 1·6 ± 1·0 h). The apparent clearance (Cl/F) ranged from 0·12 to 1·12 L/h/kg (mean: 0·50 ± 0·29 L/h/kg), and the elimination half-life from 3·2 to 12·2 h (mean: 5·5 ± 0·8 h). Five patients experienced moderate (n = 4) to severe (n = 1) aggressive behaviour and another gained weight on gabapentin. Conclusions: Our data suggests that gabapentin pharmacokinetics can vary substantially among paediatric patients. Gabapentin was well tolerated in patients with uncontrolled partial seizures up to 6 months of therapy.

There is ample evidence that the same pathophysiological processes that affect cardiovascular function in adults with end-stage renal disease (ESRD) also operate in children with ESRD. In adults undergoing hemodialysis (HD), a good correlation has been established between left ventricular mass (LVM) and aortic distensibility (AD) as markers of cardiovascular disease progression; however, this correlation has not been established in children. Therefore, in this retrospective study we investigated some aspects of cardiovascular damage (i.e., LVM, LVMI, and AD) in children with ESRD undergoing HD (n=9) or peritoneal dialysis (PD, n=9), and analyzed the relationship between AD, LVM, LVMI, pre-dialysis, post-dialysis blood pressure (BP), and demographic factors in children and adolescents with ESRD. Both LVM and AD were significantly greater in the dialysis population than in a control population derived from our institutional files (P=0.015, P=0.001). LVM and LVMI in children undergoing HD (92.9+/-83.7 g, 80.1+/-31.1 g/cm) were not statistically different from the values in children on PD (130.0+/-89.2 g, 89.6+/-35.9 g/cm), (P=0.3, P=0.5). AD in children on HD (2.2+/-0.55 cm2* dynes(-1*(10-6)) was significantly lower than in children on PD (2.7+/-0.54 cm2* dynes(-1*(10-6)), (P=0.01). The findings in this study confirm earlier studies that demonstrated that LVMI is greater in children on dialysis. This study also demonstrates that abnormal vascular stiffness, as defined by AD, is present in these children. The degree of vascular stiffness in children receiving HD is greater than in children receiving PD. However, further study is needed to address how control of BP, uremia, and other factors may affect these abnormalities in children with ESRD.

OBJECTIVE: To review the indication, pharmacology, pharmacokinetics, efficacy, and adverse effects of recombinant human growth hormone in children with idiopathic short stature (ISS). DATA SOURCES: A MEDLINE search (1966–December 2003) was performed using the key words human growth hormone, somatropin, Humatrope, normal children, somatrem, and idiopathic short stature. Food and Drug Administration Advisory Committee Meeting minutes were also reviewed. STUDY SELECTION AND DATA EXTRACTION: The data presented in this review were obtained from published literature, abstracts presented at scientific meetings, and information on file with the manufacturer. Additional articles from these sources were also identified. Current issues of pediatric and endocrinology journals were reviewed for the most recent articles. Articles only addressing the use of growth hormone in normal, healthy children were used. DATA SYNTHESIS: Somatropin is indicated for use in children with ISS. Studies have shown modest benefit to final height achieved and, at the doses used for ISS, there have been no adverse effects associated with somatropin. Many questions still exist, however, concerning the most appropriate age to initiate treatment and duration of treatment. There are also many ethical concerns surrounding patient selection criteria and potential for increased off-label use. CONCLUSIONS: Growth hormone has been found to have modest efficacy in improving final height in children with ISS. The specific patient population likely to achieve maximal benefit, optimal dosage regimens, and the long-term adverse effects of extended duration of therapy are unknown.

BACKGROUND Many herbal supplements used for weight loss contain stimulants. The poison control center has noted an increase in reports of adverse events with intentional and unintentional ingestion of herbal weight-loss supplements. OBJECTIVE To identify characteristics of the callers (eg, demographic properties, underlying type of ingestion) and, from this information, determine populations at increased risk for adverse events secondary to intentional and unintentional herbal weight-loss supplement ingestion. METHODS Demographic information such as patient weight, age, gender, and medical history was recorded from ingestions reported to the Central Ohio Poison Control Center (COPC) in 2000. Ingredients, concurrent medications, ingestion and treatment site, clinical presentation, and therapies received were documented. Type of ingestion, acuity, clinical presentation, and treatment site were used to identify patients at increased risk of adverse events secondary to herbal supplement ingestion. RESULTS Eighty calls were recorded in 2000 (49 females involved). Underlying reasons for ingestion differed between males and females (p = 0.025). Twenty-five percent of the intentional ingestions and 51% of the unintentional ingestions occurred in males. Reported symptoms differed with the underlying reason for ingestion (p ≤ 0.001) and were more common in intentional ingestions (80%). Symptoms were reported more often with unknown or higher-than-recommended doses (78%); however, 70% (n = 10) of subjects ingesting the recommended dose reported at least one symptom (p = 0.15). CONCLUSIONS Intentional and unintentional ingestions of herbal supplements for weight loss vary with age and gender. The significant presence of symptoms in nonabusers requires more study to assess overall safety and potential toxicity of agents such as Stacker 2. Patients who abuse or misuse herbal weight-loss supplements are generally women, who may seek medical treatment more often.

OBJECTIVE To evaluate the efficacy and safety of pharmacologic therapy in the treatment of HIV-associated lipodystrophy, with a focus on the treatment of fat redistribution. Drug therapies that have been shown to be beneficial in other forms of lipodystrophy and are currently being evaluated in HIV-associated lipodystrophy are also discussed. DATA SOURCES A MEDLINE search was conducted from 1996 to February 2003. Bibliographies of all articles were reviewed and pertinent articles were included. Abstracts from major meetings in 2002 and 2003 were also reviewed. STUDY SELECTION AND DATA EXTRACTION All published studies were included in the review. DATA SYNTHESIS Lipodystrophy has become more prevalent in patients with HIV. Lipodystrophy consists of adipose redistribution and metabolic abnormalities including dyslipidemia and insulin resistance. Treatment of lipodystrophy has been directed at either decreasing the amount of visceral adipose tissue (VAT), dorsocervical adipose tissue (commonly known as buffalo hump) and/or increase subcutaneous adipose tissue (SAT). Recombinant human growth hormone (rhGH) decreases VAT and buffalo hump, although it has been associated with a high frequency of adverse effects. Metformin and the thiazolidinediones have favorable metabolic effects, but were not found to be effective in correcting body compositional changes associated with lipodystrophy. Anabolic steroids and L-carnitine are not effective in the treatment of lipodystrophy. CONCLUSION No drug therapy exists to fully ameliorate or correct the cosmetic changes of HIV-associated lipodystrophy. Clinicians must weigh the benefits and risks of each agent and individualize treatment for each patient.

Attention-deficit/hyperactivity disorder (ADHD) occurs in approximately 3% to 10% of the pediatric population. Most of the drugs typically used to treat ADHD are stimulants, which, because of their addictive properties and potential for abuse, are controlled substances. Although these drugs are the mainstay of treatment for ADHD, nearly one third of patients may not respond to or be able to tolerate them. Atomoxetine hydrochloride, a nonstimulant approved by the US Food and Drug Administration for the treatment of ADHD, may provide an alternative to the use of stimulants.The goal of this review was to describe the chemistry, mechanism of action, pharmacokinetics, drug interactions, and efficacy and safety profiles of atomoxetine in pediatric and adult patients with ADHD, as well as relevant pharmacoeconomic considerations.Relevant publications were identified through a search of the English-language literature indexed on PreMEDLINE and MEDLINE (1966-May 2003) using the search terms atomoxetine, tomoxetine, and LY139603. These terms were also applied to the Google search engine. All articles were reviewed for suitability for inclusion. The manufacturer of atomoxetine provided both published and unpublished data.In the data reviewed, atomoxetine was more efficacious than placebo in patients with ADHD (P0.05 to P0.01). Therapeutic doses ranged from 45 mg or placebo (P0.05). These results add support to the hypothesis that atomoxetine may not cause the increase in dopamine concentrations in the nucleus accumbens that is associated with pleasurable effects and abuse potential.

BACKGROUND:In adults with HIV infection, lipodystrophy syndrome may develop, characterized by peripheral wasting in the extremities, central obesity, hyperlipidemia, and insulin resistance. This syndrome occurs in HIV-positive pediatric patients who take protease inhibitors (PIs). However, the full characteristics of the syndrome in this population is not fully understood.OBJECTIVE:To evaluate the association between the use of PIs and the occurrence of lipodystrophy in HIV-infected children.METHODS:Pediatric patients attending an outpatient HIV clinic between 1994 and 2000 were prospectively enrolled. All patients were between 1 and 17 years of age and had received a PI for at least 1 month. The medical records were reviewed monthly for 3 months before PI therapy was started and then monthly for 36 months. At each evaluation, serum total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, and blood glucose concentrations were recorded, as well as physician-documented physical examination findings including subcutaneous fat in the arms, face, and legs, and abdominal girth. Baseline clinical and laboratory data were compared with follow-up data using a paired t-test.RESULTS:Twenty-one pediatric patients received a PI. Of these, 2 developed lipodystrophy, one at 15 months and one at 18 months after PI therapy was started. Neither child had had lipodystrophy before therapy. Twelve children who were taking ritonavir or nelfinavir, including 1 who developed lipodystrophy, developed abnormally high total cholesterol and triglyceride blood concentrations. All patients receiving indinavir also experienced a substantial increase in their triglyceride concentrations at follow-up evaluations, but no significant increases in total cholesterol occurred. Blood glucose concentrations were not significantly different between baseline and follow-up examinations in our patients.CONCLUSIONS:Lipodystrophy may occur in some HIV-infected children receiving PIs, and dyslipidemias may also develop in some patients taking these drugs.

Although most generic drugs can be substituted for brands cost-effectively, the following case suggests that this may not be possible for some patients on fluoxetine. A 38-year-old woman presented to her family physician in May 1996 complaining of "feeling sad all the time for no logical reason," difficulty sleeping through the night, loss of interest in all things that were previously pleasurable, withdrawal from social interactions, and suicidal ideation. After being diagnosed with major depression, she was prescribed 10 mg of fluoxetine (Prozac) daily. The symptoms began to diminish, but were still present. The dosage was increased to 20 mg daily in November 1996, which relieved her symptoms until April 1997, when she began feeling depressed monthly for approximately 1 week prior to menstruation. After consultation with a psychiatrist, the dose of Prozac was increased to 30 mg daily. The symptoms disappeared until November 1997, when she reported feeling depressed prior to menstruation. The dose was then increased to 40 mg daily. She remained symptom free until October 2001, when the generic form of fluoxetine became available on the U.S. market. The patient's insurance company would no longer pay for Prozac and the patient was switched to an equivalent dose of a generic fluoxetine, 40 mg daily. There was no washout period between taking the brand name and the generic. Sixteen days after the treatment with generic fluoxetine, the patient reported that she was "feeling sad all the time for no logical reason" and having difficulty sleeping through the night. Since her insurance would no longer cover Prozac, her physician recommended switching to Prozac Weekly, which was not available in generic form and, therefore, would be covered by the insurance company. The patient stopped taking generic fluoxetine on November 9, 2001, and began taking Prozac Weekly, 90 mg, twice weekly on Mondays and Thursdays, on November 12, 2001. On a follow-up visit to her physician 2 weeks later, the patient was symptom free. In November 2002, the patient again reported suicidal ideation and sleep disturbances. She was prescribed 10 mg of Elavil at bedtime to help with the sleep disturbances. Two weeks later, the patient reported she was able to sleep through the night, but was still having suicidal ideations. It was realized that the twice weekly dose of Prozac Weekly averaged 25.7 mg/day, which was considerably less than the 40 rag/day dose of Prozac at which the patient had previously remained symptom free for several years. …

Although the literature on infections transmitted via transfused blood focuses on viruses, Yersinia enterocolitica can also cause severe infections in patients receiving transfusions. A 13-year-old patient developed severe sepsis after an autologous blood transfusion contaminated with Y. enterocolitica . The patient was an otherwise healthy female undergoing posterior spinal fusion for congenital scoliosis. Prior to surgery, the patient donated blood for perioperative and postoperative use. A few days before the donation, she had complained of abdominal pain and was experiencing mild diarrhea. The patient received four units of packed red blood cells (PRBCs) during the surgery. Intraoperatively, the patient developed fever up to 103.6 °F, became hypotensive requiring epinephrine and dopamine, and developed metabolic acidosis with serum bicarbonate concentration dropping to 16 mmol/l. The surgery team believed the patient was experiencing malignant hyperthermia and attempted to cool patient during the procedure. Postoperatively, the patient was transferred to the pediatric intensive care unit and treated for severe shock of unknown etiology. The patient further developed disseminated intravascular coagulation. The patient received supportive care and was started on ampicillin/sulbactam on postoperative day (POD) one which was changed to clindamycin, ciprofloxacin and tobramycin on POD two when blood cultures grew gram-negative bacilli. On POD three, cultures were identified as Y. enterocolitica and antibiotics were changed to tobramycin and cefotaxime based on susceptibility data. Sequelae of the shock included adult respiratory distress syndrome requiring intubation and a tracheostomy and multiple intracranial hemorrhagic infarcts with subsequent seizure disorder. Due to severe lower extremity ischemia, she required a bilateral below the knee amputation. The cultures of the snippets from the bags of blood transfused to the patient also grew Y. enterocolitica . This case illustrates the importance of considering transfusion related bacterial infections in patients receiving PRBCs. All patients in shock following any type of transfusion may require aggressive antibiotic therapy, until the diagnosis and etiology are known.

OBJECTIVE To provide a concise review of the presentation and treatment of botulism. DATA SOURCES Searches of MEDLINE (1966–November 2001), tertiary references, and public and government Internet sites were conducted. STUDY SELECTION All articles and additional references from those articles were thoroughly evaluated. DATA SYNTHESIS Clostridium botulinum toxin blocks acetylcholine release in a dose-dependent fashion, resulting in acute symmetric diplopia, dysarthria, dysphonia, dysphagia, and possible neurologic sequelae despite the route of exposure (i.e., food-borne, wound, intestinal, inhalation). Disease secondary to genetically engineered C. botulinum may differ from that of inadvertent exposure. Present treatment is primarily supportive care, respiratory support, rapid decontamination, and antitoxin administration (i.e., trivalent, pentavalent, heptavalent antitoxin). Early initiation of antitoxin limits the extent of paralysis, but does not reverse it. CONCLUSIONS Supportive care and the use of antitoxin have been effective in the treatment of botulism from food-borne, intestinal, and wound exposure. However, the effectiveness of antitoxin in the treatment of inhaled C. botulinum has not been proven.