Utility of serial 12-lead electrocardiograms in children with Marfan syndrome.

OBJECTIVES: The goal of this study was to assess the utility of serial electrocardiograms in routine follow-up of paediatric Marfan patients. METHODS: Children ⩽18 years who met the revised Ghent criteria for Marfan syndrome and received a 12-lead electrocardiogram and echocardiogram within a 3-month period were included. Controls were matched by age, body surface area, gender, race, and ethnicity, and consisted of patients assessed in clinic with a normal cardiac evaluation. Demographic, clinical, echocardiographic, and electrocardiographic data were collected. RESULTS: A total of 45 Marfan patients (10.8 [2.4-17.1] years) and 37 controls (12.8 [1.3-17.1] years) were included. Left atrial enlargement and left ventricular hypertrophy were more frequently present on 12-lead electrocardiogram of Marfan patients compared with controls (12 (27%) versus 0 (0%), p<0.001; and 8 (18%) versus 0 (0%), p=0.008, respectively); however, only two patients with left atrial enlargement on 12-lead electrocardiogram were confirmed to have left atrial enlargement by echocardiogram, and one patient had mild left ventricular hypertrophy by echocardiogram, not appreciated on 12-lead electrocardiogram. QTc interval was longer in Marfan patients compared with controls (427±16 versus 417±22 ms, p=0.03), with four Marfan patients demonstrating borderline prolonged QTc intervals for gender. CONCLUSIONS: While Marfan patients exhibited a higher frequency of left atrial enlargement and left ventricular hypertrophy on 12-lead electrocardiograms compared with controls, these findings were not supported by echocardiography. Serial 12-lead electrocardiograms in routine follow-up of asymptomatic paediatric Marfan patients may be more appropriate for a subgroup of Marfan patients only, specifically those with prolonged QTc interval at their baseline visit.

A Randomized, Controlled Multisite Study of Behavioral Interventions for Veterans with Mental Illness and Antipsychotic Medication-Associated Obesity.

BACKGROUND: Weight gain and other metabolic sequelae of antipsychotic medications can lead to medication non-adherence, reduced quality of life, increased costs, and premature mortality. Of the approaches to address this, behavioral interventions are less invasive, cost less, and can result in sustained long-term benefits. OBJECTIVE: We investigated behavioral weight management interventions for veterans with mental illness across four medical centers within the Veterans Affairs (VA) Healthcare System. DESIGN: We conducted a 12-month, multi-site extension of our previous randomized, controlled study, comparing treatment and control groups. PARTICIPANTS: Veterans (and some non-veteran women) diagnosed with mental illness, overweight (defined as having a BMI over 25), and required ongoing antipsychotic therapy. INTERVENTIONS: One group received "Lifestyle Balance" (LB; modified from the Diabetes Prevention Program) consisting of classes and individual nutritional counseling with a dietitian. A second group received less intensive "Usual Care" (UC) consisting of weight monitoring and provision of self-help. MAIN MEASURES: Participants completed anthropometric and nutrition assessments weekly for 8 weeks, then monthly. Psychiatric, behavioral, and physical assessments were conducted at baseline and months 2, 6, and 12. Metabolic and lipid laboratory tests were performed quarterly. KEY RESULTS: Participants in both groups lost weight. LB participants had a greater decrease in average waist circumference [F(1,1244) = 11.9, p < 0.001] and percent body fat [F(1,1121) = 4.3, p = 0.038]. Controlling for gender yielded statistically significant changes between groups in BMI [F(1,1246) = 13.9, p < 0.001]. Waist circumference and percent body fat decreased for LB women [F(1,1243) = 22.5, p < 0.001 and F(1,1221) = 4.8, p = 0.029, respectively]. The majority of LB participants kept food and activity journals (92%), and average daily calorie intake decreased from 2055 to 1650 during the study (p < 0.001). CONCLUSIONS: Behavioral interventions specifically designed for individuals with mental illness can be effective for weight loss and improve dietary behaviors. "Lifestyle Balance" integrates well with VA healthcare's patient-centered "Whole Health" approach. ClinicalTrials.gov identifier NCT01052714.

Pacemaker upgrade causing new-onset heart failure in a patient with complete congenital atrioventricular block.

For infants with congenital complete atrioventricular block (CCAVB), the choice of pacing modalities is limited. Due to their size and surgical limitations, neonates typically start with an epicardial right ventricular pacing system, then upgrade to right-sided dual-chamber pacing once appropriate size is achieved. These modes are generally well tolerated. However, the reported case involved a patient with CCAVB who paradoxically experienced congestive heart failure after upgrading to a dual-chamber system, a theoretically superior pacing modality. With conversion to biventricular pacing, a relatively new modality for adults with very little pediatric experience to date, the patient's symptoms dramatically improved.

Epidemiology and Economic Burden of Serotonin Syndrome With Concomitant Use of Serotonergic Agents: A Retrospective Study Utilizing Two Large US Claims Databases.

OBJECTIVE: Serotonin syndrome (SS) is an adverse drug reaction occurring among patients receiving serotonergic agents (SAs), and although SAs are commonly prescribed, the epidemiology and economic burden of SS with concomitant SA use have not been comprehensively examined. The objective of this study was to investigate the prevalence, incidence, and economic burden of SS with SA use. METHODS: A retrospective cohort study was conducted using Veterans Health Administration (VHA) records (identification period: October 1, 2008-September 30, 2012) and commercially insured patient records (Intercontinental Marketing Services PharMetrics Plus; identification period: January 1, 2010-December 31, 2013). Cohorts were based on drug classification and exposure: single monoamine oxidase inhibitor (MAOI), MAOIs in combination with SAs, single non-MAOI SA, and multiple non-MAOI SAs (2, 3, 4, ≥ 5). Participants were aged ≥ 18 years with continuous health plan enrollment for 12 months prior to the first SA claim. Outcomes were SS events (ICD-9-CM: 333.99), annual incidence and prevalence, related health care utilization and costs, and SS incidence relative risk. RESULTS: Over 15 million patients were identified and categorized by SA prescription type. SS incidence in both populations decreased: 0.19%-0.07% (VHA) and 0.17%-0.09% (commercially insured). Overall SS prevalence decreased during the study period. Compared to single non-MAOI SA patients, SS incidence relative risk was highest among patients prescribed ≥ 5 non-MAOI SAs. Inpatient stays accounted for 4.35% (VHA) and 0.88% (commercially insured) of all SS events. Of SS-related inpatient stays, median costs were $8,765 (VHA) and $10,792 (commercially insured). CONCLUSIONS: SS incidence and prevalence and SS-related hospitalization risk among patients prescribed SAs were low in both populations. This study provides additional information regarding SS risk associated with SA use.

Lorcaserin in Obese and Overweight Patients Taking Prohibited Serotonergic Agents: A Retrospective Analysis.

PURPOSE: Lorcaserin is a selective serotonin 2C receptor (5-HT2C) agonist approved in the United States for use in chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity. Its pharmacologic activity is limited to 5-HT subtype 2 receptors. The potency of lorcaserin for the 5-HT2C receptor is 14-fold greater than its potency for the 5-HT2A receptor and 61-fold greater than its potency for the 5-HT2B receptor. Although 5-HT receptors have been implicated in serotonin syndrome, the precise pathogenesis is unknown. Given a theoretic risk for this syndrome in patients administered lorcaserin either alone or in combination with certain serotonergic agents (eg, selective serotonin reuptake inhibitors [SSRIs] and serotonin-norepinephrine reuptake inhibitors [SNRIs]), patients taking prohibited serotonergic agents were excluded from the Phase III clinical trials. This retrospective analysis evaluated the tolerability of lorcaserin in patients who took protocol-allowed or proscribed serotonergic agents for varying durations of up to 1 year during the BLOOM, BLOSSOM, and BLOOM-DM studies. METHODS: Patients randomly assigned to receive either lorcaserin 10 mg QD, lorcaserin 10 mg BID, or placebo and who took a spectrum of serotonergic agents were evaluated at week 52 of treatment (814 and 624 patients receiving lorcaserin and placebo, respectively, were found to have taken allowed or prohibited serotonergic agents during these trials). After the use of a proscribed serotonergic agent was discovered, these patients were discontinued from the trial and followed. FINDINGS: None of the patients in the serotonergic agent subpopulation or in the overall safety population met the clinical criteria of serotonin syndrome. The proportions of patients experiencing any adverse event (AE) were balanced in the lorcaserin and placebo groups in the prohibited serotonergic agent subpopulation. The prevalences of the most common AEs were similar between the serotonergic agent subpopulation and the overall safety population. IMPLICATIONS: The concurrent use of lorcaserin and prohibited or allowed serotonergic agents did not appear to have increased the spectrum or intensity of AEs potentially associated with serotonin excess in this limited dataset. However, the sample population was too small to rule out an effect on a rare event such as serotonin syndrome. ClinicalTrials.gov identifiers: NCT00395135, NCT00603902, and NCT00603291.

Aripiprazole partial agonism at 5-HT2C: a comparison of weight gain associated with aripiprazole adjunctive to antidepressants with high versus low serotonergic activities.

OBJECTIVE: 5-HT2C receptor antagonists are thought to contribute toward increased appetite and obesity. Aripiprazole acts as a partial agonist at the 5-HT2C receptor; hence, it is thought to cause little or no significant weight gain when used alone. We theorize that, in the presence of antidepressants with high serotonergic activity, aripiprazole acts as an antagonist at the 5-HT2C receptor, thus increasing the potential for weight gain. Conversely, in environments with low serotonergic activity, aripiprazole acts as an agonist at the 5-HT2C receptor, therefore having less potential for weight gain. METHOD: A retrospective electronic medical record chart review of the Veterans Integrated Service Network 22 Veterans Affairs database was performed comparing patients' weight and body mass index (BMI) while taking aripiprazole alone (n = 1,177), versus aripiprazole plus a high-serotonergic antidepressant (citalopram, fluoxetine, paroxetine, sertraline, or venlafaxine) (n = 145), versus aripiprazole plus a low-serotonergic antidepressant (bupropion) (n = 77) for a minimum continuous duration of 6 months of aripiprazole monotherapy or combination treatment. The study was conducted from January 2010 through June 2011. RESULTS: In our patient population, only the aripiprazole plus high-serotonergic antidepressants group had a statistically significant increase in weight (P = .0027) and BMI (P = .0016). CONCLUSIONS: Our data suggest that, in the presence of antidepressants with high serotonergic activity, aripiprazole may act as an antagonist at the 5-HT2C receptor, resulting in weight gain. Conversely, when aripiprazole is used in the presence of antidepressants with low serotonergic activity, it may act as an agonist and result in little or no weight gain. This varying effect at the 5-HT2C receptor may explain why aripiprazole has not been associated with significant weight gain in previous studies focusing on schizophrenia and bipolar disorder.

Retroperitoneal teratoma presenting as an abscess in childhood.

Retroperitoneal teratomas are rare, representing only 1% to 11% of primary retroperitoneal neoplasms. They typically present as an asymptomatic abdominal mass but can grow to enormous size. This case describes a patient who initially presented in childhood with an acute abdomen because of an abdominal abscess that was treated with surgical drainage and antibiotics. Fifteen years later, the patient had a recurrence of symptoms and the abscess was ultimately recognized to be an infected retroperitoneal teratoma. There have been reports of intraabdominal and pelvic teratomas presenting as abscesses in adults. However, to our knowledge, there has been no prior description of this phenomenon in children. In an otherwise healthy child who presents with an unexplained abscess in the sacrococcygeal area, gonads, mediastinum, or retroperitoneum, one should entertain the diagnosis of teratoma.

Olanzapine in the treatment of developmental stuttering: a double-blind, placebo-controlled trial.

Stuttering is a speech disorder that affects one-percent of all adults and much has been learned recently of its neurologic correlates. Stuttering has been associated with excessive cerebral activity of the neurotransmitter, dopamine. Pharmacologic research has suggested that older generation dopamine antagonist (i.e. "typical antipsychotic") medications improve stuttering symptoms, but are associated with poorly tolerated adverse effects. The purpose of this study was to compare the efficacy and tolerability of olanzapine, a novel dopamine antagonist (or "atypical antipsychotic"), versus placebo in the treatment of adult developmental stuttering. Twenty-four adults who stutter participated in a twelve-week, randomized, double-blind, placebo-controlled trial conducted at two separate sites. Subjects received either olanzapine (2.5 mg titrated to 5 mg) or matching placebo. Subjects were rated on an objective measure of stuttering severity (SSI-3), a clinician based global impression (CGI), and a subject-rated self-assessment of stuttering (SSS). Subjects were also monitored for potential side-effects. Twenty-three of the twenty-four subjects enrolled in the trial successfully completed the full course of the study. Olanzapine was statistically superior to placebo on the three ratings of stuttering severity, the SSI-3, the CGI and SSS (p < .05). Olanzapine is a promising medication for the treatment of stuttering and further research is warranted.