Riddle Hospital

BACKGROUND: Fetal exposure of animals to antiepileptic drugs at doses lower than those required to produce congenital malformations can produce cognitive and behavioral abnormalities, but cognitive effects of fetal exposure of humans to antiepileptic drugs are uncertain. METHODS: Between 1999 and 2004, we enrolled pregnant women with epilepsy who were taking a single antiepileptic agent (carbamazepine, lamotrigine, phenytoin, or valproate) in a prospective, observational, multicenter study in the United States and the United Kingdom. The primary analysis is a comparison of neurodevelopmental outcomes at the age of 6 years after exposure to different antiepileptic drugs in utero. This report focuses on a planned interim analysis of cognitive outcomes in 309 children at 3 years of age. RESULTS: At 3 years of age, children who had been exposed to valproate in utero had significantly lower IQ scores than those who had been exposed to other antiepileptic drugs. After adjustment for maternal IQ, maternal age, antiepileptic-drug dose, gestational age at birth, and maternal preconception use of folate, the mean IQ was 101 for children exposed to lamotrigine, 99 for those exposed to phenytoin, 98 for those exposed to carbamazepine, and 92 for those exposed to valproate. On average, children exposed to valproate had an IQ score 9 points lower than the score of those exposed to lamotrigine (95% confidence interval [CI], 3.1 to 14.6; P=0.009), 7 points lower than the score of those exposed to phenytoin (95% CI, 0.2 to 14.0; P=0.04), and 6 points lower than the score of those exposed to carbamazepine (95% CI, 0.6 to 12.0; P=0.04). The association between valproate use and IQ was dose dependent. Children's IQs were significantly related to maternal IQs among children exposed to carbamazepine, lamotrigine, or phenytoin but not among those exposed to valproate. CONCLUSIONS: In utero exposure to valproate, as compared with other commonly used antiepileptic drugs, is associated with an increased risk of impaired cognitive function at 3 years of age. This finding supports a recommendation that valproate not be used as a first-choice drug in women of childbearing potential.

IMPORTANCE: Breastfeeding is known to have beneficial effects, but concern exists that breastfeeding during maternal antiepileptic drug (AED) therapy may be harmful. We previously noted no adverse effects of breastfeeding associated with AED use on IQ at age 3 years, but IQ at age 6 years is more predictive of school performance and adult abilities. OBJECTIVES: To examine the effects of AED exposure via breastfeeding on cognitive functions at age 6 years. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational multicenter study of long-term neurodevelopmental effects of AED use. Pregnant women with epilepsy receiving monotherapy (ie, carbamazepine, lamotrigine, phenytoin, or valproate) were enrolled from October 14, 1999, through April 14, 2004, in the United States and the United Kingdom. At age 6 years, 181 children were assessed for whom we had both breastfeeding and IQ data. All mothers in this analysis continued taking the drug after delivery. MAIN OUTCOMES AND MEASURES: Differential Ability Scales IQ was the primary outcome. Secondary measures included measures of verbal, nonverbal, memory, and executive functions. For our primary analysis, we used a linear regression model with IQ at age 6 years as the dependent variable, comparing children who breastfed with those who did not. Similar secondary analyses were performed for the other cognitive measures. RESULTS: In total, 42.9% of children were breastfed a mean of 7.2 months. Breastfeeding rates and duration did not differ across drug groups. The IQ at age 6 years was related to drug group (P < .001 [adjusted IQ worse by 7-13 IQ points for valproate compared to other drugs]), drug dosage (regression coefficient, -0.1; 95% CI, -0.2 to 0.0; P = .01 [higher dosage worse]), maternal IQ (regression coefficient, 0.2; 95% CI, 0.0 to 0.4; P = .01 [higher child IQ with higher maternal IQ]), periconception folate use (adjusted IQ 6 [95% CI, 2-10] points higher for folate, P = .005), and breastfeeding (adjusted IQ 4 [95% CI, 0-8] points higher for breastfeeding, P = .045). For the other cognitive domains, only verbal abilities differed between the breastfed and nonbreastfed groups (adjusted verbal index 4 [95% CI, 0-7] points higher for breastfed children, P = .03). CONCLUSIONS AND RELEVANCE: No adverse effects of AED exposure via breast milk were observed at age 6 years, consistent with another recent study at age 3 years. In our study, breastfed children exhibited higher IQ and enhanced verbal abilities. Additional studies are needed to fully delineate the effects of all AEDs. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00021866.

We previously reported that foetal valproate exposure impairs intelligence quotient. In this follow-up investigation, we examined dose-related effects of foetal antiepileptic drug exposure on verbal and non-verbal cognitive measures. This investigation is an ongoing prospective observational multi-centre study in the USA and UK, which has enrolled pregnant females with epilepsy on monotherapy from 1999 to 2004. The study seeks to determine if differential long-term neurodevelopmental effects exist across four commonly used drugs (carbamazepine, lamotrigine, phenytoin and valproate). This report compares verbal versus non-verbal cognitive outcomes in 216 children who completed testing at the age of three years. Verbal and non-verbal index scores were calculated from the Differential Ability Scales, Preschool Language Scale, Peabody Picture Vocabulary Test and Developmental Test of Visual-Motor Integration. Verbal abilities were lower than non-verbal in children exposed in utero to each drug. Preconceptional folate use was associated with higher verbal outcomes. Valproate was associated with poorer cognitive outcomes. Performance was negatively associated with valproate dose for both verbal and non-verbal domains and negatively associated with carbamazepine dose for verbal performance. No dose effects were seen for lamotrigine and phenytoin. Since foetal antiepileptic drug exposure is associated with lower verbal than non-verbal abilities, language may be particularly susceptible to foetal exposure. We hypothesize that foetal drug exposure may alter normal cerebral lateralization. Further, a dose-dependent relationship is present for both lower verbal and non-verbal abilities with valproate and for lower verbal abilities with carbamazepine. Preconceptional folate may improve cognitive outcomes. Additional research is needed to confirm these findings, extend the study to other drugs, define the risks associated with drug treatment for seizures in the neonates, and understand the underlying mechanisms.

OBJECTIVE: To examine outcomes at age 4.5 years and compare to earlier ages in children with fetal antiepileptic drug (AED) exposure. METHODS: The NEAD Study is an ongoing prospective observational multicenter study, which enrolled pregnant women with epilepsy on AED monotherapy (1999-2004) to determine if differential long-term neurodevelopmental effects exist across 4 commonly used AEDs (carbamazepine, lamotrigine, phenytoin, or valproate). The primary outcome is IQ at 6 years of age. Planned analyses were conducted using Bayley Scales of Infant Development (BSID at age 2) and Differential Ability Scale (IQ at ages 3 and 4.5). RESULTS: Multivariate intent-to-treat (n = 310) and completer (n = 209) analyses of age 4.5 IQ revealed significant effects for AED group. IQ for children exposed to valproate was lower than each other AED. Adjusted means (95% confidence intervals) were carbamazepine 106 (102-109), lamotrigine 106 (102-109), phenytoin 105 (102-109), valproate 96 (91-100). IQ was negatively associated with valproate dose, but not other AEDs. Maternal IQ correlated with child IQ for children exposed to the other AEDs, but not valproate. Age 4.5 IQ correlated with age 2 BSID and age 3 IQ. Frequency of marked intellectual impairment diminished with age except for valproate (10% with IQ <70 at 4.5 years). Verbal abilities were impaired for all 4 AED groups compared to nonverbal skills. CONCLUSIONS: Adverse cognitive effects of fetal valproate exposure persist to 4.5 years and are related to performances at earlier ages. Verbal abilities may be impaired by commonly used AEDs. Additional research is needed.

PURPOSE: The vagal nerve stimulator (VNS) and corpus callosotomy can reduce seizure frequency when seizures are refractory to medications. However, the efficacy and safety of these two procedures have not been compared. This study evaluates the two procedures for generalized seizures. METHODS: All patients with refractory generalized seizures (generalized tonic-clonic, tonic, or atonic) who underwent a corpus callosotomy (anterior or complete) (n = 53) without other forms of epilepsy surgery and those who underwent VNS placement (n = 25) were evaluated for this study. Seizure response and procedure complications were evaluated. RESULTS: For those with a corpus callosotomy and generalized tonic-clonic seizures (n = 50), 79.5% had >or=50% decrease in the frequency of generalized tonic-clonic seizures, and 60% had >or=80% seizure reduction. For those with a VNS and generalized tonic-clonic seizures (n = 21), 50% had >or=50% seizure reduction, and 33% had >or=80% seizure reduction. Tonic and atonic seizures decreased after either VNS or a corpus callosotomy. The complication rate for corpus callosotomy was higher (21% all complications, 3.8% permanent) than that for VNS (8%; none permanent), but complications for both corpus callosotomy and VNS were rarely permanent. CONCLUSIONS: Both corpus callosotomy and VNS are effective in reducing generalized seizures. Corpus callosotomy is associated with greater efficacy but higher risk for complications, although these were generally transient.

OBJECTIVE: Although lamotrigine use during pregnancy has substantially increased over the past decade secondary to accumulated reproductive safety data, systematic data on lamotrigine during breastfeeding remains sparse. We sought to characterize the determinants of lamotrigine concentrations in breast milk and nursing-infant plasma. PATIENTS AND METHODS: Women who enrolled in a prospective investigation of perinatal medication pharmacokinetics, were treated with lamotrigine, and chose to continue lamotrigine while breastfeeding were included in the analysis. Breast milk samples were collected via breast pump from foremilk to hindmilk from a single breast to determine the excretion gradient and serial samples over 24 hours to determine the time course of excretion. Paired maternal/infant plasma samples were also collected. Lamotrigine concentrations in all of the samples were determined by using high-performance liquid chromatography with ultraviolet detection. Statistical analyses of breast milk and infant plasma concentrations and their determinants were conducted. RESULTS: Thirty women and their nursing infants participated in the study, providing a total of 210 breast milk samples. The mean milk/plasma ratio was 41.3%. There was a nonsignificant trend for higher lamotrigine concentrations in breast milk 4 hours after the maternal dose. Infant plasma concentrations were 18.3% of maternal plasma concentrations. The theoretical infant lamotrigine dose was 0.51 mg/kg per day, and the relative infant lamotrigine dose was 9.2%. Mild thrombocytosis was present in 7 of 8 infants at the time of serum sampling. No other adverse events were observed or reported in the breastfed infants. CONCLUSIONS: Consistent with previous investigations of medications in breast milk, the lamotrigine milk/plasma ratio is highly variable. The rate of lamotrigine excretion into human breast milk is similar to that observed with other antiepileptic drugs. These data expand the extant literature on lamotrigine in breastfeeding and demonstrate relatively comparable nursing-infant exposure to lamotrigine compared with other antiepileptic drugs.

Glycosylated hemoglobin concentration (GHb), which is considered an indication of glycemia over the preceding several months, was examined in 50 patients hospitalized for recent stroke or transient ischemic attacks (TIA), and compared to that in several reference populations. Patients with stroke or TIA had GHb (mean %A1 +/- SD, 10.2 +/- 2.3) higher than in hospital controls without cerebrovascular disease (8.3 +/- 0.9, p less than 0.005), and equivalent to values for ambulatory diabetic patients treated with diet or diet plus oral agents (9.5 +/- 2.4) or with insulin (10.7 +/- 2.9). Twenty percent (10/50) of the stroke/TIA group were previously known to have abnormal glucose tolerance or diabetes; when this subgroup was excluded, there remained 42% of the original group (21/50) with abnormal GHb (greater than 10% A1) not previously known to have hyperglycemia, and the difference between GHb values for the stroke/TIA patients not known to have glycemic abnormality and for the hospital control group remained significant (p less than 0.005). Sixty-two percent of stroke/TIA patients (31/50) were under treatment for glycemic abnormality, or had high GHb, or both. The high prevalence of elevated GHb in this population could not be attributed to a relationship to age, sex, smoking history, hypercholesterolemia, or hypertension. We conclude that hyperglycemia commonly precedes stroke and TIA, is usually unrecognized, and has been under-appreciated as a risk factor for cerebrovascular disease.

Knee osteoarthritis (OA) is a prevalent condition typically measured by the level of joint space thinning. However, it has been shown that the degree of joint space narrowing correlates poorly with the incidence and magnitude of knee pain. A review of recent and past literature suggests that chronic bone marrow edema (BME) or bone marrow lesions may be linked to pain, the progression of cartilage damage, and the acceleration of joint degeneration. The literature further provides strong support that chronic BME may be an additional target for treatment. This case study has shown that a treatment to repair BME by restoring support and relieving abnormal stresses with accepted internal fixation and bone stimulating surgical techniques is effective in relieving knee OA pain. The literature review and case study herein are provided as a basis for the treatment of chronic BME as an important addition to the current knee OA treatment paradigm.

PURPOSE: To define characteristics of subclinical seizures (SCS) and their prognostic significance after epilepsy surgery. METHODS: Reports from intracranial video-EEG monitoring were reviewed for patients who had epilepsy surgery between 1989 and 2003. Relationships between SCS and clinical seizures were categorized as either: complete colocalization (Group A), when both SCS and clinical seizures originated from the same single focus, or incomplete and no colocalization (Group B), when some or all SCS and clinical seizures originated from different foci in different lobes or hemispheres. RESULTS: A total of 111 patients were included in this review. Seventy-one (64%) patients had 2,821 SCS and most SCS came from the mesial temporal lobe. The mean duration of SCS was shorter than complex partial seizures and generalized tonic-clonic seizures but similar to simple partial seizures. SCS rarely propagated beyond the site of origin and the majority of SCS had the same area of origin as clinical seizures. Sixty-five patients had both SCS and clinical seizures and underwent resective surgery. Group A patients had a higher seizure-free outcome rate (77.5%) than Group B patients (37.5%). The colocalization rate of SCS and clinical seizures may impact seizure-free outcome. The presence or absence of SCS, SCS duration, and extent of propagation of SCS did not influence surgical outcome. CONCLUSION: SCS commonly originate from the same cortical area as clinical seizures and are related to postsurgical outcome. These findings suggest they should be viewed as having similar significance in the surgical decision process as clinical seizures.

Letters19 May 2009Reversal of Haloperidol-Induced Cardiac Arrest by Using Lipid EmulsionGuy Weinberg, MD, Guido Di Gregorio, MD, David Hiller, MD, Agnes Hewett, MD, and Archie Sirianni, MDGuy Weinberg, MDFrom University of Illinois at Chicago College of Medicine, Chicago, IL 60612, and Riddle Memorial Hospital, Media, PA 19063., Guido Di Gregorio, MDFrom University of Illinois at Chicago College of Medicine, Chicago, IL 60612, and Riddle Memorial Hospital, Media, PA 19063., David Hiller, MDFrom University of Illinois at Chicago College of Medicine, Chicago, IL 60612, and Riddle Memorial Hospital, Media, PA 19063., Agnes Hewett, MDFrom University of Illinois at Chicago College of Medicine, Chicago, IL 60612, and Riddle Memorial Hospital, Media, PA 19063., and Archie Sirianni, MDFrom University of Illinois at Chicago College of Medicine, Chicago, IL 60612, and Riddle Memorial Hospital, Media, PA 19063.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-150-10-200905190-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: Infusion of lipid emulsion has been reported to be an effective way to treat local anesthetic–induced cardiac toxicity, and recent reports suggest that it might also be effective in other forms of drug-related cardiac arrest (1).Objective: To report a case of successful resuscitation of a patient with haloperidol-induced cardiac arrest after lipid emulsion infusion.Case Report: A 45-year-old woman came to the hospital reporting palpitations and chest pain. Her medical history included untreated hypertension, anxiety, depression, opioid abuse, and cigarette smoking. She was extremely agitated. Her heart rate was 64 beats/min, respiratory rate was 30 breaths/min, and blood ...References1. Picard J, Harrop-Griffiths W. Lipid emulsion to treat drug overdose: past, present and future [Editorial]. Anaesthesia. 2009;64:119-21. [PMID: 19143685] CrossrefMedlineGoogle Scholar2. Straus SM, Bleumink GS, Dieleman JP, van der Lei J, 't Jong GW, Kingma JH, et al. Antipsychotics and the risk of sudden cardiac death. Arch Intern Med. 2004;164:1293-7. [PMID: 15226162] CrossrefMedlineGoogle Scholar3. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350:1013-22. [PMID: 14999113] CrossrefMedlineGoogle Scholar4. Weinberg G, Ripper R, Feinstein DL, Hoffman W. Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med. 2003;28:198-202. [PMID: 12772136] CrossrefMedlineGoogle Scholar5. Harvey M, Cave G. Intralipid outperforms sodium bicarbonate in a rabbit model of clomipramine toxicity. Ann Emerg Med. 2007;49:178-85, 185. [PMID: 17098328] CrossrefMedlineGoogle Scholar6. Bania TC, Chu J, Perez E, Su M, Hahn IH. Hemodynamic effects of intravenous fat emulsion in an animal model of severe verapamil toxicity resuscitated with atropine, calcium, and saline. Acad Emerg Med. 2007;14:105-11. [PMID: 17267527] CrossrefMedlineGoogle Scholar7. Weinberg GL. Lipid infusion therapy: translation to clinical practice [Editorial]. Anesth Analg. 2008;106:1340-2. [PMID: 18420841] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From University of Illinois at Chicago College of Medicine, Chicago, IL 60612, and Riddle Memorial Hospital, Media, PA 19063.Disclosures:Patents received: Dr. Weinberg was awarded US Patent 7,261,903 B1, related to lipid therapy. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byIntravenous Lipid Emulsion as Salvage Treatment for Haloperidol ToxicityLipid emulsion for acute organophosphate insecticide poisoning – a pilot observational safety studyLipid emulsion mitigates impaired pulmonary function induced by limb ischemia/reperfusion in rats through attenuation of local cellular injury and the subsequent systemic inflammatoryThe use of intravenous lipid emulsion therapy in acute methamphetamine toxicityUse of Intravenous Fat Emulsion in the Emergency Department for the Critically Ill Poisoned PatientEvaluation of intravenous lipid emulsion on haloperidol-induced hypotension in rabbitsSystematic review of the effect of intravenous lipid emulsion therapy for non-local anesthetics toxicityThe possible role of intravenous lipid emulsion in the treatment of chemical warfare agent poisoningA randomized, controlled clinical trial of intravenous lipid emulsion as an adjunctive treatment for permethrin toxicosis in catsLipid Emulsion in Treatment of Local Anesthetic ToxicityInvolvement of Opioid Receptors in the Lipid Rescue of Bupivacaine-Induced CardiotoxicityThe effects of intravenous lipid emulsion on prolongation of survival in a rat model of calcium channel blocker toxicityIntravenous Lipid Emulsion as Antidote: Experience in Hong KongHaloperidol imprinted polymer: preparation, evaluation, and application for drug assay in brain tissueShould we consider the infusion of lipid emulsion in the resuscitation of poisoned patients?Intravenous Lipids: Antidotal Therapy for Drug Overdose and Toxic Effects of Local AnestheticsPretreatment With Intravenous Lipid Emulsion Reduces Mortality From Cocaine Toxicity in a Rat ModelReview of the Use of Lipid Emulsion in Nonlocal Anesthetic PoisoningLipid rescue: does the sink hold water? And other controversiesResuscitation with Lipid EmulsionIntravenous Lipid Emulsion for the Treatment of Drug ToxicityIntravenous Lipid Emulsion Alters the Hemodynamic Response to Epinephrine in a Rat ModelRapid Cardiotonic Effects of Lipid Emulsion Infusion*Inotropic Effect of Lipid EmulsionIvermectin-induced blindness treated with intravenous lipid therapy in a dogThe Use of IV Lipid Emulsion for Lipophilic Drug ToxicitiesUse of intravenous lipid emulsion to treat ivermectin toxicosis in a Border ColliePartition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergenciesThe use of intravenous lipid emulsion as an antidote in veterinary toxicologyReview article: Intravenous lipid emulsion as antidote: A summary of published human experienceLes émulsions lipidiques dans le traitement des effets cardiotoxiques des médicaments lipophiles autres que les anesthésiques locaux: antidote ou traitement d'exception?The role of lipid emulsion during advanced cardiac life support for local anesthetic toxicityLocal Anesthetic ToxicityComplications of peripheral nerve blocksSafety of High Volume Lipid Emulsion InfusionGift of the glob goes globalLipid rescue: the use of lipid emulsions to treat local anaesthetic toxicityLipid resuscitation for local anesthetic toxicity: is it really lifesaving?A commentary on the effect of lipid emulsions on pathology testsIntravenous Lipid Emulsion as Antidote Beyond Local Anesthetic Toxicity: A Systematic Review 19 May 2009Volume 150, Issue 10Page: 737-738KeywordsDrug administrationDrugsElectrocardiographyHeartHeart rateLipidsResuscitationTachycardiaToxicity ePublished: 19 May 2009 Issue Published: 19 May 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. 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Enterobacter hormaechei was first identified as a unique species in 1989. Between 29 November 1992 and 17 March 1993, an outbreak of E. hormaechei occurred among premature infants in the intensive care nursery (ICN) at The Hospital of the University of Pennsylvania. The 10 infants whose cultures were positive for E. hormaechei (six were infected and four were colonized) had a lower median estimated gestational age and birth weight than did other ICN infants; other risk factors for infection or colonization with E. hormaechei were not identified. Cultures from three isolettes and a doorknob in the ICN were positive for E. hormaechei. Pulsed-field gel electrophoresis of isolates from six patients and two isolettes were identical. Observations of health care workers revealed breaks in infection control techniques that may have allowed transmission of this organism. We found that E. hormaechei is a nosocomial pathogen that can infect vulnerable hospitalized patients and that can be transmitted from patient to patient when infection control techniques are inadequate.

BACKGROUND: Postoperative nausea and vomiting (PONV) is frequent after joint arthroplasty; in addition to causing patient distress, it interferes with early mobilization and hospital discharge. Various antiemetic agents reduce PONV, but their action is limited by a short half-life. Aprepitant, an antiemetic developed for patients receiving chemotherapy, has a duration of action much longer than other antiemetics. QUESTIONS/PURPOSES: We asked whether a single dose of preoperative aprepitant (40 mg orally) reduced postoperative nausea and vomiting after THA or TKA. METHODS: Fifty patients who received a preoperative dose of aprepitant (study group) were matched demographically to 50 patients who did not receive aprepitant (control group) from a group of patients undergoing THA or TKA. Patients' charts were reviewed to identify episodes of PONV, number of doses of antiemetics needed for breakthrough PONV, and length of stay. Aprepitant side effects, and complications. RESULTS: Aprepitant reduced the percentage of patients with PONV (39% of study and 70% of control patients). Moderate or severe PONV occurred in 22% of study and 40% of control patients. The number of episodes of PONV during hospitalization was 2.9 for the control group and 1.6 for the study group. Postoperatively, the control group required on average 1.3 doses of ondansetron compared with 0.6 doses for the study group. Hospital length of stay was reduced from 3.3 days for the control group and to 2.3 days for the study group. CONCLUSIONS: These data suggest a single preoperative dose of aprepitant reduces the number of episodes and severity of PONV, the need for additional antiemetics, and the length of stay. LEVEL OF EVIDENCE: Level II, prognostic study. See guidelines for authors for a complete description of levels of evidence.

Maintaining normothermia is important for patient safety, positive surgical outcomes, and increased patient satisfaction. Causes of unplanned hypothermia in the OR include cold room temperatures, the effects of anesthesia, cold IV and irrigation fluids, skin and wound exposure, and patient risk factors. Nurses at Riddle Memorial Hospital in Media, Pennsylvania, performed a quality improvement project to evaluate the effectiveness of using warm blankets, warm irrigation fluids, or forced-air warming on perioperative patients to maintain their core temperature during the perioperative experience. Results of the project showed that 75% of patients who received forced-air warming perioperatively had temperatures that reached or were maintained at 36° C (96.8° F) or higher within 15 minutes after leaving the OR.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a disorder of progressive autonomic dysfunction (AD) associated with diabetes and other chronic diseases. Orthostatic hypotension (OH) is one of the most incapacitating symptoms of CAN and AD. AD in OH can include sympathetic withdrawal (SW). To detect and diagnose SW, parasympathetic and sympathetic changes must be clearly differentiated from each other. This is accomplished by means of the novel autonomic nervous system (ANS) method based on the simultaneous spectral analyses of respiratory activity (RA) and heart rate variability (HRV). METHODS: We performed autonomic profiling of 184 (142 females) consecutive, arrhythmia-free patients with type 2 diabetes using the ANX-3.0 autonomic monitoring system. The patient cohort included 86 (64 female) patients for whom an alpha(1)-agonist was the only drug changed and increased from one test to the next; 37 (33 female) for whom the alpha(1)-agonist was discontinued; and 61 (45 female) who were on an alpha(1)-agonist, but for whom no drug changes were made. The tests averaged 3.1 +/- 1.4 months apart; midodrine (ProAmatine) was the alpha(1)-agonist prescribed. Of the group, 99 patients also had hypertension and 47 also had cardiovascular disease. No patient had supine hypertension. RESULTS: Changes in parameters from the HRV (without respiration) and ANS methods were compared with changes in heart rate and blood pressure (BP) as measured from one test (test N) to the next (test N + 1). SW with a BP drop of less than the clinical definition may be a trend that can be an early indicator of orthostasis. In this study, patients were treated with low-dose, short-term alpha(1)-agonist (vasopressor) therapy, which tended to correct the abnormal trend of SW with a drop in BP. Included in the findings was a systolic BP trend in response to vasopressor therapy of an (expected) initial increase in BP followed by an eventual decrease in systolic BP as SW was reversed. CONCLUSIONS: The ANS method enables quantitative assessment of CAN by independently and simultaneously quantifying the two branches of the ANS, sympathetic and parasympathetic. The ANS method modifies standard spectral analysis of HRV (without RA analysis) by incorporating spectral analysis of RA. The ANS method appears to model the normal and abnormal responses to upright posture and changes in vasopressor therapy with greater fidelity than the HRV method. Independent, simultaneous assessment of progressive parasympathetic and sympathetic dysfunction, autonomic imbalance, and responses of the two ANS branches to therapy seems to enable early detection and early intervention. Orthostasis, by way of example, illustrates that frequent, sensitive assessments of both ANS branches can improve the negative outcomes associated with CAN.

INTRODUCTION: Sexual health care remains an unmet need for women with cancer. Many barriers are described, such as provider discomfort and lack of training; however, there is little evidence-based guidance regarding how to effectively address these obstacles. AIM: This pilot study was performed to determine whether brief, targeted sexual health training for oncology providers results in improved provider comfort level and frequency of addressing female cancer-related sexual issues. METHODS: A brief (30-45 minute), targeted sexual health training program focused on improving comfort level, knowledge and communication skills when addressing breast cancer-related sexual issues was developed by the primary author. Using a pretest-posttest format, this educational program was provided to oncology providers (physicians and nurses/other allied health) from a suburban health-care system. Surveys based on 5-point Likert scales were provided before and 3-6 month post training. MAIN OUTCOME MEASURES: Primary endpoints were changes in mean Likert scores for provider comfort level and self-reported frequency of addressing sexual issues. A secondary endpoint was change in mean Likert scores for perception of access to sexual health resources/referrals. RESULTS: Eligible respondents included 8 oncologists, 4 surgeons, and 62 nurses/other allied health. For total respondents, comparison of mean Likert scores for survey 1 (n = 71) and survey 2 (n = 36) demonstrated statistically significant increases for all parameters queried, including provider comfort level with bringing up (Pre mean Likert score = 3.4, Post = 4.3, P < 0.0001) and coordinating care (Pre = 3.5, Post = 4.6, P < 0.0001), and frequency of addressing sexual issues for both diagnosis/treatment and surveillance phase (Pre = 2.4, Post = 3.3, P ≤ 0.0052). CONCLUSION: Brief, targeted sexual health training for oncology providers positively correlated with improved provider comfort level and frequency of addressing female cancer-related sexual issues.

Rupture of a splenic artery aneurysm is an uncommon occurrence but carries a high maternal and fetal mortality rate. This article presents the seventh case of both maternal and fetal survival and discusses some features salient to spontaneous rupture of a splenic artery aneurysm.

We report a retrospective survey of 263 patients with prostate cancer presenting between 1975 and 1979, with a minimum follow-up period of 5 years. We have evaluated the effects of anti-cancer therapy on survival and disease-free interval. The mean survival time of all patients was 39.6 months. Of 91 patients (37.7%) with demonstrable bone metastases at presentation, 64 (70.3%) have died of prostatic cancer, the mean duration of survival being 25 months. There was no difference in terms of response to treatment or of duration of symptom-free life between patients treated by immediate hormone manipulation and those in whom treatment was delayed. Of 115 patients without metastases at presentation, 42 (36.5%) received no anti-cancer treatment. Thirty-seven (32.2%) have died of unrelated causes and 39 (33.9%) are alive and well. Neither survival nor subjective response to treatment was adversely affected by delaying treatment.

There is a need to identify strategic investments in Asian elephant (Elephas maximus) health that will yield maximal benefits for overall elephant health and conservation. As an exploratory first step, a survey was administered to veterinarians from Asian elephant range countries at a workshop and via email to help prioritize health-related concerns that will mostly benefit elephants. Responses were received from 45 veterinarians from eight countries that had a range of experience with captive and wild elephants. The occurrence of medical conditions and responses to treatment varied among responses. However, injuries, parasitism, and gastrointestinal disease were reported as the most common syndromes responsible for elephant morbidity, whereas injury and infectious disease not due to parasitism were the most commonly reported sources of elephant mortality. Substandard nutrition, water quality and quantity deficiencies, and inadequate or absent shelter were among the factors listed as barriers to optimal elephant health. While this survey's results do not support definitive conclusions, they can be used to identify where and how subsequent investigations should be directed. Rigorous assessment of the relative costs and benefits of available options is required to ensure that investments in individual and population health yield the maximal benefits for elephants.

We recently described the clinical presentation and treatment of 18 elephants from six herds infected with TB. Treatment protocols and methods varied between herds to include both oral and rectal dosing using multiple drug doses and formulations. In this paper we present information regarding the pharmacokinetics (PK) of isoniazid (INH) in elephants and provide suggestions regarding initial treatment regimens. Forty-one elephants received INH daily by either oral or rectal administration with different formulations. Population PK analysis was performed using Non-linear Mixed Effect Modeling (NONMEM). Results of oral administration indicated that compared with premixed INH solution, the drug exposure was highest with a suspension prepared freshly with INH powder. When INH was concomitantly given as an admixture over food, Tmax was delayed and variability in drug absorption was significantly increased. Compared with oral administration, similar drug exposures were found when INH was dosed rectally. The data generated suggest that a starting dose of 7.5 mg/kg of INH is appropriate for initial TB treatment in elephants when premixed solution is administered directly into the oropharynx or rectal vault and 4 mg/kg are when INH is administered following immediate suspension from powdered form.

OBJECTIVE: To assess the success and baseline predictors of maintaining glycemic control for up to 5 years of therapy using basal insulin glargine or standard glycemic care in people with dysglycemia treated with zero or one oral glucose-lowering agents. RESEARCH DESIGN AND METHODS: Data from 12,537 participants in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial were examined by baseline glycemic status (with or without type 2 diabetes) and by therapeutic approach (titrated insulin glargine or standard therapy) using an intention-to-treat analysis. Median values for fasting plasma glucose (FPG) and A1C and percentages with A1C<6.5% (48 mmol/mol) during randomized treatment were calculated. Factors independently associated with maintaining updated mean A1C<6.5% were analyzed with linear regression models. RESULTS: Median A1C in the whole population was 6.4% at baseline; at 5 years, it was 6.2% with glargine treatment and 6.5% with standard care. Of those with diabetes at baseline, 60% using glargine and 45% using standard care had A1C<6.5% at 5 years. Lack of diabetes and lower baseline A1C were independently associated with 5-year mean A1C<6.5%. Maintaining mean A1C<6.5% was more likely with glargine (odds ratio [OR] 2.98 [95% CI 2.67-3.32], P<0.001) than standard care after adjustment for other independent predictors. CONCLUSIONS: Systematic intervention with basal insulin glargine or standard care early in the natural history of dysglycemia can maintain glycemic control near baseline levels for at least 5 years, whether diabetes is present at baseline or not. Keeping mean A1C<6.5% is more likely in people with lower baseline A1C and with the glargine-based regimen.