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Sample records for extended-release diltiazem ingestion

  1. Two-way pharmacokinetic interaction studies between saxagliptin and cytochrome P450 substrates or inhibitors: simvastatin, diltiazem extended-release, and ketoconazole

    Directory of Open Access Journals (Sweden)

    Patel C

    2011-06-01

    Full Text Available Chirag G Patel, Li Li, Suzette Girgis, David M Kornhauser, Ernest U Frevert, David W BoultonBristol-Myers Squibb, Princeton, NJ, USABackground: Many medicines, including several cholesterol-lowering agents (eg, lovastatin, simvastatin, antihypertensives (eg, diltiazem, nifedipine, verapamil, and antifungals (eg, ketoconazole are metabolized by and/or inhibit the cytochrome P450 (CYP 3A4 metabolic pathway. These types of medicines are commonly coprescribed to treat comorbidities in patients with type 2 diabetes mellitus (T2DM and the potential for drug-drug interactions of these medicines with new medicines for T2DM must be carefully evaluated.Objective: To investigate the effects of CYP3A4 substrates or inhibitors, simvastatin (substrate, diltiazem (moderate inhibitor, and ketoconazole (strong inhibitor on the pharmacokinetics and safety of saxagliptin, a CYP3A4/5 substrate; and the effects of saxagliptin on these agents in three separate studies.Methods: Healthy subjects were administered saxagliptin 10 mg or 100 mg. Simvastatin, diltiazem extended-release, and ketoconazole doses of 40 mg once daily, 360 mg once daily, and 200 mg twice daily, respectively, were used to determine two-way pharmacokinetic interactions.Results: Coadministration of simvastatin, diltiazem extended-release, or ketoconazole increased mean area under the concentration-time curve values (AUC of saxagliptin by 12%, 109%, and 145%, respectively, versus saxagliptin alone. Mean exposure (AUC of the CYP3A4-generated active metabolite of saxagliptin, 5-hydroxy saxagliptin, decreased with coadministration of simvastatin, diltiazem, and ketoconazole by 2%, 34%, and 88%, respectively. All adverse events were considered mild or moderate in all three studies; there were no serious adverse events or deaths.Conclusion: Saxagliptin, when coadministered with simvastatin, diltiazem extended-release, or ketoconazole, was safe and generally well tolerated in healthy subjects. Clinically

  2. Acute opioid withdrawal precipitated by ingestion of crushed embeda (morphine extended release with sequestered naltrexone): case report and the focused review of the literature.

    Science.gov (United States)

    Ruan, Xiulu; Chen, Tao; Gudin, Jeff; Couch, John Patrick; Chiravuri, Srinivas

    2010-01-01

    The introduction of newly formulated extended release (ER) morphine with sequestered naltrexone (Embeda) has provided another treatment option for moderate to severe persistent pain. Embeda was designed to be an abuse-deterrent opioid formulation. Naltrexone is a centrally acting opioid receptor antagonist that blocks the action of opioid. When taken as directed, insignificant amount of sequestered naltrexone would reach systemic circulation, but upon tampering, the released naltrexone may blunt the euphoria of opioids, and possibly precipitate opioid withdrawal in opioid-dependent patient. To describe a case report ofa 50-year-old opioid-dependent male who developed acute opioid withdrawal after taking crushed Embeda. A 50-year-old male with severe, chronic low back pain due to degenerative disc disease was referred to our clinic for pain management. He was taking ER oxycodone 80 mg tid and Roxicodone 30 mg qid prn, with inadequate pain relief A trial of ER oxymorphone was decided, at 40 mg 1-2 doses bid. The patient returned to the clinic 1 week early, out of his ER oxymorphone. At this time, the decision to switch him to Embeda was made, at 80 mg/3.2 mg, 1-2 doses bid. The patient and his family members were counseled about risk involved with tampering with Embeda. A few hours later, our clinic was informed that the patient was brought to emergency room by ambulance, in severe opioid withdrawal. He was treated with IV fluid, antiemetics, clonidine, and IV hydromorphone. His condition improved and he was discharged home the next morning. Later on, the patient admitted that he took two prescribed Embeda within half an hour, the 1st one whole and the 2nd one crushed. He further admitted that he did so against our medical advice. CONCLUSION. Taking tampered Embeda may precipitate opioid withdrawal in opioid-tolerant patient. To the best of our knowledge, this is the first report of induced opioid withdrawal following consumption of crushed Embeda.

  3. Diltiazem-induced acute generalised exanthematous pustulosis.

    Science.gov (United States)

    Wakelin, S H; James, M P

    1995-07-01

    Pustulation is a major feature in several different dermatoses, and it may also occur as a manifestation of drug hypersensitivity. Acute generalized exanthematous pustulosis (AGEP) is an uncommon eruption characterized by acute, extensive formation of sterile pustules, fever and peripheral blood leucocytosis. It shares several clinical and histological features in common with pustular psoriasis. Most reported cases have been triggered by ingestion of broad spectrum antibiotics, particularly betalactams and macrolides. There is usually rapid resolution of the eruption on drug withdrawal. We report the case of a 58 year-old woman who developed AGEP shortly after commencing treatment with the calcium channel blocker diltiazem hydrochloride. The eruption followed a biphasic course, and improved following treatment with systemic corticosteroids and methotrexate. AGEP appears to be a rare adverse cutaneous reaction to diltiazem, whereas a wide range of other skin eruptions have been reported more commonly with this drug.

  4. Features of the extended-release metformin

    Directory of Open Access Journals (Sweden)

    T O Yalochkina

    2013-03-01

    Full Text Available Реферат по материалам статьи Ali S, Fonseca V. Overview of metformin: special focus on metformin extended release. Expert Opin Pharmacother. 2012 Aug;13(12:1797-805.

  5. Floating Microparticulate Oral Diltiazem Hydrochloride Delivery ...

    African Journals Online (AJOL)

    Delivery System for Improved Delivery to Heart ... Conclusion: Microparticulate floating (gastroretentive) oral drug delivery system of diltiazem prepared ..... treatment of cardiac disease. ... hydrochloride-loaded mucoadhesive microspheres.

  6. Compound list: diltiazem [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available diltiazem DIL 00092 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/diltia...zem.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/diltia...zem.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/diltia...open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/diltiazem.Rat.in_vivo.Liver.Repeat.zip ...

  7. Design and evaluation of nicorandil extended-release tablet

    Directory of Open Access Journals (Sweden)

    Ju-Young Kim

    2015-04-01

    Full Text Available The aim of this study was to design and evaluate extended-release formulations of a model drug, nicorandil, in order to achieve the desired steady-state plasma concentration of drug in vivo. Simulation was employed to estimate optimum dissolution and absorption rate of nicorandil. The dissolution test was employed using pH 1.2, 4.0, 6.8 buffer solution, or water, to measure the in vitro release behaviors of nicorandil formulations. A single dose (15 mg of each formulation was orally administered to four beagle dogs under fasted conditions, and the pharmacokinetic parameters were calculated. The in vitro/in vivo relationship of the extended-release formulation was confirmed using in vitro dissolution profiles and plasma concentrations of drug in beagle dogs. Nicorandil was released completely within 30 min from the immediate-release tablets and released for 24 h from the extended-release tablets. The nicorandil plasma concentration could be modified by adjusting the drug release rate from the extended-release formulation. The release rate of nicorandil was the rate-limiting step in the overall absorption of drug from the extended-release formulations. These results highlight the potential of a nicorandil extended-release formulation in the treatment of angina pectoris.

  8. Pramipexole Extended Release: A Novel Treatment Option in Parkinson's Disease

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    Wolfram Eisenreich

    2010-01-01

    Full Text Available Pramipexole, the most commonly prescribed dopamine agonist worldwide, meanwhile serves as a reference substance for evaluation of new drugs. Based on numerous clinical data and vast experiences, efficacy and safety profiles of this non-ergoline dopamine agonist are well characterized. Since October 2009, an extended-release formulation of pramipexole has been available for symptomatic treatment of Parkinson's disease. Pramipexole administration can be cut down from three times to once a day due to the newly developed extended-release formulation. This is considerable progress in regard to minimizing pill burden and enhancing compliance. Moreover, the 24 h continuous drug release of the once-daily extended-release formulation results in fewer fluctuations in plasma concentrations over time compared to immediate-release pramipexole, given three times daily. The present study summarizes pharmacokinetics and all essential pharmacological and clinical characteristics of the extended-release formulation. In addition, it provides all study data, available so far, with regard to transition and de-novo administration of extended-release formulation for patients with Parkinson's disease. It further compares efficacy and safety data of immediate-release pramipexole with the extended-release formulation of pramipexole.

  9. Ispaghula Husk-Based Extended Release Tablets of Diclofenac ...

    African Journals Online (AJOL)

    1Vels College of Pharmacy, Pallavaram, Chennai, India, 2Jeffrey Cheah School of Medicine and Health Sciences, Monash University, ... Keywords: Ispaghula husk, Extended release tablet, Diclofenac sodium, Release kinetics. .... release, i.e., Qt vs t, log (Q0-Qt) vs t and Qt vs .... Wallis TE, Textbook of Pharmacognosy, CBS.

  10. Ispaghula Husk-Based Extended Release Tablets of Diclofenac ...

    African Journals Online (AJOL)

    Purpose: To formulate extended-release tablets of diclofenac sodium based on ispaghula husk. Methods: Tablets with varying proportions of diclofenac sodium and ispaghula husk were formulated by wet granulation technique at a fixed compression force of 10 kN. The formulated tablets were evaluated for ...

  11. Floating Microparticulate Oral Diltiazem Hydrochloride Delivery ...

    African Journals Online (AJOL)

    Purpose: To formulate and evaluate floating microparticulate oral diltiazem delivery system for possible delivery to the heart. Method: Floating microspheres were prepared using cellulose acetate and Eudragit RS100 polymers by emulsion solvent evaporation technique. The dried floating microspheres were evaluated for ...

  12. Development and evaluation of diltiazem hydrochloride controlled-release pellets by fluid bed coating process

    Directory of Open Access Journals (Sweden)

    Mikkilineni Bhanu Prasad

    2013-01-01

    Full Text Available The aim of the present study was to develop controlled-release pellets of diltiazem HCl with ethyl cellulose and hydroxylpropyl methylcellulose phthalate as the release rate retarding polymers by fluid bed coating technique. The prepared pellets were evaluated for drug content, particle size, subjected to Scanning Electron Microscopy (SEM and Differential Scanning Calori metry (DSC, and evaluated for in vitro release. Stability studies were carried out on the optimized formulations for a period of 3 months. The drug content was in the range of 97%-101%. The mean particle size of the drug-loaded pellets was in the range 700-785 μm. The drug release rate decreased as the concentration of ethyl cellulose increased in the pellet formulations. Among the prepared formulations, FDL10 and FDL11 showed 80% drug release in 16 h, matching with USP dissolution test 6 for diltiazem HCl extended-release capsules. SEM photographs confirmed that the prepared formulations were spherical in nature with a smooth surface. The compatibility between drug and polymers in the drug-loaded pellets was confirmed by DSC studies. Stability studies indicated that the pellets were stable.

  13. Metoprolol succinate extended release/hydrochlorothiazide combination tablets

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    James W Hainer

    2007-07-01

    Full Text Available James W Hainer, Jennifer SuggAstraZeneca LP, Wilmington, DE, USAAbstract: Lowering elevated blood pressure (BP with drug therapy reduces the risk for catastrophic fatal and nonfatal cardiovascular events such as stroke and myocardial infarction. Given the heterogeneity of hypertension as a disease, the marked variability in an individual patient’s BP response, and low response rates with monotherapy, expert groups such as the Joint National Committee (JNC emphasize the value of combination antihypertensive regimens, noting that combinations, usually of different classes, have additive antihypertensive effects. Metoprolol succinate extended-release tablet is a beta-1 (cardio-selective adrenoceptor-blocking agent formulated to provide controlled and predictable release of metoprolol. Hydrochlorothiazide (HCT is a well-established diuretic and antihypertensive agent, which promotes natruresis by acting on the distal renal tubule. The pharmacokinetics, efficacy, and safety/tolerability of the antihypertensive combination tablet, metoprolol extended release hydrochlorothiazide, essentially reflect the well-described independent characteristics of each of the component agents. Not only is the combination product more effective than monotherapy with the individual components but the combination product allows a low-dose multidrug regimen as an alternative to high-dose monotherapy, thereby, minimizing the likelihood of dose-related side-effects.Keywords: antihypertensive, blood pressure, cardiovascular disease, combination product

  14. Formulation of Sustained-Release Diltiazem Matrix Tablets Using ...

    African Journals Online (AJOL)

    Formulation of Sustained-Release Diltiazem Matrix Tablets Using Hydrophilic Gum Blends. A Moin, H.G Shivakumar. Abstract. Purpose: To develop sustained release matrix tablets of diltiazem hydrochloride (DTZ) using karaya gum (K) alone or in combination with locust bean gum (LB) and hydroxypropyl methylcellulose ...

  15. Herbal carrier-based floating microparticles of diltiazem ...

    African Journals Online (AJOL)

    Purpose: To formulate and characterize a gastroretentive floating drug delivery system for diltiazem hydrochloride using psyllium husk and sodium alginate as natural herbal carriers to improve the therapeutic effect of the drug in cardiac patients. Methods: Floating microparticles containing diltiazem hydrochloride were ...

  16. Magnesium and diltiazem relaxes phenylephrine-precontracted rat aortic rings

    Science.gov (United States)

    Dogan, Mustafa; Peker, Recep O.; Donmez, Soner; Gokalp, Osman

    2012-01-01

    Perioperative vasospasm during cardiovascular surgery is a challenging problem. Several vasodilator agents are frequently utilized for its prevention in surgical practice. Magnesium and diltiazem both have known potential vasorelaxant effects. We planned to compare the efficacy of diltiazem and magnesium in relieving phenylephrine-precontracted rat aortic rings. Ten young adult female Wistar albino rats weighing 230–260 g were used in this study. The aortic rings in the organ bath equilibrated and reached their baseline tension. Precontraction was induced by 0.001 mmol/l phenylephrine and cumulative concentration–relaxation curves were obtained by consecutively increasing the addition of either diltiazem (10−6-0.1 mmol/l) or magnesium (0.1–10 mmol/l). The mean maximal relaxation responses observed by diltiazem and magnesium on separate aortic rings were 90 ± 3 and 53 ± 2%, respectively. The calculated EC50 of diltiazem was 0.01035 mmol/l, whereas the EC50 of magnesium was 4.064 mmol/l (P < 0.05). Both magnesium and diltiazem produced vasorelaxation on phenylephrine-precontracted rat aortic rings in this study, but the potency of diltiazem regarding the EC50 value was significantly higher than that of magnesium. Magnesium could be a candidate together with diltiazem to inhibit vasospasm on arterial grafts during coronary bypass surgery. PMID:22523136

  17. Tramadol extended-release in the management of chronic pain

    Science.gov (United States)

    McCarberg, Bill

    2007-01-01

    Chronic, noncancer pain such as that associated with osteoarthritis of the hip and knee is typically managed according to American College of Rheumatology guidelines. Patients unresponsive to first-line treatment with acetaminophen receive nonsteroidal antiinflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors. However, many patients may have chronic pain that is refractory to these agents, or they may be at risk for the gastrointestinal, renal, and cardiovascular complications associated with their use. Tramadol, a mild opioid agonist and norepinephrine and serotonin reuptake inhibitor, is recommended by current guidelines for the treatment of moderate to moderately severe pain in patients who have not responded to previous oral therapy, or in patients who have contraindications to COX-2 inhibitors and nonselective NSAIDs. An extended-release (ER) formulation of tramadol was approved by the US Food and Drug Administration in September 2005. In contrast with immediate-release (IR) tramadol, this ER formulation allows once-daily dosing, providing around-the-clock analgesia. In clinical studies, tramadol ER has demonstrated a lower incidence of adverse events than that reported for IR tramadol. Unlike nonselective NSAIDs and COX-2 inhibitors, tramadol ER is not associated with gastrointestinal, renal, or cardiovascular complications. Although tramadol is an opioid agonist, significant abuse has not been demonstrated after long-term therapy. It is concluded that tramadol ER has an efficacy and safety profile that warrants its early use for the management of chronic pain, either alone or in conjunction with nonselective NSAIDs and COX-2 inhibitors. PMID:18488071

  18. Herbal carrier-based floating microparticles of diltiazem ...

    African Journals Online (AJOL)

    hydrochloride using psyllium husk and sodium alginate as natural herbal carriers to improve the ... Keywords: Diltiazem, Cardiac disease, Psyllium husk, Sodium alginate, Microsphere, ..... Barkai A, Pathak YV, Benita S. Polyacrylate (Eudragit.

  19. Tapentadol extended release for the management of chronic neck pain

    Directory of Open Access Journals (Sweden)

    Billeci D

    2017-03-01

    Full Text Available Domenico Billeci,1 Flaminia Coluzzi2 1Division of Neurosurgery, Ca’Foncello Hospital, University of Padova, Treviso, 2Department of Medical and Surgical Sciences and Biotechnologies, Unit of Anaesthesiology, Intensive Care Medicine, and Pain Therapy, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Latina, Italy Background: The role of opioids in the management of chronic neck pain is still poorly investigated. No data are available on tapentadol extended release (ER. In this article, we present 54 patients with moderate-to-severe chronic neck pain treated with tapentadol ER. Patients and methods: Patients received tapentadol ER 100 mg/day; dosage was then adjusted according to clinical needs. The following parameters were recorded: pain; Douleur Neuropathique 4 score; Neck Disability Index score; range of motion; pain-associated sleep interference; quality of life (Short Form [36] Health Survey; Patient Global Impression of Change (PGIC; Clinician GIC; opioid-related adverse effects; and need for other analgesics. Results: A total of 44 of 54 patients completed the 12-week observation. Tapentadol ER daily doses increased from 100 mg/day to a mean (standard deviation dosage of 204.5 (102.8 mg/day at the final evaluation. Mean pain intensity at movement significantly decreased from baseline (8.1 [1.1] to all time points (P<0.01. At baseline, 70% of patients presented a positive neuropathic component. This percentage dropped to 23% after 12 weeks. Tapentadol improved Neck Disability Index scores from 55.6 (18.6 at baseline to 19.7 (20.9 at the final evaluation (P<0.01. Tapentadol significantly improved neck range of motion in all three planes of motion, particularly in lateral flexion. Quality of life significantly improved in all Short Form (36 Health Survey subscales (P<0.01 and in both physical and mental status (P<0.01. Based on PGIC results, approximately 90% of patients rated their overall condition as much/very much

  20. 78 FR 66009 - Determination That INVEGA (Paliperidone) Extended-Release Tablet, 12 Milligrams, Was Not...

    Science.gov (United States)

    2013-11-04

    ...] Determination That INVEGA (Paliperidone) Extended-Release Tablet, 12 Milligrams, Was Not Withdrawn From Sale for... Food and Drug Administration (FDA) has determined that INVEGA (paliperidone) extended-release tablet...-release tablet, 12 mg, if all other legal and regulatory requirements are met. FOR FURTHER INFORMATION...

  1. Clinical and biochemical efficacy of diltiazem in hyperthyroidism

    International Nuclear Information System (INIS)

    Marwat, M.A.

    2008-01-01

    To evaluate the effect of diltiazem on the adrenergic manifestations of hyperthyroidism and thyroid function tests. This prospective, interventional study included 19 newly diagnosed patients (16 females, 3 males with mean age of 35.31+-0.36 years) of hyperthyroidism attending the out patient department of Institute of Radiotherapy and Nuclear Medicine, Peshawar. All patients took diltiazem 30 mg three times a day for 6 weeks. Clinical assessment was done before starting therapy and then serially after 1, 2, 4 and 6 weeks (+-3 days) using Standardized and modified hyperthyroid symptom score. Serum free T/sub 4/ measurements were done before starting diltiazem and then serially after 2, 4 and 6 weeks (+-3 days) of therapy. Following therapy with diltiazem the hyperthyroid systems core decreased significantly at 1, 2, 4 and 6 weeks of therapy. With individual values dropping from 14.42 to 12.89 pmol/L after 1 week (P 0.05). Diltiazem effectively controls the clinical manifestation of hyperthyroidism. It also causes some decline in free thyroxine levels. (author)

  2. Design and development of controlled porosity osmotic tablet of diltiazem hydrochloride

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    Sadhana R Shahi

    2012-01-01

    Full Text Available The present work aims towards the design and development of extended release formulation of freely water-soluble drug diltiazem hydrochloride (DLTZ based on osmotic technology by using controlled porosity approach. DLTZ is an ideal candidate for a zero-order drug delivery system because it is freely water-soluble and has a short half-life (2-3 h. Sodium chloride (Osmogen was added to the core tablet to alter the solubility of DLTZ in an aqueous medium. Cellulose acetate (CA and sorbitol were used as semipermeable membrane and pore former, respectively. The effect of different formulation variables namely concentration of osmogen in the core tablet, % pore former, % weight gain, pH of the dissolution medium and agitation intensity on the in vitro release was studied. DLTZ release was directly proportional to % pore former and inversely proportional to % weight gain. The optimized formulation (F8 delivered DLTZ independent of pH and agitation intensity for 12 h at the upper level concentration of % pore former (25% w/w and middle level concentration of % weight gain (6% w/w. The comparative study of elementary osmotic pump (EOP and controlled porosity osmotic pump revealed that it superior than conventional EOP and also easier and cost effective to formulate.

  3. Formulation and Evaluation of Extended- Release Tablet of Zolpidem Tartrate by Wet Granulation Technique

    OpenAIRE

    Fatemeh Pourhashem; Mohammad Reza Avadi

    2016-01-01

    The goal of this study was to design and evaluate extended - release system of the hypnotic agent, Zolpidem tartrate usefulness for the treatment of insomnia. The half-life of this drug is about 1.9 - 3 hours that indicating it a candidate for the extended release formulation. Our investigation relates to development of extended drug delivery system based on Hydroxy propyl methyl cellulose (HPMCK4M) as release retardant, polyvinyl pyrrolidone (PVP k30) as binder and Magnesium S...

  4. Once daily, extended release ciprofloxacin for complicated urinary tract infections and acute uncomplicated pyelonephritis.

    Science.gov (United States)

    Talan, David A; Klimberg, Ira W; Nicolle, Lindsay E; Song, James; Kowalsky, Steven F; Church, Deborah A

    2004-02-01

    We assessed the efficacy and safety of 1,000 mg extended release ciprofloxacin orally once daily vs conventional 500 mg ciprofloxacin orally twice daily, each for 7 to 14 days, in patients with a complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis (AUP). In this prospective, randomized, double-blind, North American multicenter clinical trial adults were stratified based on clinical presentation of cUTI or AUP and randomized to extended release ciprofloxacin or ciprofloxacin twice daily. Efficacy valid patients had positive pretherapy urine cultures (105 or greater cFU/ml) and pyuria within 48 hours of study entry. Bacteriological and clinical outcomes were assessed at the test of cure visit (5 to 11 days after therapy) and the late followup visit (28 to 42 days after therapy). The intent to treat population comprised 1,035 patients (extended release ciprofloxacin in 517 and twice daily in 518), of whom 435 were efficacy valid (cUTI in 343 and AUP in 92). For efficacy valid patients (cUTI and AUP combined) bacteriological eradication rates at test of cure were 89% (183 of 206) vs 85% (195 of 229) (95% CI -2.4%, 10.3%) and clinical cure rates were 97% (198 of 205) vs 94% (211 of 225) (95% CI -1.2%, 6.9%) for extended release vs twice daily ciprofloxacin. Late followup outcomes were consistent with test of cure findings. Eradication rates for Escherichia coli, which accounted for 58% of pathogens, were 97% or greater per group. Drug related adverse event rates were similar for extended release and twice daily ciprofloxacin (13% and 14%, respectively). Extended release ciprofloxacin at a dose of 1,000 mg once daily was as safe and effective as conventional treatment with 500 mg ciprofloxacin twice daily, each given orally for 7 to 14 days in adults with cUTI or AUP. It provides a convenient, once daily, empirical treatment option.

  5. Pharmacological and clinical evidence of nevirapine immediate- and extended-release formulations

    Directory of Open Access Journals (Sweden)

    Ena J

    2012-11-01

    Full Text Available Javier Ena, Concepción Amador, Conxa Benito, Francisco PasquauHIV Unit, Hospital Marina Baixa, Villajoyosa, SpainAbstract: We reviewed the current information available on nevirapine immediate- and extended-release formulations and its role in single-dose and combination antiretroviral therapy. Nevirapine was approved in 1996 and was the first non-nucleoside reverse-transcriptase inhibitor available for the treatment of HIV-1 infection. Nevirapine has demonstrated good efficacy and a well-characterized safety profile. A major drawback is the low genetic barrier, allowing the emergence of resistance in the presence of single mutations in the reverse-transcriptase gene. This shortcoming is particularly relevant when nevirapine is administered in a single dose to prevent mother-to-child transmission of HIV-1 infection, compromising the efficacy of future non-nucleoside reverse transcriptase–inhibitor regimens. Studies published recently have probed the noninferiority of nevirapine compared to ritonavir-boosted atazanavir with both tenofovir disoproxil fumarate and emtricitabine in antiretroviral treatment–naïve patients. In 2011, a new formulation of nevirapine (nevirapine extended release that allowed once-daily dosing was approved by the Food and Drug Administration and by the European Medicines Agency. VERxVe, a study comparing nevirapine extended release with nevirapine immediate release in antiretroviral treatment–naïve patients, and TRANxITION, a study carried out in antiretroviral treatment–experienced patients who switched therapy from nevirapine immediate release to nevirapine extended release, provided data on the noninferiority of the new formulation of nevirapine compared with nevirapine immediate release in terms of efficacy and safety. Nevirapine extended release will further increase the durability and persistence of nevirapine-containing antiretroviral therapy, allowing once-daily dosing regimens.Keywords: nevirapine

  6. Treatment-Continuity of ADHD Compared Using Immediate-Release and Extended-Release MPH

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-07-01

    Full Text Available The continuity of methylphenidate (MPH therapy for ADHD in young Medicaid beneficiaries (ages 6 to 17 years treated with immediate-release (IR or extended-release (ER MPH formulations was compared in an analysis of statewide California Medicaid claims (2000-2003 conducted at Columbia University, New York; University of Pennsylvania, Philadelphia; and McNeil Pharmaceuticals, Fort Washington, PA.

  7. Simulated Driving Changes in Young Adults with ADHD Receiving Mixed Amphetamine Salts Extended Release and Atomoxetine

    Science.gov (United States)

    Kay, Gary G.; Michaels, M. Alex; Pakull, Barton

    2009-01-01

    Background: Psychostimulant treatment may improve simulated driving performance in young adults with attention-deficit/hyperactivity disorder (ADHD). Method: This was a randomized, double-blind, placebo-controlled, crossover study of simulated driving performance with mixed amphetamine salts--extended release (MAS XR) 50 mg/day (Cohort 1) and…

  8. Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

    Science.gov (United States)

    Shen, Jie; Burgess, Diane J

    2012-07-01

    This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  9. Accelerated in vitro release testing methods for extended release parenteral dosage forms

    Science.gov (United States)

    Shen, Jie; Burgess, Diane J.

    2012-01-01

    Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

  10. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

    DEFF Research Database (Denmark)

    Sacco, Ralph L; Diener, Hans-Christoph; Yusuf, Salim

    2008-01-01

    BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly...

  11. Clonidine Extended-Release Tablets for Pediatric Patients with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Jain, Rakesh; Segal, Scott; Kollins, Scott H.; Khayrallah, Moise

    2011-01-01

    Objective: This study examined the efficacy and safety of clonidine hydrochloride extended-release tablets (CLON-XR) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: This 8-week, placebo-controlled, fixed-dose trial, including 3 weeks of dose escalation, of patients 6 to 17 years old with ADHD evaluated the…

  12. A Controlled Trial of Extended-Release Guanfacine and Psychostimulants for Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Wilens, Timothy E.; Bukstein, Oscar; Brams, Matthew; Cutler, Andrew J.; Childress, Ann; Rugino, Thomas; Lyne, Andrew; Grannis, Kara; Youcha, Sharon

    2012-01-01

    Objective: To examine efficacy, tolerability, and safety of guanfacine extended release (GXR; less than or equal to 4 mg/d) adjunctive to a long-acting psychostimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents 6 to 17 years of age with suboptimal, but partial, response to psychostimulant…

  13. Diltiazem enhances tumor blood flow: MRI study in a murine tumor

    International Nuclear Information System (INIS)

    Muruganandham, M.; Kasiviswanathan, A.; Jagannathan, N.R.; Raghunathan, P.; Jain, P.C.; Jain, V.

    1999-01-01

    Purpose: Diltiazem, a calcium-channel blocker, is known to differentially influence the radiation responses of normal and murine tumor tissues. To elucidate the underlying mechanisms, the effects of diltiazem on the radiation response of Ehrlich ascites tumor (EAT) in mice have been investigated, and the hemodynamic changes induced by diltiazem in tumor and normal muscle have been studied using magnetic resonance imaging (MRI) techniques. Methods and Materials: Ehrlich ascites tumors were grown subcutaneously in Swiss albino strain A mice. Dynamic gadodiamide and blood oxygen level dependent (BOLD) contrast enhanced 1 H MR imaging studies of EAT and normal muscle were performed after administration of diltiazem in mice using a 4.7 Tesla MR scanner. Tumor radiotherapy experiments (total dose = 10 Gy, 0.4-0.5 Gy/min, single fraction) were carried out with 30 min preadministration of diltiazem (27.5 or 55 mg/kg i.p.) to EAT-bearing mice using a teletherapy machine. Results: The diltiazem+ radiation treated group showed significant tumor regression (in congruent with 65% of the animals) and enhanced animal survival. MR-gadodiamide contrast kinetics revealed a higher magnitude of signal enhancement in diltiazem treated groups as compared to the controls. The observed changes in the magnitude of kinetic parameters were the same for both tumor and normal muscle. BOLD-MR images at 30 min after diltiazem administration showed a 25% and 8% (average) intensity enhancement from their basal values in tumor and normal muscle regions, respectively. The control group showed no significant changes. Conclusion: The present studies demonstrate the radiosensitization potential of diltiazem in the mice EAT model. The enhanced radiation response observed with diltiazem correlates with the diltiazem-induced increase in tumor blood flow (TBF) and tumor oxygenation. The present results also demonstrate the applications of BOLD-MR measurements in investigating the alterations in tumor

  14. Randomised, double-blind trial of intravenous diltiazem versus glyceryl trinitrate for unstable angina pectoris

    NARCIS (Netherlands)

    Gobel, EJAM; Hautvast, RWM; vanGilst, WH; Spanjaard, JN; Hillege, HL; DeJongste, MJL; Molhoek, GP; Lie, KI

    1995-01-01

    The effect of dihydropyridines in patients with unstable angina is discouraging. To find out the effect of the non- dihydropyridine-like calcium-channel blocker diltiazem, a randomised, double-blind trial was conducted comparing diltiazem with glyceryl trinitrate. both given intravenously, in 129

  15. Formulation and Evaluation of Extended- Release Tablet of Zolpidem Tartrate by Wet Granulation Technique

    Directory of Open Access Journals (Sweden)

    Fatemeh Pourhashem

    2016-06-01

    Full Text Available The goal of this study was to design and evaluate extended - release system of the hypnotic agent, Zolpidem tartrate usefulness for the treatment of insomnia. The half-life of this drug is about 1.9 - 3 hours that indicating it a candidate for the extended release formulation. Our investigation relates to development of extended drug delivery system based on Hydroxy propyl methyl cellulose (HPMCK4M as release retardant, polyvinyl pyrrolidone (PVP k30 as binder and Magnesium Stearate using Factorial design. In vitro release study of matrix tablets was carried out in 0.01N HCl for 2 hours. All prepared matrix tablets were evaluated for physicochemical evaluation and drug content. The formulation that had release profile according to United State Pharmacopoeia selected for stability study according to ICH guidelines.

  16. Rhabdomyolysis following Acute Extended-Release Quetiapine Poisoning: A Case Report

    Directory of Open Access Journals (Sweden)

    Antonios Liolios

    2012-01-01

    Full Text Available Background. During the past few years, there have been a number of case reports concerning rhabdomyolysis following quetiapine poisoning; however, there has been none concerning the medication in its extended-release form. Methods. We present the case report of a 48-year-old man presenting a major depressive disorder and borderline personality disorder, who after voluntary intoxication with 12000 mg of quetiapine extended-release developed signs of acute rhabdomyolysis. Results. The rhabdomyolysis was confirmed by the laboratory and the clinical findings, with elevated levels of creatinine, creatine phosphokinase, and CRP. Discussion. We would like to pinpoint the importance of this complication and our concern of prescribing it for psychiatric patients with chronic somatic comorbidities.

  17. Direct and indirect effects of paliperidone extended-release tablets on negative symptoms of schizophrenia

    OpenAIRE

    Bossie, Cynthia

    2008-01-01

    Ibrahim Turkoz, Cynthia A Bossie, Bryan Dirks, Carla M CanusoOrtho-McNeil Janssen Scientific Affairs, LLC, Titusville, NJ, USAAbstract: Direct and indirect effects of the new psychotropic paliperidone extended-release (paliperidone ER) tablets on negative symptom improvement in schizophrenia were investigated using path analysis. A post hoc analysis of pooled data from three 6-week, double-blind, placebo-controlled studies of paliperidone ER in patients experiencing acute exacerbation was con...

  18. Long-Term Effectiveness and Safety of Dexmethylphenidate Extended-Release Capsules in Adult ADHD

    Science.gov (United States)

    Adler, Lenard A.; Spencer, Thomas; McGough, James J.; Jiang, Hai; Muniz, Rafael

    2009-01-01

    Objective: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. Method: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness…

  19. Update on prescription extended-release opioids and appropriate patient selection

    Directory of Open Access Journals (Sweden)

    Brennan MJ

    2013-07-01

    Full Text Available Michael J Brennan The Pain Center of Fairfield, Fairfield, CT, USA Abstract: Chronic pain is largely underdiagnosed, often undertreated, and expected to increase as the American population ages. Many patients with chronic pain require long-term treatment with analgesic medications, and pain management may involve use of prescription opioids for patients whose pain is inadequately controlled through other therapies. Yet because of the potential for abuse and addiction, many clinicians hesitate to treat their patients with pain with potentially beneficial agents. Finding the right opioid for the right patient is the first – often complicated – step. Ensuring that patients continue to properly use the medication while achieving therapeutic analgesic effects is the long-term goal. Combined with careful patient selection and ongoing monitoring, new formulations using extended-release technologies incorporating tamper-resistant features may help combat the growing risk of abuse or misuse, which will hopefully reduce individual suffering and the societal burden of chronic pain. The objective of this manuscript is to provide an update on extended-release opioids and to provide clinicians with a greater understanding of which patients might benefit from these new opioid formulations and how to integrate the recommended monitoring for abuse potential into clinical practice. Keywords: chronic pain, opioid analgesics, extended release, abuse prevention

  20. Development and evaluation of microporous osmotic tablets of diltiazem hydrochloride

    Directory of Open Access Journals (Sweden)

    Afifa Bathool

    2012-01-01

    Full Text Available Microporous osmotic tablet of diltiazem hydrochloride was developed for colon targeting. These prepared microporous osmotic pump tablet did not require laser drilling to deliver the drug to the specific site of action. The tablets were prepared by wet granulation method. The prepared tablets were coated with microporous semipermeable membrane and enteric polymer using conventional pan coating process. The incorporation of sodium lauryl sulfate (SLS, a leachable pore-forming agent, could form in situ delivery pores while coming in contact with gastrointestinal medium. The effect of formulation variables was studied by changing the amounts of sodium alginate and NaCMC in the tablet core, osmogen, and that of pore-forming agent (SLS used in the semipermeable coating. As the amount of hydrophilic polymers increased, drug release rate prolonged. It was found that drug release was increased as the concentration of osmogen and pore-former was increased. Fourier transform infrared spectroscopy and Differential scanning calorimetry results showed that there was no interaction between drug and polymers. Scanning electron microscopic studies showed the formation of pores after predetermined time of coming in contact with dissolution medium. The formation of pores was dependent on the amount of pore former used in the semipermeable membrane. in vitro results showed acid-resistant, timed release at an almost zero order up to 24 hours. The developed osmotic tablets could be effectively used for prolonged delivery of Diltiazem HCl.

  1. Acute cardiovascular effects of diltiazem in anesthetized dogs with induced atrial fibrillation.

    Science.gov (United States)

    Miyamoto, M; Nishijima, Y; Nakayama, T; Hamlin, R L

    2001-01-01

    Atrial fibrillation (AF) is one of the most important arrhythmias of dogs. In a previous study, we determined the dosage of intravenously administered diltiazem necessary to reduce ventricular response (VR), cardiac output (CO), and mean systemic arterial pressure (P(Ao)) to values similar to those observed during sinus rhythm (SR) before induction of AF. The present study was conducted to establish an acute, effective dosage of diltiazem given PO. AF was produced by rapid atrial pacing in healthy, anesthetized Beagle Hounds. Dogs were instrumented to record hemodynamic and electrophysiological parameters. Four dogs were given 2.5 mg/kg diltiazem, and another 4 dogs were given 5 mg/kg diltiazem by stomach tube, whereas 4 other dogs received vehicle in equivalent volumes. Plasma concentrations of diltiazem were measured at various intervals after dosing. A dosage of 5 mg/kg diltiazem produced plasma concentrations of 32-100 ng/mL 3 hours after administration, concentrations within the published effective range for dogs with naturally occurring AF. Between 2 and 3 hours after this dosage, the rate pressure product (RPP) and an index of left ventricular efficiency returned to values similar to those observed during SR. Thus, we believe that diltiazem at anorally administered dosages of 5 mg/kg should be considered to produce therapeutic blood concentrations and favorable hemodynamic effects in dogs with naturally occurring AF. These data must be extrapolated with caution to dogs with long-standing AF produced by natural causes.

  2. Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) vs Extended-Release Morphine Administered Intranasally in Nondependent Recreational Opioid Users.

    Science.gov (United States)

    Webster, Lynn R; Smith, Michael D; Lawler, John; Lindhardt, Karsten; Dayno, Jeffrey M

    2017-09-01

    To compare the relative human abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets. A randomized, double-blind, double-dummy, active- and placebo-controlled five-way crossover study was performed with adult volunteers who were experienced, nondependent, recreational opioid users. After intranasal (IN) administration of manipulated high-volume (HV) morphine-ADER-IMT (60 mg), participants were randomized (1:1:1:1) to receive IN manipulated low-volume (LV) morphine ER (60 mg), IN manipulated LV morphine-ADER-IMT, intact oral morphine-ADER-IMT (60 mg), and placebo in crossover fashion. Pharmacodynamic and pharmacokinetic assessments included peak effect of drug liking (E max ; primary endpoint) using drug liking visual analog scale (VAS) score, E max using overall drug liking, and take drug again (TDA) VASs scores, and mean abuse quotient (AQ), a pharmacokinetic parameter associated with drug liking. Forty-six participants completed the study. After insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT, drug liking E max was significantly lower ( P  <   0.0001) compared with IN morphine ER. Overall drug liking and TDA E max values were significantly lower ( P  <   0.0001) after insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT compared with IN morphine ER. Mean AQ was lower after insufflation of HV (9.2) and LV (2.3) morphine-ADER-IMT or ingestion of oral morphine-ADER-IMT (5.5) compared with insufflation of LV morphine ER (37.2). All drug liking, take drug again, and abuse quotient endpoints support a significantly lower abuse potential with insufflation of manipulated morphine-ADER-IMT compared with manipulated and insufflated non-AD ER morphine. © 2016 American Academy of Pain Medicine.

  3. Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures

    Directory of Open Access Journals (Sweden)

    Carol M Ulloa

    2009-09-01

    Full Text Available Carol M Ulloa, Allen Towfigh, Joseph SafdiehDepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USAAbstract: Levetiracetam is a second-generation antiepileptic drug (AED with a unique chemical structure and mechanism of action. The extended release formulation of levetiracetam (Keppra XR™; UCB Pharma was recently approved by the Food and Drug Administration for adjunctive therapy in the treatment of partial-onset seizures in patients 16 years of age and older with epilepsy. This approval is based on a double-blind, randomized, placebo-controlled, multicenter, multinational trial. Levetiracetam XR allows for once-daily dosing, which may increase compliance and, given the relatively constant plasma concentrations, may minimize concentration-related adverse effects. Levetiracetam’s mode of action is not fully elucidated, but it has been found to target high-voltage, N-type calcium channels as well as the synaptic vesicle protein 2A (SV2A. Levetiracetam has nearly ideal pharmacokinetics. It is rapidly and almost completely absorbed after oral ingestion, is ‹10% protein-bound, demonstrates linear kinetics, is minimally metabolized through a pathway independent of the cytochrome P450 system, has no significant drug–drug interactions, and has a wide therapeutic index. The most common reported adverse events with levetiracetam XR were somnolence, irritability, dizziness, nausea, influenza, and nasopharyngitis. Levetiracetam XR provides an efficacious and well-tolerated treatment option for adjunctive therapy in the treatment of partial-onset seizures.Keywords: levetiracetam, partial-onset seizures, antiepileptic drugs

  4. Critical appraisal of extended-release hydrocodone for chronic pain: patient considerations

    Directory of Open Access Journals (Sweden)

    Gould HJ III

    2015-10-01

    Full Text Available Harry J Gould III,1,3–7 Dennis Paul1–8 1Department of Neurology, 2Department of Pharmacology and Experimental Therapeutics, 3Department of Internal Medicine, Section of Physical Medicine and Rehabilitation, 4Department of Anesthesiology, 5Neuroscience Center of Excellence, 6Center of Excellence for Oral and Craniofacial Biology, 7Pain Mastery Center of Louisiana, 8Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, USA Abstract: Opioid analgesics are currently the most effective pharmacologic option for the management of both acute and chronic forms of moderate-to-severe pain. Although the “as-needed” use of immediate-release formulations is considered optimum for treating acute, painful episodes of limited duration, the scheduled dosing of extended-release formulations with immediate-release supplementation for breakthrough pain is regarded to be most effective for managing chronic conditions requiring around-the-clock treatment. The recent introduction of extended-release formulations of the opioid analgesic hydrocodone potentially broadened the possibility of providing pain relief for individuals for whom current formulations are either ineffective or not tolerated. However, reaction to the approval of the new formulations has fueled controversy over the general safety and need for opioid medications, in light of their potential for misuse, abuse, diversion, and addiction. Here, we discuss how the approval of extended-release formulations of hydrocodone and the emotionally charged controversy over their release may affect physician prescribing and the care available to patients in need of chronic opioid therapy for the management of pain. Keywords: opioid analgesics, patient risks, patient benefits, misuse, addiction

  5. Quetiapine extended release versus aripiprazole in children and adolescents with first-episode psychosis

    DEFF Research Database (Denmark)

    Pagsberg, Anne Katrine; Jeppesen, Pia; Klauber, Dea Gowers

    2017-01-01

    of quetiapine-extended release (quetiapine-ER) versus aripiprazole in children and adolescents with first-episode psychosis, to determine whether differences between the two treatments were sufficient to guide clinicians in their choice of one drug over the other. METHODS: In this multicentre, double-blind...... (47 [92%] vs 39 [71%]), orthostatic dizziness (42 [78%] vs 46 [81%]), depression (43 [80%] vs 44 [77%]), tension/inner unrest (37 [69%] vs 50 [88%]), failing memory (41 [76%] vs 44 [77%]), and weight gain (46 [87%] vs 38 [68%]). INTERPRETATION: This first head-to-head comparison of quetiapine...

  6. Acute coronary hemodynamic effects of equihypotensive doses of nisoldipine and diltiazem

    NARCIS (Netherlands)

    H. Suryapranata (Harry); P.W.J.C. Serruys (Patrick); A.L. Soward; J. Planellas; G. Vanhaleweyk; P.G. Hugenholtz (Paul)

    1985-01-01

    textabstractThe hemodynamic effects of nisoldipine and diltiazem were investigated in two groups of patients undergoing investigation for suspected coronary artery disease. Emphasis was placed on the coronary hemodynamic changes. Approximately equihypotensive doses of these two calcium channel

  7. Risk based In Vitro Performance Assessment of Extended Release Abuse Deterrent Formulations

    Science.gov (United States)

    Xu, Xiaoming; Gupta, Abhay; Al-Ghabeish, Manar; Calderon, Silvia N.; Khan, Mansoor A.

    2016-01-01

    High strength extended release opioid products, which are indispensable tools in the management of pain, are associated with serious risks of unintentional and potentially fatal overdose, as well as of misuse and abuse that might lead to addiction. The issue of drug abuse becomes increasingly prominent when the dosage forms can be readily manipulated to release a high amount of opioid or to extract the drug in certain products or solvents. One approach to deter opioid drug abuse is by providing novel abuse deterrent formulations (ADF), with properties that may be viewed as barriers to abuse of the product. However, unlike regular extended release formulations, assessment of ADF technologies are challenging, in part due to the great variety of formulation designs available to achieve deterrence of abuse by oral, parenteral, nasal and respiratory routes. With limited prior history or literature information, and lack of compendial standards, evaluation and regulatory approval of these novel drug products become increasingly difficult. The present article describes a risk-based standardized in-vitro approach that can be utilized in general evaluation of abuse deterrent features for all ADF products. PMID:26784976

  8. Profile of extended-release oxycodone/acetaminophen for acute pain

    Directory of Open Access Journals (Sweden)

    Bekhit MH

    2015-10-01

    Full Text Available Mary Hanna Bekhit1–51David Geffen School of Medicine, 2Ronald Reagan UCLA Medical Center, 3UCLA Ambulatory Surgery Center, 4UCLA Wasserman Eye Institute, 5UCLA Martin Luther King Community Hospital, University of California Los Angeles, Los Angeles, CA, USA Abstract: This article provides a historical and pharmacological overview of a new opioid analgesic that boasts an extended-release (ER formulation designed to provide both immediate and prolonged analgesia for up to 12 hours in patients who are experiencing acute pain. This novel medication, ER oxycodone/acetaminophen, competes with current US Food and Drug Administration (FDA-approved opioid formulations available on the market in that it offers two benefits concurrently: a prolonged duration of action, and multimodal analgesia through a combination of an opioid (oxycodone with a nonopioid component. Current FDA-approved combination analgesics, such as Percocet (oxycodone/acetaminophen, are available solely in immediate-release (IR formulations. Keywords: opioid, analgesic, xartemis, acute postsurgical pain, substance abuse, acetaminophen, extended release 

  9. Tapentadol extended-release for treatment of chronic pain: a review

    Directory of Open Access Journals (Sweden)

    Vadivelu N

    2011-08-01

    Full Text Available Nalini Vadivelu1, Alexander Timchenko1, Yili Huang2, Raymond Sinatra11Department of Anesthesiology, Yale University School of Medicine, New Haven, CT; 2Internal Medicine, North Shore-LIJ Plainview Hospital, Plainview, NY, USAAbstract: Tapentadol is a centrally acting analgesic with a dual mechanism of action of mu receptor agonism and norepinephrine reuptake inhibition. Tapentadol immediate-release is approved by the US Food and Drug Administration for the management of moderate-to-severe acute pain. It was developed to decrease the intolerability issue associated with opioids. Tapentadol extended-release has a 12-hour duration of effect, and has recently been evaluated for pain in patients with chronic osteoarthritis, low back pain, and pain associated with diabetic peripheral neuropathy. Tapentadol extended-release was found to provide safe and highly effective analgesia for the treatment of chronic pain conditions, including moderate-to-severe chronic osteoarthritis pain and low back pain. Initial trials demonstrating efficacy in neuropathic pain suggest that tapentadol has comparable analgesic effectiveness and better gastrointestinal tolerability than opioid comparators, and demonstrates effectiveness in settings of inflammatory, somatic, and neuropathic pain. Gastrointestinal intolerance and central nervous system effects were the major adverse events noted. Tapentadol will need to be rigorously tested in chronic neuropathic pain, cancer-related pain, and cancer-related neuropathic pain.Keywords: osteoarthritis, neuropathic pain, analgesic, opioids, norepinephrine

  10. Management of obesity and cardiometabolic risk – role of phentermine/extended release topiramate

    Directory of Open Access Journals (Sweden)

    Sweeting AN

    2014-02-01

    Full Text Available Arianne N Sweeting,1 Eddy Tabet,1 Ian D Caterson,1,2 Tania P Markovic1,2 1Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 2Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, NSW, Australia Abstract: The US Food and Drug Administration (FDA recently approved lorcaserin and the combination of phentermine and extended release topiramate (phentermine/topiramate ER for the treatment of obesity in conjunction with a lifestyle intervention, expanding the therapeutic options for long-term obesity pharmacotherapy, which was previously limited to orlistat. Combination phentermine/topiramate ER is associated with greater weight loss compared to its constituent monotherapy, with a more favorable adverse effect profile. Phentermine/topiramate ER also appears to have beneficial effects on cardiometabolic risk, although longer-term cardiovascular safety data are required. While there are no head-to-head studies among the currently available obesity pharmacotherapy agents, phentermine/topiramate ER appears to have a superior weight loss profile. This review will discuss the epidemiology, natural history, and cardiometabolic risk associated with obesity, provide an overview on current obesity pharmacotherapy, and summarize the recent clinical efficacy and safety data underpinning the FDA's approval of both phentermine/topiramate ER and lorcaserin as pharmacotherapy for a long-term obesity intervention. Keywords: obesity, phentermine/topiramate extended release, safety and efficacy, review

  11. Topiramate Extended-Release Options: A Focus on Efficacy and Safety in Epilepsy and Comorbidities

    Directory of Open Access Journals (Sweden)

    Yuchen Wang

    2017-02-01

    Full Text Available Topiramate (TPM is effective for multiple seizure types and epilepsy syndromes in children and adults. Topiramate has adverse effects (including cognitive, depression, renal stones, but many of these are low incidence when started at a low dose and slowly titrated to 100 to 200 mg/day. Also, TPM has proven benefit for migraine, obesity, eating disorders, and alcohol use disorders, which can be comorbid in patients with epilepsy and may also be effective in subpopulations within specific psychiatric diagnoses. Recently approved extended-release formulations of TPM (Trokendi and Qudexy in the United States have reliable data supporting their safety and efficacy for patients with epilepsy. They have potential for more rapid titration within 1 month to 200 mg/day and have better patient retention than TPM immediate-release, but there are no robust double-blind randomized controlled trials comparing the different formulations. We expect the once per day extended-release formulations to improve medication adherence compared with the twice per day formulations. This has significant potential to improve outcomes in epilepsy and the other TPM-responsive disorders.

  12. Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

    Energy Technology Data Exchange (ETDEWEB)

    Bhunia, Tridib [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India); Goswami, Luna [KIIT School of Biotechnology, KIIT University Campus XI, Patia, Bhubaneswar 751024, Orissa (India); Chattopadhyay, Dipankar [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India); Bandyopadhyay, Abhijit, E-mail: abpoly@caluniv.ac.in [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India)

    2011-08-15

    Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

  13. Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

    Science.gov (United States)

    Bhunia, Tridib; Goswami, Luna; Chattopadhyay, Dipankar; Bandyopadhyay, Abhijit

    2011-08-01

    Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

  14. Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

    International Nuclear Information System (INIS)

    Bhunia, Tridib; Goswami, Luna; Chattopadhyay, Dipankar; Bandyopadhyay, Abhijit

    2011-01-01

    Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

  15. USE OF EXTENDED-RELEASE PRAMIPEXOLE IN EARLY-STAGE PARKINSON’S DISEASE: DESCRIPTION OF A CLINICAL CASE

    Directory of Open Access Journals (Sweden)

    N. V. Fedorova

    2014-11-01

    Full Text Available The paper considers a clinical case of early-stage mixed Parkinson’s disease (PD with significant affective disorders and restless legs syndrome. Once-daily extended-release pramipexole 3 mg significantly improved a patient’s status and led to regression of movement and affective disorders. The paper gives data on the efficacy of dopamine receptor agonists in treating PD and the benefits of their extended-release formulations.

  16. Differential scanning calorimetry as a screening technique in compatibility studies of acyclovir extended release formulations

    International Nuclear Information System (INIS)

    Barboza, Fernanda M.; Vecchia, Debora D.; Tagliari, Monika P.; Ferreira, Andrea Granada; Silva, Marcos A.S.; Stulzer, Hellen K.

    2009-01-01

    Acyclovir (ACV) has been investigated during the past years, mainly due to its antiviral activity. Assessment of possible incompatibility between an active component and different excipients along with the evaluation of thermal stability are crucial parts of a normal study prior to the final formulation setting of a medicine. Thermal analysis studies were used as important and complementary tools during pre-formulation to determine the compatibility of drug excipients with the purpose of developing an acyclovir extended release formulation. Fourier transform infrared spectroscopy and X-ray powder diffraction analyses were also realized. The results showed that ACV only exhibited interaction which could influence the stability of the product in the binary mixtures of ACV/magnesium stearate. (author)

  17. Update on extended release quetiapine fumarate in schizophrenia and bipolar disorders

    Directory of Open Access Journals (Sweden)

    El-Khalili N

    2012-11-01

    Full Text Available Nizar El-KhaliliAlpine Clinic, Lafayette, IN, USAAbstract: The atypical antipsychotic quetiapine fumarate is available both as an immediate release (IR and as an extended release (XR formulation allowing flexibility of dosing for individual patients. Approved uses of quetiapine XR include the treatment of schizophrenia (including maintenance therapy for prevention of relapse, the treatment of bipolar disorder (manic and depressive episodes, and the prevention of recurrence in patients with bipolar disorder who respond to quetiapine XR. This narrative review provides an update on quetiapine XR in these indications. The pharmacological profile of quetiapine, including a moderate affinity for dopamine D2 receptors and higher affinity for serotonin 5-hydroxytryptophan (5-HT2A receptors, may explain its broad efficacy and low propensity for extrapyramidal symptoms (EPS. The XR formulation has similar bioavailability but prolonged plasma levels compared with the IR formulation, allowing for less frequent (once-daily dosing. Clinical studies have confirmed the efficacy of quetiapine XR in relieving the acute symptoms of schizophrenia during short-term trials, and reducing the risk for relapse in long-term studies. Direct switching from the IR formulation to the same dose of the XR formulation did not reveal any loss of efficacy or tolerability issues, and switching patients to quetiapine XR from conventional or other atypical antipsychotics (for reasons of insufficient efficacy or tolerability also proved to be beneficial and generally well tolerated. In bipolar disorder, quetiapine XR has also proven effective in relieving acute depressive and manic symptoms. Adverse events with quetiapine XR in patients with either schizophrenia or bipolar disorder are similar to those associated with the IR formulation, the most common being sedation, dry mouth, somnolence, dizziness, and headache. The low propensity for EPS is maintained with the XR formulation

  18. Prevention of gamma radiation induced anaemia in mice by diltiazem

    International Nuclear Information System (INIS)

    Nunia, V.; Goyal, P.K.

    2004-01-01

    Intraperitoneal administration of diltiazem (DTZ), half an hour prior to whole body gamma irradiation (2.5, 5.0, and 7.5 Gy), showed the protection of animals from radiation-induced anaemia. Radiation exposure significantly (p<0.001) reduced the number of pro- and normoblasts in bone marrow and red blood cell (RBC) counts, hemoglobin (Hb), hematocrit (Hct), and erythropoietin (EPO) level in blood, but increased myeloid/erythroid ratio. At all the radiation doses, the maximum decrease in these values was noted on the 3rd day, followed by a gradual recovery from the 7th day, but it was not recorded as normal even until the end of experimentation. In animals pretreated with DTZ, these values were measured higher at all the time periods in comparison to corresponding control, and these were almost normal at the last autopsy interval only at 2.5 Gy radiation dose. DTZ maintained the higher EPO level in blood, which acted on bone marrow and spleen colony forming unit for erythroblast (CFU-E), and stimulated such cells to produce RBCs. These results confirm that DTZ has the potency to alter anaemic condition favorably through the protection of bone marrow stem cells, and subsequently it maintains the higher number of pro-and normoblasts in bone marrow, RBC counts, Hb, Hct percentage, and EPO level in blood and the lower myeloid/erythroid ratio in bone marrow. (author)

  19. Paliperidone extended-release: does it have a place in antipsychotic therapy?

    Directory of Open Access Journals (Sweden)

    Carlos Schönfeldt-Lecuona

    2011-03-01

    Full Text Available Maximilian Gahr1,*, Markus A Kölle1,*, Carlos Schönfeldt-Lecuona1, Peter Lepping2, Roland W Freudenmann11Department of Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany; 2Department of Psychiatry, Glyndwr University, Wales, UK *Both authors contributed equally and their order was determined by coin toss.Abstract: Paliperidone (9-hydroxy-risperidone, the active metabolite of risperidone, was approved for treating schizophrenia worldwide in 2006 as paliperidone extended-release (PER, and became the first second-generation antipsychotic specifically licensed for treating schizoaffective disorder in 2009. However, at the same time, its comparatively high cost gave rise to concerns about the cost-effectiveness of PER as compared with its precursor, risperidone. This paper reviews the existing knowledge of the pharmacology, kinetics, efficacy, tolerability, and fields of application of PER, and compares PER with risperidone in order to determine whether it has a place in antipsychotic therapy. An independent assessment of all relevant publications on PER published until July 2010 was undertaken. PER has a unique pharmacological profile, including single dosing, predominantly renal excretion, low drug–drug interaction risk, and differs from risperidone in terms of mode of action and pharmacokinetics. High-level evidence suggests that PER is efficacious and safe in schizophrenia, schizoaffective disorder, and acute manic episodes. There is a striking lack of published head-to-head comparisons between PER and risperidone, irrespective of indication. Low-level evidence shows a lower risk for hyperprolactinemia and higher patient satisfaction with PER than with risperidone. PER adds to the still limited arsenal of second-generation antipsychotics. In the absence of direct comparisons with risperidone, it remains difficult to come to a final verdict on the potential additional therapeutic benefits of PER which would justify its substantially

  20. The effect of diltiazem on the manifestations of hyperthyroidism and thyroid function tests.

    Science.gov (United States)

    Keleştimur, F; Aksu, A

    1996-01-01

    The aim of this study is to evaluate the effect of diltiazem on the symptoms and signs of hyperthyroidism and thyroid function tests and to assess whether diltiazem can be used associated with an anti-thyroid drug, propylthiouracil. Twenty-two patients with hyperthyroidism were included in a prospective, randomized and placebo controlled study. Group 1 (n:12) patients received diltiazem, 60 mg twice a day, for 30 days. Group 2 (n:10) patients received placebo for 30 days. The patients in both groups were given propylthiouracil, 100 mg three times a day, for the last 20 days of the study period. The patients remained in the hospital during the first 10 days. A standardized hyperthyroid symptom score (HSS) and thyroid function tests including thyroid-stimulating hormone (TSH), free thyroxine (free T4), free triiodothyronine (free T3), total thyroxine (T4) and total triiodothyronine (T3) were evaluated before and after 10 and 30 days of the study period. HSS decreased from 27.80 +/- 4.54 to 22.51 +/- 4.04 after 10 days of diltiazem therapy in Group 1 (p 0.01). No significant changes in thyroid function tests have occurred in both groups after 10 days of treatment. Diltiazem can be used in patients with hyperthyroidism to alleviate adrenergic manifestations. It can also be safely combined with propylthiouracil.

  1. A COMPARATIVE STUDY OF LATERAL SPHINCTEROTOMY AND LOCAL APPLICATION OF 2% DILTIAZEM GEL IN TREATMENT OF CHRONIC ANAL FISSURE

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    Rajashekar

    2015-11-01

    Full Text Available BACKGROUND AND OBJECTIVES Anal fissures are commonly encountered in routine colorectal practice. Chronic fissures have traditionally been treated surgically. Developments in the pharmacological understanding of the internal anal sphincter have resulted in more conservative approaches towards treatment. In this study, we compare topical 2% Diltiazem gel and lateral internal sphincterotomy with respect to symptomatic relief, healing and side effects in the treatment of chronic fissure in ano. METHODS 60 patients with chronic fissure in ano were randomly divided into Diltiazem gel and internal sphincterotomy groups. Patients were followed up at weekly intervals for minimum of eight weeks. Data was recorded accordingly. RESULTS Fissure completely healed in 28(93.33% out of 30 patients treated with 2% Diltiazem gel between 4-8 weeks. Healing was 100% with internal sphincterotomy. The mean duration required for healing of fissure was 4.86 weeks in Diltiazem gel group and 3.66 weeks in internal sphincterotomy group. 61.5% patients were free from pain after treatment with Diltiazem gel whereas in internal sphicterotomy group 66.66% patients had pain relief at the end of 4 weeks. INTERPRETATION AND CONCLUSION Comparison between Diltiazem gel application and internal sphincterotomy did not show any significant difference in fissure healing and pain relief. No side effects were seen in Diltiazem gel therapy. Topical Diltiazem should be the initial treatment in chronic fissure in ano. It is better to reserve internal sphincterotomy for patients with relapse or therapeutic failure to prior pharmacological treatment.

  2. Extended-release naltrexone for pre-release prisoners: A randomized trial of medical mobile treatment

    Science.gov (United States)

    Gordon, Michael S.; Vocci, Frank J.; Fitzgerald, Terrence T.; O'Grady, Kevin E.; O'Brien, Charles P.

    2017-01-01

    Background Extended-release naltrexone (XR-NTX), is an effective treatment for opioid use disorder but is rarely initiated in US prisons or with criminal justice populations. Mobile treatment for chronic diseases have been implemented in a variety of settings. Mobile treatment may provide an opportunity to expand outreach to parolees to surmount barriers to traditional clinic treatment. Methods Male and female prisoners (240) with pre-incarceration histories of opioid use disorder who are within one month of release from prison will be enrolled in this randomized clinical trial. Participants are randomized to one of two study arms: 1) [XR-NTX-OTx] One injection of long-acting naltrexone in prison, followed by 6 monthly injections post-release at a community opioid treatment program; or 2) [XR-NTX+ MMTx] One injection of long-acting naltrexone in prison followed by 6 monthly injections post-release at the patient's place of residence utilizing mobile medical treatment. The primary outcomes are: treatment adherence; opioid use; criminal activity; re-arrest; reincarceration; and HIV risk-behaviors. Results We describe the background and rationale for the study, its aims, hypotheses, and study design. Conclusions The use of long-acting injectable naltrexone may be a promising form of treatment for pre-release prisoners. Finally, as many individuals in the criminal justice system drop out of treatment, this study will assess whether treatment at their place of residence will improve adherence and positively affect treatment outcomes. PMID:28011389

  3. Safety and Efficacy of Paliperidone Extended-Release in Acute and Maintenance Treatment of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Edoardo Spina

    2011-01-01

    Full Text Available Paliperidone, the major active metabolite of risperidone, is a second-generation antipsychotic that has been developed as an extended-release (ER tablet formulation that minimizes peak-trough fluctuations in plasma concentrations, allowing once-daily administration and constant drug delivery. Paliperidone ER has demonstrated efficacy in the reduction of acute schizophrenia symptoms in 6-week, placebo-controlled, double-blind trials and clinical benefits were maintained in the longer-term according to extension studies of up to 52 weeks in duration. Compared with quetiapine, paliperidone ER was associated with a more rapid symptom improvement. In addition, it was more effective than placebo in the prevention of symptom recurrence. Paliperidone ER is generally well tolerated with a predictable adverse event profile. Like risperidone, it is associated with a dose-dependent risk of extrapyramidal symptoms and prolactin elevation. Short-and longer-term studies have indicated a low liability for paliperidone ER to cause metabolic (ie, weight gain, hyperglycaemia and lipid dysregulation or cardiovascular adverse effects. Available safety data from elderly patients appear to be promising. Due to negligible hepatic biotransformation, paliperidone ER is unlikely to be involved in clinically significant metabolic drug-drug interactions. Additional active comparator trials evaluating efficacy, tolerability and cost-effectiveness are required to better define the role of paliperidone ER in the treatment of schizophrenia in relation to other currently available second-generation antipsychotics, particularly risperidone.

  4. Film Coating of Nifedipine Extended Release Pellets in a Fluid Bed Coater with a Wurster Insert

    Directory of Open Access Journals (Sweden)

    Luciane Franquelin Gomes de Souza

    2014-01-01

    Full Text Available The objective of this work was to study the coating process of nifedipine extended release pellets using Opadry and Opadry II, in a fluid bed coater with a Wurster insert. The coating process was studied using a complete experimental design of two factors at two levels for each polymer. The variables studied were the inlet air temperature and the coating suspension flow rate. The agglomerate fraction and coating efficiency were the analyzed response variables. The air temperature was the variable that most influenced the coating efficiency for both polymers. In addition, a study of the dissolution profiles of coated and uncoated pellets using 0.5% sodium lauryl sulfate in simulated gastric fluid without enzymes (pH 1.2 was conducted. The results showed a prolonged release profile for the coated and uncoated pellets that was very similar to the standards established by the U.S. Pharmacopoeia. The drug content and the release profiles were not significantly affected by storage at 40°C and 75% relative humidity. However, when exposed to direct sunlight and fluorescent light (light from fluorescent bulbs, the coated pellets lost only 5% of the drug content, while the uncoated ones lost more than 35%; furthermore, the dissolution profile of the uncoated pellets was faster.

  5. Granisetron Extended-Release Injection: A Review in Chemotherapy-Induced Nausea and Vomiting.

    Science.gov (United States)

    Deeks, Emma D

    2016-12-01

    An extended-release (ER) subcutaneously injectable formulation of the first-generation 5-HT 3 receptor antagonist granisetron is now available in the USA (Sustol ® ), where it is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide combination chemotherapy regimens in adults. Granisetron ER is administered as a single subcutaneous injection and uses an erosion-controlled drug-delivery system to allow prolonged granisetron release. Primary endpoint data from phase III studies after an initial cycle of chemotherapy indicate that, when used as part of an antiemetic regimen, granisetron ER injection is more effective than intravenous ondansetron in preventing delayed CINV following highly emetogenic chemotherapy (HEC); is noninferior to intravenous palonosetron in preventing both acute CINV following MEC or HEC and delayed CINV following MEC; and is similar, but not superior, to palonosetron in preventing delayed CINV following HEC. The benefits of granisetron ER were seen in various patient subgroups, including those receiving anthracycline plus cyclophosphamide-based HEC, and (in an extension of one of the studies) over multiple MEC or HEC cycles. Granisetron ER injection is generally well tolerated, with an adverse event profile similar to that of ondansetron or palonosetron. Thus, granisetron ER injection expands the options for preventing both acute and delayed CINV in adults with cancer receiving MEC or anthracycline plus cyclophosphamide-based HEC.

  6. A flexible-dose dispenser for immediate and extended release 3D printed tablets.

    Science.gov (United States)

    Pietrzak, Katarzyna; Isreb, Abdullah; Alhnan, Mohamed A

    2015-10-01

    The advances in personalised medicine increased the demand for a fast, accurate and reliable production method of tablets that can be digitally controlled by healthcare staff. A flexible dose tablet system is presented in this study that proved to be suitable for immediate and extended release tablets with a realistic drug loading and an easy-to-swallow tablet design. The method bridges the affordable and digitally controlled Fused Deposition Modelling (FDM) 3D printing with a standard pharmaceutical manufacturing process, Hot Melt Extrusion (HME). The reported method was compatible with three methacrylic polymers (Eudragit RL, RS and E) as well as a cellulose-based one (hydroxypropyl cellulose, HPC SSL). The use of a HME based pharmaceutical filament preserved the linear relationship between the mass and printed volume and was utilized to digitally control the dose via an input from computer software with dose accuracy in the range of 91-95%. Higher resolution printing quality doubled the printing time, but showed a little effect on in vitro release pattern of theophylline and weight accuracy. Physical characterization studies indicated that the majority of the model drug (theophylline) in the 3D printed tablet exists in a crystal form. Owing to the small size, ease of use and the highly adjustable nature of FDM 3D printers, the method holds promise for future individualised treatment. Copyright © 2015. Published by Elsevier B.V.

  7. Tramadol Extended-Release for the Management of Pain due to Osteoarthritis

    Science.gov (United States)

    Guetti, Cristiana; Paladini, Antonella; Varrassi, Giustino

    2013-01-01

    Current knowledge on pathogenesis of osteoarticular pain, as well as the consequent several, especially on the gastrointestinal, renal, and cardiovascular systems, side effects of NSAIDs, makes it difficult to perform an optimal management of this mixed typology of pain. This is especially observable in elderly patients, the most frequently affected by osteoarthritis (OA). Tramadol is an analgesic drug, the action of which has a twofold action. It has a weak affinity to mu opioid receptors and, at the same time, can result in inhibition of the reuptake of noradrenaline and serotonin in nociceptorial descending inhibitory control system. These two mechanisms, “opioidergic” and “nonopioidergic,” are the grounds for contrasting certain types of pain that are generally less responsive to opioids, such as neuropathic pain or mixed OA pain. The extended-release formulation of tramadol has good efficacy and tolerability and acts through a dosing schedule that allows a high level of patients compliance to therapies with a good recovery outcome for the patients' functional status. PMID:27335872

  8. Pharmacokinetic drug evaluation of extended release lorcaserin for the treatment of obesity.

    Science.gov (United States)

    Hurren, Kathryn M; Dunham, Marissa W

    2017-08-01

    Lorcaserin is a serotonin 2C receptor antagonist that was FDA approved in 2012. Lorcaserin is recently available as an extended-release (ER) formulation for the treatment of obesity as an adjunct to lifestyle modification. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy, and safety of lorcaserin ER will be reviewed. Expert opinion: Lorcaserin ER 20mg daily provides drug exposure bioequivalent to lorcaserin immediate release (IR) 10mg twice daily. Lorcaserin IR is associated with 3.3 and 3.0% placebo-subtracted weight loss in patients without and with diabetes, respectively. A1C was reduced by 0.9% in patients with diabetes. Common side effects include headache, dry mouth, constipation, dizziness, fatigue, and nausea. Lorcaserin provides potential advantages over other antiobesity medications in regards to tolerability and simplicity of medication initiation, but may not be as effective as other options. Lorcaserin ER offers improved ease of administration and anticipated adherence compared to the IR formulation. The place in therapy for lorcaserin ER and other antiobesity medications will be further clarified by results of pending clinical trials addressing cardiovascular outcomes as well as the role pharmacogenomics and comorbid disease states may play in choosing patient-specific therapy.

  9. Film Coating of Nifedipine Extended Release Pellets in a Fluid Bed Coater with a Wurster Insert

    Science.gov (United States)

    de Souza, Luciane Franquelin Gomes; Nitz, Marcello; Taranto, Osvaldir Pereira

    2014-01-01

    The objective of this work was to study the coating process of nifedipine extended release pellets using Opadry and Opadry II, in a fluid bed coater with a Wurster insert. The coating process was studied using a complete experimental design of two factors at two levels for each polymer. The variables studied were the inlet air temperature and the coating suspension flow rate. The agglomerate fraction and coating efficiency were the analyzed response variables. The air temperature was the variable that most influenced the coating efficiency for both polymers. In addition, a study of the dissolution profiles of coated and uncoated pellets using 0.5% sodium lauryl sulfate in simulated gastric fluid without enzymes (pH 1.2) was conducted. The results showed a prolonged release profile for the coated and uncoated pellets that was very similar to the standards established by the U.S. Pharmacopoeia. The drug content and the release profiles were not significantly affected by storage at 40°C and 75% relative humidity. However, when exposed to direct sunlight and fluorescent light (light from fluorescent bulbs), the coated pellets lost only 5% of the drug content, while the uncoated ones lost more than 35%; furthermore, the dissolution profile of the uncoated pellets was faster. PMID:24772426

  10. Preparation and scale up of extended-release tablets of bromopride

    Directory of Open Access Journals (Sweden)

    Guilherme Neves Ferreira

    2014-04-01

    Full Text Available Reproducibility of the tablet manufacturing process and control of its pharmaceutics properties depends on the optimization of formulation aspects and process parameters. Computer simulation such as Design of Experiments (DOE can be used to scale up the production of this formulation, in particular for obtaining sustained-release tablets. Bromopride formulations are marketed in the form of extended-release pellets, which makes the product more expensive and difficult to manufacture. The aim of this study was to formulate new bromopride sustained release formulations as tablets, and to develop mathematical models to standardize the scale up of this formulation, controlling weight and hardness of the tablets during manufacture according to the USP 34th edition. DOE studies were conducted using Minitab(tm software. Different excipient combinations were evaluated in order to produce bromopride sustained-release matrix tablets. In the scale-up study, data were collected and variations in tableting machine parameters were measured. Data were processed by Minitab(tm software, generating mathematical equations used for prediction of powder compaction behavior, according to the settings of the tableting machine suitable for scale-up purposes. Bromopride matrix tablets with appropriate characteristics for sustained release were developed. The scale-up of the formulation with the most suitable sustained release profile was established by using mathematical models, indicating that the formulation can be a substitute for the pellets currently marketed.

  11. Use of partial AUC to demonstrate bioequivalence of Zolpidem Tartrate Extended Release formulations.

    Science.gov (United States)

    Lionberger, Robert A; Raw, Andre S; Kim, Stephanie H; Zhang, Xinyuan; Yu, Lawrence X

    2012-04-01

    FDA's bioequivalence recommendation for Zolpidem Tartrate Extended Release Tablets is the first to use partial AUC (pAUC) metrics for determining bioequivalence of modified-release dosage forms. Modeling and simulation studies were performed to aid in understanding the need for pAUC measures and also the proper pAUC truncation times. Deconvolution techniques, In Vitro/In Vivo Correlations, and the CAT (Compartmental Absorption and Transit) model were used to predict the PK profiles for zolpidem. Models were validated using in-house data submitted to the FDA. Using dissolution profiles expressed by the Weibull model as input for the CAT model, dissolution spaces were derived for simulated test formulations. The AUC(0-1.5) parameter was indicative of IR characteristics of early exposure and effectively distinguished among formulations that produced different pharmacodynamic effects. The AUC(1.5-t) parameter ensured equivalence with respect to the sustained release phase of Ambien CR. The variability of AUC(0-1.5) is higher than other PK parameters, but is reasonable for use in an equivalence test. In addition to the traditional PK parameters of AUCinf and Cmax, AUC(0-1.5) and AUC(1.5-t) are recommended to provide bioequivalence measures with respect to label indications for Ambien CR: onset of sleep and sleep maintenance.

  12. The management of schizophrenia: focus on extended-release quetiapine fumarate

    Directory of Open Access Journals (Sweden)

    Peuskens J

    2011-09-01

    Full Text Available Joseph Peuskens Universitair Psychiatrisch Centrum KU Leuven, Campus St Jozef Kortenberg, Kortenberg, Belgium Abstract: Effective management of schizophrenia remains a significant clinical challenge. While antipsychotic medications have proven efficacy in this disease, there remains an opportunity to further improve symptom control and long-term relapse prevention. Also, a number of factors, including tolerability and complex dosing regimens, can result in nonadherence to medication. Quetiapine is an atypical antipsychotic with proven efficacy and an established tolerability profile in schizophrenia. The once-daily extended-release formulation (quetiapine XR offers a simplified dosing regimen and titration schedule. Short-term clinical studies have shown that quetiapine XR (400–800 mg/d is efficacious in the acute treatment of schizophrenia, while a long-term study has shown that quetiapine XR was significantly more effective than placebo at preventing relapse. Furthermore, an investigation in which stable patients switched from the immediate-release formulation (quetiapine IR to quetiapine XR showed that quetiapine XR is generally well tolerated and has no loss of efficacy compared with quetiapine IR. In patients who experienced insufficient efficacy or poor tolerability on their previous antipsychotic, switching to quetiapine XR significantly improved efficacy compared with the previous treatment. In conclusion, quetiapine XR is an effective and generally well tolerated treatment for schizophrenia. Furthermore, once-daily dosing may improve patient adherence, which may impact positively on patient outcomes. Keywords: adherence, atypical antipsychotics, adverse events

  13. Opioid rotation with extended-release opioids: where should we begin?

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    Nalamachu S

    2011-12-01

    Full Text Available Srinivas NalamachuInternational Clinical Research Institute and Pain Management Institute, Overland Park, KS, USAAbstract: Opioid rotation is a common and necessary clinical practice in the management of chronic non-cancer pain to improve therapeutic efficacy with the lowest opioid dose. When dose escalations fail to achieve adequate analgesia or are associated with intolerable side effects, a trial of a new opioid should be considered. Much of the scientific rationale of opioid rotation is based on the wide interindividual variability in sensitivity to opioid analgesics and the novel patient response observed when introducing an opioid-tolerant patient to a new opioid. This article discusses patient indicators for opioid rotation, the conversion process between opioid medications, and additional practical considerations for increasing the effectiveness of opioid therapy during a trial of a new opioid. A Patient vignette that demonstrates a step-wise approach to opioid rotation is also presented.Keywords: extended-release opioids, chronic pain, opioid rotation

  14. Optimization of Melatonin Dissolution from Extended Release Matrices Using Artificial Neural Networking.

    Science.gov (United States)

    Martarelli, D; Casettari, L; Shalaby, K S; Soliman, M E; Cespi, M; Bonacucina, G; Fagioli, L; Perinelli, D R; Lam, J K W; Palmieri, G F

    2016-01-01

    Efficacy of melatonin in treating sleep disorders has been demonstrated in numerous studies. Being with short half-life, melatonin needs to be formulated in extended-release tablets to prevent the fast drop of its plasma concentration. However, an attempt to mimic melatonin natural plasma levels during night time is challenging. In this work, Artificial Neural Networks (ANNs) were used to optimize melatonin release from hydrophilic polymer matrices. Twenty-seven different tablet formulations with different amounts of hydroxypropyl methylcellulose, xanthan gum and Carbopol®974P NF were prepared and subjected to drug release studies. Using dissolution test data as inputs for ANN designed by Visual Basic programming language, the ideal number of neurons in the hidden layer was determined trial and error methodology to guarantee the best performance of constructed ANN. Results showed that the ANN with nine neurons in the hidden layer had the best results. ANN was examined to check its predictability and then used to determine the best formula that can mimic the release of melatonin from a marketed brand using similarity fit factor. This work shows the possibility of using ANN to optimize the composition of prolonged-release melatonin tablets having dissolution profile desired.

  15. Potential role of gabapentin and extended- release gabapentin in the management of menopausal hot flashes

    Directory of Open Access Journals (Sweden)

    Yadav M

    2013-08-01

    Full Text Available Manisha Yadav, Judith Volkar Center for Specialized Women’s Health, Cleveland Clinic Foundation, Cleveland, Ohio, USA Abstract: About 80% of postmenopausal women experience vasomotor symptoms, such as hot flashes and night sweats – symptoms that are associated with sleep disruption and can lead to fatigue and mood changes. Moreover, hot flashes can be embarrassing for women, causing difficulties at work and in their social lives. Many therapies have been advocated for relief of vasomotor symptoms, but only hormone therapy has been US Food and Drug Administration approved. However, after the Women's Health Initiative Study suggested that there was a correlation between hormone therapy and increased risk for breast cancer and cardiovascular events, many women stopped taking hormone therapy, and many do not want to initiate it. Hormone therapy is also contraindicated in certain women, such as those with a history of hormone-stimulated cancer like breast and uterine cancer. Gabapentin (Neurontin has shown efficacy in relieving vasomotor symptoms and is used as off-label for this indication. A new extended-release formulation of gabapentin has also shown efficacy in treating hot flashes and improving sleep quality with possibly fewer side effects than regular gabapentin. Keywords: Hot flushes, vasomotor symptoms, postmenopausal, hormone-sensitive cancer, non-hormonal therapy, gastric-retentive, Breeze

  16. Caustic Ingestions

    Directory of Open Access Journals (Sweden)

    M Rafeey

    2014-04-01

    Full Text Available Prevention has a main role in reducing the occurrence of corrosive ingestion especially in children, yet this goal is far from being reached in developing countries, where such injuries are largely unreported and their true prevalence simply cannot be extrapolated from random articles or personal experience. Because of the accidental nature of the ingestions, the case fatality rate for pediatric patients is significantly less than that of adolescents and adults.  Currently, esophagoscopy is recommended for all patients with a history of caustic substance ingestion because clinical criteria have not proved to be reliable predictors of esophageal injury. The presence or absence of three serious signs and symptoms-vomiting, drooling, and stridor—as well as the presence and location of oropharyngeal burns could be  compared with the findings on subsequent esophagoscopy. Medical or endoscopic prevention of stricture is debatable, yet esophageal stents, absorbable or not, show promising data. The purpose of this lecture is to outline the current epidemiology, mechanism of injury, clinical manifestations, management and long-term complications of caustic ingestions in pediatric patients.   Key Words: Caustic, Children, Ingestions.

  17. Successful treatment of polymedicamentous poisoning with metoprolol, diltiazem and cilazapril

    Directory of Open Access Journals (Sweden)

    Radovanović Milan R.

    2009-01-01

    Full Text Available Introduction. Poisoning caused by drugs with cardiodepressive effects is an urgent condition in medicine which is associated with high mortality rate regardless of modern therapeutic methods. Accidental or intentional poisoning whit these drugs produces heart activity depression and cardiovascular collapse as consequences. Current therapy for severe poisoning caused by beta-blockers and calcium channel blockers includes both unspecific and specific antidote therapy whit glucagon, as well as application of adrenergic drugs, calcium, phosphodiesterase inhibitors and hyperinsulinemia/euglycemia therapy. However, even whit the application of these drugs, prompt measures of unspecific detoxication therapy and cardiopulmonary reanimation are crucial for survival of patients with severe poisoning. Case report. A 28-year-old female patient was hospitalized for cardiogenic shock and altered state of conscioussnes (Glasgow coma score = 4, caused by acute poisoning with 2 g of metoprolol (Presolol®, 1.8 g of diltiazem (Cortiazem® and 50 mg of cilazapril (Zobox®. Prolonged cardiopulmonary resuscitation was applied during the first 16 hours of hospitalization, including administration of crystaline solutions (8 L, 17 mg of adrenaline, 4 mg of atropine, 4 mg of glucagone and 1.6 g of dopamine, with electro-stimulation by temporary pacemaker and mechanical ventilation. In a defined time period, normalized state of consciousness was registered, mechanical ventilation was stopped and normal heart activity and hemodynamic stability were accomplished. During hospitalization the patient was treated for mild pneumonia and after ten days, completely recovered, was released and sent to home treatment. Conclusion. Prompt measures of cardiopulmonary resuscitation and multidisciplinary treatment in intensive care units significantly increase the chances of complete recovery of a patient with severe poisoning caused by drugs with cardiodepressive efects.

  18. Development and validation of a dissolution test for diltiazem hydrochloride in immediate release capsules

    Directory of Open Access Journals (Sweden)

    Taciane Ferreira Mendonça

    2011-01-01

    Full Text Available This work describes the development and validation of a dissolution test for 60 mg of diltiazem hydrochloride in immediate release capsules. The best dissolution in vitro profile was achieved using potassium phosphate buffer at pH 6.8 as the dissolution medium and paddle as the apparatus at 50 rpm. The drug concentrations in the dissolution media were determined by UV spectrophotometry and HPLC and a statistical analysis revealed that there were significant differences between HPLC and spectrophotometry. This study illustrates the importance of an official method for the dissolution test, since there is no official monograph for diltiazem hydrochloride in capsules.

  19. Acceptability of Extended-Release Naltrexone by Heroin-Dependent Patients and Addiction Treatment Providers in the Netherlands

    NARCIS (Netherlands)

    Zaaijer, Eline; Goudriaan, Anna E.; Koeter, Maarten W. J.; Booij, Jan; van den Brink, Wim

    2016-01-01

    Background: Extended-release naltrexone (XRNT) was developed to overcome poor treatment compliance with oral naltrexone in alcohol and opioid-dependent patients. XRNT injections are registered in the United States and Russia, but not in The Netherlands. However, XRNT can be obtained for individual

  20. Guanfacine Extended Release in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Placebo-Controlled Trial

    Science.gov (United States)

    Sallee, Floyd R.; McGough, James; Wigal, Tim; Donahue, Jessica; Lyne, Andrew; Biederman, Joseph

    2009-01-01

    A double-blind, 9-week, randomized trial was done to compare the efficacy of guanfacine extended release (GXR) with a placebo in treating children and adolescents with attention-deficit/hyperactivity disorders (ADHD). Results find a significant reduction in ADHD from baseline to endpoint for all daily doses of GXR which were measured at 1-, 2-,…

  1. 76 FR 68766 - Draft Blueprint for Prescriber Education for Long-Acting/Extended-Release Opioid Class-Wide Risk...

    Science.gov (United States)

    2011-11-07

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0771] Draft Blueprint for Prescriber Education for Long-Acting/ Extended-Release Opioid Class-Wide Risk... announcing the availability of a draft document entitled ``Blueprint for Prescriber Education for the Long...

  2. 76 FR 53908 - Determination That OPANA ER (Oxymorphone Hydrochloride) Extended-Release Tablets, 7.5 Milligrams...

    Science.gov (United States)

    2011-08-30

    ... proceedings that could result in the withdrawal of approval of the ANDAs that refer to the listed drug. OPANA... relief of moderate to severe pain in patients requiring continuous, around-the-clock opioid treatment for... withdrawal of OPANA ER (oxymorphone HCl) extended-release tablets, 7.5 mg and 15 mg, from sale. We have also...

  3. Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    S Yu Vorotnikova

    2012-09-01

    Full Text Available Реферат по статье: Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus Juliana Levy, Roberta A Cobas, Marilia B Gomes. Diabetol Metab Syndr. 2010 Mar 18; 2:16.

  4. A single 2 g oral dose of extended-release azithromycin for treatment of gonococcal urethritis.

    Science.gov (United States)

    Yasuda, Mitsuru; Ito, Shin; Kido, Akira; Hamano, Kiminari; Uchijima, Yutaka; Uwatoko, Noriyasu; Kusuyama, Hiroyuki; Watanabe, Akiko; Miyamura, Ryuzou; Miyata, Kazutoyo; Deguchi, Takashi

    2014-11-01

    We treated gonococcal urethritis in men with a single 2 g dose of azithromycin extended-release formulation (azithromycin-SR) to determine its microbiological outcomes and tolerability. We enrolled 189 Japanese men with gonococcal urethritis between April 2009 and December 2013. The patients were given a single 2 g dose of azithromycin-SR. Microbiological efficacy was evaluated by the results of the post-treatment molecular testing of Neisseria gonorrhoeae. MIC testing was performed only for pretreatment isolates of N. gonorrhoeae collected from the patients. We evaluated 130 patients for microbiological outcomes. Of these patients, 122 (93.8%) were judged to be microbiologically cured on the basis of negative test results. All isolates for which the azithromycin MICs were ≤0.25 mg/L were eradicated, whereas 5 of 12 isolates for which the MICs were 1 mg/L persisted after the treatment. Forty-six adverse events occurred in 41 patients. However, all adverse events were classified as mild. The eradication rate of N. gonorrhoeae was 93.8% in men with gonococcal urethritis treated with a single 2 g dose of azithromycin-SR. The breakpoint MIC of a 2 g dose of azithromycin-SR for gonococcal urethritis associated with clinical treatment failures appeared to be 1 mg/L. With regard to side effects of higher doses of azithromycin, the 2 g dose of azithromycin-SR appeared to improve tolerability. However, the widespread use of a high-dose regimen of azithromycin might lead to the development of further resistance to azithromycin. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Clinical utility of guanfacine extended release in the treatment of ADHD in children and adolescents

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    Bello NT

    2015-06-01

    Full Text Available Nicholas T Bello Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Abstract: Attention deficit hyperactivity disorder (ADHD is the most common psychiatric illness in children and adolescents. Several stimulant medications, such as methylphenidate and amphetamine derivatives, are available to treat ADHD in pediatric patients. Nonstimulant medications are more preferred by some parents, other caregivers, and patients because they lack the abuse potential of stimulant medications. In the US, one available nonstimulant option is guanfacine extended release (XR. As a selective α2A adrenergic receptor, guanfacine acts on the central noradrenergic pathways and cortical noradrenergic targets to improve working memory and attention. The XR formulation of guanfacine, compared with the immediate-release formulation, is more effective for the long-term management of ADHD and is associated with fewer adverse effects. Available data also indicate that guanfacine XR is superior to atomoxetine and is as effective as the nonselective α2 adrenergic receptor agonist, clonidine XR. The most common adverse effects associated with guanfacine XR are somnolence, fatigue, bradycardia, and hypotension. Somnolence is the most often cited reason for discontinuation. Guanfacine XR is also labeled for use as an adjuvant to stimulant treatment for ADHD. A similar profile of adverse effects as reported with monotherapy is reported when guanfacine XR is “added on” to stimulant therapy with somnolence as the most commonly reported adverse event. This review discusses the clinical efficacy and patient preference of guanfacine XR based on available published data on the safety, relative effectiveness, and tolerance of this medication to treat ADHD. Keywords: Intuniv, norepinephrine, prefrontal cortex, locus coeruleus, impulsivity, inattentive

  6. Levomilnacipran Extended-Release Treatment in Patients With Major Depressive Disorder: Improvements in Functional Impairment Categories

    Science.gov (United States)

    Gommoll, Carl P.; Chen, Changzheng; Greenberg, William M.; Ruth, Adam

    2015-01-01

    Objective: In this post hoc analysis, improvement in functional impairment in patients with major depressive disorder (MDD) treated with levomilnacipran extended release (ER) was evaluated by assessing shifts from more severe to less severe functional impairment categories on individual Sheehan Disability Scale (SDS) subscales. Method: SDS data were pooled from 5 phase II/III studies conducted between December 2006 and March 2012 of levomilnacipran ER versus placebo in adult patients with MDD (DSM-IV-TR criteria). Proportions of patients shifting from moderate-extreme baseline impairment (score ≥ 4) to mild-no impairment (score ≤ 3) at end of treatment were assessed for each SDS subscale. Proportions of patients shifting from marked-extreme (score ≥ 7) baseline impairment to moderate-no (score ≤ 6) or mild-no impairment (score ≤ 3) at end of treatment, and shifts in which patients worsened from moderate-no to marked-extreme impairment, were also evaluated. Results: A significantly higher proportion of patients treated with levomilnacipran ER than placebo-treated patients improved from more severe categories of functional impairment at baseline to less severe impairment categories across all SDS subscales: work/school, social life, and family life/home responsibilities (P impairment at baseline improved to mild or no impairment, compared with no more than 40% of placebo patients on any subscale. Almost half (42%–47%) of levomilnacipran ER–treated patients versus only about one-third (29%–34%) of placebo patients improved from marked-extreme to mild or no impairment across functional domains. Conclusions: These results suggest that functional improvement was observed across the SDS functional domains. To our knowledge, this is the first such categorical analysis of functional improvement, as measured by the SDS, for an antidepressant. Trial Registration: ClinicalTrials.gov identifiers: NCT00969709, NCT01377194, NCT00969150, and NCT01034462 and Eudra

  7. Role of paliperidone extended-release in treatment of schizoaffective disorder.

    Science.gov (United States)

    Canuso, Carla M; Turkoz, Ibrahim; Fu, Dong Jing; Bossie, Cynthia A

    2010-10-05

    Schizoaffective disorder is characterized by the presence of symptoms of both schizophrenia and a major mood disorder. The coexistence of these symptoms can be difficult to manage, and these patients are generally treated with antipsychotics as well as mood stabilizers and/or antidepressants. Additionally, no established treatment guidelines exist for this disorder. This review describes the combined results of two international, double-blind, placebo-controlled clinical studies of paliperidone extended-release (ER), an atypical antipsychotic recently approved in the US for the treatment of schizoaffective disorder. Subjects in these six-week trials were aged 18-65 years, had a diagnosis of schizoaffective disorder based on the Structural Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) Disorders, and were experiencing an acute exacerbation. The subjects from these studies had significant symptomatology as evidenced by a mean (standard deviation) baseline Positive and Negative Syndrome Scale total score of 92.8 (13.0). Based on Young Mania Rating Scale and/or a 21-item Hamilton Rating Scale for Depression score of ≥16 at baseline, 79.5% and 66.9% of subjects presented with prominent manic and depressive symptoms, respectively, and 46.4% presented with mixed symptoms. Approximately half (45%) of subjects were taking adjunctive mood stabilizers and/or antidepressants. Paliperidone ER was found to be effective in improving psychotic and mood symptoms in these subjects. Paliperidone ER was also effective as monotherapy or adjunctive to mood stabilizers and/or antidepressants for subjects with prominent manic, depressive, or mixed symptoms at baseline. No new tolerability signals were observed in this population. To the best of our awareness, these pooled data provide the largest data set of patients with schizoaffective disorder, and extend our knowledge of disease characteristics and treatment response.

  8. Extended-release naltrexone for pre-release prisoners: A randomized trial of medical mobile treatment.

    Science.gov (United States)

    Gordon, Michael S; Vocci, Frank J; Fitzgerald, Terrence T; O'Grady, Kevin E; O'Brien, Charles P

    2017-02-01

    Extended-release naltrexone (XR-NTX), is an effective treatment for opioid use disorder but is rarely initiated in US prisons or with criminal justice populations. Mobile treatment for chronic diseases has been implemented in a variety of settings. Mobile treatment may provide an opportunity to expand outreach to parolees to surmount barriers to traditional clinic treatment. Male and female prisoners (240) with pre-incarceration histories of opioid use disorder who are within one month of release from prison will be enrolled in this randomized clinical trial. Participants are randomized to one of two study arms: 1) [XR-NTX-OTx] One injection of long-acting naltrexone in prison, followed by 6 monthly injections post-release at a community opioid treatment program; or 2) [XR-NTX+ MMTx] One injection of long-acting naltrexone in prison followed by 6 monthly injections post-release at the patient's place of residence utilizing mobile medical treatment. The primary outcomes are: treatment adherence; opioid use; criminal activity; re-arrest; reincarceration; and HIV risk-behaviors. We describe the background and rationale for the study, its aims, hypotheses, and study design. The use of long-acting injectable naltrexone may be a promising form of treatment for pre-release prisoners. Finally, as many individuals in the criminal justice system drop out of treatment, this study will assess whether treatment at their place of residence will improve adherence and positively affect treatment outcomes. ClinicalTrials.gov: NCT02867124. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. A randomized, double-blind study of hydromorphone hydrochloride extended-release tablets versus oxycodone hydrochloride extended-release tablets for cancer pain: efficacy and safety in Japanese cancer patients (EXHEAL: a Phase III study of EXtended-release HydromorphonE for cAncer pain reLief

    Directory of Open Access Journals (Sweden)

    Inoue S

    2017-08-01

    Full Text Available Satoshi Inoue,1 Yoji Saito,2 Satoru Tsuneto,3 Etsuko Aruga,4 Azusa Ide,1 Yasuyuki Kakurai5 1Clinical Development Department, R&D Division, Daiichi Sankyo, Tokyo,2Department of Anesthesiology, Faculty of Medicine, Shimane University, Shimane, 3Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, 4Department of Palliative Medicine, School of Medicine, Teikyo University, Tokyo, 5Biostatistics and Data Management Department, R&D Division, Daiichi Sankyo, Tokyo, Japan Background: In Japan, there are limited options for switching opioid analgesics. Hydromorphone is an opioid analgesic that is routinely used instead of morphine for cancer pain; however, it is not yet available in Japan. The aim of this study was to assess the efficacy and safety of hydromorphone (DS-7113b extended-release tablets in opioid-naïve patients with cancer pain not relieved by non-opioid analgesics.Subjects and methods: This was a multicenter, randomized, double-blind, parallel-group trial. A double-dummy method was used for blinding. Each randomized subject received either hydromorphone extended-release tablets plus placebo oxycodone hydrochloride extended-release tablets 4 mg/day (n=88 or placebo hydromorphone extended-release tablets plus oxycodone hydrochloride extended-release tablets 10 mg/day (n=93 orally for 7 days (once-daily dosing for hydromorphone and twice-daily dosing for oxycodone. The doses were adjusted as necessary. Efficacy was evaluated by change in visual analog scale (VAS score from baseline to completion of treatment.Results: The between-group difference in least squares mean changes in VAS score from baseline to completion or discontinuation of treatment was −0.4 mm (95% CI −5.9 to 5 mm by analysis of covariance where the baseline VAS score was used as a covariate. The upper limit of the 95% CI was below 10 mm, which was predefined as the noninferiority limit. This verified the noninferiority of hydromorphone tablets

  10. Cost-effectiveness of lurasidone vs quetiapine extended-release (XR) in patients with bipolar depression.

    Science.gov (United States)

    Rajagopalan, Krithika; Meyer, Kellie; O'Day, Ken; Denno, Melissa; Loebel, Antony

    2015-01-01

    Bipolar disorder imposes a high economic burden on patients and society. Lurasidone and quetiapine extended-release (XR) are atypical antipsychotic agents indicated for monotherapy treatment of bipolar depression. Lurasidone is also indicated as adjunctive therapy with lithium or valproate for depressive episodes associated with bipolar disorder. The objective of this analysis was to estimate the cost-effectiveness of lurasidone and quetiapine XR in patients with bipolar depression. A cost-effectiveness model was developed to compare lurasidone to quetiapine XR. The model was based on a US third-party payer perspective over a 3-month time horizon. The effectiveness measure in the model was the percentage of patients achieving remission (Montgomery-Åsberg Depression Rating Scale [MADRS] total score ≤12 by weeks 6-8). The comparison of remission rates was made through an adjusted indirect treatment comparison of lurasidone and quetiapine XR pivotal trials using placebo as the common comparator. Resource utilization for remission vs no remission was estimated from published expert panel data, and resource costs were obtained from a retrospective database study of bipolar I depression patients. Drug costs were estimated using the mean dose from clinical trials and wholesale acquisition costs. Over the 3-month model time period, lurasidone and quetiapine XR patients, respectively, had similar mean numbers of emergency department visits (0.48 vs 0.50), inpatient days (2.1 vs 2.2), and office visits (9.3 vs 9.6). More lurasidone than quetiapine XR patients achieved remission (52.0% vs 43.2%) with slightly higher total costs ($4982 vs $4676), resulting in an incremental cost-effectiveness ratio of $3474 per remission. The probabilistic sensitivity analysis showed lurasidone had an 86% probability of being cost-effective compared to quetiapine XR at a willingness-to-pay threshold of $10,000 per remission. Lurasidone may be a cost-effective option when compared to

  11. Healthcare utilization in adults with opioid dependence receiving extended release naltrexone compared to treatment as usual.

    Science.gov (United States)

    Soares, William E; Wilson, Donna; Rathlev, Niels; Lee, Joshua D; Gordon, Michael; Nunes, Edward V; O'Brien, Charles P; Friedmann, Peter D

    2018-02-01

    Opioid use disorders have reached epidemic proportions, with overdose now the leading cause of accidental death in the United States. Extended release naltrexone (XR-NTX) has emerged as a medication treatment that reduces opioid use and craving. However, the effect of XR-NTX therapy on acute healthcare utilization, including emergency department visits and inpatient hospitalizations, remains uncertain. The objective of the current study is to evaluate hospital-based healthcare resource utilization in adults involved in the criminal justice system with a history of opioid use disorder randomized to XR-NTX therapy compared with treatment as usual (TAU) during a 6-month treatment phase and 12months post-treatment follow up. This retrospective exploratory analysis uses data collected in a published randomized trial. Comparisons of the number of emergency department visits and hospital admissions (for drug detox, psychiatric care and other medical reasons) were performed using chi square tests for any admission and negative binomial models for number of admissions. Of the 308 participants randomized, 96% had utilization data (76% complete 6months, 67% complete follow up). No significant differences were seen in overall healthcare utilization (IRR=0.88, 95%CI 0.63-1.23, p=0.45), or substance use-related drug detox hospitalizations (IRR=0.83, 95%CI 0.32-2.16, p=0.71). Despite having more participants report chronic medical problems at baseline (43% vs. 32%, p=0.05), those receiving XR-NTX generally experienced equivalent or lower rates of healthcare utilization compared to TAU. The XR-NTX group had significantly lower medical/surgical related hospital admissions (IRR=0.55, 95%CI 0.30-1.00, p=0.05) during the course of the entire study. XR-NTX did not significantly increase rates of healthcare utilization compared to TAU. Provider concerns regarding healthcare utilization should not preclude the consideration of XR-NTX as therapy for opioid use disorders. Copyright © 2018

  12. The effect of extended release tolterodine used for overactive bladder treatment on female sexual function

    Directory of Open Access Journals (Sweden)

    Athanasios Zachariou

    Full Text Available ABSTRACT Introduction Overactive bladder (OAB is a common condition, especially in middle aged women, requiring long term therapy with anticholinergics to maintain symptoms relief. The aim of the study was to determine the effect of tolterodine extended release (ER used for OAB treatment on the sexual function of women. Materials and Methods Between August 2010 and August 2014, 220 women with confirmed OAB, attended Urogynecology Outpatient Clinic and were prospectively enrolled in this study. 158 women were evaluated, with a comprehensive history, physical examination, urodynamic studies and Female Sexual Function Index (FSFI questionnaire. 73 patients of group A (control group received no treatment and 85 patients of group B received an anticholinergic regimen – tolterodine ER 4mg once daily. Data were evaluated again in accordance with FSFI after three months, using SPSS software. Results A statistically significant increase was noted in group B in domains of desire (pre-treatment 2.5±0.2 to 4.5±0.2 post-treatment, arousal (3.1±0.2 to 3.1±0.2 respectively, lubrication (3.4±0.3 to 4.3±0.3 respectively, orgasm (3.5±0.3 to 4.5±0.3 respectively, satisfaction (2.6±0.2 to 4.2±0.3 respectively and pain (2.4±0.2 to 4.6±0.4 respectively after three months treatment with tolterodine ER. In group A there were no statistically significant changes in pre and post treatment values (p>0.05. Total FSFI score for group B was significantly higher after tolterodine treatment (26.5±1.5 compared to pre-treatment values (17.4±1.4, p0,05 respectively. Conclusions This preliminary study demonstrates that treatment of OAB with tolterodine ER was found to have positive effect on sexual function of patients with OAB.

  13. Pharmacokinetics of nalbuphine hydrochloride extended release tablets in hemodialysis patients with exploratory effect on pruritus.

    Science.gov (United States)

    Hawi, Amale; Alcorn, Harry; Berg, Jolene; Hines, Carey; Hait, Howard; Sciascia, Thomas

    2015-04-08

    Uremic pruritus is a common and deleterious condition among hemodialysis (HD) patients. Central gating of μ/κ opiate circuitry plays an important role in mediating and countering pruritogenic sensation. The objective of this study was to assess the safety and pharmacokinetics (PK) of the mixed μ-antagonist/κ-agonist nalbuphine, administered orally as nalbuphine HCl extended release (ER) tablets in HD patients, and explore its effect on pruritus. In this open-label multiple escalating dose study, 15 HD patients with pruritus and 9 matched healthy subjects were enrolled. Nalbuphine HCl ER dose was escalated from 30 mg QD to 240 mg BID over 15 days. A full PK profile was obtained under dialysis and non-dialysis conditions as a function of dose. Clearance during dialysis was determined by sampling dialysate and arterial/venous blood during dialysis. Pruritus severity was assessed twice daily using a Visual Analog Scale (VAS). Safety monitoring included extensive monitoring of EKG, blood pressure, and pulse oximetry. In HD patients, nalbuphine concentration peaked within 4-9 hours and attained steady state within 2-3 days, with no significant accumulation. Mean half-life was 14.2 hours, mean Cmax and AUCtau ranged between 13 and 83 ng/mL and 118 and 761 ng∙h/mL, respectively, with exposure increasing in a nearly dose-proportional fashion. Exposure in HD patients was about 2-fold higher than in healthy subjects. There was no meaningful difference between exposure on dialysis and non-dialysis days with 1% or less of the dose removed by dialysis. Nalbuphine suppressed itch in a dose-dependent manner, reducing mean VAS score from 4.0 to 1.2 at 180 mg and 0.4 at 240 mg. Nalbuphine HCl ER tablets can be safely administered to HD patients without dose adjustment up to 240 mg BID and may hold promise in treating uremic pruritus.

  14. Attention benefits after a single dose of metadoxine extended release in adults with predominantly inattentive ADHD.

    Science.gov (United States)

    Manor, Iris; Rubin, Jonathan; Daniely, Yaron; Adler, Lenard A

    2014-09-01

    To assess the first-dose effectiveness and tolerability of metadoxine extended release (MDX) in adults with predominantly inattentive attention-deficit/hyperactivity disorder (ADHD-PI). In this double-blind, placebo-controlled, crossover study, adults with ADHD-PI were randomized 1:1:1 to receive a single dose of MDX 1400 mg, MDX 700 mg, and placebo (ClinicalTrials.gov identifier: NCT01685281). The primary efficacy end point was the mean change in the Test of Variables of Attention (TOVA) ADHD score from baseline to 3 to 5 hours after drug administration. Secondary assessments included TOVA subscores, TOVA response rates (defined as an increase of 0.8 points in the TOVA ADHD score), and the Cambridge Neuropsychological Automated Test Battery. Safety assessments included adverse events and vital signs. The intention-to-treat population included 36 patients (52.8% men; mean age, 32 years). The efficacy of MDX 1400 mg was demonstrated by a statistically significant difference in the mean (± SD) change in the TOVA ADHD score at baseline to 3 to 5 hours after drug administration compared with placebo (2.0 [4.2]; P = 0.009). The TOVA response time variability subscore was significantly different between MDX 1400 mg and placebo (mean difference, 7.9 [19.2] points; P = 0.022). Significantly more adults responded to single-dose MDX 1400 mg versus placebo (97.1% vs 71.4%, P = 0.006). There were no statistically significant differences between MDX 700 mg and placebo on any measures. Exploratory analyses of the Cambridge Neuropsychological Automated Test Battery did not yield significant findings. Fatigue and headache were the 2 most frequently reported adverse events. There were no clinically significant abnormalities in laboratory values, vital signs measurements, Columbia-Suicide Severity Rating Scale scores, or electrocardiographic parameters. Single-dose MDX 1400 mg significantly improved sustained and selective attention in adults with ADHD-PI as measured by the TOVA

  15. Dalfampridine extended release tablets: 1 year of postmarketing safety experience in the US

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    Jara M

    2013-03-01

    Full Text Available Michele Jara,1 Graham Barker,2 Herbert R Henney 3rd1 1Acorda Therapeutics, Inc, Ardsley, NY, USA; 2Biogen Idec, Inc, Maidenhead, Berkshire, UK Background: Dalfampridine extended release tablets (dalfampridine-ER; prolonged-, modified, or sustained-release fampridine in some countries were approved in the US to improve walking in patients with multiple sclerosis, as demonstrated by improvement in walking speed. Postmarketing safety experience is available from exposure of approximately 46,000 patients in the US from product approval through March 2011. Objective: To provide a descriptive analysis of all spontaneously reported postmarketing adverse events (AEs for dalfampridine-ER since product launch. Methods: AE data were extracted from the safety database from product launch through March 31, 2011; AEs were classified using the Medical Dictionary for Regulatory Activities. Seizure cases were reviewed for patient demographics, time to event from treatment onset, and presence of additional risk factors. Results: The most frequently reported postmarketing AEs were similar to those reported during clinical development: dizziness, insomnia, balance disorder, headache, nausea, urinary tract infection, asthenia, and back pain (all included in US product labeling. New clinically significant findings are related to lack of efficacy and inappropriate dosing. Of the approximately 46,000 patients exposed, 85 seizures were reported (~5.4/1000 patient-years, of which 82 were reported or confirmed by a health care practitioner (~5.2/1000 patient-years. Beyond the intrinsic multiple sclerosis-related seizure risk, more than half of the 85 cases (62% had an additional potential risk factor for seizure including a previous history of convulsions, renal impairment, incorrect dosing, or use of concurrent medications with a labeled seizure risk. Duration of treatment prior to the seizure ranged from one dose to 365 days; 26/85 (31% patients suffered a seizure

  16. Dose comparison and side effect profile of metformin extended release versus metformin immediate release

    International Nuclear Information System (INIS)

    Hameed, M.; Khan, K.; Salman, S.; Mehmood, N.

    2017-01-01

    Diabetes Mellitus type 2 is very common worldwide, with majority of cases in Asia Pacific region. Metformin is the first line therapy, along with lifestyle modification for all type 2 diabetics as recommended by ADA. Metformin is available as conventional Metformin Immediate Release (MIR) and Metformin Extended Release (MXR). Metformin XR has better gastrointestinal tolerability and fewer side effects as compared to Metformin IR, with similar efficacy regarding anti-hyperglycaemic effects. The objective of this study was to determine whether metformin XR is as effective as Metformin IR in maintaining glycaemic control at equivalent doses or even at reduced doses; and to compare the side effect profile of the two preparations. Methods: This randomized control trial was conducted at Medical and Endocrinology OPD of Jinnah Hospital Lahore A total of 90 type 2 diabetics of both genders were recruited using nonprobability purposive sampling. Patients were randomized into 3 groups; 30 in each group. Group 1 received Metformin IR 1000 mg twice daily; group 2 received metformin XR 1000mg twice daily; and group 3 received metformin XR 500 mg twice daily, for a period of three months. HbA1c was done at baseline and after three months of therapy along with fasting blood sugars and random blood sugars weekly. Results: The mean age of patients was 46+-9 years, with 54% being males and 46% being females. There was a 1% reduction in HbA1c in group 1, 0.7% reduction in group 2 and only 0.4% reduction in group 3. Similarly, all three therapies were equally effective in reducing blood sugar fasting and blood sugar random at three months. Side effects namely diarrhoea, dyspepsia and flatulence were greatest with Metformin IR (40%) but less than half with Metformin XR at equivalent dose and negligible at half the dose. Conclusions: All three Metformin groups were effective in reduction of HbA1C and glycaemic control clinically and there is no statistical difference in HbA1c reduction

  17. Nematode burdens of pastured cattle treated once at turnout with eprinomectin extended-release injection.

    Science.gov (United States)

    Rehbein, S; Baggott, D G; Johnson, E G; Kunkle, B N; Yazwinski, T A; Yoon, S; Cramer, L G; Soll, M D

    2013-03-01

    The efficacy of eprinomectin in an extended-release injection (ERI) formulation was evaluated against infections with third-stage larvae or eggs of gastrointestinal and pulmonary nematodes in cattle under 120-day natural challenge conditions in a series of five studies conducted in the USA (three studies) and in Europe (two studies). For each study, 30 nematode-free (four studies) or 30 cattle harboring naturally acquired nematode infections (one study) were included. The cattle were of various breeds or crosses, weighed 107.5-273 kg prior to treatment and aged approximately 4-11 months. For each study, animals were blocked based on pre-treatment bodyweight and then randomly allocated to treatment: ERI vehicle (control) at 1 mL/50 kg bodyweight or Eprinomectin 5% (w/v) ERI at 1 mL/50 kg bodyweight (1.0 mg eprinomectin/kg) for a total of 15 and 15 animals in each group. Treatments were administered once on Day 0 by subcutaneous injection in front of the shoulder. In each study, all animals grazed one naturally contaminated pasture for 120 days. At regular intervals during the studies, fecal samples from all cattle were examined for nematode egg and larval counts. In four studies pairs of tracer cattle were used to monitor pasture infectivity at 28-day intervals before and/or during the grazing period. All calves were weighed before turnout onto pasture and at regular intervals until housing on Day 120. For parasite recovery, all study animals were humanely euthanized 27-30 days after removal from pasture. Cattle treated with Eprinomectin ERI had significantly (p92%: Dictyocaulus viviparus (adults and fourth-stage larvae (L4), Bunostomum phlebotomum, Cooperia curticei, Cooperia oncophora, Cooperia punctata, Cooperia surnabada, Cooperia spp. inhibited L4, Haemonchus contortus, Haemonchus placei, Haemonchus spp. inhibited L4, Nematodirus helvetianus, Nematodirus spp. inhibited L4, Oesophagostomum radiatum, Oesophagostomum spp. inhibited L4, Ostertagia leptospicularis

  18. Single-dose and steady-state pharmacokinetics of diltiazem administered in two different tablet formulations

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Bonde, J; Rasmussen, S N

    1992-01-01

    Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr r...

  19. Suppressive effects of diltiazem and verapamil on delayed rectifier K(+)-channel currents in murine thymocytes.

    Science.gov (United States)

    Baba, Asuka; Tachi, Masahiro; Maruyama, Yoshio; Kazama, Itsuro

    2015-10-01

    Lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in their plasma membranes, and these channels play crucial roles in the lymphocyte activation and proliferation. Since diltiazem and verapamil, which are highly lipophilic Ca(2+) channel blockers (CCBs), exert relatively stronger immunomodulatory effects than the other types of CCBs, they would affect the Kv1.3-channel currents in lymphocytes. Employing the standard patch-clamp whole-cell recording technique in murine thymocytes, we examined the effects of these drugs on the channel currents and the membrane capacitance. Both diltiazem and verapamil significantly suppressed the peak and the pulse-end currents of the channels, although the effects of verapamil were more marked than those of diltiazem. Both drugs significantly lowered the membrane capacitance, indicating the interactions between the drugs and the plasma membranes. This study demonstrated for the first time that CCBs, such as diltiazem and verapamil, exert inhibitory effects on Kv1.3-channels expressed in lymphocytes. The effects of these drugs may be associated with the mechanisms of immunomodulation by which they decrease the production of inflammatory cytokines. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  20. A PROSPECTIVE RANDOMISED STUDY OF THE EFFECT OF DILTIAZEM IN THE DRE AND PROCTOSCOPIC EXAMINATION

    Directory of Open Access Journals (Sweden)

    R. C. Thampan

    2018-01-01

    Full Text Available BACKGROUND Digital Rectal Examination (DRE and proctoscopy is an important routine investigation done by surgeons, gastroenterologists’, etc. Most of the patients complain of pain and discomfort during the procedure. Anal sphincter complex contracts to the penetrating index finger as a voluntary reflex try to avoid hurting. A good lubricant jelly (with 2% lignocaine and extreme gentleness should be the rule to this procedure to avoid discomfort and pain to the patients. Even with maximum precautions, majority of patients complain discomfort or pain during the procedure. To overcome this problem, we tried lubricant jelly and diltiazem gel combination. MATERIALS AND METHODS We evaluated 500 patients in this trial during the period 2010 to 2015 from the OPD of our institution with lubricant jelly alone and with diltiazem in the interval of two weeks. Analysis showed most of the patients is comfortable with combination lubricant jelly and diltiazem gel rather than lubricant jelly alone. RESULTS A total of 625 patients were screened for this study, but only 560 considered and enrolled (mean age 40 years. 60 patients failed to attend for the second examination, hence they were excluded from the final analysis. CONCLUSION The importance of DRE and proctoscopy known to every clinician, since it provides valuable information about anorectal pathology. Some patients are reluctant to give consent thinking that it will hurt them. By mixing lubricant jelly with diltiazem, the procedure becomes really comfortable due to good relaxation of anal sphincter complex.

  1. Interaction between timolol eyedrops and oral nicardipine or oral diltiazem in healthy Japanese subjects.

    Science.gov (United States)

    Yatsuka, Y I; Tsutsumi, K; Kotegawa, T; Nakamura, K; Nakano, S; Nakatsuka, K

    1998-04-01

    Timolol is widely used for the topical therapy of glaucoma. Adverse cardiovascular effects include slowing of the heart rate and weakening of myocardial contractility. We investigated pharmacodynamic interactions with respect to cardiovascular and ocular responses between timolol ophthalmic solution and either nicardipine, which does not directly inhibit cardiac conduction, or diltiazem, which does. Two studies utilized a randomized, double-blind, Latin-square, placebo-controlled design involving four separate treatments given at least 1 week apart. Eight healthy male Japanese volunteers received a single drop of 0.5% timolol or artificial tears in each eye with or without a single oral dose of nicardipine (40 mg), and with or without a single oral dose of diltiazem (60 mg). Subjects exercised on a bicycle ergometer before and 1.5 and 3 h after dosing. At these times, heart rate and blood pressure were measured at rest and after exercise. The intraocular pressure was measured at rest. One drop of 0.5% timolol per eye significantly reduced the exercise-induced increase in heart rate and blood pressure, and intraocular pressure at rest. The timolol ophthalmic solution suppressed the reflex sympathetic cardiac stimulation that resulted from the primarily vasodilative action of nicardipine. No additional reduction in heart rate occurred when the ophthalmic timolol solution was administered in conjunction with diltiazem. The concomitant use of timolol and nicardipine or diltiazem did not induce an additional reduction in intraocular pressure. Oral nicardipine or diltiazem did not reduce intraocular pressure. Care should be taken when using topical timolol in patients with cardiovascular or respiratory diseases.

  2. Effects of paliperidone extended release on hostility among Thai patients with schizophrenia

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    Jariyavilas A

    2017-01-01

    Full Text Available Apichat Jariyavilas,1 Nuntika Thavichachart,2 Ronnachai Kongsakon,3 Sunanta Chantakarn,4 Suwanna Arunpongpaisal,5 Vasu Chantarasak,6 Piyadit Jaroensook,7 Khanogwan Kittiwattanagul,8 Osot Nerapusee9 1Srithanya Hospital, Department of Mental Health, Ministry of Public Health, Bangkok, 2Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, 3Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Bangkok, 4Department of Psychiatry, Faculty of Medicine, Siriraj Hospital, Bangkok, 5Department of Psychiatry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 6Somdetchaopraya Institute of Psychiatry, Bangkok, 7Prasrimahabhodhi Hospital, Ubon Ratchathani, 8Khon Kaen Rajanagarindra Psychiatric Hospital, Khon Kaen, 9Medical Affairs, Janssen-Cilag, Bangkok, Thailand Objective: This open-label prospective study investigated the effects of paliperidone extended release (ER on hostility in Thai patients with schizophrenia. Background: Patients diagnosed with schizophrenia may be hostile or exhibit aggressive behavior, which can occasion their admission to psychiatric hospital. Antipsychotic medications are often used to treat hostility and aggression in such patients. Paliperidone ER is effective and well tolerated in the treatment of schizophrenia. However, there are no data available for paliperidone ER with regard to its efficacy on hostility and aggression among Thai patients. This study was a part of the PERFEcT study, a 6-month, open-label, multicenter, multicountry, prospective trial to explore the safety, efficacy, and functionality of paliperidone ER tablets. The current study included only the data obtained from Thai participants. Materials and methods: Flexible dosing of paliperidone ER in a range of 3–12 mg/day was used, allowing investigators to adjust the dosage of each subject individually. The 199 Thai patients had a stable Clinical Global Impression – severity score before enrollment. Demographic

  3. Efficacy of Tramadol Extended-Release for Opioid Withdrawal: A Randomized Clinical Trial.

    Science.gov (United States)

    Dunn, Kelly E; Tompkins, D Andrew; Bigelow, George E; Strain, Eric C

    2017-09-01

    Opioid use disorder (OUD) is a significant public health problem. Supervised withdrawal (ie, detoxification) from opioids using clonidine or buprenorphine hydrochloride is a widely used treatment. To evaluate whether tramadol hydrochloride extended-release (ER), an approved analgesic with opioid and nonopioid mechanisms of action and low abuse potential, is effective for use in supervised withdrawal settings. A randomized clinical trial was conducted in a residential research setting with 103 participants with OUD. Participants' treatment was stabilized with morphine, 30 mg, administered subcutaneously 4 times daily. A 7-day taper using clonidine (n = 36), tramadol ER (n = 36), or buprenorphine (n = 31) was then instituted, and patients were crossed-over to double-blind placebo during a post-taper period. The study was conducted from October 25, 2010, to June 23, 2015. Retention, withdrawal symptom management, concomitant medication utilization, and naltrexone induction. Results were analyzed over time and using area under the curve for the intention-to-treat and completer groups. Of the 103 participants, 88 (85.4%) were men and 43 (41.7%) were white; mean (SD) age was 28.9 (10.4) years. Buprenorphine participants (28 [90.3%]) were significantly more likely to be retained at the end of the taper compared with clonidine participants (22 [61.1%]); tramadol ER retention was intermediate and did not differ significantly from that of the other groups (26 [72.2%]; χ2 = 8.5, P = .01). Time-course analyses of withdrawal revealed significant effects of phase (taper, post taper) for the Clinical Opiate Withdrawal Scale (COWS) score (taper mean, 5.19 [SE, .26]; post-taper mean, 3.97 [SE, .23]; F2,170 = 3.6, P = .03) and Subjective Opiate Withdrawal Scale (SOWS) score (taper mean,8.81 [SE, .40]; post-taper mean, 4.14 [SE, .30]; F2,170 = 15.7, P withdrawal severity between the taper and post-taper periods for clonidine (taper mean, 13.1; post

  4. Evaluation of chitosan–anionic polymers based tablets for extended-release of highly water-soluble drugs

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    Yang Shao

    2015-02-01

    Full Text Available The objective of this study is to develop chitosan–anionic polymers based extended-release tablets and test the feasibility of using this system for the sustained release of highly water-soluble drugs with high drug loading. Here, the combination of sodium valproate (VPS and valproic acid (VPA were chosen as the model drugs. Anionic polymers studied include xanthan gum (XG, carrageenan (CG, sodium carboxymethyl cellulose (CMC-Na and sodium alginate (SA. The tablets were prepared by wet granulation method. In vitro drug release was carried out under simulated gastrointestinal condition. Drug release mechanism was studied. Compared with single polymers, chitosan–anionic polymers based system caused a further slowdown of drug release rate. Among them, CS–xanthan gum matrix system exhibited the best extended-release behavior and could extend drug release for up to 24 h. Differential scanning calorimetry (DSC and Fourier transform infrared spectroscopy (FTIR studies demonstrated that polyelectrolyte complexes (PECs were formed on the tablet surface, which played an important role on retarding erosion and swelling of the matrix in the later stage. In conclusion, this study demonstrated that it is possible to develop highly water-soluble drugs loaded extended-release tablets using chitosan–anionic polymers based system.

  5. Interaction of rivaroxaban with amiodarone, verapamil and diltiazem in patients with atrial fibrillation: terra incognita

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    S. N. Bel'diev

    2016-01-01

    Full Text Available Currently there are no generally accepted guidelines for the use of rivaroxaban together with amiodarone, verapamil or diltiazem in patients with creatinine clearance (CrCl<80 ml/min. Some researchers suggest that in renal failure amiodarone, verapamil and diltiazem contribute to a significant increase in plasma concentrations of rivaroxaban that is accompanied by increased risk of bleeding. According to preliminary calculations, it seems rational to reduce the dose of rivaroxaban when co-administered with these drugs: to 15 mg/day in patients with ClCr 50-79 ml/min and to 10 mg/day in patients with ClCr<50 ml/min.

  6. Uniquely different PVA-xanthan gum irradiated membranes as transdermal diltiazem delivery device.

    Science.gov (United States)

    Bhunia, Tridib; Giri, Arindam; Nasim, Tanbir; Chattopadhyay, Dipankar; Bandyopadhyay, Abhijit

    2013-06-05

    This paper reports interesting differences between physical and mechanical properties of various membranes prepared from high and low molecular weight poly (vinyl alcohol) (PVA) and xanthan gum (XG) blends irradiated under low dose electron beam. The membranes were designed for sustained delivery of diltiazem hydrochloride through skin. Electron beam irradiation produced crosslinks and turned PVA into crystalline phase from its amorphous organization in the unirradiated state. PVA crystals were fibrillar at low XG content (1 wt.%) when the molecular weight was high while similar orientation at higher XG content (5 wt.%) when the molecular weight was low. Low molecular weight PVA-XG membranes showed equivalent physical properties under dry condition but wet-mechanical properties were superior for high molecular weight PVA-XG hybrids. Both of them showed slow and sustained diltiazem release but the later induced slightly slower release despite low drug encapsulation efficiency due to its better wet mechanical strength. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus

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    Levy Juliana

    2010-03-01

    Full Text Available Abstract Aims To determine prospectively the efficacy, tolerability and patient satisfaction of an extended release formulation of metformin (metformin XR in hospital based outpatients with type 2 diabetes mellitus currently treated with standard metformin. Methods Patients on immediate release standard metformin either alone or combined with other oral agents were switched to extended release metformin XR 500 mg tablets and titrated to a maximum dose of 2000 mg/day Measurements to include glucose and lipid control, blood pressure, body weight, waist circumference, C-reactive protein, adverse events and patient satisfaction were recorded at baseline, three and six months. Results Complete data were obtained for 35 of the 61 patients enrolled to the study. At three and six months no changes were reported for any of the cardiovascular risk factors except for lipids where there was a modest rise in plasma triglycerides. These effects were achieved with a reduced dose of metformin XR compared to pre-study dosing with standard metformin (1500 mg +/- 402 vs 1861 +/- 711 p = 0.004. A total of 77% of patients were free of gastrointestinal side effects and 83% of patients stated a preference for metformin XR at the end of the study. Ghost tablets were reported in the faeces by the majority of the patients (54.1%. Conclusions Patients switched to extended release metformin XR derived the same clinical and metabolic benefits as for standard metformin but with reduced dosage, fewer gastrointestinal side effects and a greater sense of well being and satisfaction on medication.

  8. Effects of Vascular and Nonvascular Adverse Events and of Extended-Release Niacin With Laropiprant on Health and Healthcare Costs.

    Science.gov (United States)

    Kent, Seamus; Haynes, Richard; Hopewell, Jemma C; Parish, Sarah; Gray, Alastair; Landray, Martin J; Collins, Rory; Armitage, Jane; Mihaylova, Borislava

    2016-07-01

    Extended-release niacin with laropiprant did not significantly reduce the risk of major vascular events and increased the risk of serious adverse events in Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), but its net effects on health and healthcare costs are unknown. 25 673 participants aged 50 to 80 years with previous cardiovascular disease were randomized to 2 g of extended-release niacin with 40 mg of laropiprant daily versus matching placebo, in addition to effective statin-based low-density lipoprotein cholesterol-lowering treatment. The net effects of niacin-laropiprant on quality-adjusted life years and hospital care costs (2012 UK £; converted into US $ using purchasing power parity index) during 4 years in HPS2-THRIVE were evaluated using estimates of the impact of serious adverse events on health-related quality of life and hospital care costs. During the study, participants assigned niacin-laropiprant experienced marginally but not statistically significantly lower survival (0.012 fewer years [standard error (SE) 0.007]), fewer quality-adjusted life years (0.023 [SE 0.007] fewer using UK EQ-5D scores; 0.020 [SE 0.006] fewer using US EQ-5D scores) and accrued greater hospital costs (UK £101 [SE £37]; US $145 [SE $53]). Stroke, heart failure, musculoskeletal events, gastrointestinal events, and infections were associated with significant decreases in health-related quality of life in both the year of the event and in subsequent years. All serious vascular and nonvascular events were associated with substantial increases in hospital care costs. In HPS2-THRIVE, the addition of extended-release niacin-laropiprant to statin-based therapy reduced quality of life-adjusted survival and increased hospital costs. URL: http://clinicaltrials.gov. Unique identifier: NCT00461630. © 2016 American Heart Association, Inc.

  9. The Direct and Indirect Effects of Paliperidone Extended-release on Depressive Symptoms in Schizoaffective Disorder: A Path Analysis.

    Science.gov (United States)

    Turkoz, Ibrahim; Fu, Dong-Jing; Bossie, Cynthia A; Alphs, Larry

    2015-01-01

    This analysis evaluates improvement in symptoms of depression in patients with schizoaffective disorder administered oral paliperidone extended-release by accounting for the magnitude of direct and indirect (changes in negative and positive symptoms and worsening of extrapyramidal symptoms) treatment effects on depressive symptoms. Data for this post hoc analysis were drawn from two six-week, randomized, placebo-controlled studies of paliperidone extended-release versus placebo in adult subjects with schizoaffective disorder (N=614; NCT00412373, NCT00397033). Subjects with baseline 17-item Hamilton Rating Scale for Depression scores of 16 or greater were included. Structural equation models (path analyses) were used to separate total effects into direct and indirect effects on depressive symptoms. Change from baseline in 17-item Hamilton Rating Scale for Depression score at the Week 6 end point was the dependent variable; changes in Positive and Negative Syndrome Scale positive and negative factors and Simpson-Angus Scale (to evaluate extrapyramidal symptoms) scores were independent variables. At baseline, 332 of 614 (54.1%) subjects had a 17-item Hamilton Rating Scale for Depression score of 16 or greater. Path analysis determined that up to 26.4 percent of the paliperidone extended-release versus placebo effect on depressive symptoms may be attributed to a direct treatment effect, and 45.8 percent and 28.4 percent were mediated indirectly through improvements on positive and negative symptoms, respectively. No effects were identified as mediated through extrapyramidal symptoms changes (-0.7%). RESULTS of this analysis suggest that paliperidone's effect on depressive symptoms in subjects with schizoaffective disorder participating in two six-week, randomized, placebo-controlled studies is mediated through indirect effects (e.g., positive and negative symptom changes) and a direct treatment effect.

  10. Efficacy of diltiazem as an adjunct to lignocaine in intravenous regional anesthesia

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    Puneet Khanna

    2013-01-01

    Full Text Available Background: Various adjuncts have been used with lignocaine to decrease tourniquet pain and prolong post-operative analgesia during intravenous regional anesthesia (IVRA. Calcium-channel blockers potentiate the analgesic effect of local anesthetics. This study was designed to evaluate the efficacy of diltiazem as an adjunct to lignocaine in IVRA with respect to tourniquet tolerance, perioperative analgesia, and quality of anesthesia. Methods: In this prospective, randomized, and double-blind study, 40 patients (American Society for Anesthesiologists grade I/II undergoing elective hand surgery under IVRA were assigned into two groups of 20 each and administered IVRA either with lignocaine 3 mg/kg (group Lignocaine (L or lignocaine 3 mg/kg plus diltiazem 0.2 mg/kg (group Lignocaine-Diltiazem (LD with normal saline (total volume-40 ml. Hemodynamic parameters, onset of the complete sensory blockade, motor blockade, and intraoperative (tourniquet pain and post-operative Visual Analogue Scale scores, total intraoperative and consumption of post-operative fentanyl intraoperative were recorded. Results: Sensory block was established in 2.5±0.688 min in group LD verses 5.60±0.851 min in group L. Motor blockade was established in 8.65±0.933 min in group LD and 13.46±0.604 min in group L. The mean VAS scores >3 were attained early at 30 min (3.1±0.912 in group L. Patients in group L requested early rescue analgesic at 30±8.633 min compared with 49.64±7.958 min in group LD. Conclusions: Diltiazem as an adjunct to lignocaine provided enhanced intraoperative and post-operative analgesia without any significant side effects.

  11. Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for Male Patients with Urethritis

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    Satoshi Takahashi

    2014-04-01

    Full Text Available To clarify the clinical efficacy of a single oral 2 g dose of azithromycin extended-release for heterosexual male patients with urethritis, and the current antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective clinical trial was conducted from 2011–2013. In patients with gonococcal urethritis, the eradication rate was 90.9% (30 of 33. The susceptibility rates of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime and azithromycin were 100%, 100%, 95.3% (41/43 and 37.2% (16/43, respectively. In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45 of 50. The microbiological eradication rates for the pathogens were 90.9% (30/33 for Neisseria gonorrhoeae, 91.5% (43/47 for Chlamydia trachomatis, 71.4% (5/7 for Mycoplasma genitalium, and 100% (13/13 for Ureaplasma urealyticum. The main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120. The symptom of diarrhea was mostly temporary and resolved spontaneously. The conclusion was that the treatment regimen with a single oral 2 g dose of azithromycin extended-release would be effective for patients with urethritis. However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and Mycoplasma genitalium should be carefully monitored because of possible treatment failure.

  12. Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for Male Patients with Urethritis.

    Science.gov (United States)

    Takahashi, Satoshi; Kiyota, Hiroshi; Ito, Shin; Iwasawa, Akihiko; Hiyama, Yoshiki; Uehara, Teruhisa; Ichihara, Koji; Hashimoto, Jiro; Masumori, Naoya; Sunaoshi, Kenichi; Takeda, Koichi; Suzuki, Nobukazu; Hosobe, Takahide; Goto, Hirokazu; Suzuki, Hidenori; Onodera, Shoichi

    2014-04-02

    To clarify the clinical efficacy of a single oral 2 g dose of azithromycin extended-release for heterosexual male patients with urethritis, and the current antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective clinical trial was conducted from 2011-2013. In patients with gonococcal urethritis, the eradication rate was 90.9% (30 of 33). The susceptibility rates of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime and azithromycin were 100%, 100%, 95.3% (41/43) and 37.2% (16/43), respectively. In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45 of 50). The microbiological eradication rates for the pathogens were 90.9% (30/33) for Neisseria gonorrhoeae, 91.5% (43/47) for Chlamydia trachomatis, 71.4% (5/7) for Mycoplasma genitalium, and 100% (13/13) for Ureaplasma urealyticum. The main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120). The symptom of diarrhea was mostly temporary and resolved spontaneously. The conclusion was that the treatment regimen with a single oral 2 g dose of azithromycin extended-release would be effective for patients with urethritis. However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and Mycoplasma genitalium should be carefully monitored because of possible treatment failure.

  13. Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly patients with hypertension and coronary artery disease

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    Serro-Azul João Batista

    2001-01-01

    Full Text Available OBJETIVE: Antihypertensive therapy with thiazides decreases coronary events in elderly patients. However, the influence of diuretics on myocardial ischemia has not been fully investigated. The aim of this study was to compare the effect of chlorthalidone and diltiazem on myocardial ischemia. METHODS: Following a randomized, double-blind, crossover protocol, we studied 15 elderly hypertensive patients aged 73.6±4.6 years with myocardial ischemia. All patients had angiographically documented coronary artery disease. We measured patients using 48- hour ambulatory electrocardiogram monitoring and exercise testing. After a 2-week period using placebo, patients received chlorthalidone or diltiazem for 4 weeks. RESULTS: Both treatments lowered systolic and diastolic blood pressures. The number of ischemic episodes on ambulatory electrocardiogram recordings was reduced with the use of chlorthalidone (2.5±3.8 and diltiazem (3.2±4.2 when compared with placebo (7.9±8.8; p<0.05. The total duration of ischemic episodes was reduced in both treatments when compared with placebo (chlorthalidone: 19.2±31.9min; diltiazem: 19.3±29.6min; placebo: 46.1±55.3min; p<0.05. CONCLUSION: In elderly hypertensive patients with coronary artery disease, chlorthalidone reduced myocardial ischemia similarly to diltiazem. This result is consistent with epidemiological studies and suggests that reduction of arterial blood pressure with thiazide therapy plays an important role in decreasing myocardial ischemia.

  14. Enhanced Oral Bioavailability of Diltiazem by the Influence of Gallic Acid and Ellagic Acid in Male Wistar Rats: Involvement of CYP3A and P-gp Inhibition.

    Science.gov (United States)

    Athukuri, Bhargavi Latha; Neerati, Prasad

    2017-09-01

    The oral bioavailability of diltiazem is very low due to rapid first pass metabolism in liver and intestine. The purpose of the study was to investigate the effect of gallic acid and ellagic acid on intestinal transport and oral bioavailability of diltiazem in rats. The intestinal transport and permeability of diltiazem was evaluated by in vitro non-everted sac method and in situ single pass intestinal perfusion study. The oral pharmacokinetics was evaluated by conducting oral bioavailability study. The intestinal transport and apparent permeability of diltiazem were significantly enhanced in duodenum, jejunum, and ileum of gallic and ellagic acid-treated groups. The effective permeability of diltiazem was significantly enhanced in ileum part of gallic and ellagic acid-treated groups. When compared with control group, the presence of these two phytochemicals significantly enhanced the area under plasma concentration-time curve and the peak plasma concentration of diltiazem (C max ). Gallic acid and ellagic acid significantly increased the bioavailability of diltiazem due to the inhibition of both CYP3A-mediated metabolism and P-glycoprotein-mediated efflux in the intestine and/or liver. Based on these results, the clinical experiments are warranted for the confirmation to reduce the dose of diltiazem when concomitantly administered with these phytochemicals. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  15. APF530 (granisetron injection extended-release) in a three-drug regimen for delayed CINV in highly emetogenic chemotherapy.

    Science.gov (United States)

    Schnadig, Ian D; Agajanian, Richy; Dakhil, Christopher; Gabrail, Nashat Y; Smith, Robert E; Taylor, Charles; Wilks, Sharon T; Schwartzberg, Lee S; Cooper, William; Mosier, Michael C; Payne, J Yvette; Klepper, Michael J; Vacirca, Jeffrey L

    2016-06-01

    APF530, extended-release granisetron, provides sustained release for ≥5 days for acute- and delayed-phase chemotherapy-induced nausea and vomiting (CINV). We compared efficacy and safety of APF530 versus ondansetron for delayed CINV after highly emetogenic chemotherapy (HEC), following a guideline-recommended three-drug regimen. HEC patients received APF530 500 mg subcutaneously or ondansetron 0.15 mg/kg intravenously, with dexamethasone and fosaprepitant. Primary end point was delayed-phase complete response (no emesis or rescue medication). A higher percentage of APF530 versus ondansetron patients had delayed-phase complete response (p = 0.014). APF530 was generally well tolerated; treatment-emergent adverse event incidence was similar across arms, mostly mild-to-moderate injection-site reactions. APF530 versus the standard three-drug regimen provided superior control of delayed-phase CINV following HEC. ClinicalTrials.gov : NCT02106494.

  16. A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Wilens, Timothy E; Robertson, Brigitte; Sikirica, Vanja; Harper, Linda; Young, Joel L; Bloomfield, Ralph; Lyne, Andrew; Rynkowski, Gail; Cutler, Andrew J

    2015-11-01

    Despite the continuity of attention-deficit/hyperactivity disorder (ADHD) into adolescence, little is known regarding use of nonstimulants to treat ADHD in adolescents. This phase 3 trial evaluated the safety and efficacy of guanfacine extended release (GXR) in adolescents with ADHD. This 13-week, multicenter, randomized, double-blind, placebo-controlled trial evaluated once-daily GXR (1-7 mg per day) in adolescents with ADHD aged 13 to 17 years. The primary endpoint was the change from baseline in the ADHD Rating Scale-IV (ADHD-RS-IV) total score; key secondary endpoints included scores from the Clinical Global Impressions-Severity of Illness (CGI-S), and Learning and School domain and Family domain scores from the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at week 13. A total of 314 participants were randomized (GXR, n = 157; placebo, n = 157). The majority of participants received optimal doses of 3, 4, 5, or 6 mg (30 [22.9%], 26 [19.8%], 27 [20.6%], or 24 [18.3%] participants, respectively), with 46.5% of participants receiving an optimal dose above the currently approved maximum dose limit of 4 mg. Participants receiving GXR showed improvement in ADHD-RS-IV total score compared with placebo (least-squares mean score change, -24.55 [GXR] versus -18.53 [placebo]; effect size, 0.52; p ADHD symptoms in adolescents. GXR was well tolerated, with no new safety signals reported. Dose-Optimization in Adolescents Aged 13-17 Diagnosed With Attention-Deficit/Hyperactivity Disorder (ADHD) Using Extended-Release Guanfacine HCl; http://ClinicalTrials.gov/; NCT01081132. Copyright © 2015. Published by Elsevier Inc.

  17. A Single-Dose, Single-Period Pharmacokinetic Assessment of an Extended-Release Orally Disintegrating Tablet of Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Childress, Ann; Newcorn, Jeffrey; Stark, Jeffrey G; McMahen, Russ; Tengler, Mark; Sikes, Carolyn

    2016-08-01

    To determine the pharmacokinetic (PK) profile of a proprietary formulation of methylphenidate (MPH) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in a phase 1 study. Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) combine two technologies in a single-tablet formulation-an extended-release profile that was designed for once-daily dosing in an ODT that does not require water or chewing for ingestion. This was a single-dose, open-label, single-period, single-treatment study, in which 32 children with ADHD who were receiving MPH in doses of 40 or 60 mg before beginning the study each received a 60-mg dose (2 × 30 mg) of MPH XR-ODT. The following plasma PK parameters of MPH were determined for participants grouped by age (6-7, 8-9, 10-12, and 13-17 years old): maximum concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (T½), area under the curve from 0 hours to infinity (AUCinf), oral clearance (CL/F), and volume of distribution in the terminal phase (Vz/F). Safety and tolerability were also assessed. A total of 32 participants received the study drug. For all participants, plasma concentration-time profiles of MPH exhibited a broad peak after administration of MPH XR-ODT through ∼8 hours, indicating extended release from the formulation, followed by an apparent first-order elimination phase. As age increased, MPH exposure decreased and mean estimates of CL/F increased; however, weight-normalized CL/F values were comparable across age groups. Similarly, mean estimates of Vz/F increased with age, but weight-normalization decreased differences across age groups, with the exception of the youngest age group, which had higher values. All adverse events (AEs) were mild. This XR-ODT formulation of MPH demonstrated weight-normalized clearance rates that were consistent across all age groups, a PK profile consistent with once-daily dosing, and an AE profile consistent with

  18. Lipids bearing extruded-spheronized pellets for extended release of poorly soluble antiemetic agent-Meclizine HCl.

    Science.gov (United States)

    Qazi, Faaiza; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Nasiri, Muhammad Iqbal; Ahmed, Kamran; Ahmad, Mansoor

    2017-04-12

    Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated. Thirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol ® ), Glyceryl palmitostearate (Precirol ® ), Glyceryl behenate (Compritol ® ) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found. Sphericity indicated by shape factor (e R ) varied with type and concentration of lipids: Geleol ® (e R  = 0.891-0.997), Precirol ® (e R  = 0.611-0.743), Compritol ® (e R  = 0.665-0.729) and Carnauba wax (e R  = 0.499-0.551). Highly spherical pellets were obtained with Geleol ® (Aspect ratio = 1.005-1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153-1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol ® and Compritol ® , (ii) Geleol ® and Carnauba wax and (iii) Geleol ® , Compritol ® and Carnauba wax. Scanning electron microscopy of Compritol ® pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol ® and Compritol ® pellets, explained by Korsmeyer-Peppas (R 2  = 0.978-0.993) indicated

  19. Profile of guanfacine extended release and its potential in the treatment of attention-deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Martinez-Raga J

    2015-05-01

    Full Text Available Jose Martinez-Raga,1,2 Carlos Knecht,3 Raquel de Alvaro4 1Teaching Unit of Psychiatry and Psychological Medicine, University Hospital Doctor Peset, University of Valencia, 2CEU Cardenal Herrera University, 3Área de Salud Mental, Hospital Padre Jofré, Valencia, 4Hospital General, Consorcio Hospitalario Provincial, Castellon, Spain Abstract: The α2-adrenergic receptor agonist guanfacine, in its extended-release formulation (GXR, is the most recent nonstimulant medication approved in several countries for the treatment of attention-deficit hyperactivity disorder (ADHD as monotherapy and as adjunctive pharmacotherapy to stimulants in children and adolescents. The present paper aims to review comprehensively and critically the pharmacodynamic and pharmacokinetic characteristics and the published evidence on the efficacy and safety profile of GXR in the treatment of ADHD. A comprehensive search of relevant databases (PubMed, Embase, and PsycInfo was conducted to identify studies published in peer-reviewed journals until January 15, 2015. Though the precise mechanism of action of guanfacine in the treatment of ADHD is not fully understood, it is thought to act directly by enhancing noradrenaline functioning via α2A-adrenoceptors in the prefrontal cortex. Weight-adjusted doses should be used, with a dosing regime on a milligram per kilogram basis, starting at doses in the range 0.05–0.08 mg/kg/day, up to 0.12 mg/kg/day. As evidenced in short-term randomized controlled trials and in long-term open-label extension studies, GXR has been shown to be effective as monotherapy in the treatment of ADHD. Furthermore, GXR has also been found to be effective as adjunctive therapy to stimulant medications in patients with suboptimal responses to stimulants. Many of the adverse reactions associated with GXR, particularly sedation-related effects, were dose-related, transient, mild to moderate in severity, and did not interfere with attention or overall

  20. Combination of niacin extended-release and simvastatin results in a less atherogenic lipid profile than atorvastatin monotherapy

    Directory of Open Access Journals (Sweden)

    William Insull Jr

    2010-11-01

    Full Text Available William Insull Jr1, Peter P Toth2, H Robert Superko3, Roopal B Thakkar4, Scott Krause4, Ping Jiang4, Rhea A Parreno4, Robert J Padley41Baylor College of Medicine and Methodist Hospital, Houston, Texas; 2University of Illinois College of Medicine, Peoria, Illinois; 3Celera, Alameda, California, Mercer University, Atlanta, Georgia; 4Abbott, Abbott Park, Illinois, USAObjective: To compare the effects of combination niacin extended-release + simvastatin (NER/S versus atorvastatin alone on apolipoproteins and lipid fractions in a post hoc analysis from SUPREME, a study which compared the lipid effects of niacin extended-release + simvastatin and atorvastatin in patients with hyperlipidemia or mixed dyslipidemia.Patients and methods: Patients (n = 137 with dyslipidemia (not previously receiving statin therapy or having discontinued any lipid-altering treatment 4–5 weeks prior to the study received NER/S (1000/40 mg/day for four weeks, then 2000/40 mg/day for eight weeks or atorvastatin 40 mg/day for 12 weeks. Median percent changes in apolipoprotein (apo A-1, apo B, and the apo B:A-I ratio, and nuclear magnetic resonance lipoprotein subclasses from baseline to week 12 were compared using the Wilcoxon rank-sum test and Fisher’s exact test.Results: NER/S treatment produced significantly greater percent changes in apo A-I and apo B:A-I, and, at the final visit, apo B <80 mg/dL was attained by 59% versus 33% of patients, compared with atorvastatin treatment (P = 0.003. NER/S treatment resulted in greater percent reductions in calculated particle numbers for low-density lipoprotein (LDL, 52% versus 43%; P = 0.022, small LDL (55% versus 45%; P = 0.011, very low-density lipoprotein (VLDL and total chylomicrons (63% versus 39%; P < 0.001, and greater increases in particle size for LDL (2.7% versus 1.0%; P = 0.007 and VLDL (9.3% versus 0.1%; P < 0.001, compared with atorvastatin.Conclusion: NER/S treatment significantly improved apo A-I levels and the apo

  1. Treatment satisfaction with paliperidone extended-release tablets: open-label study in schizophrenia patients dissatisfied with previous antipsychotic medication

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    Yang FD

    2017-04-01

    Full Text Available Fu De Yang,1 Juan Li,1 Yun Long Tan,1 Wei Ye Liang,1 Rongzhen Zhang,1 Ning Wang,1 Wei Feng,1 Shangli Cai,2 Jian Min Zhuo,2 Li Li Zhang2 1Beijing Hui-Long-Guan Hospital, 2Department of Medical Affairs, Xian Janssen Pharmaceutical Ltd, Beijing, People’s Republic of China Objective: The aim of this study was to evaluate the changes in treatment satisfaction after switching to paliperidone extended-release (ER in Chinese schizophrenia patients dissatisfied with their previous antipsychotic treatment.Methods: In this 8-week, open-label, single-arm, multicenter, prospective study, 1,693 patients dissatisfied with previous antipsychotic medication were enrolled and switched to paliperidone ER tablets (3–12 mg/d based on clinical judgment. The primary efficacy end point was change in Medication Satisfaction Questionnaire (MSQ score from baseline to week 8. The secondary end points included percentage of patients with MSQ score ≥4, as well as changes in Clinical Global Improvement-Severity (CGI-S and Personal and Social Performance (PSP scores.Results: MSQ scores increased significantly from baseline (mean [standard deviation {SD}]: 2.48 [0.55] to week 8 (5.47 [0.89], P<0.0001; primary end point, full analysis set. The percentage of patients with MSQ score ≥4 was 95.9% at week 8, indicating that most of the patients were satisfied with their treatment. Significant (P<0.0001 improvements from baseline to week 8 were noted in CGI-S score (2.37 [1.20] and PSP score (25.5 [15.0]. A total of 174 (10.28% patients experienced adverse events (AEs. The most common (>10 patients events were extrapyramidal disorder (n=84, 4.96%, poor quality sleep (n=18, 1.06% and akathisia (n=13, 0.77%. The majority of AEs were mild to moderate in severity. No deaths occurred.Conclusion: Treatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia. Keywords: atypical antipsychotics, open label

  2. Extended-Release Guanfacine Does Not Show a Large Effect on Tic Severity in Children with Chronic Tic Disorders.

    Science.gov (United States)

    Murphy, Tanya K; Fernandez, Thomas V; Coffey, Barbara J; Rahman, Omar; Gavaletz, Allison; Hanks, Camille E; Tillberg, Caitlin S; Gomez, Laura Ibanez; Sukhodolsky, Denis G; Katsovich, Lily; Scahill, Lawrence

    2017-11-01

    To evaluate the tolerability, safety, and preliminary efficacy of extended-release guanfacine in children with chronic tic disorders, including Tourette's disorder (collectively referred to as CTD). This was a multisite, 8-week, randomized, double-blind, placebo-controlled trial. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS) total score. Key secondary outcomes included the Improvement item of Clinical Global Impressions-Improvement (CGI-I) scale and the Tic Symptom Self-report (TSSR). Adverse events were monitored at each visit. Thirty-four subjects (23 boys and 11 girls) of ages 6 to 17 years (mean = 11.1 ± 3.1) with CTD were randomly assigned to extended-release guanfacine (n = 16) or placebo (n = 18). At baseline, the mean YGTSS total score was 26.3 ± 6.6 for the guanfacine group versus 27.7 ± 8.7 for the placebo group. Within the guanfacine group (mean final daily dose of 2.6 ± 1.1 mg, n = 14), the mean YGTSS total score declined to 23.6 ± 6.42 [t(15) = 1.84, p = 0.08; effect size = 0.35]. The results were similar in the placebo group with a score of 24.7 ± 10.54 at week 8 [t(17) = 1.83, p = 0.08; effect size = 0.38]. There was no significant difference in the rate of positive response on the CGI-I between the guanfacine group and placebo (19% [3/16] vs. 22% [4/18], p = 1.0). The most common adverse events were fatigue, drowsiness, dry mouth, headache, and irritability. Two subjects in the guanfacine group discontinued early-one because of an adverse event (depressed mood) and one because of lack of efficacy; two subjects in the placebo group discontinued because of lack of efficacy. This pilot study did not confirm a clinically meaningful effect size within the guanfacine group. These results do not support the launch of a larger efficacy trial for tics in children and adolescents with CTD.

  3. Rates of opioid dispensing and overdose after introduction of abuse-deterrent extended-release oxycodone and withdrawal of propoxyphene.

    Science.gov (United States)

    Larochelle, Marc R; Zhang, Fang; Ross-Degnan, Dennis; Wharam, J Frank

    2015-06-01

    In the second half of 2010, abuse-deterrent extended-release oxycodone hydrochloride (OxyContin; Purdue Pharma) was introduced and propoxyphene was withdrawn from the US market. The effect of these pharmaceutical market changes on opioid dispensing and overdose rates is unknown. To evaluate the association between 2 temporally proximate changes in the opioid market and opioid dispensing and overdose rates. Claims from a large national US health insurer were analyzed, using an interrupted time series study design. Participants included an open cohort of 31.3 million commercially insured members aged 18 to 64 years between January 1, 2003, and December 31, 2012, with median follow-up of 20 months (last follow-up, December 31, 2012). Introduction of abuse-deterrent OxyContin (resistant to crushing or dissolving) on August 9, 2010, and market withdrawal of propoxyphene on November 19, 2010. Standardized opioid dispensing rates and prescription opioid and heroin overdose rates were the primary outcomes. We used segmented regression to analyze changes in outcomes from 30 quarters before to 8 quarters after the 2 interventions. Two years after the opioid market changes, total opioid dispensing decreased by 19% from the expected rate (absolute change, -32.2 mg morphine-equivalent dose per member per quarter [95% CI, -38.1 to -26.3]). By opioid subtype, the absolute change in dispensing by milligrams of morphine-equivalent dose per member per quarter at 2 years was -11.3 (95% CI, -12.4 to -10.1) for extended-release oxycodone, 3.26 (95% CI, 1.40 to 5.12) for other long-acting opioids, -8.19 (95% CI, -9.30 to -7.08) for propoxyphene, and -16.2 (95% CI, -18.8 to -13.5) for other immediate-release opioids. Two years after the market changes, the estimated overdose rate attributed to prescription opioids decreased by 20% (absolute change, -1.10 per 100,000 members per quarter [95% CI, -1.47 to -0.74]), but heroin overdose increased by 23% (absolute change, 0.26 per 100

  4. Atorvastatin-Diltiazem Combination Induced Rhabdomyolysis Leading to Diagnosis of Hypothyroidism

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    N. D. B. Ehelepola

    2017-01-01

    Full Text Available Statins and hypothyroidism, independently, can rarely cause rhabdomyolysis. The combination of them especially with concurrent intake of drugs such as diltiazem increases the risk of rhabdomyolysis. Hashimoto’s encephalopathy is a rare condition associated with Hashimoto’s thyroiditis and some patients with that can present with a stroke like picture. An elderly male who has been on atorvastatin for three years and on diltiazem for a week presented with sudden onset inability to walk and confusion. On examination muscle tenderness was noticed and creatine kinase levels indicated rhabdomyolysis which we attributed to atorvastatin. Patient developed a seizure and myoclonus of masseters. Considering this, his confusion and his neutrophilia and high C-reactive protein levels, empirical antibiotics with dexamethasone were started and the patient responded to that. His cerebrospinal fluid and blood culture reports that arrived later did not show sepsis. After going home also his CK (creatine kinase levels remained high; TSH (thyroid-stimulating hormone level test was done and hypothyroidism was diagnosed. His antithyroid peroxidase antibody levels were also very high. We retrospectively think he had Hashimoto’s encephalopathy as well. His lipid profile and TSH and CK values returned to normal in that order after a few months of levothyroxine therapy.

  5. Development of modified release diltiazem HCl tablets using composite index to identify optimal formulation.

    Science.gov (United States)

    Gohel, M C; Patel, M M; Amin, A F

    2003-05-01

    This article reports the preparation of tartaric acid treated ispaghula husk powder for the development of modified release tablets of diltiazem HCl by adopting direct compression technique and a 32 full factorial design. The modified ispaghula husk powder showed superior swelling and gelling as compared to untreated powder. Addition of compaction augmenting agent such as dicalcium phosphate was found to be essential for obtaining tablets with adequate crushing strength. In order to improve the crushing strength of diltiazem HCl tablets, to modulate drug release pattern, and to obtain similarity of dissolution profiles in distilled water and simulated gastric fluid (pH 1.2), modified guar gum was used along with modified ispaghula husk powder and tartaric acid. A novel composite index, which considers a positive or a negative deviation from an ideal value, was calculated considering percentage drug release in 60, 300, and 540 min as dependent variables for the selection of a most appropriate batch. Polynomial equation and contour plots are presented. The concept of similarity factor (f2) was used to prove similarity of dissolution in water and simulated gastric fluid (pH 1.2).

  6. Effect of diltiazem on myocardial infarct size estimated by enzyme release, serial thallium-201 single-photon emission computed tomography and radionuclide angiography

    International Nuclear Information System (INIS)

    Zannad, F.; Amor, M.; Karcher, G.; Maurin, P.; Ethevenot, G.; Sebag, C.; Bertrand, A.; Pernot, C.; Gilgenkrantz, J.M.

    1988-01-01

    Diltiazem is a calcium antagonist with demonstrated experimental cardioprotective effects. Its effects on myocardial infarct size were studied in 34 patients admitted within 6 hours after the first symptoms of acute myocardial infarction. These patients were randomized, double-blind to placebo or diltiazem (10-mg intravenous bolus followed by 15 mg/hr intravenous infusion during 72 hours, followed by 4 X 60 mg during 21 days). Myocardial infarct size was assessed by plasma creatine kinase and creatine kinase-MB indexes, perfusion defect scores using single-photon emission computed tomography with thallium-201 and left ventricular ejection fraction measured by radionuclide angiography. Tomographic and angiographic scanning was performed serially before randomization, after 48 hours and 21 days later. Groups were comparable in terms of age, sex, inclusion time and baseline infarct location and size. Results showed no difference in creatine kinase and creatine kinase-MB data between controls and treated patients, a significant decrease in the perfusion defect scores in the diltiazem group (+0.1 +/- 3.0 placebo vs -2.2 +/- 1.9 diltiazem, p less than 0.02) and a better ejection fraction recovery in the diltiazem group (-4.2 +/- 7.4 placebo vs +7.7 +/- 11.2 diltiazem, p less than 0.05). Myocardial infarct size estimates from perfusion defect scores and enzyme data were closely correlated. These preliminary results suggest that diltiazem may reduce ischemic injury in acute myocardial infarction

  7. Efficacy of extended-release divalproex combined with "condensed" dialectical behavior therapy for individuals with borderline personality disorder.

    Science.gov (United States)

    Moen, Richelle; Freitag, Mary; Miller, Michael; Lee, Susanne; Romine, Ann; Song, Sue; Adityanjee, Adit; Schulz, S Charles

    2012-11-01

    Borderline personality disorder (BPD) is a significant psychiatric illness for which medication treatments are still being explored. The goal of this study was to assess divalproex extended release (ER) vs placebo for patients receiving dialectal behavior therapy (DBT). Patients with BPD received 4 weeks of "condensed DBT." Those with Symptom Checklist-90 (SCL-90) scores >150 after this treatment were then randomly and blindly assigned to placebo or divalproex ER for 12 weeks. Repeated measures analysis of variance utilizing last observation carried forward was used to assess the results. Seventeen participants completed the full assessment. Two patients had a significant decrease in SCL-90 in the first 4 weeks, leaving 15 patients for the medication phase of the trial. There were no significant differences between the participants assigned to divalproex ER compared with placebo. However, there was a significant improvement in both groups from baseline to endpoint (P = .001). The response of 2 of 17 participants in the first 4 weeks prior to medication may point to a practice strategy in approaching outpatients with BPD. Although the patients had a decrease in symptoms during the study, there was no advantage observed for divalproex ER and DBT over placebo and DBT.

  8. Application of Physiologically Based Absorption Modeling to Characterize the Pharmacokinetic Profiles of Oral Extended Release Methylphenidate Products in Adults.

    Directory of Open Access Journals (Sweden)

    Xiaoxia Yang

    Full Text Available A previously presented physiologically-based pharmacokinetic model for immediate release (IR methylphenidate (MPH was extended to characterize the pharmacokinetic behaviors of oral extended release (ER MPH formulations in adults for the first time. Information on the anatomy and physiology of the gastrointestinal (GI tract, together with the biopharmaceutical properties of MPH, was integrated into the original model, with model parameters representing hepatic metabolism and intestinal non-specific loss recalibrated against in vitro and in vivo kinetic data sets with IR MPH. A Weibull function was implemented to describe the dissolution of different ER formulations. A variety of mathematical functions can be utilized to account for the engineered release/dissolution technologies to achieve better model performance. The physiological absorption model tracked well the plasma concentration profiles in adults receiving a multilayer-release MPH formulation or Metadate CD, while some degree of discrepancy was observed between predicted and observed plasma concentration profiles for Ritalin LA and Medikinet Retard. A local sensitivity analysis demonstrated that model parameters associated with the GI tract significantly influenced model predicted plasma MPH concentrations, albeit to varying degrees, suggesting the importance of better understanding the GI tract physiology, along with the intestinal non-specific loss of MPH. The model provides a quantitative tool to predict the biphasic plasma time course data for ER MPH, helping elucidate factors responsible for the diverse plasma MPH concentration profiles following oral dosing of different ER formulations.

  9. Extended Release of an Anti–Heparan Sulfate Peptide From a Contact Lens Suppresses Corneal Herpes Simplex Virus-1 Infection

    Science.gov (United States)

    Jaishankar, Dinesh; Buhrman, Jason S.; Valyi-Nagy, Tibor; Gemeinhart, Richard A.; Shukla, Deepak

    2016-01-01

    Purpose To prolong the release of a heparan sulfate binding peptide, G2-C, using a commercially available contact lens as a delivery vehicle and to demonstrate the ability of the released peptide to block herpes simplex virus-1 (HSV-1) infection using in vitro, ex vivo, and in vivo models of corneal HSV-1 infection. Methods Commercially available contact lenses were immersed in peptide solution for 5 days prior to determining the release of the peptide at various time points. Cytotoxicity of the released samples was determined by MTT and cell cycle analysis, and the functional activity of the released samples were assessed by viral entry, and viral spread assay using human corneal epithelial cells (HCE). The ability to suppress infection in human and pig cornea ex vivo and mouse in vivo models were also assessed. Results Peptide G2-C was released through the contact lens. Following release for 3 days, the peptide showed significant activity by inhibiting HSV-1 viral entry and spread in HCE cells. Significant suppression of infection was also observed in the ex vivo and in vivo experiments involving corneas. Conclusions Extended release of an anti–HS peptide through a commercially available contact lens can generate significant anti–HSV-1 activity and provides a new and effective way to control corneal herpes. PMID:26780322

  10. Once-Daily Tacrolimus Extended-Release Formulation: 1 Year after Conversion in Stable Pediatric Kidney Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Lars Pape

    2011-01-01

    Full Text Available It is speculated that a once-daily dosage of immunosuppression can increase adherence and thereby graft survival. Until now, there have been no studies on once-daily use of Tacrolimus extended-release formulation (TAC-ER in children following pediatric kidney transplantation. In 11 stable pediatric kidney recipients >10 years, efficacy, safety, and tolerability of a switch to TAC-ER were observed over one year. Adherence was determined by use of the BAASIS-Scale Interview and comparison of individual variability of Tacrolimus trough levels. Over the observation period, two acute rejections were observed in one girl with nonadherence and repeated Tacrolimus trough levels of 0 ng/m. Beside this, there were no acute rejections in this trial. TAC dose was increased in 3/11 patients and decreased in 2/11 patients within the course of the study. Six patients did not require a dose adjustment. All but one patient had a maximum of 1 dose change during therapy. Mean Tacrolimus dose, trough levels, and Glomerular filtration rates were also stable. Adherence, as measured by BAASIS-Scale Interview and coefficient of variation of Tacrolimus trough levels, was good at all times. It is concluded that conversion to Tac-ER is safe in low-risk children following pediatric kidney transplantation.

  11. Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial*

    Science.gov (United States)

    Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L.

    2013-01-01

    Background Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: 1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and 2) whether cessation of ER tramadol produces opioid withdrawal. Methods Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Results Use of breakthrough withdrawal medication differed significantly (popioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. PMID:23755929

  12. Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: a two-phase randomized controlled trial.

    Science.gov (United States)

    Lofwall, Michelle R; Babalonis, Shanna; Nuzzo, Paul A; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L

    2013-11-01

    Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: (1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and (2) whether cessation of ER tramadol produces opioid withdrawal. Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Use of breakthrough withdrawal medication differed significantly (popioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Diltiazem tópico en el dolor postoperatorio de hemorroidectomía con técnica cerrada

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    U. Rodríguez-Wong

    2016-04-01

    Conclusiones: En este estudio, el diltiazem administrado por vía tópica disminuyó el dolor, en los pacientes postoperados de hemorroidectomía con técnica cerrada, de manera estadísticamente significativa.

  14. Diltiazem como alternativa ao betabloqueador na angiotomografia de artérias coronárias

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Rochitte

    2012-08-01

    Full Text Available FUNDAMENTO: A redução da frequência cardíaca (FC na angiografia por tomografia das artérias coronarianas (ATCCor é fundamental para a qualidade de imagem. A eficácia dos bloqueadores de cálcio como alternativas para pacientes com contraindicações aos betabloqueadores não foi definida. OBJETIVOS: Comparar a eficácia na redução da FC e variabilidade RR do metoprolol e diltiazem na ATCCor. MÉTODOS: Estudo prospectivo, randomizado, aberto, incluiu pacientes com indicação clínica de ATCCor, em ritmo sinusal, com FC>70bpm e sem uso de agentes que interferissem com a FC. Cinquenta pacientes foram randomizados para grupos: metoprolol IV 5-15 mg ou até FC≤60 bpm(M, e diltiazem IV 0,25-0,60mg/kg ou até FC≤60 bpm (D. Pressão arterial (PA e FC foram aferidas na condição basal, 1min, 3min e 5min após agentes, na aquisição e após ATCCor. RESULTADOS: A redução da FC em valores absolutos foi maior no grupo M que no grupo D (1, 3, 5min, aquisição e pós-exame. A redução percentual da FC foi significativamente maior no grupo M apenas no 1 min e 3 min após início dos agentes. Não houve diferença no 5 min, durante a aquisição e após exame. A variabilidade RR percentual do grupo D foi estatisticamente menor do que a do grupo M durante a aquisição (variabilidade RR/ FC média da aquisição. Um único caso de BAV, 2:1 Mobitz I, revertido espontaneamente ocorreu (grupo D. CONCLUSÃO: Concluímos que o diltiazem é uma alternativa eficaz e segura aos betabloqueadores na redução da FC na realização de angiografia por tomografia computadorizada das artérias coronarianas. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0

  15. A Double-Blind, Randomized, Placebo-Controlled Trial of Divalproex Extended-Release in the Treatment of Bipolar Disorder in Children and Adolescents

    Science.gov (United States)

    Wagner, Karen Dineen; Redden, Laura; Kowatch, Robert A.; Wilens, Timothy E.; Segal, Scott; Chang, Kiki; Wozniak, Patricia; Vigna, Namita V.; Abi-Saab, Walid; Saltarelli, Mario

    2009-01-01

    A double-blind study that involves 150 patients aged 10-17 on the effect of divalproex extended-release in the treatment of bipolar disorder shows that the drug was similar to placebo based on adverse events and that no treatment effect was observed in the drug. The drug is not suitable for treatment of youths with bipolar I disorder, mixed or…

  16. Effect of the Glucagon-like Peptide-1 Analogue Exenatide Extended Release in Cats with Newly Diagnosed Diabetes Mellitus.

    Science.gov (United States)

    Riederer, A; Zini, E; Salesov, E; Fracassi, F; Padrutt, I; Macha, K; Stöckle, T M; Lutz, T A; Reusch, C E

    2016-01-01

    Exenatide extended release (ER) is a glucagon-like peptide-1 analogue that increases insulin secretion, inhibits glucagon secretion and induces satiation in humans with type 2 diabetes mellitus. The use of exenatide ER is safe and stimulates insulin secretion in healthy cats. The objective of this study is to assess the safety of exenatide ER and its effect on body weight, remission and metabolic control in newly diagnosed diabetic cats receiving insulin and a low-carbohydrate diet. Thirty client-owned cats. Prospective placebo-controlled clinical trial. Cats were treated with exenatide ER or 0.9% saline, administered SC, once weekly. Both groups received insulin glargine and a low-carbohydrate diet. Exenatide ER was administered for 16 weeks, or in cats that achieved remission it was given for 4 weeks after discontinuing insulin treatment. Nonparametric tests were used for statistical analysis. Cats in the exenatide ER and placebo groups had transient adverse signs including decreased appetite (60% vs. 20%, respectively, P = .06) and vomiting (53% vs. 40%, respectively, P = .715). Body weight increased significantly in the placebo group (P = .002), but not in cats receiving exenatide ER. Cats on exenatide ER achieved remission or good metabolic control in 40% or 89%, respectively, whereas in control cats percentages were 20% or 58% (P = .427 and P = .178, respectively). Exenatide ER is safe in diabetic cats and does not result in weight gain. Our pilot study suggests that, should there be an additional clinically relevant beneficial effect of exenatide ER in insulin-treated cats on rate of remission and good metabolic control, it would likely approximate 20% and 30%, respectively. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  17. Patient preferences and extended-release naltrexone: A new opportunity to treat opioid use disorders in Ukraine.

    Science.gov (United States)

    Marcus, Ruthanne; Makarenko, Iuliia; Mazhnaya, Alyona; Zelenev, Alexei; Polonsky, Maxim; Madden, Lynn; Filippovych, Sergii; Dvoriak, Sergii; Springer, Sandra A; Altice, Frederick L

    2017-10-01

    Scaling up HIV prevention for people who inject drugs (PWID) using opioid agonist therapies (OAT) in Ukraine has been restricted by individual and structural factors. Extended-release naltrexone (XR-NTX), however, provides new opportunities for treating opioid use disorders (OUDs) in this region, where both HIV incidence and mortality continue to increase. Survey results from 1613 randomly selected PWID from 5 regions in Ukraine who were currently, previously or never on OAT were analyzed for their preference of pharmacological therapies for treating OUDs. For those preferring XR-NTX, independent correlates of their willingness to initiate XR-NTX were examined. Among the 1613 PWID, 449 (27.8%) were interested in initiating XR-NTX. Independent correlates associated with interest in XR-NTX included: being from Mykolaiv (AOR=3.7, 95% CI=2.3-6.1) or Dnipro (AOR=1.8, 95% CI=1.1-2.9); never having been on OAT (AOR=3.4, 95% CI=2.1-5.4); shorter-term injectors (AOR=0.9, 95% CI 0.9-0.98); and inversely for both positive (AOR=0.8, CI=0.8-0.9), and negative attitudes toward OAT (AOR=1.3, CI=1.2-1.4), respectively. In the context of Eastern Europe and Central Asia where HIV is concentrated in PWID and where HIV prevention with OAT is under-scaled, new options for treating OUDs are urgently needed. here suggest that XR-NTX could become an option for addiction treatment and HIV prevention especially for PWID who have shorter duration of injection and who harbor negative attitudes to OAT. Decision aids that inform patient preferences with accurate information about the various treatment options are likely to guide patients toward better, patient-centered treatments and improve treatment entry and retention. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Steady-state pharmacokinetics of fluvastatin in healthy subjects following a new extended release fluvastatin tablet, Lescol XL.

    Science.gov (United States)

    Barilla, Denise; Prasad, Pratapa; Hubert, Martine; Gumbhir-Shah, Kavita

    2004-03-01

    This was an open-label, randomized, three-period, three-treatment, multiple dose, crossover study in 12 healthy male and female subjects. This study evaluated single dose and steady-state pharmacokinetics of fluvastatin following single and multiple dose administrations of a new extended release fluvastatin 8 h matrix tablet, Lescol XL 80 mg and 160 mg doses once a day. The study also included a twice a day administration of an immediate release (IR) form of fluvastatin capsule, Lescol, for comparative purposes. All doses were administered for 7 days. The safety and tolerability were also assessed. The pharmacokinetics of fluvastatin were evaluated on days 1 and 7 following each treatment. Fluvastatin systemic exposure was 50% less when administered as Lescol XL 80 mg qd compared with Lescol IR 40 mg bid. Conversely, fluvastatin systemic exposure was 22% higher when administered as Lescol XL 160 mg qd compared with Lescol IR 40 mg bid. Single doses of Lescol XL 80 mg and 160 mg were dose proportional but, deviation (30%) from dose proportionality was observed for the Lescol XL 160 mg at steady-state. There appeared to be moderate (20%-40%) accumulation of serum fluvastatin maximal concentrations and exposure after multiple doses of Lescol XL tablets. Both Lescol XL 80 mg and 160 mg showed delayed absorption and longer apparent elimination half-life compared with fluvastatin IR capsule. Single and multiple doses of fluvastatin were generally well tolerated in this healthy volunteer population. Adverse event profiles were consistent with the published safety profile of the marketed formulations. Aside from one incidence of creatine phosphokinase (CPK) elevation (following Lescol XL 160 mg qd treatment), there were no safety concerns with any of the treatments when administered acutely (7 days). Copyright 2004 John Wiley & Sons, Ltd.

  19. Are Branded and Generic Extended-Release Ropinirole Formulations Equally Efficacious? A Rater-Blinded, Switch-Over, Multicenter Study

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    Edit Bosnyák

    2014-01-01

    Full Text Available The aim of this study was to compare the efficacy of the branded and a generic extended-release ropinirole formulation in the treatment of advanced Parkinson’s disease (PD. Of 22 enrolled patients 21 completed the study. A rater blinded to treatment evaluated Unified Parkinson’s Disease Rating Scale, Fahn-Tolosa-Marin Tremor Rating Scale, Nonmotor Symptoms Assessment Scale, and a structured questionnaire on ropinirole side effects. Besides, the patients self-administered EQ-5D, Parkinson’s Disease Sleep Scale (PDSS-2, and Beck Depression Inventories. Branded and generic ropinirole treatment achieved similar scores on all tests measuring severity of motor symptoms (primary endpoint, UPDRS-III: 27.0 versus 28.0 points, P=0.505. Based on patient diaries, the lengths of “good time periods” were comparable (10.5 and 10.0 hours for branded and generic ropinirole, resp., P=0.670. However, generic ropinirole therapy achieved almost 3.0 hours shorter on time without dyskinesia (6.5 versus. 9.5 hours, P<0.05 and 2.5 hours longer on time with slight dyskinesia (3.5 versus. 1.0 hours, P<0.05 than the branded ropinirole did. Except for gastrointestinal problems, nonmotor symptoms were similarly controlled. Patients did not prefer either formulation. Although this study has to be interpreted with limitations, it demonstrated that both generic and branded ropinirole administration can achieve similar control on most symptoms of PD.

  20. Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets.

    Science.gov (United States)

    Philosophe, Benjamin; Leca, Nicolae; West-Thielke, Patricia M; Horwedel, Timothy; Culkin-Gemmell, Christine; Kistler, Kristin; Stevens, Daniel R

    2018-02-20

    The majority of United States kidney transplant patients are treated with tacrolimus, a drug effective in preventing graft rejection, but with a narrow therapeutic range, necessitating close monitoring to avoid increased risks of transplant rejection or toxicity if the tacrolimus concentration is too low or too high, respectively. The trough drug concentration tests are time sensitive; patients treated on a twice-daily basis have blood draws exactly 12 hours after their previous dose. The schedule's rigidity causes problems for both patients and health care providers. Novel once-daily tacrolimus formulations such as LCPT (an extended-release tablet by Veloxis Pharmaceuticals, Inc., Cary, North Carolina) have allowed for blood draws on a once-daily basis; however, even that schedule can be restrictive. Results from tests taken either before or after that 24-hour target time may be discarded, or worse, may lead to inappropriate dose changes. Data from ASTCOFF, a phase 3B pharmacokinetic clinical trial (NCT02339246), demonstrated that the unique pharmacokinetic curve of LCPT may allow for a therapeutic monitoring window that extends for 3 hours before or after the 24-hour monitoring target. Furthermore, important tools to help clinicians interpret these levels, such as formulas to estimate the 24-hour trough level if an alternative monitoring time is used, were constructed from these data. These study results give treating clinicians access to data that allow them to safely use and monitor LCPT in their patients and expand the body of evidence surrounding differentiation and practical application of the novel LCPT tacrolimus formulation. © 2018, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  1. A dose-finding, placebo-controlled study on extended-release felodipine once daily in treatment of hypertension.

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    Cambell, L M; Ross, J R; Goves, J R; Lees, C T; McCullagh, A; Barnes, P; Timerick, S J; Richardson, P D

    1989-12-01

    Hypertensive patients received a beta-blocker plus placebo once daily for 4 weeks. If their diastolic blood pressure (DBP) was then 95-115 mm Hg, they were randomized to receive, in addition to the beta-blocker, placebo (n = 36), felodipine-extended release (ER) 10 mg (n = 36), or felodipine-ER 20 mg (n = 37) in a 4-week double-blind parallel-group trial. All medication was administered once daily and, when BP was measured 24 h after the last dose, felodipine-ER 10 mg reduced DBP by 14 +/- 9 mm Hg (mean +/- SD) from a mean of 103 mm Hg and felodipine-ER 20 mg reduced DBP by 18 +/- 9 mm Gg from 101 mm Hg. The reductions in DBP with both doses of felodipine were greater than reductions with placebo (5 +/- 8 mm Hg, from 102 mm Hg--both p less than 0.001). At the end of the study, 21% of patients receiving placebo had a DBP less than or equal to 90 mm Hg. In contrast, 69% of patients receiving felodipine-ER 10 mg and 82% receiving 20 mg attained this level. More than 90% of patients receiving 10 mg felodipine-ER once daily had a reduction in DBP greater than 5 mm Hg 24 h postdose. Felodipine-ER was well tolerated. Felodipine-ER once daily is an effective antihypertensive drug for patients who require therapy in addition to a beta-blocker; the tolerability in this study was good, and a starting dose greater than 10 mg once daily is not indicated.

  2. Extended-release niacin/laropiprant significantly improves lipid levels in type 2 diabetes mellitus irrespective of baseline glycemic control

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    Bays HE

    2015-02-01

    Full Text Available Harold E Bays,1 Eliot A Brinton,2 Joseph Triscari,3 Erluo Chen,3 Darbie Maccubbin,3 Alexandra A MacLean,3 Kendra L Gibson,3 Rae Ann Ruck,3 Amy O Johnson-Levonas,3 Edward A O’Neill,3 Yale B Mitchel3 1Louisville Metabolic & Atherosclerosis Research Center (L-MARC, Louisville, KY, USA; 2Utah Foundation for Biomedical Research, Salt Lake City, UT, USA; 3Merck & Co, Inc., Whitehouse Station, NJ, USA Background: The degree of glycemic control in patients with type 2 diabetes mellitus (T2DM may alter lipid levels and may alter the efficacy of lipid-modifying agents. Objective: Evaluate the lipid-modifying efficacy of extended-release niacin/laropiprant (ERN/LRPT in subgroups of patients with T2DM with better or poorer glycemic control. Methods: Post hoc analysis of clinical trial data from patients with T2DM who were randomized 4:3 to double-blind ERN/LRPT or placebo (n=796, examining the lipid-modifying effects of ERN/LRPT in patients with glycosylated hemoglobin or fasting plasma glucose levels above and below median baseline levels. Results: At Week 12 of treatment, ERN/LRPT significantly improved low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C, non-high-density lipoprotein cholesterol, triglycerides, and lipoprotein (a, compared with placebo, with equal efficacy in patients above or below median baseline glycemic control. Compared with placebo, over 36 weeks of treatment more patients treated with ERN/LRPT had worsening of their diabetes and required intensification of antihyperglycemic medication, irrespective of baseline glycemic control. Incidences of other adverse experiences were generally low in all treatment groups. Conclusion: The lipid-modifying effects of ERN/LRPT are independent of the degree of baseline glycemic control in patients with T2DM (NCT00485758. Keywords: lipid-modifying agents, hyperglycemia, LDL, HDL, triglycerides

  3. Pharmaceutical Product Lead Optimization for Better In vivo Bioequivalence Performance: A case study of Diclofenac Sodium Extended Release Matrix Tablets.

    Science.gov (United States)

    Shahiwala, Aliasgar; Zarar, Aisha

    2018-01-01

    In order to prove the validity of a new formulation, a considerable amount of effort is required to study bioequivalence, which not only increases the burden of carrying out a number of bioequivalence studies but also eventually increases the cost of the optimization process. The aim of the present study was to develop sustained release matrix tablets containing diclofenac sodium using natural polymers and to demonstrate step by step process of product development till the prediction of in vivo marketed product equivalence of the developed product. Different batches of tablets were prepared by direct compression. In vitro drug release studies were performed as per USP. The drug release data were assessed using model-dependent, modelindependent and convolution approaches. Drug release profiles showed that extended release action were in the following order: Gum Tragacanth > Sodium Alginate > Gum Acacia. Amongst the different batches prepared, only F1 and F8 passed the USP criteria of drug release. Developed formulas were found to fit Higuchi kinetics model with Fickian (case I) diffusion-mediated release mechanism. Model- independent kinetics confirmed that total of four batches were passed depending on the similarity factors based on the comparison with the marketed Diclofenac. The results of in vivo predictive convolution model indicated that predicted AUC, Cmax and Tmax values for batch F8 were similar to that of marketed product. This study provides simple yet effective outline of pharmaceutical product development process that will minimize the formulation development trials and maximize the product success in bioequivalence studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Pharmacokinetics of an oral extended-release formulation of doxycycline hyclate containing acrylic acid and polymethacrylate in dogs.

    Science.gov (United States)

    Ruiz, Sara Melisa Arciniegas; Olvera, Lilia Gutiérrez; Chacón, Sara del Carmen Caballero; Estrada, Dinorah Vargas

    2015-04-01

    To determine the pharmacokinetics of doxycycline hyclate administered orally in the form of experimental formulations with different proportions of acrylic acid-polymethacrylate-based matrices. 30 healthy adult dogs. In a crossover study, dogs were randomly assigned (in groups of 10) to receive a single oral dose (20 mg/kg) of doxycycline hyclate without excipients (control) or extended-release formulations (ERFs) containing doxycycline, acrylic acid polymer, and polymethacrylate in the following proportions: 1:0.5:0.0075 (ERF1) or 1:1:0.015 (ERF2). Serum concentrations of doxycycline were determined for pharmacokinetic analysis before and at several intervals after each treatment. Following oral administration to the study dogs, each ERF resulted in therapeutic serum doxycycline concentrations for 48 hours, whereas the control treatment resulted in therapeutic serum doxycycline concentrations for only 24 hours. All pharmacokinetic parameters for ERF1 and ERF2 were significantly different; however, findings for ERF1 did not differ significantly from those for the control treatment. Results indicated that both ERFs containing doxycycline, acrylic acid polymer, and polymethacrylate had an adequate pharmacokinetic-pharmacodynamic relationship for a time-dependent drug and a longer release time than doxycycline alone following oral administration in dogs. Given the minimum effective serum doxycycline concentration of 0.26 μg/mL, a dose interval of 48 hours can be achieved for each tested ERF. This minimum inhibitory concentration has the potential to be effective against several susceptible bacteria involved in important infections in dogs. Treatment of dogs with either ERF may have several benefits over treatment with doxycycline alone.

  5. Population pharmacokinetics of methylphenidate hydrochloride extended-release multiple-layer beads in pediatric subjects with attention deficit hyperactivity disorder

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    Teuscher NS

    2015-05-01

    Full Text Available Nathan S Teuscher,1 Akwete Adjei,2 Robert L Findling,3,4 Laurence L Greenhill,5 Robert J Kupper,2 Sharon Wigal6 1PK/PD Associates, Trophy Club, TX, 2Rhodes Pharmaceuticals L.P., Coventry, RI, 3Department of Psychiatric Services and Research, Kennedy Krieger Institute, Baltimore, MD, 4Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, 5Department of Psychiatry, Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY, 6AVIDA Inc., Newport Beach, CA, USA Abstract: A new multilayer-bead formulation of extended-release methylphenidate hydrochloride (MPH-MLR has been evaluated in pharmacokinetic studies in healthy adults and in Phase III efficacy/safety studies in children and adolescents with attention deficit hyperactivity disorder (ADHD. Using available data in healthy adults, a two-input, one-compartment, first-order elimination population pharmacokinetic model was developed using nonlinear mixed-effect modeling. The model was then extended to pediatric subjects, and was found to adequately describe plasma concentration–time data for this population. A pharmacokinetic/pharmacodynamic model was also developed using change from baseline in the ADHD Rating Scale (ADHD-RS-IV total scores from a pediatric Phase III trial and simulated plasma concentration–time data. During simulations for each MPH-MLR dose level (10–80 mg, increased body weight resulted in decreased maximum concentration. Additionally, as maximum concentration increased, ADHD-RS-IV total score improved (decreased. Knowledge of the relationship between dose, body weight, and clinical response following the administration of MPH-MLR in children and adolescents may be useful for clinicians selecting initial dosing of MPH-MLR. Additional study is needed to confirm these results. Keywords: population pharmacokinetics, Aptensio XR™, MPH-MLR, methylphenidate

  6. Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease.

    Science.gov (United States)

    Sprague, Stuart M; Crawford, Paul W; Melnick, Joel Z; Strugnell, Stephen A; Ali, Shaukat; Mangoo-Karim, Roberto; Lee, Sungchun; Petkovich, P Martin; Bishop, Charles W

    2016-01-01

    Vitamin D insufficiency and secondary hyperparathyroidism (SHPT) are associated with increased morbidity and mortality in chronic kidney disease (CKD) and are poorly addressed by current treatments. The present clinical studies evaluated extended-release (ER) calcifediol, a novel vitamin D prohormone repletion therapy designed to gradually correct low serum total 25-hydroxyvitamin D, improve SHPT control and minimize the induction of CYP24A1 and FGF23. Two identical multicenter, randomized, double-blind, placebo-controlled studies enrolled subjects from 89 US sites. A total of 429 subjects, balanced between studies, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency were randomized 2:1 to receive oral ER calcifediol (30 or 60 µg) or placebo once daily at bedtime for 26 weeks. Most subjects (354 or 83%) completed dosing, and 298 (69%) entered a subsequent open-label extension study wherein ER calcifediol was administered without interruption for another 26 weeks. ER calcifediol normalized serum total 25-hydroxyvitamin D concentrations (>30 ng/ml) in >95% of per-protocol subjects and reduced plasma intact parathyroid hormone (iPTH) by at least 10% in 72%. The proportion of subjects receiving ER calcifediol who achieved iPTH reductions of ≥30% increased progressively with treatment duration, reaching 22, 40 and 50% at 12, 26 and 52 weeks, respectively. iPTH lowering with ER calcifediol was independent of CKD stage and significantly greater than with placebo. ER calcifediol had inconsequential impact on serum calcium, phosphorus, FGF23 and adverse events. Oral ER calcifediol is safe and effective in treating SHPT and vitamin D insufficiency in CKD. © 2016 S. Karger AG, Basel.

  7. Efficacy of Guanfacine Extended Release in the Treatment of Combined and Inattentive Only Subtypes of Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Kollins, Scott H.; Wigal, Timothy L.

    2012-01-01

    Abstract Background Extended-release guanfacine (GXR) is approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6–17 years. This post-hoc analysis further examines the effects of GXR on hyperactivity-impulsivity and inattentiveness. Method Data from two large double-blind placebo-controlled pivotal trials of GXR in the treatment of ADHD were analyzed. Using the pooled population to provide sufficient sample size and associated statistical power, the impact of GXR treatment on core ADHD symptoms was examined by comparing ADHD Rating Scale IV (ADHD-RS-IV) total scores in the overall GXR and placebo groups in subjects with each of the three ADHD subtypes. ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores in the overall study population by randomized dose group (vs. placebo) were also examined. Results The full analysis set included 631 subjects aged 6–17 years (GXR: n=490; placebo: n=141). Among subjects with the predominantly inattentive subtype of ADHD, differences in least squares (LS) mean reductions from baseline in ADHD-RS-IV total scores were significantly greater in GXR-treated subjects (n=127) than in placebo-treated subjects (n=38) at treatment weeks 3 through 5 and end point (p≤0.020). Among subjects with combined type ADHD, differences in LS mean ADHD-RS-IV total score reductions from baseline were significantly greater in the GXR group (n=354) than in the placebo group (n=100) at treatment weeks 1 through 5 and end point (p≤0.011). The dearth of predominantly hyperactive-impulsive type subjects (n=12) precluded analysis of this subgroup. Each randomized GXR dose group in each trial demonstrated significantly greater reductions from baseline in ADHD-RS-IV Hyperactivity-Impulsivity and Inattentiveness subscale scores than did the respective placebo group at end point (p≤0.05 for all). Conclusions The results support the use of GXR in the treatment of core ADHD symptoms

  8. The social functional outcome of being naturalistically treated with paliperidone extended-release in patients with schizophrenia

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    Nakagawa R

    2015-06-01

    Full Text Available Ryoko Nakagawa,1 Takashi Ohnishi,1 Hisanori Kobayashi,1 Akihide Wakamatsu,2 Ai Tanimura,3 Kazuo Morita,3 Toshio Yamaoka,3 Hideo Usui,3 Yoshimasa Ogawa,3 Akiko Fujino,3 Kazutake Yoshizawa11Evidence Generation Department, Medical Affairs Division, 2Medical Affairs Strategy Department, Medical Affairs Division, 3Drug Safety Surveillance Department, Japan Safety and Surveillance Division, Janssen Pharmaceutical K.K., Tokyo, JapanBackground: Social functioning is an important outcome for patients with schizophrenia. To evaluate the effects of paliperidone extended-release (PAL-ER on social function, symptomatology, and safety in the routine clinical practice, we conducted a 1-year post-marketing surveillance study of PAL-ER. We also explored relationships between symptomatic improvement and socially functional outcome in patients with schizophrenia.Patients and methods: Patients with an established diagnosis of schizophrenia were allowed flexible 3–12 mg/day dosing during the surveillance. Patients were assessed on social functioning using the Social and Occupational Functioning Assessment Scale (SOFAS and on symptomatology using the Clinical Global Impression–Schizophrenia scale. All adverse events (AEs were also collected.Results: A total of 1,429 patients were enrolled in the surveillance study, of whom 1,405 were evaluable for safety and 1,142 were evaluable for efficacy. The treatment discontinuation rate for any reason during the observation period was 34.66%. Significant improvements were observed on both Social and Occupational Functioning Assessment Scale and Clinical Global Impression–Schizophrenia scale during the observation period. The percentage of patients with socially functional remission (SOFAS ≥61 also increased significantly. A significant association between early improvements in positive symptoms, sex, severity of negative symptoms at baseline, and socially functional remission was observed. A total of 33.52% of patients

  9. Treatment patterns and health care resource utilization associated with dalfampridine extended release in multiple sclerosis: a retrospective claims database analysis

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    Guo A

    2016-05-01

    Full Text Available Amy Guo,1 Michael Grabner,2 Swetha Rao Palli,2 Jessica Elder,1 Matthew Sidovar,1 Peter Aupperle,1 Stephen Krieger3 1Acorda Therapeutics Inc., Ardsley, New York, NY, USA; 2HealthCore Inc., Wilmington, DE, USA; 3Corinne Goldsmith Dickinson Center for MS, Icahn School of Medicine at Mount Sinai, New York, NY, USA Background: Although previous studies have demonstrated the clinical benefits of dalfampridine extended release (D-ER tablets in patients with multiple sclerosis (MS, there are limited real-world data on D-ER utilization and associated outcomes in patients with MS. Purpose: The objective of this study was to evaluate treatment patterns, budget impact, and health care resource utilization (HRU associated with D-ER use in a real-world setting. Methods: A retrospective claims database analysis was conducted using the HealthCore Integrated Research DatabaseSM. Adherence (measured by medication possession ratio, or [MPR] and persistence (measured by days between initial D-ER claim and discontinuation or end of follow-up were evaluated over 1-year follow-up. Budget impact was calculated as cost per member per month (PMPM over the available follow-up period. D-ER and control cohorts were propensity-score matched on baseline demographics, comorbidities, and MS-related resource utilization to compare walking-impairment-related HRU over follow-up. Results: Of the 2,138 MS patients identified, 1,200 were not treated with D-ER (control and 938 were treated with D-ER. Patients were aged 51 years on average and 74% female. Approximately 82.6% of D-ER patients were adherent (MPR >80%. The estimated budget impact range of D-ER was $0.014–$0.026 PMPM. Propensity-score-matched D-ER and controls yielded 479 patients in each cohort. Postmatching comparison showed that the D-ER cohort was associated with fewer physician (21.5% vs 62.4%, P<0.0001 and other outpatient visits (22.8% vs 51.4%, P<0.0001 over the 12-month follow-up. Changes in HRU from follow

  10. Safety profile of dalfampridine extended release in multiple sclerosis: 5-year postmarketing experience in the United States

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    Jara M

    2015-12-01

    Full Text Available Michele Jara, Thomas Aquilina, Peter Aupperle, Adrian L Rabinowicz Acorda Therapeutics, Inc., Ardsley, NY, USA Background: Dalfampridine extended release tablets (dalfampridine-ER; prolonged-, modified, or sustained-release fampridine outside the US, 10 mg twice daily, was approved by the US Food and Drug Administration (FDA in January 2010 to improve walking in people with multiple sclerosis, as determined by an increase in walking speed. Objective: To provide a descriptive analysis of reported adverse events (AEs for commercially available dalfampridine-ER from March 2010 through March 31, 2015. Methods: Five-year postmarketing data for dalfampridine-ER were available from the exposure of approximately 107,000 patients in the US (103,700 patient-years. Commonly reported AEs (≥2% of all reported AEs and serious AEs were determined. The incidence of reported seizures was determined and the events were further investigated. Results: Among the 107,000 patients exposed to dalfampridine-ER (70% female; mean age 52.1, the most common AEs were dizziness (3.7%, insomnia (3.2%, balance disorder (3%, fall (2.4%, headache (2.4%, nausea (2.1%, and urinary tract infection (2%. Other common AEs were drug ineffectiveness (5.8%, gait disturbance (4.6%, and inappropriate dosing (3.1%. Serious AEs included rare anaphylactic reactions (five cases and drug hypersensitivity reactions (eight cases. A total of 657 seizure cases were reported (6.3/1,000 patient-years; of these, 324 were medically confirmed (3.1/1,000 patient-years. Incidence of reported seizures was stable over time. Duration of treatment prior to a seizure ranged from a single dose to >4 years; 12% of the seizures occurred within a week of starting treatment. Conclusion: The 5-year US postmarketing safety data of dalfampridine-ER is consistent with the safety profile observed in clinical trials. Incidence of reported seizures remained stable over time. Since commercial availability in March 2010, a

  11. Niacin extended-release/simvastatin combination therapy produces larger favorable changes in high-density lipoprotein particles than atorvastatin monotherapy

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    Toth PP

    2012-01-01

    Full Text Available Peter P Toth1, Kamlesh M Thakker2, Ping Jiang2, Robert J Padley21University of Illinois College of Medicine, Peoria, and CGH Medical Center, Sterling, 2Abbott, Abbott Park, IL, USABackground: The purpose of this research was to compare the effects of niacin extended-release in combination with simvastatin (NER/S versus atorvastatin monotherapy on high-density lipoprotein (HDL particle number and size in patients with hyperlipidemia or dyslipidemia from the SUPREME study.Methods: This was a post hoc analysis of patients (n = 137 who completed the SUPREME study and who had lipid particle number and size measurements at both baseline and at week 12 by nuclear magnetic resonance spectroscopy. Following ≥4 weeks without lipid-modifying therapy (washout period, the patients received NER/S 1000/40 mg/day for 4 weeks followed by NER/S 2000/40 mg/day for 8 weeks, or atorvastatin 40 mg/day for 12 weeks. Median percent changes in HDL particle number and size from baseline to week 12 were compared between the NER/S and atorvastatin treatment groups using the Wilcoxon rank-sum test. Distribution of HDL particle subclasses at week 12 was compared between the treatment groups using the Cochran–Mantel–Haenszel test.Results: Treatment with NER/S resulted in a significantly greater percent reduction in small HDL particle number at week 12 compared with atorvastatin monotherapy (-1.8% versus 4.2%, P = 0.014, and a numerically greater percent increase in large HDL particle number (102.4% versus 39.2%, P = 0.078 compared with atorvastatin monotherapy. A significantly greater percent increase in HDL particle size from baseline at week 12 was observed with NER/S compared with atorvastatin (6.0% versus 1.3%, P < 0.001. NER/S treatment also resulted in a significant shift in HDL particle size from small and medium at baseline to large at week 12 (P < 0.0001.Conclusion: Treatment with NER/S resulted in larger favorable changes in number and size of HDL particle

  12. Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) Study.

    Science.gov (United States)

    Auiler, J F; Liu, K; Lynch, J M; Gelotte, C K

    2002-01-01

    Stimulant therapy is the mainstay of treatment for children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Once-daily, extended-release oral formulations offer long acting control of symptoms by modifying drug delivery and absorption. In particular, consistency in early drug exposure is important for symptom control during school or work hours. Because these once-daily formulations are usually taken in the morning, the timing of the doses with breakfast is important. This study compared the effect of a high-fat breakfast on early drug exposure from a morning dose of two extended-release stimulant formulations: the osmotic-controlled OROS tablet of methylphenidate HCI (CONCERTA) and the capsule containing extended-release beads of mixed amphetamine salts (ADDERALL XR). The study had a single-dose, open-label, randomised, four-treatment, crossover design in which healthy subjects received either 36 mg CONCERTA or 20 mg ADDERALL XR in the morning after an overnight fast or a high-fat breakfast. Serial blood samples were collected over 28h to determine plasma concentrations of methylphenidate and amphetamine. The food effect on early drug exposure and the pharmacokinetic profiles up to 8 h after dosing of the two extended-release stimulants were directly compared using partial area (AUC(p4h), AUC(p6h) and AUC(p8h)) fed/fasted ratios. Amphetamine concentrations were markedly lower when the subjects had eaten breakfast, resulting in lower early drug exposures (p food, for patients with ADHD.

  13. Pharmacokinetics of a once-daily extended-release formulation of pramipexole in healthy male volunteers: three studies.

    Science.gov (United States)

    Jenner, Peter; Könen-Bergmann, Michael; Schepers, Cornelia; Haertter, Sebastian

    2009-11-01

    Pramipexole is a dopamine agonist used in the treatment of Parkinson's disease. The currently available immediate-release (IR) formulation is taken orally 3 times daily. These studies were conducted to evaluate the pharmacokinetic properties of a variety of prototypes for a once-daily extended-release (ER) formulation of pramipexole and to further characterize the prototype whose pharmacokinetics best matched those of the IR formulation. Three Phase I studies were conducted, all in healthy adult men aged food effect. In the third study, steady-state pharmacokinetics of the optimal ER formulation were assessed across a range of pramipexole doses (0.375-4.5 mg/d), including investigation of the food effect at steady state for the highest dose. Tolerability was assessed throughout all studies based on physical examinations, laboratory measurements, and adverse events (AEs). The 3 studies included 18, 15, and 39 subjects, respectively. Among the ER prototypes tested at 0.75 mg once daily in study 1, a matrix tablet had the optimal pharmacokinetic resemblance to IR pramipexole 0.25 mg TID, with a geometric mean AUC(0-24h,ss) of 17.4 ng.h/mL (vs 16.0 ng.h/mL for the IR formulation), C(max,ss) of 0.967 ng/mL (vs 1.09 ng/mL), and C(min,ss) of 0.455 ng/mL (vs 0.383 ng/mL). For single-dose ER 0.375 mg administered in the fasted state in study 2, in vivo bioavailability was predictable from in vitro dissolution data, with internal mean absolute percent prediction errors of 3.18% for AUC(0-30h) and 4.87% for C(max), and external mean absolute prediction errors of 6.61% and 3.34%, respectively, satisfying current guidelines for a level A IVIVC. For single-dose ER 0.375 mg administered in the fed state, the upper bound of the 90% CI for fed:fasted values was 119.8 for AUC(0-30h) (within the bioequivalence limits of 80%-125%) and 134.1 for C(max). At steady state in study 3 (subjects' 5th treatment day), dosing at 0.375 to 4.5 mg in the fasted state was associated with a linear

  14. Guanfacine extended release for children and adolescents with attention-deficit/hyperactivity disorder: efficacy following prior methylphenidate treatment

    Directory of Open Access Journals (Sweden)

    Huss M

    2016-05-01

    Full Text Available Michael Huss,1 Vanja Sikirica,2 Amaia Hervas,3,4 Jeffrey H Newcorn,5 Valerie Harpin,6 Brigitte Robertson71Child and Adolescent Psychiatry, Johannes Gutenberg University Mainz, Mainz, Germany; 2Global Health Economics, Outcomes Research and Epidemiology, Shire, Wayne, PA, USA; 3Child and Adolescent Mental Health Unit, University Hospital Mútua de Terressa, Barcelona, Spain; 4Developmental Disorders Unit (UETD, Hospital San Juan de Dios, Barcelona, Spain; 5Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 6Ryegate Children’s Centre, Sheffield Children’s NHS Foundation Trust, Sheffield, UK; 7Global Clinical Development, Shire, Wayne, PA, USAAbstract: Guanfacine extended release (GXR and atomoxetine (ATX are nonstimulant treatments for attention-deficit/hyperactivity disorder (ADHD. As nonstimulant treatments are often used after stimulants in ADHD, GXR was assessed relative to prior stimulant treatment in a randomized controlled trial (RCT, in which ATX was included as a reference arm, and in the open-label phase of a randomized-withdrawal study (RWS. Participants were 6–17 years old with ADHD Rating Scale version IV (ADHD-RS-IV scores ≥32 and Clinical Global Impressions – Severity scores ≥4. RCT participants received dose-optimized GXR (1–7 mg/day, ATX (10–100 mg/day, or placebo for 10–13 weeks. RWS participants received dose-optimized GXR (1–7 mg/day for 13 weeks. Participants’ last stimulant medication prior to enrolment, and reasons for stopping this medication, were collected at baseline. Change from baseline ADHD-RS-IV score and the proportion of responders were assessed by prior stimulant exposure. Of 163 RCT and 296 RWS participants who had previously received stimulant treatment, 142 and 224, respectively, had received methylphenidate (MPH; due to the low number of participants and the heterogeneity of non-MPH treatments, we only report data for prior MPH treatment. The most

  15. Drug Release Kinetics and Front Movement in Matrix Tablets Containing Diltiazem or Metoprolol/λ-Carrageenan Complexes

    Directory of Open Access Journals (Sweden)

    Ruggero Bettini

    2014-01-01

    Full Text Available In this work we investigated the moving boundaries and the associated drug release kinetics in matrix tablets prepared with two complexes between λ-carrageenan and two soluble model drugs, namely, diltiazem HCl and metoprolol tartrate aiming at clarifying the role played by drug/polymer interaction on the water uptake, swelling, drug dissolution, and drug release performance of the matrix. The two studied complexes released the drug with different mechanism indicating two different drug/polymer interaction strengths. The comparison between the drug release behaviour of the complexes and the relevant physical mixtures indicates that diltiazem gave rise to a less soluble and more stable complex with carrageenan than metoprolol. The less stable metoprolol complex afforded an erodible matrix, whereas the stronger interaction between diltiazem and carrageenan resulted in a poorly soluble, slowly dissolving matrix. It was concluded that the different stability of the studied complexes affords two distinct drug delivery systems: in the case of MTP, the dissociation of the complex, as a consequence of the interaction with water, affords a classical soluble matrix type delivery system; in the case of DTZ, the dissolving/diffusing species is the complex itself because of the very strong interaction between the drug and the polymer.

  16. A comparison of the extended-release and standard-release formulations of tacrolimus in de novo kidney transplant recipients: a 12-month outcome study.

    Science.gov (United States)

    Fanous, Helen; Zheng, Rebecca; Campbell, Carolyn; Huang, Michael; Nash, Michelle M; Rapi, Lindita; Zaltzman, Jeffrey S; Prasad, G V Ramesh

    2013-02-01

    BACKGROUND: Limited comparative data are available on the outcomes between extended-release and standard-release tacrolimus when used de novo in kidney transplant recipients (KTRs). METHODS: We identified KTRs transplanted at our institution during 2009-10 routinely prescribed extended-release tacrolimus and compared them with those transplanted during 2008-09 prescribed standard-release tacrolimus. Graft function (eGFR by MDRD-7 equation) at 12 months post-transplant (primary outcome); new-onset diabetes and other cardiovascular risk factors, BK viremia incidence, acute rejection, and graft survival to 12 months (secondary outcomes) were compared by intent-to-treat analysis. Time-to-steady-state concentration and number of dose adjustments required to attain steady state were recorded. RESULTS: There were no important demographic differences between the extended-release (N = 106) and standard-release (N = 95) cohorts. The estimated glomerular filtration rate (eGFR) at 12 months was similar (58.8 ± 17 versus 59.2 ± 18 mL/min/1.73 m(2), P = 0.307). There was no difference in new-onset diabetes (17 versus 20%, P = 0.581), BK viremia (10 versus 7%, P = 0.450), acute rejection (7 versus 16%, P = 0.067) or graft survival (97 versus 95%, P = 0.301). Time-to-steady state was similar (9.2 ± 1.1 versus 8.1 ± 4.7 days, P = 0.490) although extended-release patients required fewer adjustments to attain steady state (1.2 ± 1.7 [0-8] versus 1.7 ± 1.5 [0-7], P = 0.030) but a similar dose (7.2 ± 2.4 [2-17] versus 7 ± 2.7 [2-16] mg/day, P = 0.697). CONCLUSION: De novo KTRs prescribed extended-release or standard-release tacrolimus demonstrate similar 12-month outcomes.

  17. The Effect of a Novel form of Extended-Release Gabapentin on Pain and Sleep in Fibromyalgia Subjects: An Open-Label Pilot Study.

    Science.gov (United States)

    North, James M; Hong, Kyung-Soo J; Rauck, Richard L

    2016-07-01

    We assessed the efficacy and safety of extended-release gabapentin in a 15-week, open-label, single-arm, single-center study in patients with fibromyalgia (FM). Subjects with documented diagnosis of FM were allowed to participate in the study. We opened enrollment to those who have tried and failed gabapentinoids such as gabapentin or pregabalin due to side effects. Subjects with autoimmune conditions, and or taking opioids for management of their FM pain, were excluded from the study. Subjects were given an extended-release gabapentin starter pack and treated for total of 12 weeks. The primary study endpoint of pain relief was measured using Numeric Pain Rating System (NPRS) scores, and secondary study endpoints were measured with Fibromyalgia Impact Questionnaire (FIQ), Patient's Global Impression of Change (PGIC), and Medical Outcome Sleep questionnaires (MOS). A total of 34 subjects were enrolled and 29 subjects completed the starter pack (85%). Patients reported significant pain relief on NPRS by end of 4 weeks (P life by end of 4 weeks on FIQ (P quality. Improvements in primary and secondary measurements were reflected in PGIC, with significant improvement in patient's impression of FM by week 8. Small sample size, geographical bias, relatively short duration of treatment, and single-arm study without control group. Extended-release gabapentin relieved FM pain symptoms and improved quality-of-life for the FM subjects studied. Subjects reported improvements in both quantity and quality of sleep. © 2015 World Institute of Pain.

  18. Review of extended-release formulations of Tramadol for the management of chronic non-cancer pain: focus on marketed formulations

    Science.gov (United States)

    Kizilbash, Arshi; Ngô-Minh, Cường

    2014-01-01

    Patients with chronic non-malignant pain report impairments of physical, social, and psychological well-being. The goal of pain management should include reducing pain and improving quality of life. Patients with chronic pain require medications that are able to provide adequate pain relief, have minimum dosing intervals to maintain efficacy, and avoid breakthrough pain. Tramadol has proven efficacy and a favourable safety profile. The positive efficacy and safety profile has been demonstrated historically in numerous published clinical studies as well as from post-marketing experience. It is a World Health Organization “Step 2” opioid analgesic that has been shown to be effective, well-tolerated, and valuable, where treatment with strong opioids is not required. A number of extended release formulations of Tramadol are available in Canada and the United States. An optimal extended release Tramadol formulation would be expected to provide consistent pain control with once daily dosing, few sleep interruptions, flexible dosing schedules, and no limitation on taking with meals. Appropriate treatment options should be based on the above proposed attributes. A comparative review of available extended release Tramadol formulations shows that these medications are not equivalent in their pharmacokinetic profile and this may have implications for selecting the optimal therapy for patients with pain syndromes where Tramadol is an appropriate analgesic agent. Differences in pharmacokinetics amongst the formulations may also translate into varied clinical responses in patients. Selection of the appropriate formulation by the health care provider should therefore be based on the patient’s chronic pain condition, needs, and lifestyle. PMID:24711710

  19. Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers

    OpenAIRE

    Yoon, Seonghae; Lee, Howard; Kim, Tae-Eun; Lee, SeungHwan; Chee, Dong-Hyun; Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin

    2014-01-01

    Seonghae Yoon,1,* Howard Lee,2,* Tae-Eun Kim,1 SeungHwan Lee,1 Dong-Hyun Chee,3 Joo-Youn Cho,1 Kyung-Sang Yu,1 In-Jin Jang1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Clinical Trials Center, Seoul National University Hospital, 3AbbVie Ltd., Seoul, Republic of Korea *These authors contributed equally to this work Background: This study was conducted to compare the oral bioavailability of an itopride extended-release (ER...

  20. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation

    DEFF Research Database (Denmark)

    Franek, F; Jarlfors, A; Larsen, F.

    2015-01-01

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step...... not imply low intestinal permeability, as indicated by the BDDCS, merely low duodenal/jejunal permeability....... for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq®, an extended release formulation...

  1. The changing landscape of opioid prescribing: long-acting and extended-release opioid class-wide Risk Evaluation and Mitigation Strategy

    Directory of Open Access Journals (Sweden)

    Gudin JA

    2012-05-01

    Full Text Available Jeffrey A GudinEnglewood Hospital and Medical Center, Englewood, NJ, USAAbstract: Prescriptions for opioid analgesics to manage moderate-to-severe chronic noncancer pain have increased markedly over the last decade, as have postmarketing reports of adverse events associated with opioids. As an unintentional consequence of greater prescription opioid utilization, there has been the parallel increase in misuse, abuse, and overdose, which are serious risks associated with all opioid analgesics. In response to these concerns, the Food and Drug Administration announced the requirement for a class-wide Risk Evaluation and Mitigation Strategy (REMS for long-acting and extended-release (ER opioid analgesics in April 2011. An understanding of the details of this REMS will be of particular importance to primary care providers. The class-wide REMS is focused on educating health care providers and patients on appropriate prescribing and safe use of ER opioids. Support from primary care will be necessary for the success of this REMS, as these clinicians are the predominant providers of care and the main prescribers of opioid analgesics for patients with chronic pain. Although currently voluntary, future policy will likely dictate that providers undergo mandatory training to continue prescribing medications within this class. This article outlines the elements of the class-wide REMS for ER opioids and clarifies the impact on primary care providers with regard to training, patient education, and clinical practice.Keywords: long-acting opioid, extended-release opioid, risk, REMS, FDA, primary care

  2. [Therapeutic effects of venlafaxine extended release for patients with depressive and anxiety disorders in the German outpatient setting - results of 2 observational studies including 8500 patients].

    Science.gov (United States)

    Anghelescu, I-G; Dierkes, W; Volz, H-P; Loeschmann, P-A; Schmitt, A B

    2009-11-01

    The therapeutic effects of venlafaxine extended release have been investigated by two prospective observational studies including 8506 patients in the outpatient setting of office based general practitioners and specialists. The efficacy has been documented by the Clinical Global Impression (CGI) scale and by the Hamilton depression (HAMD-21) scale. The tolerability has been assessed by the documentation of adverse events. About (2/3) of the patients were treated because of depression and about (1/3) mainly because of anxiety disorder. The patients of specialists did receive higher dosages and were more severely affected. The response rate on the CGI scale was 87.4 for the patients of general practitioners and 74.2 % for the patients of specialists. The results of the HAMD-21 scale, which has been used by specialists, showed a response rate of 71.8 and a remission rate of 56.3 %. These positive effects could be demonstrated even for the more severely and chronically affected patients. The incidence of adverse events was low in both studies and comparable to the tolerability profile of randomized studies. Importantly, the good tolerability profile was similar even for patients with concomitant cardiovascular disease. In conclusion, these results confirm the efficacy and good tolerability of venlafaxine extended release in the outpatient setting in Germany. Georg Thieme Verlag KG Stuttgart, New York.

  3. Enhanced drug encapsulation and extended release profiles of calcium-alginate nanoparticles by using tannic acid as a bridging cross-linking agent.

    Science.gov (United States)

    Abulateefeh, Samer R; Taha, Mutasem O

    2015-01-01

    Calcium alginate nanoparticles (NPs) suffer from sub-optimal stability in bio-relevant media leading to low drug encapsulation efficiency and uncontrolled release profiles. To sort out these drawbacks, a novel approach is proposed herein based on introducing tannic acid into these NPs to act as a bridging cross-linking aid agent. Calcium-alginate NPs were prepared by the ionotropic gelation method and loaded with diltiazem hydrochloride as a model drug. These NPs were characterized in terms of particle size, zeta potential, and morphology, and results were explained in accordance with Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The incorporation of tannic acid led to more than four folds increase in drug encapsulation efficiency (i.e. from 15.3% to 69.5%) and reduced burst drug release from 44% to around 10% within the first 30 min. These findings suggest the possibility of improving the properties of Ca-alginate NPs by incorporating cross-linking aid agents under mild conditions.

  4. Paraffin ingestion - the problem

    African Journals Online (AJOL)

    The incidence of paraffin ingestion is higher in the summer months. This is because ... where the average cost per patient was R348 per day. The total cost to ... petroleum companies and/or entrepreneurs and distributed ... paraffin, coal and gas. As South Africa ... and more people become involved, making control difficult.

  5. A long-term, open-label safety study of single-entity hydrocodone bitartrate extended release for the treatment of moderate to severe chronic pain

    Directory of Open Access Journals (Sweden)

    Nalamachu S

    2014-11-01

    Full Text Available Srinivas Nalamachu,1,2 Richard L Rauck,3 Martin E Hale,4 Orlando G Florete Jr,5 Cynthia Y Robinson,6 Stephen J Farr,6 1International Clinical Research Institute, Overland Park, KS, USA; 2Kansas University Medical Center, Kansas City, KS, USA; 3Carolinas Pain Institute, Center for Clinical Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA; 4Gold Coast Research, LLC, Weston, FL, USA; 5Institute of Pain Management, Jacksonville, FL, USA; 6Zogenix, Inc., Emeryville, CA, USA Objective: To evaluate the long-term safety, tolerability, and effectiveness of single-entity extended-release hydrocodone in opioid-experienced subjects with moderate to severe chronic pain not receiving adequate pain relief or experiencing intolerable side effects from their current opioid. Methods: This multicenter, open-label study started with a conversion/titration phase (≤6 weeks where subjects (n=638 were converted to individualized doses (range 20–300 mg of extended-release hydrocodone dosed every 12 hours, followed by a 48-week maintenance phase (n=424. The primary objective (safety and tolerability and the secondary objective (long-term efficacy as measured by change in average pain score; 0= no pain, 10= worst imaginable pain were monitored throughout the study. Results: Subjects were treated for a range of chronic pain etiologies, including osteoarthritis, low back pain, and neuropathic and musculoskeletal conditions. The mean hydrocodone equivalent dose at screening was 68.9±62.2 mg/day and increased to 139.5±81.7 mg/day at the start of the maintenance phase. Unlimited dose adjustments were permitted at the investigator's discretion during the maintenance phase, reflecting typical clinical practice. No unexpected safety issues were reported. Common adverse events during the conversion/titration and maintenance phases, respectively, were constipation (11.3% and 12.5%, nausea (10.7% and 9.9%, vomiting (4.1% and 9.7%, and somnolence (7

  6. The cost effectiveness of long-acting/extended-release antipsychotics for the treatment of schizophrenia: a systematic review of economic evaluations.

    Science.gov (United States)

    Achilla, Evanthia; McCrone, Paul

    2013-04-01

    Antipsychotic medication is the mainstay of treatment in schizophrenia. Long-acting medication has potential advantages over daily medication in improving compliance and thus reducing hospitalization and relapse rates. The high acquisition and administration costs of such formulations raise the need for pharmacoeconomic evaluation. The aim of this article is to provide a comprehensive review of the available evidence on the cost effectiveness of long-acting/extended-release antipsychotic medication and critically appraise the strength of evidence reported in the studies from a methodological viewpoint. Relevant studies were identified by searching five electronic databases: PsycINFO, MEDLINE, EMBASE, the NHS Economic Evaluation Database and the Health Technology Assessment database (HTA). Search terms included, but were not limited to, 'long-acting injection', 'economic evaluation', 'cost-effectiveness' and 'cost-utility'. No limits were applied for publication dates and language. Full economic evaluations on long-acting/extended-release antipsychotics were eligible for inclusion. Observational studies and clinical trials were also checked for cost-effectiveness information. Conference abstracts and poster presentations on the cost effectiveness of long-acting antipsychotics were excluded. Thirty-two percent of identified studies met the selection criteria. Pertinent abstracts were reviewed independently by two reviewers. Relevant studies underwent data extraction by one reviewer and were checked by a second, with any discrepancies being clarified during consensus meetings. Eligible studies were assessed for methodological quality using the quality checklist for economic studies recommended by the NICE guideline on interventions in the treatment and management of schizophrenia. After applying the selection criteria, the final sample consisted of 28 studies. The majority of studies demonstrated that risperidone long-acting injection, relative to oral or other long

  7. Lithium carbonate as a treatment for paliperidone extended-release-induced leukopenia and neutropenia in a patient with schizoaffective disorder; a case report.

    Science.gov (United States)

    Matsuura, Hiroki; Kimoto, Sohei; Harada, Izumi; Naemura, Satoshi; Yamamuro, Kazuhiko; Kishimoto, Toshifumi

    2016-05-26

    Antipsychotic drug treatment can potentially lead to adverse events such as leukopenia and neutropenia. Although these events are rare, they represent serious and life-threatening hematological side effects. We present a case study of a patient with schizoaffective disorder in a 50-year-old woman. We report a case of paliperidone extended-release (ER)-induced leukopenia and neutropenia in a female patient with schizoaffective disorder. Initiating lithium carbonate treatment and decreasing the dose of valproic acid improved the observed leukopenia and neutropenia. This treatment did not influence psychotic symptoms. The combination of paliperidone ER and valproic acid induces increased paliperidone ER plasma levels. Lithium carbonate was successfully used to treat paliperidone ER-induced leukopenia and neutropenia.

  8. A Randomized Double-blind, Placebo Controlled Trial of Venlafaxine-Extended Release for Co-occurring Cannabis Dependence and Depressive Disorders

    Science.gov (United States)

    Levin, Frances R.; Mariani, John; Brooks, Daniel J.; Pavlicova, Martina; Nunes, Edward V.; Agosti, Vito; Bisaga, Adam; Sullivan, Maria A.; Carpenter, Kenneth M.

    2013-01-01

    Aim To evaluate whether venlafaxine-extended release (VEN-XR) is an effective treatment for cannabis dependence with concurrent depressive disorders. Design This was a randomized, 12 week, double-blind, placebo-controlled trial of outpatients (n = 103) with DSM-IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN-XR on a fixed-flexible schedule or placebo. All patients received weekly individual cognitive-behavioral psychotherapy that primarily targeted marijuana use. Settings The trial was conducted at two university research centers in the United States. Participants One hundred and three cannabis dependent adults participated in the trial. Measurements The primary outcome measures were 1) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and 2) improvement in depressive symptoms based on the Hamilton Depression Rating Scale. Findings The proportion of patients achieving a clinically significant mood improvement [50% decrease in Hamilton Depression score from baseline] was high and did not differ between groups receiving VEN-XR (63%) and placebo (69%) (X12=0.48, p-value= 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN-XR (11.8%) compared to placebo (36.5%) (X12=7.46, p-valuemarijuana use in the placebo group (F1,179=30.49, p-valuedepressed, cannabis-dependent patients, venlafaxine-extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use. PMID:23297841

  9. A randomized double-blind, placebo-controlled trial of venlafaxine-extended release for co-occurring cannabis dependence and depressive disorders.

    Science.gov (United States)

    Levin, Frances R; Mariani, John; Brooks, Daniel J; Pavlicova, Martina; Nunes, Edward V; Agosti, Vito; Bisaga, Adam; Sullivan, Maria A; Carpenter, Kenneth M

    2013-06-01

    To evaluate whether venlafaxine-extended release (VEN-XR) is an effective treatment for cannabis dependence with concurrent depressive disorders. This was a randomized, 12-week, double-blind, placebo-controlled trial of out-patients (n = 103) with DSM-IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN-XR on a fixed-flexible schedule or placebo. All patients received weekly individual cognitive-behavioral psychotherapy that primarily targeted marijuana use. The trial was conducted at two university research centers in the United States. One hundred and three cannabis-dependent adults participated in the trial. The primary outcome measures were (i) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and (ii) improvement in depressive symptoms based on the Hamilton Depression Rating Scale. The proportion of patients achieving a clinically significant mood improvement (50% decrease in Hamilton Depression score from baseline) was high and did not differ between groups receiving VEN-XR (63%) and placebo (69%) (χ1 (2)  = 0.48, P = 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN-XR (11.8%) compared to placebo (36.5%) (χ1 (2)  = 7.46, P marijuana use in the placebo group (F1,179  = 30.49, P depressed, cannabis-dependent patients, venlafaxine-extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use. © 2013 Society for the Study of Addiction.

  10. A Simple and Improved HPLC-PDA Method for Simultaneous Estimation of Fexofenadine and Pseudoephedrine in Extended Release Tablets by Response Surface Methodology

    Directory of Open Access Journals (Sweden)

    Ruhul Kayesh

    2017-01-01

    Full Text Available A simple RP-HPLC method has been developed for simultaneous estimation of fexofenadine and pseudoephedrine in their extended release tablet. The method was developed based on statistical design of experiments (DoE and Response Surface Methodology. Separation was achieved on double end-capped C18 column (250 mm × 4 mm, 5 μm. In this experiment, two components of mobile phase, namely, acetonitrile (% v/v and methanol (% v/v, were the factors whereas retention and resolution of the chromatographic peaks were the responses. The effects of different composition of factors on the corresponding responses were investigated. The optimum chromatographic condition for the current case was found as an isocratic mobile phase consisting of 20 mM phosphate buffer (pH 6.8 and acetonitrile and methanol in a ratio of 50 : 36 : 14 (% v/v at a flow rate of 1 mL/min for 7 minutes. The retention of pseudoephedrine and fexofenadine was found to be 2.6 min and 4.7 min, respectively. The method was validated according to the ICH and FDA guidelines and various validation parameters were determined. Also, forced degradation studies in acid, base, oxidation, and reduction media and in thermal condition were performed to establish specificity and stability-indicating property of this method. Practical applicability of this method was checked in extended release tablets available in Bangladeshi market.

  11. Randomized, double-blind trial of guanfacine extended release in children with attention-deficit/hyperactivity disorder: morning or evening administration.

    Science.gov (United States)

    Newcorn, Jeffrey H; Stein, Mark A; Childress, Ann C; Youcha, Sharon; White, Carla; Enright, Gail; Rubin, Jonathan

    2013-09-01

    To examine the efficacy and tolerability of guanfacine extended release (GXR) administered in the morning or evening in children with attention-deficit/hyperactivity disorder (ADHD). In this multicenter, double-blind, placebo-controlled, dose-optimization study, children 6 to 12 years of age with ADHD were randomized to receive GXR (1-4 mg/d) in the morning and placebo in the evening (GXR am), placebo in the morning and GXR in the evening (GXR pm), or twice-daily placebo. The primary efficacy measure was the ADHD Rating Scale-IV (ADHD-RS-IV). A total of 333 child participants received study drug in the following cohorts: GXR am (n = 107), GXR pm (n = 114), or placebo (n = 112). Mean (standard deviation) changes from baseline to week 8 (visit 10 or last observation carried forward) in ADHD-RS-IV total scores were significant for both GXR treatment groups combined (GXR all-active: -20.0 [12.97]) and separately (GXR am: -19.8 [12.95]; GXR pm: -20.1 [13.04]) compared with placebo (-11.0 [12.93]; p ADHD symptoms. The levels of response and tolerability observed with GXR were similar regardless of time of dosing (morning versus evening), indicating that once-daily GXR monotherapy is effective whether administered in the morning or evening. Clinical trial registration information-Tolerability and Efficacy of AM and PM Once Daily Dosing With Extended-release Guanfacine Hydrochloride in Children 6-12 With Attention-Deficit/Hyperactivity Disorder (ADHD) (The ADHD Tempo Study. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Diltiazem como alternativa ao betabloqueador na angiotomografia de artérias coronárias Diltiazem as an alternative to beta-blocker in coronary artery computed tomography angiography

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Rochitte

    2012-08-01

    Full Text Available FUNDAMENTO: A redução da frequência cardíaca (FC na angiografia por tomografia das artérias coronarianas (ATCCor é fundamental para a qualidade de imagem. A eficácia dos bloqueadores de cálcio como alternativas para pacientes com contraindicações aos betabloqueadores não foi definida. OBJETIVOS: Comparar a eficácia na redução da FC e variabilidade RR do metoprolol e diltiazem na ATCCor. MÉTODOS: Estudo prospectivo, randomizado, aberto, incluiu pacientes com indicação clínica de ATCCor, em ritmo sinusal, com FC>70bpm e sem uso de agentes que interferissem com a FC. Cinquenta pacientes foram randomizados para grupos: metoprolol IV 5-15 mg ou até FC≤60 bpm(M, e diltiazem IV 0,25-0,60mg/kg ou até FC≤60 bpm (D. Pressão arterial (PA e FC foram aferidas na condição basal, 1min, 3min e 5min após agentes, na aquisição e após ATCCor. RESULTADOS: A redução da FC em valores absolutos foi maior no grupo M que no grupo D (1, 3, 5min, aquisição e pós-exame. A redução percentual da FC foi significativamente maior no grupo M apenas no 1 min e 3 min após início dos agentes. Não houve diferença no 5 min, durante a aquisição e após exame. A variabilidade RR percentual do grupo D foi estatisticamente menor do que a do grupo M durante a aquisição (variabilidade RR/ FC média da aquisição. Um único caso de BAV, 2:1 Mobitz I, revertido espontaneamente ocorreu (grupo D. CONCLUSÃO: Concluímos que o diltiazem é uma alternativa eficaz e segura aos betabloqueadores na redução da FC na realização de angiografia por tomografia computadorizada das artérias coronarianas. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0BACKGROUND: Reducing heart rate (HR in CT angiography of the coronary arteries (CTACor is critical to image quality. The effectiveness of calcium channel blockers as alternatives for patients with contraindications to beta-blockers has not been established. OBJECTIVES: To compare the efficacy in the

  13. An Overview of Analytical Determination of Diltiazem, Cimetidine, Ranitidine, and Famotidine by UV Spectrophotometry and HPLC Technique

    Directory of Open Access Journals (Sweden)

    Nighat Shafi

    2013-01-01

    Full Text Available This review article recapitulates the analytical methods for the quantitative determinations of diltiazem and three H2 receptor antagonists (cimetidine, ranitidine, and famotidine by one of the spectroscopic technique (UV spectrophotometery and separation technique such as high-performance liquid chromatography (HPLC. The clinical and pharmaceutical analysis of these drugs requires effective analytical procedures for quality control, pharmaceutical dosage formulations, and biological fluids. An extensive survey of the literature published in various analytical and pharmaceutical chemistry-related journals has been compiled in its review. A synopsis of reported spectrophotometric and high-performance liquid chromatographic methods for individual drug is integrated. This appraisal illustrates that majority of the HPLC methods reviewed are based on the quantitative analysis of drugs in biological fluids, and they are appropriate for therapeutic drug monitoring purpose.

  14. Cost-effectiveness of extended release naltrexone to prevent relapse among criminal justice-involved individuals with a history of opioid use disorder.

    Science.gov (United States)

    Murphy, Sean M; Polsky, Daniel; Lee, Joshua D; Friedmann, Peter D; Kinlock, Timothy W; Nunes, Edward V; Bonnie, Richard J; Gordon, Michael; Chen, Donna T; Boney, Tamara Y; O'Brien, Charles P

    2017-08-01

    Criminal justice-involved individuals are highly susceptible to opioid relapse and overdose-related deaths. In a recent randomized trial, we demonstrated the effectiveness of extended-release naltrexone (XR-NTX; Vivitrol ® ) in preventing opioid relapse among criminal justice-involved US adults with a history of opioid use disorder. The cost of XR-NTX may be a significant barrier to adoption. Thus, it is important to account for improved quality of life and downstream cost-offsets. Our aims were to (1) estimate the incremental cost per quality-adjusted life-year (QALY) gained for XR-NTX versus treatment as usual (TAU) and evaluate it relative to generally accepted value thresholds; and (2) estimate the incremental cost per additional year of opioid abstinence. Economic evaluation of the aforementioned trial from the taxpayer perspective. Participants were randomized to 25 weeks of XR-NTX injections or TAU; follow-up occurred at 52 and 78 weeks. Five study sites in the US Northeast corridor. A total of 308 participants were randomized to XR-NTX (n = 153) or TAU (n = 155). Incremental costs relative to incremental economic and clinical effectiveness measures, QALYs and abstinent years, respectively. The 25-week cost per QALY and abstinent-year figures were $162 150 and $46 329, respectively. The 78-week figures were $76 400/QALY and $16 371/abstinent year. At 25 weeks, we can be 10% certain that XR-NTX is cost-effective at a value threshold of $100 000/QALY and 62% certain at $200 000/QALY. At 78 weeks, the cost-effectiveness probabilities are 59% at $100 000/QALY and 76% at $200 000/QALY. We can be 95% confident that the intervention would be considered 'good value' at $90 000/abstinent year at 25 weeks and $500/abstinent year at 78 weeks. While extended-release naltrexone appears to be effective in increasing both quality-adjusted life-years (QALYs) and abstinence, it does not appear to be cost-effective using generally accepted value

  15. Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Yoon S

    2014-01-01

    Full Text Available Seonghae Yoon,1,* Howard Lee,2,* Tae-Eun Kim,1 SeungHwan Lee,1 Dong-Hyun Chee,3 Joo-Youn Cho,1 Kyung-Sang Yu,1 In-Jin Jang1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Clinical Trials Center, Seoul National University Hospital, 3AbbVie Ltd., Seoul, Republic of Korea *These authors contributed equally to this work Background: This study was conducted to compare the oral bioavailability of an itopride extended-release (ER formulation with that of the reference immediate-release (IR formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. Methods: A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22–48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax and area under the plasma concentration versus time curve over 24 hours after dosing (AUC0–24h, were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. Results: A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC0–24h were contained within the conventional bioequivalence range of 0.80–1.25 (0.94 [0.88–1.01], although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC0–24h was not affected. There were no serious adverse events and both formulations were

  16. US Food and Drug Administration's Risk Evaluation and Mitigation Strategy for extended-release and long-acting opioids: pros and cons, and a European perspective.

    Science.gov (United States)

    Mercadante, Sebastiano; Craig, David; Giarratano, Antonello

    2012-12-24

    Prescriptions for opioid analgesics to manage moderate-to-severe chronic non-cancer pain have increased markedly over the last decade. An unintentional consequence of greater prescription opioid utilization has been the parallel increase in misuse, abuse and overdose, which are serious risks associated with all opioid analgesics. In response to disturbing rises in prescription opioid abuse, the US Food and Drug Administration (FDA) has proposed the implementation of aggressive Risk Evaluation and Mitigation Strategies (REMS). While REMS could dramatically change the development, release, marketing and prescription of extended-release opioids, questions remain on how these programmes may influence prescribing practices, patient safety and ultimately patient access to these agents. The extent of the availability and misuse of prescription opioids in Europe is difficult to assess from the data currently available, due in large part to the considerable differences in prescribing patterns and regulations between countries. Balancing the availability of prescription opioids for those patients who have pain, while discouraging illicit use, is a complex challenge and requires effective efforts on many levels, particularly in Europe where policies are quite different between countries.

  17. Tamarind seed gum-hydrolyzed polymethacrylamide-g-gellan beads for extended release of diclofenac sodium using 32 full factorial design.

    Science.gov (United States)

    Nandi, Gouranga; Nandi, Amit Kumar; Khan, Najim Sarif; Pal, Souvik; Dey, Sibasish

    2018-07-15

    Development of tamarind seed gum (TSG)-hydrolyzed polymethacrylamide-g-gellan (h-Pmaa-g-GG) composite beads for extended release of diclofenac sodium using 3 2 full factorial design is the main purpose of this study. The ratio of h-Pmaa-g-GG and TSG and concentration of cross-linker CaCl 2 were taken as independent factors with three different levels of each. Effects of polymer ratio and CaCl 2 on drug entrapment efficiency (DEE), drug release, bead size and swelling were investigated. Responses such as DEE and different drug release parameters were statistically analyzed by 3 2 full factorial design using Design-Expert software and finally the formulation factors were optimized to obtain USP-reference release profile. Drug release rate was found to decrease with decrease in the ratio of h-Pmaa-g-GG:TSG and increase in the concentration of Ca 2+ ions in cross-linking medium. The optimized formulation showed DEE of 93.25% and an extended drug release profile over a period of 10h with f 2 =80.13. Kinetic modeling unveiled case-I-Fickian diffusion based drug release mechanism. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Changes in misuse and abuse of prescription opioids following implementation of Extended-Release and Long-Acting Opioid Analgesic Risk Evaluation and Mitigation Strategy.

    Science.gov (United States)

    Bucher Bartelson, Becki; Le Lait, M Claire; Green, Jody L; Cepeda, M Soledad; Coplan, Paul M; Maziere, Jean-Yves; Wedin, Gregory P; Dart, Richard C

    2017-09-01

    An unintended consequence of extended-release (ER) and long-acting (LA) prescription opioids is that these formulations can be more attractive to abusers than immediate-release (IR) formulations. The US Food and Drug Administration recognized these risks and approved the ER/LA Opioid Analgesic Risk Evaluation and Mitigation Strategy (ER/LA REMS), which has a goal of reducing opioid misuse and abuse and their associated consequences. The primary objective of this analysis is to determine whether ER/LA REMS implementation was associated with decreased reports of misuse and abuse. Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS(R)) System Poison Center Program were utilized. Poison center cases are assigned a reason for exposure, a medical outcome, and a level of health care received. Rates adjusted for population and drug utilization were analyzed over time. RADARS System Poison Center Program data indicate a notable decrease in ER/LA opioid rates of intentional abuse and misuse as well as major medical outcomes or hospitalizations following implementation of the ER/LA REMS. While similar decreases were observed for the IR prescription opioid group, the decreasing rate for the ER/LA opioids exceeded the decreasing rates for the IR prescription opioids and was distinctly different than that for the prescription stimulants, indicating that the ER/LA REMS program may have had an additional effect on decreases in opioid abuse and intentional misuse beyond secular trends. Copyright © 2017 John Wiley & Sons, Ltd.

  19. A double-blind, placebo-controlled, multicenter study with alprazolam and extended-release alprazolam in the treatment of panic disorder.

    Science.gov (United States)

    Pecknold, J; Luthe, L; Munjack, D; Alexander, P

    1994-10-01

    This is a double-blind, placebo-controlled, flexible-dose, multicenter, 6-week study comparing regular alprazolam (compressed tablet, CT), given four times per day, and extended release alprazolam (XR), given once in the morning. The aim of the XR preparation is to offer less frequent dosing and to reduce interdose anxiety. Of the intent-to-treat group of 209 patients, 184 completed 3 weeks of medication and were evaluated according to protocol. There was a completer rate for the 6 weeks of 94% (CT), 97% (XR), and 87% (placebo). On global measures, Hamilton Rating Scale for Anxiety, phobia rating, and work disability measures, both active treatment groups were equally effective and significantly more efficacious than the placebo cell on endpoint MANOVA analysis. On analysis of the panic factor with endpoint data, both active treatment groups were equally effective throughout the 6-week trial and significantly more efficacious than the placebo group. Drowsiness occurred more frequently with CT alprazolam (86% of patients) than with the XR preparation (79%) or placebo (49%).

  20. Metformin extended release treatment of adolescent obesity: a 48-week randomized, double-blind, placebo-controlled trial with 48-week follow-up.

    Science.gov (United States)

    Wilson, Darrell M; Abrams, Stephanie H; Aye, Tandy; Lee, Phillip D K; Lenders, Carine; Lustig, Robert H; Osganian, Stavroula V; Feldman, Henry A

    2010-02-01

    Metformin has been proffered as a therapy for adolescent obesity, although long-term controlled studies have not been reported. To test the hypothesis that 48 weeks of daily metformin hydrochloride extended release (XR) therapy will reduce body mass index (BMI) in obese adolescents, as compared with placebo. Multicenter, randomized, double-blind, placebo-controlled clinical trial. The 6 centers of the Glaser Pediatric Research Network from October 2003 to August 2007. Obese (BMI > or = 95th percentile) adolescents (aged 13-18 years) were randomly assigned to the intervention (n = 39) or placebo groups. Intervention Following a 1-month run-in period, subjects following a lifestyle intervention program were randomized 1:1 to 48 weeks' treatment with metformin hydrochloride XR, 2000 mg once daily, or an identical placebo. Subjects were monitored for an additional 48 weeks. Main Outcome Measure Change in BMI, adjusted for site, sex, race, ethnicity, and age and metformin vs placebo. After 48 weeks, mean (SE) adjusted BMI increased 0.2 (0.5) in the placebo group and decreased 0.9 (0.5) in the metformin XR group (P = .03). This difference persisted for 12 to 24 weeks after cessation of treatment. No significant effects of metformin on body composition, abdominal fat, or insulin indices were observed. Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program. clinicaltrials.gov Identifiers: NCT00209482 and NCT00120146.

  1. Long-term tolerability of tolterodine extended release in children 5-11 years of age: results from a 12-month, open-label study

    DEFF Research Database (Denmark)

    Nijman, Rien J M; Borgstein, Niels G; Ellsworth, Pamela

    2007-01-01

    OBJECTIVE: To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI). METHODS: This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI...... suggestive of detrusor overactivity (>/=1 diurnal incontinence episode per 24h for >/=5 of 7 d) and >/=6 voids per 24h at baseline and had completed the 12-wk double-blind study. Patients received tolterodine ER (2mg once daily) for 12 mo. The primary end points were the incidence and severity of adverse......-blind tolterodine ER, n=221; placebo, n=97). The majority of patients were white (90%), mean+/-SD age was 7.6+/-1.5 yr, and 54% were boys. Forty-nine percent of patients reported >/=1 AE during the study, similar to that observed in the preceding 12-wk study (42%). The most frequent AEs were urinary tract infection...

  2. Development and validation of an in vitro–in vivo correlation (IVIVC model for propranolol hydrochloride extended-release matrix formulations

    Directory of Open Access Journals (Sweden)

    Chinhwa Cheng

    2014-06-01

    Full Text Available The objective of this study was to develop an in vitro–in vivo correlation (IVIVC model for hydrophilic matrix extended-release (ER propranolol dosage formulations. The in vitro release characteristics of the drug were determined using USP apparatus I at 100 rpm, in a medium of varying pH (from pH 1.2 to pH 6.8. In vivo plasma concentrations and pharmacokinetic parameters in male beagle dogs were obtained after administering oral, ER formulations and immediate-release (IR commercial products. The similarity factor f2 was used to compare the dissolution data. The IVIVC model was developed using pooled fraction dissolved and fraction absorbed of propranolol ER formulations, ER-F and ER-S, with different release rates. An additional formulation ER-V, with a different release rate of propranolol, was prepared for evaluating the external predictability. The results showed that the percentage prediction error (%PE values of Cmax and AUC0–∞ were 0.86% and 5.95%, respectively, for the external validation study. The observed low prediction errors for Cmax and AUC0–∞ demonstrated that the propranolol IVIVC model was valid.

  3. Evaluation of the Relative Abuse of an OROS® Extended-release Hydromorphone HCI Product: Results from three Post-market Surveillance Studies.

    Science.gov (United States)

    Butler, Stephen F; McNaughton, Emily C; Black, Ryan A; Cassidy, Theresa A

    2018-01-02

    Formulating prescription opioids to limit abuse remains a priority. OROS® extended-release (ER) hydromorphone HCl (EXALGO®) may have low abuse potential. Three post-marketing studies of the relative abuse liability of OROS hydromorphone ER were conducted. Estimates of abuse, unadjusted and adjusted for prescription volume, were generated for OROS hydromorphone ER and comparators from Q2 2010 through Q2 2014 for a high-risk, substance abuse treatment population and the general population using poison control center data. Comparators were selected for compound, market penetration, and route of administration (ROA) profile. ROA comparisons were made among the substance abuse treatment population. Internet discussion was examined to determine abusers' interest in and desire for the OROS formulation. Examination of abuse prevalence among adults within substance abuse treatment, intentional poison exposures and Internet discussion levels generally support the hypothesis that OROS hydromorphone ER may have lower abuse potential than many other opioid products. OROS hydromorphone ER also appears to be abused less often by alternate ROAs (e.g., snorting and injection). Lower levels of online discussion were observed along with relatively low endorsement for abuse. Abuse of OROS hydromorphone ER was observed in high-risk substance abuse and general population samples but at a very low relative prevalence. Evidence suggests it may be less often abused by alternate ROAs than some comparators. Online data did not find evidence of high levels of desire for OROS hydromorphone ER by recreational abusers. Continued monitoring of this product's abuse liability is warranted.

  4. Low-threshold extended-release naltrexone for high utilizers of public services with severe alcohol use disorder: A pilot study.

    Science.gov (United States)

    Smith-Bernardin, Shannon; Rowe, Chris; Behar, Emily; Geier, Michelle; Washington, Stuart; Santos, Glenn-Milo; Euren, Jason; Martin, Judith; Gleghorn, Alice; Coffin, Phillip O

    2018-02-01

    Extended-release naltrexone (XRNTX) is an effective treatment for alcohol use disorder (AUD). We sought to evaluate the feasibility, acceptability, and preliminary effectiveness and cost-effectiveness of XRNTX delivered as a stand-alone service to persons with severe AUD who are high utilizers of multiple urgent and emergency medical services (HUMS). Of 15 HUMS persons with severe AUD selected based on chart review, 11 agreed to participate. Participants received a mean of 4.5 injections (range 2-7). Modest benefits from XRNTX were observed in terms of patients' Urge-to-Drink Score and the costs of emergency medical services utilized. Though limited by a small sample size, costs including client utilization and study related expenses during the post-enrollment period were less than client utilization costs in the pre-enrollment period. We also observed non-significant improvements in the number of drinking days, but no change in quality of life as measured by the EQ-5D. Eighty-eight percent of participants perceived XRNTX as helping with their drinking. Findings need to be replicated in a larger study, however if replicated, the cost savings could be substantial. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Add-on-Statin Extended Release Nicotinic Acid/Laropiprant but Not the Switch to High-Dose Rosuvastatin Lowers Blood Pressure: An Open-Label Randomized Study

    Directory of Open Access Journals (Sweden)

    Anastazia Kei

    2011-01-01

    Full Text Available Introduction. Nicotinic acid (NA and statins have been associated with reductions in blood pressure (BP. Patients and Methods. We recruited 68 normotensive and hypertensive dyslipidemic patients who were treated with a conventional statin dose and had not achieved lipid targets. Patients were randomized to switch to high-dose rosuvastatin (40 mg/day or to add-on current statin treatment with extended release (ER NA/laropiprant (1000/20 mg/day for the first 4 weeks followed by 2000/40 mg/day for the next 8 weeks for 3 months. Results. Switching to rosuvastatin 40 mg/day was not associated with significant BP alterations. In contrast, the addition of ER-NA/laropiprant to current statin treatment resulted in a 7% reduction of systolic BP (from 134±12 to 125±10 mmHg, <.001 versus baseline and =.01 versus rosuvastatin group and a 5% reduction of diastolic BP (from 81±9 to 77±6 mmHg, =.009 versus baseline and =.01 versus rosuvastatin group. These reductions were significant only in the subgroup of hypertensives and were independent of the hypolipidemic effects of ER-NA/laropiprant. Conclusions. Contrary to the switch to high-dose rosuvastatin, the addition of ER-NA/laropiprant to statin treatment was associated with significant reductions in both systolic and diastolic BP.

  6. Analgesic Efficacy of a New Immediate-Release/Extended-Release Formulation of Ibuprofen: Results From Single- and Multiple-Dose Postsurgical Dental Pain Studies.

    Science.gov (United States)

    Christensen, Steven; Paluch, Ed; Jayawardena, Shyamalie; Daniels, Stephen; Meeves, Suzanne

    2017-05-01

    Analgesic effects of ibuprofen immediate-release/extended-release (IR/ER) 600-mg tablets were evaluated in 2 randomized, double-blind, placebo-controlled dental pain studies. Patients 16-40 years old with moderate-severe pain following third-molar extraction received single-dose ibuprofen 600 mg IR/ER (formulation A or B), naproxen sodium 220 mg, or placebo (2:2:2:1; study 1) or 4 doses of ibuprofen 600 mg IR/ER (formulation A) or placebo (1:1; study 2). In study 1 (n = 196), mean (standard deviation [SD]) time-weighted sum of pain intensity difference scores for placebo, ibuprofen IR/ER A, ibuprofen IR/ER B, and naproxen, respectively, were 0.05 (9.2), 16.87 (9.4), 17.34 (10.5), and 12.66 (10.0) over 0-12 hours and -0.03 (4.1), 6.57 (4.4), 7.14 (5.2), and 5.14 (5.0) over 8-12 hours (all P ibuprofen IR/ER, respectively (P ibuprofen. Gastrointestinal adverse events predominated with placebo both after study medication administration and after rescue medication use, if applicable. Ibuprofen 600 mg IR/ER provided safe and effective analgesia after single and multiple doses. © 2016, The American College of Clinical Pharmacology.

  7. Ingestion modelling in COSYMA

    International Nuclear Information System (INIS)

    Margeanu, Sorin; Angelescu, Tatiana

    2003-01-01

    One of the aims in the design of the COSYMA ingestion model was the ability to cope in a flexible manner with the various food chain related data and results at different stages of an accident consequence assessment. Since dynamic foodchain transport models themselves are normally rather complex and require significant computation times, they are usually not included in ACA codes, but are used to calculate and tabulate the needed information in the form of data libraries. Such data files contain specific activity concentrations in the foodstuff and their time integral normalised to unit deposit or unit air concentration for a series of times after the accident.They allow for calculations taking into account food restrictions. In an ACA run, the actual specific concentrations in the foodstuffs are obtained by multiplying the normalized concentrations taken from the data library by the ground or air concentrations in each grid point predicted with an atmospheric transport and deposition model. The paper presents the structure of the ingestion model: structure, methods and the libraries used for a nuclear accident consequences assessment. (authors)

  8. Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

    Directory of Open Access Journals (Sweden)

    Hale ME

    2013-05-01

    Full Text Available Martin E Hale,1 Srinivas R Nalamachu,2 Arif Khan,3 Michael Kutch4,* 1Gold Coast Research, LLC, Weston, FL, USA; 2International Clinical Research Institute, Overland Park, KS, USA; 3MedNorthwest Clinical Research Center, Bellevue, WA, USA; Duke University Medical Center, Durham, NC, USA; 4Applied Clinical Intelligence, LLC, Bala Cynwyd, PA, USA *Affiliation at the time this work was completed. Michael Kutch is currently affiliated with Cytel Inc, Chesterbrook, PA, USA Purpose: To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER during dose conversion and titration. Patients and methods: A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio, and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs and serious AEs. Results: Mean (standard deviation final daily dose of OROS hydromorphone ER was 37.5 (17.8 mg. Mean (standard error of the mean [SEM] numeric rating scale scores decreased from 6.6 (0.1 at screening to 4.3 (0.1 at the final titration visit (mean [SEM] change, -2.3 [0.1], representing a 34.8% reduction. Mean (SEM change in Patient Global Assessment was -0.6 (0.1, and mean change (SEM in the Roland–Morris Disability Questionnaire was -2.8 (0.3. Patients achieving a stable dose showed greater improvement

  9. Evaluation of the Microbiological Efficacy of a Single 2-Gram Dose of Extended-Release Azithromycin by Population Pharmacokinetics and Simulation in Japanese Patients with Gonococcal Urethritis.

    Science.gov (United States)

    Soda, Midori; Ito, Shin; Matsumaru, Naoki; Nakamura, Sakiko; Nagase, Izumi; Takahashi, Hikari; Ohno, Yuta; Yasuda, Mitsuru; Yamamoto, Miho; Tsukamoto, Katsura; Itoh, Yoshinori; Deguchi, Takashi; Kitaichi, Kiyoyuki

    2018-01-01

    The objective of this study was to analyze the relationship between the pharmacokinetic (PK)/pharmacodynamic (PD) parameters of a single 2-g dose of extended-release formulation of azithromycin (AZM-SR) and its microbiological efficacy against gonococcal urethritis. Fifty male patients with gonococcal urethritis were enrolled in this study. In 36 patients, the plasma AZM concentrations were measured using liquid chromatography-tandem mass spectrometry, the AZM MIC values for the Neisseria gonorrhoeae isolates were determined, and the microbiological outcomes were assessed. AZM-SR monotherapy eradicated N. gonorrhoeae in 30 (83%) of the 36 patients. AZM MICs ranged from 0.03 to 2 mg/liter. The mean value of the area under the concentration-time curve (AUC), estimated by population PK analysis using a two-compartment model, was 20.8 mg · h/liter. Logistic regression analysis showed that the PK/PD target value required to predict an N. gonorrhoeae eradication rate of ≥95% was a calculated AUC/MIC of ≥59.5. The AUC/MIC value was significantly higher in patients who achieved microbiological cure than in patients who achieved microbiological failure. Monte Carlo simulation using this MIC distribution revealed that the probability that AZM-SR monotherapy would produce an AUC/MIC exceeding the AUC/MIC target of 59.5 was 47%. Furthermore, the MIC distribution for strains isolated in this study was mostly consistent with that for strains currently circulating in Japan. In conclusion, in Japan, AZM-SR monotherapy may not be effective against gonococcal urethritis. Therefore, use of a single 2-g dose of AZM-SR either with or without other antibiotics could be an option to treat gonococcal urethritis if patients are allergic to ceftriaxone and spectinomycin or are diagnosed to be infected with an AZM-sensitive strain. Copyright © 2017 American Society for Microbiology.

  10. Managing severe pain and abuse potential: the potential impact of a new abuse-deterrent formulation oxycodone/naltrexone extended-release product

    Directory of Open Access Journals (Sweden)

    Pergolizzi, J

    2018-02-01

    Full Text Available Joseph V Pergolizzi, Jr,1 Robert Taylor Jr,1 Jo Ann LeQuang,1 Robert B Raffa2,3 On behalf of the NEMA Research Group 1NEMA Research Inc., Naples, FL, USA; 2University of Arizona College of Pharmacy, Tucson, AZ, USA; 3Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: Proper management of severe pain represents one of the most challenging clinical dilemmas. Two equally important goals must be attained: the humanitarian/medical goal to relieve suffering and the societal/legal goal to not contribute to the drug abuse problem. This is an age-old problem, and the prevailing emphasis placed on one or the other goal has resulted in pendulum swings that have resulted in either undertreatment of pain or the current epidemic of misuse and abuse. In an effort to provide efficacious strong pain relievers (opioids that are more difficult to abuse by the most dangerous routes of administration, pharmaceutical companies are developing products in which the opioid is manufactured in a formulation that is designed to be tamper resistant. Such a product is known as an abuse-deterrent formulation (ADF. ADF opioid products are designed to deter or resist abuse by making it difficult to tamper with the product and extracting the opioid for inhalation or injection. To date, less than a dozen opioid formulations have been approved by the US Food and Drug Administration to carry specific ADF labeling, but this number will likely increase in the coming years. Most of these products are extended-release formulations. Keywords: oxycodone/naltrexone, abuse-deterrent formulation, abuse-deterrent opioid, oxycodone, abuse liability

  11. Switch from Immediate-release Pramipexole to Extended-release Pramipexole: The Safety and Efficacy Characteristics of Sixty-eight Patients

    Directory of Open Access Journals (Sweden)

    Müge Kuzu

    2016-09-01

    Full Text Available Objective: To evaluate the safety and efficacy of switching from immediate-release pramipexole (pex to extended-release pramipexole (pex-ER. Materials and Methods: Pex-ER became available in Turkey about a year ago, since then we documented satisfactory information on patients (26 women; 38% who were switched from pex to pex-ER. We recorded pre- and post-switch pex and levodopa, equivalent doses of other anti-parkinsonian medication, and analyzed the frequency and nature of reported adverse effects. Results: The mean age of the patients was 63.3 years (range, 44-88 years, and the mean disease duration was 7.1 years (range, 1-27 years. The other drugs were levodopa (57 patients, 82.6%, entacapone (24 patients, 34.58%, rasagiline (20 patients, 29%, amantadine (18 patients, 26.1%, and apomorphine (six patients, 8.7%. Switch from pex to pex-ER was uneventful in 62 (91.2% patients. Adverse events were reported in six (8.8% patients: ankle swelling (two patients, nausea (one patient, dyskinesia (one patient, hypersexuality (one patient, and psychosis (one patient. Problems resolved with further medication change in two patients. Four patients preferred to return to pex. Conclusion: The great majority of patients (91.2% switched from three times daily pex to once daily pex-ER uneventfully. A slight increase in pex daily dose, which was tailored according to patients’ symptomatic needs, resulted in an increase in post-switch levodopa equivalent doses. Our experience is compatible with previously reported studies.

  12. Effect of Concomitant Medications on the Safety and Efficacy of Extended-Release Carbidopa-Levodopa (IPX066) in Patients With Advanced Parkinson Disease: A Post Hoc Analysis.

    Science.gov (United States)

    LeWitt, Peter A; Verhagen Metman, Leo; Rubens, Robert; Khanna, Sarita; Kell, Sherron; Gupta, Suneel

    Extended-release (ER) carbidopa-levodopa (CD-LD) (IPX066/RYTARY/NUMIENT) produces improvements in "off" time, "on" time without troublesome dyskinesia, and Unified Parkinson Disease Rating Scale scores compared with immediate-release (IR) CD-LD or IR CD-LD plus entacapone (CLE). Post hoc analyses of 2 ER CD-LD phase 3 trials evaluated whether the efficacy and safety of ER CD-LD relative to the respective active comparators were altered by concomitant medications (dopaminergic agonists, monoamine oxidase B [MAO-B] inhibitors, or amantadine). ADVANCE-PD (n = 393) assessed safety and efficacy of ER CD-LD versus IR CD-LD. ASCEND-PD (n = 91) evaluated ER CD-LD versus CLE. In both studies, IR- and CLE-experienced patients underwent a 6-week, open-label dose-conversion period to ER CD-LD prior to randomization. For analysis, the randomized population was divided into 3 subgroups: dopaminergic agonists, rasagiline or selegiline, and amantadine. For each subgroup, changes from baseline in PD diary measures ("off" time and "on" time with and without troublesome dyskinesia), Unified Parkinson Disease Rating Scale Parts II + III scores, and adverse events were analyzed, comparing ER CD-LD with the active comparator. Concomitant dopaminergic agonist or MAO-B inhibitor use did not diminish the efficacy (improvement in "off" time and "on" time without troublesome dyskinesia) of ER CD-LD compared with IR CD-LD or CLE, whereas the improvement with concomitant amantadine failed to reach significance. Safety and tolerability were similar among the subgroups, and ER CD-LD did not increase troublesome dyskinesia. For patients on oral LD regimens and taking a dopaminergic agonist, and/or a MAO-B inhibitor, changing from an IR to an ER CD-LD formulation provides approximately an additional hour of "good" on time.

  13. Costs and effects of paliperidone extended release compared with alternative oral antipsychotic agents in patients with schizophrenia in Greece: a cost effectiveness study.

    Science.gov (United States)

    Geitona, Maria; Kousoulakou, Hara; Ollandezos, Markos; Athanasakis, Kostas; Papanicolaou, Sotiria; Kyriopoulos, Ioannis

    2008-08-28

    To compare the costs and effects of paliperidone extended release (ER), a new pharmaceutical treatment for the management of schizophrenia, with the most frequently prescribed oral treatments in Greece (namely risperidone, olanzapine, quetiapine, aripiprazole and ziprasidone) over a 1-year time period. A decision tree was developed and tailored to the specific circumstances of the Greek healthcare system. Therapeutic effectiveness was defined as the annual number of stable days and the clinical data was collected from international clinical trials and published sources. The study population was patients who suffer from schizophrenia with acute exacerbation. During a consensus panel of 10 psychiatrists and 6 health economists, data were collected on the clinical practice and medical resource utilisation. Unit costs were derived from public sources and official reimbursement tariffs. For the comparators official retail prices were used. Since a price had not yet been granted for paliperidone ER at the time of the study, the conservative assumption of including the average of the highest targeted European prices was used, overestimating the price of paliperidone ER in Greece. The study was conducted from the perspective of the National Healthcare System. The data indicate that paliperidone ER might offer an increased number of stable days (272.5 compared to 272.2 for olanzapine, 265.5 f risperidone, 260.7 for quetiapine, 260.5 for ziprasidone and 258.6 for aripiprazole) with a lower cost compared to the other therapies examined (euro 7,030 compared to euro 7,034 for olanzapine, euro 7,082 for risperidone, euro 8,321 for quetiapine, euro 7,713 for ziprasidone and euro 7,807 for aripiprazole). During the sensitivity analysis, a +/- 10% change in the duration and frequency of relapses and the economic parameters did not lead to significant changes in the results. Treatment with paliperidone ER can lead to lower total cost and higher number of stable days in most of the

  14. Evaluation of sleep profile in schizophrenia patients treated with extended-release paliperidone: an open-label prospective study in Southeast Asia

    Directory of Open Access Journals (Sweden)

    Kongsakon R

    2017-10-01

    Full Text Available Ronnachai Kongsakon,1 Nuntika Thavichachart,2 Ka Fai Chung,3 Leslie Lim,4 Beverly Azucena,5 Elizabeth Rondain,6 Benson Go,7 Fe Costales,8 Osot Nerapusee9 1Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Department of Medicine, Division of Psychiatry, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand; 3Department of Psychiatry, University of Hong Kong, Hong Kong, People’s Republic of China; 4Department of Psychiatry, Singapore General Hospital, Singapore; 5National Center for Mental Health, Mandaluyong, Philippines; 6Makati Medical Center, Makati, Philippines; 7Northern Mindanao Medical Center, Cagayan De Oro, Misamis Oriental, Philippines; 8Perpetual Succour Hospital, Cebu, Philippines; 9Medical Affairs, Janssen‑Cilag, Bangkok, Thailand Objective: To evaluate the effect of 6 months of treatment with paliperidone extended-release (ER tablets on the sleep profile of patients with schizophrenia.Methods: A total of 984 patients meeting the The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV criteria for schizophrenia who switched their antipsychotic to paliperidone ER were recruited from 61 sites in five countries in Southeast Asia. We recorded patient demographics and assessed sleep quality and daytime drowsiness using visual analog scales.Results: Approximately 70% of patients completed the 6-month study. After the use of paliperidone ER, patients reported significantly better sleep quality (76.44 vs 65.48; p<0.001 and less daytime drowsiness compared with their baseline value (23.18 vs 34.22; p<0.001. Factors predicting sleep profile improvement were completion of the study and higher baseline Positive and Negative Syndrome Scale scores.Conclusion: Paliperidone ER can help schizophrenia patients to improve sleep quality and reduce daytime drowsiness; this was seen especially in the patients who completed the 6-month

  15. Post-marketing experience with nevirapine extended release (XR) tablets: effectiveness and tolerability in a population-based cohort in British Columbia, Canada.

    Science.gov (United States)

    Lepik, Katherine J; Yip, Benita; McGovern, Rachel A; Ding, Erin; Nohpal, Adriana; Watson, Birgit E; Toy, Junine; Akagi, Linda; Harrigan, P Richard; Moore, David M; Hogg, Robert S; Montaner, Julio S G; Barrios, Rolando

    2015-01-01

    Nevirapine 400 mg extended release tablets (nevirapine-XR) are a once-daily alternative to nevirapine 200 mg immediate release tablets (nevirapine-IR). Study objectives were to describe the effectiveness and tolerability of nevirapine-XR in clinical practice and, for patients who switched from once daily 2×200 mg nevirapine-IR to nevirapine-XR, compare virological suppression and plasma nevirapine concentrations during each treatment period. HIV-1-infected adults entered the study cohort if they initiated nevirapine-XR in British Columbia (BC) Canada between 1 April 2012 and 30 September 2012 and were followed until 30 September 2013. Demographic and clinical variables were abstracted from the BC Centre for Excellence in HIV/AIDS databases. Patients who switched from once daily nevirapine-IR to nevirapine-XR were monitored for 6 months pre- and post-switch with comparison of virological suppression (McNeamer's test) and median random plasma nevirapine concentrations (Wilcoxon-Mann-Whitney test) in each period. The 536 nevirapine-XR-treated patients were 96% male, median (IQR) age 49.9 (44.0-56.9) years. Median follow-up was 15.6 (14.7-16.5) months, with 474/536 (88%) maintaining virological suppression. Emergent drug resistance developed in 5/536 (1%), adverse drug reactions in 17/536 (3%) and, although 31/536 (6%) reported 'whole' tablets in their stools, this was not associated with adverse outcomes. Among the 305 patients who switched from nevirapine-IR to nevirapine-XR, median (IQR) random plasma nevirapine concentration was higher during nevirapine-IR 5,000 (3,690-6,090) ng/ml than nevirapine-XR 3,930 (3,050-5,150) ng/ml (Pmarketing study affirms the effectiveness and tolerability of nevirapine-XR as an alternative to nevirapine-IR in adults.

  16. Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients

    Science.gov (United States)

    Gaber, A. Osama; Alloway, Rita R.; Bodziak, Kenneth; Kaplan, Bruce; Bunnapradist, Suphamai

    2013-01-01

    Background LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns. Methods In this phase 2 study, adult stable kidney transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8 to 21; trough levels were to be maintained between 5 and 15 ng/mL; 24-hr pharmacokinetic assessments were done on days 7 (baseline pre-switch), 14, and 21. Results Forty-seven patients completed LCP-Tacro dosing per protocol. The mean conversion ratio was 0.71. Pharmacokinetic data demonstrated consistent exposure (AUC) at the lower conversion dose. Cmax (P=0.0001), Cmax/Cmin ratio (P<0.001), percent fluctuation (P<0.0001), and swing (P=0.0004) were significantly lower and Tmax significantly (P<0.001) longer for LCP-Tacro versus Prograf. AUC24 and Cmin correlation coefficients after 7 and 14 days of therapy were 0.86 or more, demonstrating a robust correlation between LCP-Tacro tacrolimus exposure and trough levels. There were three serious adverse events; none were related to study drug and all were resolved. Conclusions Stable kidney transplant patients can be safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allows for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displays flatter kinetics characterized by significantly lower peak-trough fluctuations. PMID:23715050

  17. Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers.

    Science.gov (United States)

    Yoon, Seonghae; Lee, Howard; Kim, Tae-Eun; Lee, SeungHwan; Chee, Dong-Hyun; Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin

    2014-01-01

    This study was conducted to compare the oral bioavailability of an itopride extended-release (ER) formulation with that of the reference immediate-release (IR) formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22-48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax) and area under the plasma concentration versus time curve over 24 hours after dosing (AUC(0-24h)), were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC(0-24h) were contained within the conventional bioequivalence range of 0.80-1.25 (0.94 [0.88-1.01]), although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC(0-24h) was not affected. There were no serious adverse events and both formulations were generally well tolerated. At steady state, once-daily itopride ER at 150 mg has a bioavailability comparable with that of itopride IR at 50 mg given three times a day under fasting conditions. Food delayed the absorption of itopride ER, with no marked change in its oral bioavailability.

  18. Employment-based reinforcement of adherence to an FDA approved extended release formulation of naltrexone in opioid-dependent adults: a randomized controlled trial.

    Science.gov (United States)

    DeFulio, Anthony; Everly, Jeffrey J; Leoutsakos, Jeannie-Marie S; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E; Silverman, Kenneth

    2012-01-01

    Naltrexone provides excellent opioid blockade, but its clinical utility is limited because opioid-dependent patients typically refuse it. An injectable suspension of naltrexone for extended release (XR-NTX) was recently approved by the FDA for treatment of opioid dependence. XR-NTX treatment may require concurrent behavioral intervention to maximize adherence and effectiveness, thus we sought to evaluate employment-based reinforcement as a method of improving adherence to XR-NTX in opiate dependent adults. Opioid-dependent adults (n=38) were detoxified and inducted onto oral naltrexone, then randomly assigned to contingency or prescription conditions. Participants received up to six doses of XR-NTX at four-week intervals. All participants could earn vouchers for attendance and performance at a therapeutic workplace. Contingency participants were required to accept XR-NTX injections to access the workplace and earn vouchers. Prescription participants could earn vouchers independent of their acceptance of XR-NTX injections. Contingency participants accepted significantly more naltrexone injections than prescription participants (87% versus 52%, p=.002), and were more likely to accept all injections (74% versus 26%, p=.004). Participants in the two conditions provided similar percentages of samples negative for opiates (72% versus 65%) and for cocaine (58% versus 54%). Opiate positivity was significantly more likely when samples were also cocaine positive, independent of naltrexone blockade (p=.002). Long-term adherence to XR-NTX in unemployed opiate dependent adults is low under usual care conditions. Employment-based reinforcement can maintain adherence to XR-NTX. Ongoing cocaine use appears to interfere with the clinical effectiveness of XR-NTX on opiate use. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Safety and tolerability of extended-release niacin-laropiprant: Pooled analyses for 11,310 patients in 12 controlled clinical trials.

    Science.gov (United States)

    McKenney, James; Bays, Harold; Gleim, Gilbert; Mitchel, Yale; Kuznetsova, Olga; Sapre, Aditi; Sirah, Waheeda; Maccubbin, Darbie

    2015-01-01

    The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) showed that adding extended-release niacin-laropiprant (ERN-LRPT) to statin provided no incremental cardiovascular benefit vs placebo (PBO). ERN-LRPT was also associated with an excess of serious adverse experiences (AEs), some of which were unexpected (infections and bleeding). These findings led to the withdrawal of ERN-LRPT from all markets. We examined the safety profile of ERN-LRPT vs the comparators ERN alone and statins in the ERN-LRPT development program to assess whether similar safety signals were observed to those seen in HPS-THRIVE and whether these might be attributed to ERN or LRPT. Postrandomization safety data from 12 clinical studies, 12 to 52 weeks in duration and involving 11,310 patients, were analyzed across 3 treatments: (1) ERN-LRPT; (2) ERN-NSP (ERN, Merck & Co, Inc or Niaspan [NSP], Abbott Laboratories); and (3) statin-PBO (statin or PBO). The safety profiles of ERN-LRPT and ERN-NSP were similar, except for less flushing with ERN-LRPT. Nonflushing AEs reported more frequently with ERN-LRPT or ERN-NSP than with statin-PBO were mostly nonserious and typical of niacin (nausea, diarrhea, and increased blood glucose). There was no evidence for an increased risk of serious AEs related to diabetes, muscle, infection, or bleeding. Pooled data from 11,310 patients revealed that, except for reduced flushing, the safety profile of ERN-LRPT was similar to that of ERN-NSP; LRPT did not appear to adversely affect the side-effect profile of ERN. The inability to replicate the unexpected AE findings in HPS2-THRIVE could be because of the smaller sample size and substantially shorter duration of these studies. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  20. Extended-Release Once-Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate-Release Tofacitinib and Impact of Food.

    Science.gov (United States)

    Lamba, Manisha; Wang, Rong; Fletcher, Tracey; Alvey, Christine; Kushner, Joseph; Stock, Thomas C

    2016-11-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended-release (XR) formulation has been designed to provide a once-daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice-daily immediate-release (IR) formulation. We conducted 2 randomized, open-label, phase 1 studies in healthy volunteers. Study A characterized single-dose and steady-state PK of tofacitinib XR 11 mg QD and intended to demonstrate equivalence of exposure under single-dose and steady-state conditions to tofacitinib IR 5 mg twice daily. Study B assessed the effect of a high-fat meal on the bioavailability of tofacitinib from the XR formulation. Safety and tolerability were monitored in both studies. In study A (N = 24), the XR and IR formulations achieved time to maximum plasma concentration at 4 hours and 0.5 hours postdose, respectively; terminal half-life was 5.9 hours and 3.2 hours, respectively. Area under plasma concentration-time curve (AUC) and maximum plasma concentration (C max ) after single- and multiple-dose administration were equivalent between the XR and IR formulations. In study B (N = 24), no difference in AUC was observed for fed vs fasted conditions. C max increased by 27% under the fed state. On repeat administration, negligible accumulation (Tofacitinib administration as an XR or IR formulation was generally well tolerated in these studies. © 2016, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  1. Long-acting injectable paliperidone palmitate versus oral paliperidone extended release: a comparative analysis from two placebo-controlled relapse prevention studies.

    Science.gov (United States)

    Markowitz, Michael; Fu, Dong-Jing; Levitan, Bennett; Gopal, Srihari; Turkoz, Ibrahim; Alphs, Larry

    2013-07-11

    Increasing availability and use of long-acting injectable antipsychotics have generated a need to compare these formulations with their oral equivalents; however, a paucity of relevant data is available. This post hoc comparison of the long-term efficacy, safety and tolerability of maintenance treatment with paliperidone palmitate (PP) versus oral paliperidone extended release (ER) used data from two similarly designed, randomised, double-blind (DB), placebo-controlled schizophrenia relapse prevention trials. Assessments included measures of time to relapse, symptom changes/functioning and treatment-emergent adverse events (TEAEs). Time to relapse between treatment groups was evaluated using a Cox proportional hazards model. Between-group differences for continuous variables for change scores during the DB phase were assessed using analysis of co-variance models. Categorical variables were evaluated using Chi-square and Fisher's exact tests. No adjustment was made for multiplicity. Approximately 45% of enrolled subjects in both trials were stabilised and randomised to the DB relapse prevention phase. Risk of relapse was higher in subjects treated with paliperidone ER than in those treated with PP [paliperidone ER/PP hazard ratio (HR), 2.52; 95% confidence interval (CI), 1.46-4.35; p 70, both approximately 58.5%; p = 1.000] compared with a 10.9% decrease for paliperidone ER (58.5% vs 47.6%, respectively; p = 0.048). The least squares mean change for Positive and Negative Syndrome Scale (PANSS) total score at DB end point in these previously stabilised subjects was 3.5 points in favour of PP (6.0 vs 2.5; p = 0.025). The rates of TEAEs and AEs of interest appeared similar. This analysis supports maintenance of effect with the injectable compared with the oral formulation of paliperidone in patients with schizophrenia. The safety profile of PP was similar to that of paliperidone ER. Future studies are needed to confirm these findings.

  2. Rapid onset of treatment effects on psychosis, depression, and mania in patients with acute exacerbation of schizoaffective disorder following treatment with oral extended-release paliperidone.

    Science.gov (United States)

    Fu, Dong-Jing; Turkoz, Ibrahim; Bossie, Cynthia A; Patel, Hiren; Alphs, Larry

    2016-03-15

    Patients with schizoaffective disorder (SCA) experience complicated interplays of psychotic, depressive, and manic symptoms. Paliperidone extended-release (pali ER) tablets have been shown to be efficacious in these patients, but treatment response has not been studied relative to the onset of effects for these symptom domains. In a pooled analysis of data from two 6-week, randomized, placebo-controlled studies, the onset of treatment effects with oral pali ER was evaluated by symptom domain (psychosis, depression, mania) in patients with an acute SCA exacerbation. Subjects were categorized as having prominent psychotic (Positive and Negative Syndrome Scale score >70), depressive (Hamilton Rating Scale for Depression-21 score ≥16), or manic (Young Mania Rating Scale score ≥16) symptoms at baseline. Of the 614 patients in these analyses, 597 (97.2%), 411 (66.9%), and 488 (79.5%) had prominent psychotic, depressive, and manic symptoms at baseline, respectively. Pali ER treatment was associated with rapid and significant improvement of all three symptom domains versus placebo within 1 week of initiation, regardless of whether treatment was given as monotherapy or in combination with mood stabilizers and/or antidepressants. Adverse events were similar to those reported in the original published studies. This post hoc analysis of two phase 3 trials requires confirmation in prospective studies. This pooled analysis suggests that treatment with pali ER is associated with rapid control of psychotic, depressive, and manic symptoms in patients with SCA. Its findings support the benefit of pali ER as a primary treatment for the management of SCA. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Cost-effectiveness of extended-release methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder sub-optimally treated with immediate release methylphenidate.

    Directory of Open Access Journals (Sweden)

    Jurjen van der Schans

    Full Text Available Attention-Deficit/Hyperactivity Disorder (ADHD is a common psychiatric disorder in children and adolescents. Immediate-release methylphenidate (IR-MPH is the medical treatment of first choice. The necessity to use several IR-MPH tablets per day and associated potential social stigma at school often leads to reduced compliance, sub-optimal treatment, and therefore economic loss. Replacement of IR-MPH with a single-dose extended release (ER-MPH formulation may improve drug response and economic efficiency.To evaluate the cost-effectiveness from a societal perspective of a switch from IR-MPH to ER-MPH in patients who are sub-optimally treated.A daily Markov-cycle model covering a time-span of 10 years was developed including four different health states: (1 optimal response, (2 sub-optimal response, (3 discontinued treatment, and (4 natural remission. ER-MPH options included methylphenidate osmotic release oral system (MPH-OROS and Equasym XL/Medikinet CR. Both direct costs and indirect costs were included in the analysis, and effects were expressed as quality-adjusted life years (QALYs. Univariate, multivariate as well as probabilistic sensitivity analysis were conducted and the main outcomes were incremental cost-effectiveness ratios.Switching sub-optimally treated patients from IR-MPH to MPH-OROS or Equasym XL/Medikinet CR led to per-patient cost-savings of €4200 and €5400, respectively, over a 10-year treatment span. Sensitivity analysis with plausible variations of input parameters resulted in cost-savings in the vast majority of estimations.This study lends economic support to switching patients with ADHD with suboptimal response to short-acting IR-MPH to long-acting ER-MPH regimens.

  4. Effect of Food Intake on the Pharmacokinetics of a Novel Methylphenidate Extended-Release Oral Suspension for Attention Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Sallee, Floyd R; Palumbo, Donna R; Abbas, Richat; Berry, Sally A; Puthli, Shivanand P; Kathala, Kalyan K

    2017-09-01

    We conducted an open-label, single-dose, randomized, crossover study in healthy adults to assess the impact of food on the bioavailability of 60 mg methylphenidate extended-release oral suspension (MEROS; Quillivant XR™)-a long-acting stimulant for the treatment of attention deficit hyperactivity disorder-by comparing the pharmacokinetic parameters under fed and fasting conditions. When MEROS 60 mg was administered under fed conditions compared with fasting conditions, the exposure of methylphenidate (d enantiomer) was higher, with a mean area under the plasma concentration-vs-time curve (AUC) 0-t of 160.2 ng·h/mL vs 140.4 ng·h/mL, and a mean AUC 0-inf of 163.2 ng·h/mL vs 143.7 ng·h/mL, respectively. The ratios of the ln-transformed geometric means for methylphenidate for AUC 0-t and AUC 0-inf were 119.5% (90%CI, 115.7% to 123.5%) and 119.0% (90%CI, 115.2% to 122.8%), respectively, within the standard 80% to 125% bioequivalence acceptance range indicating no food effect on the overall exposure (rate and extent). There was a small increase in the peak plasma concentration (127.6% [90%CI, 119.9% to 135.8%]). However, this effect was small and not likely to be clinically significant. Overall, MEROS 60 mg was safe in both the fed and fasting condition when administered to healthy volunteers in this study. © 2017 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  5. Costs and effects of paliperidone extended release compared with alternative oral antipsychotic agents in patients with schizophrenia in Greece: A cost effectiveness study

    Directory of Open Access Journals (Sweden)

    Papanicolaou Sotiria

    2008-08-01

    Full Text Available Abstract Background To compare the costs and effects of paliperidone extended release (ER, a new pharmaceutical treatment for the management of schizophrenia, with the most frequently prescribed oral treatments in Greece (namely risperidone, olanzapine, quetiapine, aripiprazole and ziprasidone over a 1-year time period. Methods A decision tree was developed and tailored to the specific circumstances of the Greek healthcare system. Therapeutic effectiveness was defined as the annual number of stable days and the clinical data was collected from international clinical trials and published sources. The study population was patients who suffer from schizophrenia with acute exacerbation. During a consensus panel of 10 psychiatrists and 6 health economists, data were collected on the clinical practice and medical resource utilisation. Unit costs were derived from public sources and official reimbursement tariffs. For the comparators official retail prices were used. Since a price had not yet been granted for paliperidone ER at the time of the study, the conservative assumption of including the average of the highest targeted European prices was used, overestimating the price of paliperidone ER in Greece. The study was conducted from the perspective of the National Healthcare System. Results The data indicate that paliperidone ER might offer an increased number of stable days (272.5 compared to 272.2 for olanzapine, 265.5 f risperidone, 260.7 for quetiapine, 260.5 for ziprasidone and 258.6 for aripiprazole with a lower cost compared to the other therapies examined (€7,030 compared to €7,034 for olanzapine, €7,082 for risperidone, €8,321 for quetiapine, €7,713 for ziprasidone and €7,807 for aripiprazole. During the sensitivity analysis, a ± 10% change in the duration and frequency of relapses and the economic parameters did not lead to significant changes in the results. Conclusion Treatment with paliperidone ER can lead to lower total cost

  6. Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial

    Science.gov (United States)

    French, JA; Baroldi, P; Brittain, ST; Johnson, JK

    2014-01-01

    Objective To evaluate the efficacy, tolerability, and safety of once-daily 1200 mg and 2400 mg SPN-804 (Oxtellar XR™, Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), added to 1-3 concomitant antiepileptic drugs (AEDs) in adults with refractory partial-onset seizures, with or without secondary generalization. Methods The Prospective, Randomized Study of OXC XR in Subjects with Partial Epilepsy Refractory (PROSPER) study was a multinational, randomized, double-blind, parallel-group Phase 3 study. The primary efficacy endpoint was median percent reduction from baseline in monthly (28-day) seizure frequency for the 16-week double-blind treatment period in the intent-to-treat (ITT) population with analyzable seizure data. Other efficacy analyses included proportion of patients with ≥ 50% seizure reduction, proportion of patients seizure free, and the relationship between clinical response and plasma concentration. Results Median percent reduction was -28.7% for placebo, −38.2% (P = 0.08 vs placebo) for once-daily SPN-804 1200 mg, and −42.9% (P = 0.003) for SPN-804 2400 mg. Responder rates were 28.1%, 36.1% (P = 0.08), and 40.7% (P = 0.02); 16-week seizure-free rates in a pragmatic ITT analysis were 3.3%, 4.9% (P = 0.59), and 11.4% (P = 0.008), respectively. When data were analyzed separately for study site clusters, a post hoc analysis demonstrated that both SPN-804 dosages were significantly superior to placebo in median percent seizure reduction (placebo: −13.3%; 1200 mg: −34.5%, P = 0.02; 2400 mg: −52.7%, P = 0.006) in the North American study site cluster. A concentration–response analysis also supported a clinically meaningful effect for 1200 mg. Adverse event types reflected the drug's established profile. Adverse event frequency was consistent with a pharmacokinetic profile in which SPN-804 produces lower peak plasma concentrations vs immediate-release OXC. Once-daily dosing was not

  7. An open-label, flexible-dose study of paliperidone extended-release in Chinese patients with first-onset psychosis

    Directory of Open Access Journals (Sweden)

    Si TM

    2015-01-01

    Full Text Available TianMei Si,1 QingRong Tan,2 KeRang Zhang,3 Yang Wang,4 Qing Rui4 1Peking University Institute of Mental health, Key Laboratory of Mental Health, Ministry of Health (Peking University, Beijing, 2Fourth Military Medical University, First Hospital, Xi’an, 3Shanxi Medical University, First Hospital, Shanxi, 4Janssen Research and Development, Beijing, People’s Republic of China Background: Antipsychotic medications facilitate the improvement of psychotic symptoms in patients with first-episode psychosis. Paliperidone extended-release (pali-ER, an atypical anti­psychotic, was assessed for efficacy and safety in Chinese patients with first-episode psychosis. Methods: In this 8-week, open-label, single-arm, multicenter study, patients with first-episode psychosis (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and a Positive and Negative Syndrome Scale (PANSS total score ≥70 were treated with flexible-dose pali-ER tablets (3–12 mg/day. The primary efficacy endpoint was the percentage of patients with an increase of ≥8 points in Personal and Social Performance (PSP score from baseline to day 56 (8 weeks. Secondary endpoints included reduction in PANSS total score, improvement in Clinical Global Impression-Severity score, PSP score, Subjective Well-being under Neuroleptics Scale score, and relationship between duration of untreated psychosis and PANSS or PSP. Incidences of treatment-emergent adverse events were used to evaluate safety.Results: Overall, 283 of 294 patients (96% achieved a ≥8-point increase in PSP (primary endpoint, analysis set. For the secondary efficacy endpoints, 284/306 patients (93% had a ≥30% reduction in PANSS total score; 266/306 patients (87% achieved a ≤3 Clinical Global Impression-Severity scale score, and 218/294 patients (74% had a PSP score ≥71. The Subjective Well-being under Neuroleptics Scale score was improved from a baseline mean of 72.7 to 94.7 at endpoint. There was a

  8. Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

    Science.gov (United States)

    Hale, Martin E; Nalamachu, Srinivas R; Khan, Arif; Kutch, Michael

    2013-01-01

    Purpose To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER) during dose conversion and titration. Patients and methods A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio), and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs) and serious AEs. Results Mean (standard deviation) final daily dose of OROS hydromorphone ER was 37.5 (17.8) mg. Mean (standard error of the mean [SEM]) numeric rating scale scores decreased from 6.6 (0.1) at screening to 4.3 (0.1) at the final titration visit (mean [SEM] change, −2.3 [0.1], representing a 34.8% reduction). Mean (SEM) change in Patient Global Assessment was −0.6 (0.1), and mean change (SEM) in the Roland–Morris Disability Questionnaire was −2.8 (0.3). Patients achieving a stable dose showed greater improvement than patients who discontinued during titration for each of these measures (P < 0.001). Almost 80% of patients achieving a stable dose (213/268) had a ≥30% reduction in pain. Commonly reported AEs were constipation (15.4%), nausea (11.9%), somnolence (8.7%), headache (7.8%), and vomiting (6.5%); 13.0% discontinued from the study due to AEs. Conclusion The majority of opioid-tolerant patients with chronic low back pain were successfully converted to effective doses of

  9. A randomized, double-blind study of the efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR monotherapy in patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Wang G

    2014-01-01

    Full Text Available Gang Wang,1 Alexander McIntyre,2 Willie R Earley,3 Shane R Raines,3 Hans Eriksson4 1Beijing Anding Hospital, Capital Medical University, Beijing, People's Republic of China; 2Department of Psychiatry, Penticton Regional Hospital, Penticton, BC, Canada; 3AstraZeneca Pharmaceuticals, Wilmington, DE, USA; 4AstraZeneca R&D, Södertälje, Sweden Objectives: To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR monotherapy in patients with major depressive disorder (MDD. Patients and methods: This was a 10-week (8-week active treatment/2-week post-treatment randomized, double-blind, placebo- and active-controlled study (D1448C00004. Patients received quetiapine XR 150 mg/day, escitalopram 10 mg/day, or placebo; patients with an inadequate response (<20% improvement in Montgomery–Åsberg Depression Rating Scale [MADRS] total score at week two received double-dose treatment. The primary end point was week eight change from randomization in MADRS total score. Secondary end points included MADRS response (≥50% improvement and remission (score ≤8; Hamilton Rating Scale for Depression total and item 1; Hamilton Rating Scale for Anxiety total, psychic, and somatic; Clinical Global Impressions – Severity of Illness total; Pittsburgh Sleep Quality Index (PSQI global; and Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form percentage maximum total scores. Tolerability was assessed throughout. Results: A total of 471 patients was randomized. No significant improvements in MADRS total score were observed at week eight (last observation carried forward with either active treatment (quetiapine XR, -17.21 [P=0.174]; escitalopram, -16.73 [P=0.346] versus placebo (-15.61. There were no significant differences in secondary end points versus placebo, with the exception of week-eight change in PSQI global score (quetiapine XR, -4.96 [P<0.01] versus placebo, -3.37. Mixed-model repeated

  10. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation.

    Science.gov (United States)

    Franek, F; Jarlfors, A; Larsen, F; Holm, P; Steffansen, B

    2015-09-18

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq(®), an extended release formulation (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp(®)) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus), respectively. Desvenlafaxine apparent permeability (Papp) at varying apical pH was investigated using the Caco-2 cell line and extrapolated to effective intestinal permeability (Peff) in human duodenum, jejunum, ileum and colon. Desvenlafaxine pKa-values and octanol-water partition coefficients (Do:w) were determined experimentally. Due to predicted rapid dissolution after IRF administration, desvenlafaxine was predicted to be available for permeation in the duodenum. Desvenlafaxine Do:w and Papp increased approximately 13-fold when increasing apical pH from 5.5 to 7.4. Desvenlafaxine Peff thus increased with pH down the small intestine. Consequently, desvenlafaxine absorption from an IRF appears rate-limited by low Peff in the upper small intestine, which "delays" the predicted

  11. Pluronic lecithin organogel (PLO) of diltiazem hydrochloride: effect of solvents/penetration enhancers on ex vivo permeation.

    Science.gov (United States)

    Parhi, Rabinarayan; Suresh, Podilam; Pattnaik, Subasini

    2016-06-01

    In the present study, pluronic lecithin organogel (PLO) of diltiazem hydrochloride (DZH) was developed by taking different ratios of organic phase to aqueous phase (1:3, 1:4, and 1:5) with varying concentration of soya lecithin (20, 30, and 40 % w/w) in organic phase (isopropyl myristate, IPM) and pluronic (20, 25, and 30 % w/w) in aqueous phase, respectively, and characterized for in vitro parameters and ex vivo permeation study. The results of in vitro parameters were found to be within permissible limit and all the PLOs were physically stable at refrigeration and ambient temperature. The influence of phase ratio and different concentrations of soya lecithin on DZH release from the PLOs was found to be significant (p < 0.05), whereas the influences of different concentrations of pluronic were insignificant. The effect of different solvents/penetration enhancers viz. IPM, propylene glycol (PG), dimethyl sulphoxide (DMSO), and D-limonene, in combination and alone, on the permeation of DZH across the dorsal skin of rat was studied. Among all, formulation containing IPM (PLO6) exhibited highest flux of 147.317 μg/cm(2)/h. Furthermore, histopathology section of treated skin sample illustrated that lipid bilayer disruption was the mechanism for the DZH permeation. The above results indicated that PLO6 may serve as a promising alternative delivery system for DZH in the effective treatment of hypertension.

  12. Some variables affecting the characteristics of Eudragit E-sodium alginate polyelectrolyte complex as a tablet matrix for diltiazem hydrochloride

    Directory of Open Access Journals (Sweden)

    Yusif Rehab Mohammad

    2014-03-01

    Full Text Available Eudragit E (EE-sodium alginate (SA polyelectrolyte complexes (PECs were prepared at pH 4 and 5.8 using sodium alginate of high (SAH and low viscosity (SAL. The optimum EE-SA complexation mass ratio was determined using viscosity measurements. Interactions between EE and SA in PECs were characterized by Fourier transform infra-red spectroscopy (FT-IR and differential scanning calorimetry (DSC. Diltiazem hydrochloride (DTZ HCl tablets were prepared using the prepared EE-SA PECs and their physical mixtures at different ratios as matrices. Tablets were evaluated for swelling characteristics and in vitro drug release. Tablets containing EE-SAH physical mixtures of ratios (1.5:1 and 1:3 as matrices were effective in achieving sustained release of DTZ HCl, where the percent drug released was significantly (p < 0.05 decreased compared to that from tablets either containing the same ratios of EE-SAL physical mixtures or the preformed EE- -SAH and EE-SAL PECs.

  13. Some variables affecting the characteristics of Eudragit E-sodium alginate polyelectrolyte complex as a tablet matrix for diltiazem hydrochloride.

    Science.gov (United States)

    Yusif, Rehab Mohammad; Abu Hashim, Irhan Ibrahim; El-Dahan, Marwa Salah

    2014-03-01

    Eudragit E (EE)-sodium alginate (SA) polyelectrolyte complexes (PECs) were prepared at pH 4 and 5.8 using sodium alginate of high (SAH) and low viscosity (SAL). The optimum EE-SA complexation mass ratio was determined using viscosity measurements. Interactions between EE and SA in PECs were characterized by Fourier transform infra-red spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Diltiazem hydrochloride (DTZ HCl) tablets were prepared using the prepared EE-SA PECs and their physical mixtures at different ratios as matrices. Tablets were evaluated for swelling characteristics and in vitro drug release. Tablets containing EE-SAH physical mixtures of ratios (1.5:1 and 1:3) as matrices were effective in achieving sustained release of DTZ HCl, where the percent drug released was significantly (p < 0.05) decreased compared to that from tablets either containing the same ratios of EE-SAL physical mixtures or the preformed EE- -SAH and EE-SAL PECs.

  14. Drug release kinetic analysis and prediction of release data via polymer molecular weight in sustained release diltiazem matrices.

    Science.gov (United States)

    Adibkia, K; Ghanbarzadeh, S; Mohammadi, G; Khiavi, H Z; Sabzevari, A; Barzegar-Jalali, M

    2014-03-01

    This study was conducted to investigate the effects of HPMC (K4M and K100M) as well as tragacanth on the drug release rate of diltiazem (DLTZ) from matrix tablets prepared by direct compression method.Mechanism of drug transport through the matrices was studied by fitting the release data to the 10 kinetic models. 3 model independent parameters; i. e., mean dissolution time (MDT), mean release rate (MRR) and release rate efficacy (RE) as well as 5 time point approaches were established to compare the dissolution profiles. To find correlation between fraction of drug released and polymer's molecular weight, dissolution data were fitted into two proposed equations.All polymers could sustain drug release up to 10 h. The release data were fitted best to Peppas and Higuchi square root kinetic models considering squared correlation coefficient and mean percent error (MPE). RE and MRR were decreased when polymer to drug ratio was increased. Conversely, t60% was increased with raising polymer /drug ratio. The fractions of drug released from the formulations prepared with tragacanth were more than those formulated using the same amount of HPMC K4M and HPMC K100M.Preparation of DLTZ matrices applying HPMCK4M, HPMC K100M and tragacanth could effectively extend the drug release. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Salt ingestion caves.

    Directory of Open Access Journals (Sweden)

    Lundquist Charles A.

    2006-01-01

    Full Text Available Large vertebrate herbivores, when they find a salt-bearing layer of rock, say in a cliff face, can produce sizable voids where, overgenerations, they have removed and consumed salty rock. The cavities formed by this natural animal process constitute a uniqueclass of caves that can be called salt ingestion caves. Several examples of such caves are described in various publications. Anexample in Mississippi U.S.A., Rock House Cave, was visited by the authors in 2000. It seems to have been formed by deer orbison. Perhaps the most spectacular example is Kitum Cave in Kenya. This cave has been excavated to a length over 100 metersby elephants. An ancient example is La Cueva del Milodon in Chile, which is reported to have been excavated by the now extinctmilodon, a giant ground sloth. Still other possible examples can be cited. This class of caves deserves a careful definition. First, thecavity in rock should meet the size and other conventions of the locally accepted definition of a cave. Of course this requirement differsin detail from country to country, particularly in the matter of size. The intent is to respect the local conventions. The characteristicthat human entry is possible is judged to be a crucial property of any recognized cave definition. Second, the cavity should besignificantly the result of vertebrate animal consumption of salt-bearing rock. The defining process is that rock removed to form thecave is carried away in the digestive track of an animal. While sodium salts are expected to be the norm, other salts for which thereis animal hunger are acceptable. Also some other speleogenesis process, such as solution, should not be excluded as long as it issecondary in formation of a cave in question.

  16. Effect of Yixinkangtai Capsule combined with diltiazem on endothelial function, blood viscosity and lipid metabolism in patients with unstable angina pectoris

    Directory of Open Access Journals (Sweden)

    Yu-Feng Yuan

    2017-10-01

    Full Text Available Objective: To discuss the effect of Yixinkangtai Capsule combined with diltiazem on endothelial function, blood viscosity and lipid metabolism in patients with unstable angina pectoris. Methods: A total of 150 patients with unstable angina pectoris who were treated in the hospital between February 2014 and February 2017 were divided into the control group (n=75 and the research group (n=75 according to the random number table method. Control group received clinical conventional therapy, research group received Yixinkangtai Capsule combined with diltiazem therapy on the basis of conventional therapy, and both groups received 3 months of treatment. Differences in endothelial function, blood viscosity and lipid metabolism were compared between the two groups of patients before and after treatment. Results: Before treatment, the differences in serum levels of endothelial function indexes, blood viscosity indexes and lipid metabolism indexes were not statistically significant between the two groups. After 3 months of treatment, serum NO level of research group was higher than that of control group while ET-1 level was lower than that of control group; serum blood viscosity index TXB2 content of research group was lower than that of control group while PGI2 content was higher than that of control group; serum lipid metabolism indexes TG, TC and LDL-C contents of research group were lower than those of control group while HDL-C content was higher than that of control group. Conclusion: Yixinkangtai Capsule combined with diltiazem therapy can effectively optimize the endothelial function, reduce the blood viscosity and balance the lipid metabolism in patients with unstable angina pectoris.

  17. Gastrobronchial fistula after toothbrush ingestion.

    Science.gov (United States)

    Karcher, Jan Christoph; von Buch, Christoph; Waag, Karl-Ludwig; Reinshagen, Konrad

    2006-10-01

    Gastrobronchial fistulous communications are uncommon complications of disease processes with only 36 previously reported cases. Described as complication of a number of conditions, such as previous gastroesophageal surgery, subphrenic abscess, and gastric ulcers (Jha P, Deiraniya A, Keeling-Robert C, et al. Gastrobronchial fistula--a recent series. Interact Cardiovasc Thorac Sur 2003;2:6-8), we report a case of fistulization caused by ingestion of a foreign body. A patient with mental retardation, admitted for the treatment of osteomyelitis, presented during hospitalization symptoms of high fever, vomiting, and respiratory distress. Endoscopy showed the presence of a gastrobronchial fistula, which developed after ingestion of a toothbrush. The toothbrush was extracted endoscopically, and the fistula was subsequently closed by surgery. The patient recovered completely. We report the first case of a gastrobronchial fistula as a complication of foreign body ingestion.

  18. Hadoop Tutorial - Efficient data ingestion

    CERN Multimedia

    CERN. Geneva; Baranowski, Zbigniew

    2016-01-01

    The Hadoop ecosystem is the leading opensource platform for distributed storage and processing of "big data". The Hadoop platform is available at CERN as a central service provided by the IT department. Real-time data ingestion to Hadoop ecosystem due to the system specificity is non-trivial process and requires some efforts (which is often underestimated) in order to make it efficient (low latency, optimize data placement, footprint on the cluster). In this tutorial attendees will learn about: The important aspects of storing the data in Hadoop Distributed File System (HDFS).  Data ingestion techniques and engines that are capable of shipping data to Hadoop in an efficient way. Setting up a full data ingestion flow into a Hadoop Distributed Files System from various sources (streaming, log files, databases) using the best practices and components available around the ecosystem (including Sqoop, Kite, Flume, Kafka...

  19. Foreign Body Ingestion in Children

    Directory of Open Access Journals (Sweden)

    Ji Hyuk Lee

    2018-03-01

    Full Text Available Foreign body (FB ingestion in children is common and most children are observed to be between 6 months and 3 years of age. Although most FBs in the gastrointestinal tract pass spontaneously without complications, endoscopic or surgical removal may be required in a few children. Thus, FB ingestion presents a significant clinical difficulty in pediatric gastroenterological practice. Parameters that need to be considered regarding the timing of endoscopic removal of ingested FBs in children are the children’s age or body weight, the clinical presentation, time lapse since ingestion, time of last meal, type as well as size and shape of the FB, and its current location in the gastrointestinal tract. Esophageal button batteries require emergency removal regardless of the presence of symptoms because they can cause serious complications. Coins, magnets, or sharp FBs in the esophagus should be removed within 2 hours in symptomatic and within 24 hours in asymptomatic children. Among those presenting with a single or multiple magnets and a metallic FB that have advanced beyond the stomach, symptomatic children need a consultation with a pediatric surgeon for surgery, and asymptomatic children may be followed with serial X-rays to assess progression. Sharp or pointed, and long or large and wide FBs located in the esophagus or stomach require endoscopic removal.

  20. Retrospective study of mistletoe ingestion.

    Science.gov (United States)

    Spiller, H A; Willias, D B; Gorman, S E; Sanftleban, J

    1996-01-01

    There are limited data concerning accidental exposure to Phoradendron flavescens (Phoradendron serotinum, American Mistletoe). The only published reports include a review of 14 cases which revealed no symptoms and a single fatality from an intentional ingestion of an unknown amount of an elixir brewed from the berries. The risk of serious toxicity from accidental exposure to this plant appears to be minimal, yet it continues to be regarded as a dangerous plant. We reviewed charts for four years (1990-1993) from three poison centers where Phoradendron flavescens is indigenous. Ninety-two human cases were located. Age ranged from four months to 42 years, with a mean of six years (SD 8.8) and median of two years. There were 14 symptomatic cases of which 11 were determined to be related to mistletoe exposure. There were six gastrointestinal upset, two mild drowsiness, one eye irritation, one ataxia (21 months), one seizure (13 months). Treatments included gastrointestinal decontamination in 54 patients (59%), ocular irrigation in one and IV benzodiazepine in one. Decontamination did not appear to affect outcome. Amount ingested ranged from one berry or leaf to more than 20 berries or five leaves. In cases with a known amount ingested, eight of ten cases with > or = 5 berries remained symptom free. In the 11 cases with leaf-only ingestion (range 1-5 leaves), three patients had gastrointestinal upset. The one case with five leaves ingested remained asymptomatic. The infant with seizures was an unwitnessed exposure, found with both berries and leaves in the crib. No arrhythmias or cardiovascular changes were reported in any case. All symptomatic cases had onset of symptoms in Cardiovascular effects were not seen.

  1. Ingestion of swimming pool water by recreational

    Data.gov (United States)

    U.S. Environmental Protection Agency — Swimming pool water ingestion data. This dataset is associated with the following publication: Dufour, A., L. Wymer, M. Magnuson, T. Behymer, and R. Cantu. Ingestion...

  2. Intestinal perforation caused by multiple magnet ingestion

    Directory of Open Access Journals (Sweden)

    Nergul Corduk

    2014-01-01

    Full Text Available Multiple magnet ingestion is rare, but can cause serious gastrointestinal complications. We report a case of 7-year-old girl with multiple intestinal perforations caused by multiple magnet ingestion. The aim of this report is to draw attention to magnetic toys, results of magnet ingestion and the importance of timing of operation.

  3. Acute Intoxication following Dimethyltryptamine Ingestion

    Science.gov (United States)

    Higgs, Kristan V.; Wiegand, Timothy J.; Gorodetsky, Rachel M.

    2018-01-01

    Ayahuasca is a hallucinogenic tea that is most commonly comprised of the vine Banisteriopsis caapi alone or in combination with other plants such as Psychotria viridis. This concoction results in an orally active form of dimethyltryptamine (DMT), a hallucinogenic amine. Despite use in South America as a medicinal agent and component in religious ceremonies, interest in its recreational use and spiritual effects has led to increased use in the United States. We describe a unique case following ingestion of ayahuasca tea in a patient with history of schizophrenia resulting in personal injury and property damage. A review of ayahuasca toxicity and evaluation of serious adverse effects is also presented. PMID:29682363

  4. Acute Intoxication following Dimethyltryptamine Ingestion

    Directory of Open Access Journals (Sweden)

    Matthew H. Bilhimer

    2018-01-01

    Full Text Available Ayahuasca is a hallucinogenic tea that is most commonly comprised of the vine Banisteriopsis caapi alone or in combination with other plants such as Psychotria viridis. This concoction results in an orally active form of dimethyltryptamine (DMT, a hallucinogenic amine. Despite use in South America as a medicinal agent and component in religious ceremonies, interest in its recreational use and spiritual effects has led to increased use in the United States. We describe a unique case following ingestion of ayahuasca tea in a patient with history of schizophrenia resulting in personal injury and property damage. A review of ayahuasca toxicity and evaluation of serious adverse effects is also presented.

  5. Liquid nitrogen ingestion followed by gastric perforation.

    Science.gov (United States)

    Berrizbeitia, Luis D; Calello, Diane P; Dhir, Nisha; O'Reilly, Colin; Marcus, Steven

    2010-01-01

    Ingestion of liquid nitrogen is rare but carries catastrophic complications related to barotrauma to the gastrointestinal tract. We describe a case of ingestion of liquid nitrogen followed by gastric perforation and respiratory insufficiency and discuss the mechanism of injury and management of this condition. Liquid nitrogen is widely available and is frequently used in classroom settings, in gastronomy, and for recreational purposes. Given the potentially lethal complications of ingestion, regulation of its use, acquisition, and storage may be appropriate.

  6. Neuroendocrine regulation of appetitive ingestive behavior

    Directory of Open Access Journals (Sweden)

    Erin eKeen-Rhinehart

    2013-11-01

    Full Text Available Food availability in nature is often irregular, and famine is commonplace. Increased motivation to engage in ingestive behaviors increases the chance of survival, providing additional potential opportunities for reproduction. Because of the advantages conferred by entraining ingestive behavior to environmental conditions, neuroendocrine mechanisms regulating the motivation to acquire and ingest food have evolved to be responsive to exogenous (i.e. food stored for future consumption and endogenous (i.e. body fat stores fuel availability. Motivated behaviors like eating occur in two phases. The appetitive phase brings animals into contact with food (e.g. foraging, food hoarding, and the more reflexive consummatory phase results in ingestion (e.g., chewing, swallowing. Quantifiable appetitive behaviors are part of many the natural ingestive behavioral repertoire of species such as hamsters and humans. This review summarizes current knowledge about neuroendocrine regulators of ingestive behavior, with an emphasis appetitive behavior. We will discuss hormonal regulators of appetitive ingestive behaviors, including the orexigenic hormone ghrelin, which potently stimulates foraging and food hoarding in Siberian hamsters. This section includes a discussion of the hormone leptin, its relation to endogenous fat stores, and its role in food deprivation-induced increases in appetitive ingestive behaviors. Next, we discuss how hormonal regulators interact with neurotransmitters involved in the regulation of ingestive behaviors, such as NPY, AgRP and alpha-MSH, to regulate ingestive behavior. Finally, we discuss the potential impact that perinatal nutrient availability can have on the neuroendocrine regulation of ingestive behavior. Understanding the hormonal mechanisms that connect metabolic fuel availability to central appetite regulatory circuits should provide a better understanding of the neuroendocrine regulation of the motivation to engage in ingestive

  7. Neuroendocrine regulation of appetitive ingestive behavior.

    Science.gov (United States)

    Keen-Rhinehart, Erin; Ondek, Katelynn; Schneider, Jill E

    2013-11-15

    Food availability in nature is often irregular, and famine is commonplace. Increased motivation to engage in ingestive behaviors increases the chance of survival, providing additional potential opportunities for reproduction. Because of the advantages conferred by entraining ingestive behavior to environmental conditions, neuroendocrine mechanisms regulating the motivation to acquire and ingest food have evolved to be responsive to exogenous (i.e., food stored for future consumption) and endogenous (i.e., body fat stores) fuel availability. Motivated behaviors like eating occur in two phases. The appetitive phase brings animals into contact with food (e.g., foraging, food hoarding), and the more reflexive consummatory phase results in ingestion (e.g., chewing, swallowing). Quantifiable appetitive behaviors are part of the natural ingestive behavioral repertoire of species such as hamsters and humans. This review summarizes current knowledge about neuroendocrine regulators of ingestive behavior, with an emphasis appetitive behavior. We will discuss hormonal regulators of appetitive ingestive behaviors, including the orexigenic hormone ghrelin, which potently stimulates foraging and food hoarding in Siberian hamsters. This section includes a discussion of the hormone leptin, its relation to endogenous fat stores, and its role in food deprivation-induced increases in appetitive ingestive behaviors. Next, we discuss how hormonal regulators interact with neurotransmitters involved in the regulation of ingestive behaviors, such as neuropeptide Y (NPY), agouti-related protein (AgRP) and α-melanocyte stimulating hormone (α-MSH), to regulate ingestive behavior. Finally, we discuss the potential impact that perinatal nutrient availability can have on the neuroendocrine regulation of ingestive behavior. Understanding the hormonal mechanisms that connect metabolic fuel availability to central appetite regulatory circuits should provide a better understanding of the

  8. Neuroendocrine regulation of appetitive ingestive behavior

    OpenAIRE

    Keen-Rhinehart, Erin; Ondek, Katelynn; Schneider, Jill E.

    2013-01-01

    Food availability in nature is often irregular, and famine is commonplace. Increased motivation to engage in ingestive behaviors increases the chance of survival, providing additional potential opportunities for reproduction. Because of the advantages conferred by entraining ingestive behavior to environmental conditions, neuroendocrine mechanisms regulating the motivation to acquire and ingest food have evolved to be responsive to exogenous (i.e., food stored for future consumption) and endo...

  9. Foreign-body ingestion: characteristics and outcomes in a lower socioeconomic population with predominantly intentional ingestion.

    Science.gov (United States)

    Palta, Renee; Sahota, Amandeep; Bemarki, Ali; Salama, Paul; Simpson, Nicole; Laine, Loren

    2009-03-01

    Previous reports of foreign-body ingestions focused primarily on accidental ingestions. To describe the characteristics and management of foreign-body ingestions, with predominantly intentional ingestion, in a lower socioeconomic status population. A retrospective case series. An urban county hospital. Patients >/=17 years old, with foreign-body ingestions between 2000 and 2006. Characteristics of ingestion cases, endoscopic extraction, need for surgery, and complications. Among 262 cases, 92% were intentional, 85% involved psychiatric patients, and 84% occurred in patients with prior ingestions. The time from ingestion to presentation was >48 hours in 168 cases (64%). The overall success rate for endoscopic extraction was 90% (165/183 cases). Surgery was performed in 30 cases (11%) and was more common for objects beyond the pylorus versus objects above the pylorus (16/43 [37%] vs 10/151 [7%], respectively) and in cases with a greater delay from ingestion to presentation (25/168 [15%] if >48 hours vs 4/77 [5%] if 48 hours vs 14/165 [8%] if ingestions in an urban county hospital occurred primarily in psychiatric patients who had repeated episodes of intentional ingestions. Endoscopic extraction was unsuccessful in 10% of cases. Long delays from ingestion to presentation and intervention may account for relatively high rates of surgery and perforation. Strategies to prevent ingestions and delays in endoscopic management are needed in this population.

  10. Esophageal button battery ingestion in children.

    Science.gov (United States)

    Şencan, Arzu; Genişol, İncinur; Hoşgör, Münevver

    2017-07-01

    Button battery lodged in the esophagus carries a high risk of morbidity and mortality. The purpose of this study was to present cases of patients with esophageal button battery ingestion treated at our clinic and to emphasize the importance of early diagnosis and treatment. Records of patients admitted to our hospital for foreign body ingestion between January 2010 and May 2015 were retrospectively reviewed. Cases with button battery lodged in the esophagus were included in the study. Patient data regarding age, sex, length of time after ingestion until admission, presenting clinical symptoms, type and localization of the battery, management, and prognosis were analyzed. Among 1891 foreign body ingestions, 71 were localized in the esophagus, and 8 of those (11.2%) were cases of button battery ingestion. Mean age was 1.7 years. Admission was within 6 hours of ingestion in 5 cases, after 24 hours had elapsed in 2, and 1 month after ingestion in 1 case. All patients but 1 knew the history of ingestion. Prompt endoscopic removal was performed for all patients. Three patients developed esophageal stricture, which responded to dilatation. Early recognition and timely endoscopic removal is mandatory in esophageal button battery ingestion. It should be suspected in the differential diagnosis of patients with persistent respiratory and gastrointestinal symptoms.

  11. 210Pb ingestion in Akita City, Japan

    International Nuclear Information System (INIS)

    Hisamatsu, Shunichi; Takizawa, Yukio; Komura, Kazuhisa; Tada, Tetsuo.

    1992-01-01

    Ingestion of 210 Pb in Akita City, northern Japan was studied with food category samples and total diet samples by means of a low energy photon spectrometry. Results for food category samples revealed that the contribution of marine products to total 210 Pb ingestion was the largest. Mean 210 Pb ingestion of the two total diet samples was found to be 0.19 Bq d -1 , and approximately 1/3 of a previous reported value which was cited in an UNSCEAR report as an example of high 210 Pb ingestion by marine foods consumption. (author)

  12. Acute toxicity of ingested fluoride.

    Science.gov (United States)

    Whitford, Gary Milton

    2011-01-01

    This chapter discusses the characteristics and treatment of acute fluoride toxicity as well as the most common sources of overexposure, the doses that cause acute toxicity, and factors that can influence the clinical outcome. Cases of serious systemic toxicity and fatalities due to acute exposures are now rare, but overexposures causing toxic signs and symptoms are not. The clinical course of systemic toxicity from ingested fluoride begins with gastric signs and symptoms, and can develop with alarming rapidity. Treatment involves minimizing absorption by administering a solution containing calcium, monitoring and managing plasma calcium and potassium concentrations, acid-base status, and supporting vital functions. Approximately 30,000 calls to US poison control centers concerning acute exposures in children are made each year, most of which involve temporary gastrointestinal effects, but others require medical treatment. The most common sources of acute overexposures today are dental products - particularly dentifrices because of their relatively high fluoride concentrations, pleasant flavors, and their presence in non-secure locations in most homes. For example, ingestion of only 1.8 ounces of a standard fluoridated dentifrice (900-1,100 mg/kg) by a 10-kg child delivers enough fluoride to reach the 'probably toxic dose' (5 mg/kg body weight). Factors that may influence the clinical course of an overexposure include the chemical compound (e.g. NaF, MFP, etc.), the age and acid-base status of the individual, and the elapsed time between exposure and the initiation of treatment. While fluoride has well-established beneficial dental effects and cases of serious toxicity are now rare, the potential for toxicity requires that fluoride-containing materials be handled and stored with the respect they deserve. Copyright © 2011 S. Karger AG, Basel.

  13. Aspirin and Extended-Release Dipyridamole

    Science.gov (United States)

    ... Mobic), nabumetone (Relafen), naproxen (Aleve, Naprosyn), oxaprozin (Daypro), piroxicam (Feldene), rofecoxib (Vioxx) (no longer available in the ... Mobic), nabumetone (Relafen), naproxen (Aleve, Naprosyn), oxaprozin (Daypro), piroxicam (Feldene), sulindac (Clinoril), and tolmetin (Tolectin); phenytoin (Dilantin); ...

  14. Extended release formulations for local anaesthetic agents.

    Science.gov (United States)

    Weiniger, C F; Golovanevski, L; Domb, A J; Ickowicz, D

    2012-08-01

    Systemic toxicity through overdose of local anaesthetic agents is a real concern. By encapsulating local anaesthetics in biodegradable carriers to produce a system for prolonged release, their duration of action can be extended. This encapsulation should also improve the safety profile of the local anaesthetic as it is released at a slower rate. Work with naturally occurring local anaestheticss has also shown promise in the area of reducing systemic and neurotoxicity. Extended duration local anaesthetic formulations in current development or clinical use include liposomes, hydrophobic based polymer particles such as Poly(lactic-co-glycolic acid) microspheres, pasty injectable and solid polymers like Poly(sebacic-co-ricinoleic acid) P(SA:RA) and their combination with synthetic and natural local anaesthetic. Their duration of action, rationale and limitations are reviewed. Direct comparison of the different agents is limited by their chemical properties, the drug doses encapsulated and the details of in vivo models described. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

  15. Gastrointestinal bleeding following NSAID ingestion in children

    African Journals Online (AJOL)

    Both presented with a history of fever and passage of bloody stools. There was a positive history of NSAID ingestion in both patients that was prescribed in the referring hospitals. ..... Bostwick HE, Halata MS, Feerick J, Newman LJ, Medow MS. Gastrointestinal bleeding in children following ingestion of low-dose. Ibuprofen.

  16. Gasoline ingestion: a rare cause of pancytopenia.

    Science.gov (United States)

    Rahman, Ifad; Narasimhan, Kanakasabai; Aziz, Shahid; Owens, William

    2009-11-01

    The majority of reported cases of gasoline intoxication involves inhalation or percutaneous absorption. Data are scarce on complications and outcomes after gasoline poisoning by oral ingestion. The major cause of mortality and morbidity associated with the ingestion of gasoline is related to pulmonary aspiration. Despite the high frequency of the ingestions, there is little documentation of nonpulmonary toxic effects of gasoline. After ingestion, the principal toxicity is aspiration pneumonia, but any documented extra pulmonary manifestations of this condition may be important in the overall management of these patients. We are reporting a rare case of pancytopenia along with aspiration pneumonia and multisystem organ failure in a 58-year-old male after prolonged intentional ingestion of gasoline. To our knowledge, this is the only reported case of gasoline toxicity causing pancytopenia.

  17. Ingestion of caustic substances and its complications

    Directory of Open Access Journals (Sweden)

    Rui Celso Martins Mamede

    2001-01-01

    Full Text Available CONTEXT: Caustic substances cause tissue destruction through liquefaction or coagulation reactions and the intensity of destruction depends on the type, concentration, time of contact and amount of the substance ingested. OBJECTIVES: To analyze the complications in patients who ingested caustic substances and correlate them with the amount of caustic soda ingested. DESIGN: Retrospective study. SETTING: University hospital, a referral center. PARTICIPANTS: A total of 239 patients who ingested caustic soda. MAIN MEASUREMENTS: The amount of granulated caustic substance ingested was measured as tablespoonfuls and the following complications were analyzed: esophagitis, esophageal stenosis and progression to cancer, fistulas, perforations, stomach lesions, brain abscesses, and death. Stenosis was classified as mild, moderate or severe according to the radiological findings. RESULTS: We observed an 89.3% incidence of esophagitis; 72.6% of the cases involved progression to stenosis and 1% died during the acute phase. Stenosis was mild in 17.6% of cases, moderate in 59.3% and severe in 23%. The incidence of stenosis was 80.8% in women and 62.5% in men. The incidence of stenosis was 46.9% in the group that ingested "fragments" and 93.6% in the group that ingested one or more tablespoonfuls of caustic substances. Among subjects who ingested one or more tablespoonfuls, 32.2% developed lesions of the stomach-duodenum, whereas the ingestion of "fragments" was not sufficient to induce these lesions. There was no correlation between the intensity of lesions of the esophagus and of the stomach. Progression to cancer of the esophagus occurred in 1.8% of cases, death during the chronic phase in 1.4%, perforations in 4.6%, fistulas in 0.9%, and brain abscesses in 1.4%. CONCLUSIONS: The complications were related to the amount of caustic soda ingested. Small amounts caused esophagitis or stenosis and large amounts increased the risk of fistulas, perforations and

  18. COMPARATIVE EFFICАCY AND TOLERABILITY OF MONOTHERAPY WITH DEPAKINE CHRONOSPHERE, DRUGS OF CARBAMAZEPINE GROUP WITH EXTENDED RELEASE AND OXCARBAZEPINE IN SYMPTOMATIC AND CRYPTOGENIC FOCAL EPILEPSY (SVT. LUKA’S INSTITUTE OF CHILD NEUROLOGY AND EPILEPSY

    Directory of Open Access Journals (Sweden)

    K. Yu. Mukhin

    2015-01-01

    Full Text Available Research on comparative efficаcy and tolerability of monotherapy with Depakine chronosphere, drugs of Carbamazepine group with extended release and oxcarbazepine in symptomatic and cryptogenic focal epilepsy has been conducted at Svt. Luka’s Institute of Child Neurology and Epilepsy (ICNE (Moscow. This retrospective study covers a random sample of patients treated in ICNE in the period from December 1, 2013 to September 1, 2014.  The study included 131 patients aged 1 to 18 years with symptomatic and cryptogenic focal epilepsy receiving treatment with one of the study drugs in monotherapy: group 1 – monotherapy with Depakine chronosphere (n = 56; group 2 – monotherapy with drugs of carbamazepine group with extended release (n = 55; group 3 – monotherapy with oxcarbazepine (trileptal (n = 20. The obtained results allow us to conclude that the effectiveness of Depakin chronosphere, carbamazepine with extended release and oxcarbazepine in monotherapy of symptomatic and cryptogenic focal epilepsy was comparable (statistically significant differences in efficacy were not found. However, carbamazepine was awarded the highest frequency of seizures aggravation. Drugs showed approximately same tolerability (statistically significant differences in tolerability were not found. However, withdrawal of the drug due to side effects was the rarest in Depakine (3.5 %, and withdrawal due to intolerance was higher in carbamazepine and oxcarbazepine (5 and 10 % respectively. Depakinum and oxcarbazepine had the best results in the blocking of pathological activity on the electroencephalogram, whereas carbamazepine was clearly inferior to them. In this regard, complete clinical-electroencephalographic remission (lasting 12 months or more was achieved under treatment of Depakine chromosphere in 21.5 % of cases, oxcarbazepi on therapy for 12 months was similar in all study drugs. Considering that the objective of epilepsy treatment is to achieve complete

  19. A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of the extended-release tramadol hydrochloride/acetaminophen fixed-dose combination tablet for the treatment of chronic low back pain.

    Science.gov (United States)

    Lee, Jae Hyup; Lee, Chong-Suh

    2013-11-01

    Chronic low back pain is a common condition that is often difficult to treat. The combination of tramadol hydrochloride and acetaminophen in an extended-release formulation has been shown to provide rapid and long-lasting analgesic effects resulting from the synergistic activity of these 2 active ingredients. The goal of this study was to evaluate the efficacy and safety of extended-release tramadol hydrochloride 75-mg/acetaminophen 650-mg fixed-dose combination tablets (TA-ER) for the treatment of chronic low back pain. This Phase III, double-blind, placebo-controlled, parallel-group study enrolled 245 patients with moderate to severe (≥4 cm on a 10-cm visual analog scale) chronic (≥3 months') low back pain insufficiently controlled by previous NSAIDs or cyclooxygenase-2-selective inhibitors and randomly assigned them to receive 4 weeks of either TA-ER or placebo. The primary efficacy end point was the percentage of patients with a pain intensity change rate ≥30% from baseline to final evaluation. Secondary end points included quality of life (Korean Short Form-36), functionality (Korean Oswestry Disability Index), and adverse events. The percentage of patients with a pain intensity change rate ≥30% was significantly higher (P Pain relief success rate from baseline was significantly higher with TA-ER versus placebo at days 8 and 15 but not at the final visit. Patients in the TA-ER group had significant improvements versus placebo in role-physical, general health, and reported health transition domains of the Korean Short Form-36 and significantly higher functional improvements in the personal care section of the Korean Oswestry Disability Index. Patient assessment of overall pain control as "very good" was also significantly higher with TA-ER than with placebo. Adverse events were reported more frequently with TA-ER than with placebo; the most common adverse events reported were nausea, dizziness, constipation, and vomiting. TA-ER was significantly more

  20. QUALITY OF LIFE AND COMPLIANCE TO THERAPY IN PATIENTS FOLLOWING SUCCESSFULTRANSLUMINAL CORONARY ANGIOPLASTY, WHO WERE PRESCRIBED FLUVASTATIN EXTENDED RELEASE ADDED TO STANDARD THERAPY. PROTOCOL OF THE OPEN-LABEL OBSERVATIONAL STUDY

    Directory of Open Access Journals (Sweden)

    A. V. Susekov

    2010-01-01

    Full Text Available Aim. To evaluate quality of life changes and compliance to therapy in patients following successful transluminal angioplasty, who have indications for fluvastatin extended release in addition to standard treatment.Material and methods. This is a national observational multicenter study. An inclusion of 60 investigator centers is planned (out-patient medical centers, the total number of patients to be included is 600. Patients (men and women with coronary heart disease following successful transluminal coronary angioplasty, who were prescribed fluvastatinextended release (Lescol Forte, Novartis 80 mg once daily will be included in the observation. The following efficacy and safety parameters will be evaluated: quality of life assessed with SF-36 scale before and during treatment; compliance to therapy; adverse events and serious adverse events. Observation period is planned for 6 months. During this period patient is expected to make 4 visits to treating physician. According to the physician’s decision, observation period can be extended to 12 months.Present study status. The study is completed. 524 patients completed the observation, including 116 patients who were followed up for 12 months. There are 414 men (79% and 110 women (21% among patients enrolled into the study.

  1. Diltiazem Reduces Mortality and Breakdown of ATP in Red Blood Cell Induced by Isoproterenol in a Freely Moving Rat Model in Vivo

    Directory of Open Access Journals (Sweden)

    Pollen K.F. Yeung

    2014-09-01

    Full Text Available The benefit of calcium channel blockers for cardiovascular prevention against heart attack and stroke has not been firmly supported. We investigated the possible cardiovascular protective effect of diltiazem (DTZ against injury induced by isoproterenol using a freely moving rat model in vivo. Sprague Dawley rats were injected subcutaneously (sc with either 5 or 10 mg/kg of DTZ, or saline as control, twice daily for five doses. One hour after the last injection, a single dose of isoproterenol (30 mg/kg was injected sc to each rat. Blood samples were collected serially for 6 h for measurement of adenine nucleotides (ATP, ADP and AMP in red blood cell (RBC by a validated HPLC. The study has shown isoproterenol induced 50% mortality and also increased RBC concentrations of AMP from 0.04 ± 0.02 to 0.29 ± 0.21 mM at the end of the experiment (p < 0.05. Treatment with 10 mg/kg of DTZ reduced mortality from 50% to <20% and attenuated the increase of RBC concentrations of AMP from +0.25 ± 0.22 in the control rats to +0.072 ± 0.092 mM (p < 0.05. The study concluded that 10 mg/kg of DTZ reduced mortality and breakdown of ATP induced by isoproterenol in rats.

  2. ARM Climate Research Facility Quarterly Ingest Status Report

    Energy Technology Data Exchange (ETDEWEB)

    Koontz, A. [DOE ARM Climate Research Facility, Washington, DC (United States); Sivaraman, C. [DOE ARM Climate Research Facility, Washington, DC (United States)

    2016-10-01

    The purpose of this report is to provide a concise status update for ingests maintained by the Atmospheric Radiation Measurement (ARM) Climate Research Facility. The report is divided into the following sections: (1) new ingests for which development has begun, (2) progress on existing ingests, (3) future ingests that have been recently approved, (4) other work that leads to an ingest, and (5) top requested ingests from the ARM Data Archive. New information is highlighted in blue text.

  3. ARM Climate Research Facility Quarterly Ingest Status Report

    Energy Technology Data Exchange (ETDEWEB)

    Koontz, A. [ARM Climate Reesearch Facility, Washington, DC (United States); Sivaraman, C. [ARM Climate Reesearch Facility, Washington, DC (United States)

    2016-07-01

    The purpose of this report is to provide a concise status update for ingests maintained by the Atmospheric Radiation Measurement (ARM) Climate Research Facility. The report is divided into the following sections: (1) new ingests for which development has begun, (2) progress on existing ingests, (3) future ingests that have been recently approved, (4) other work that leads to an ingest, and (5) top requested ingests from the ARM Data Archive. New information is highlighted in blue text.

  4. Vascular ring complicates accidental button battery ingestion.

    Science.gov (United States)

    Mercer, Ronald W; Schwartz, Matthew C; Stephany, Joshua; Donnelly, Lane F; Franciosi, James P; Epelman, Monica

    2015-01-01

    Button battery ingestion can lead to dangerous complications, including vasculoesophageal fistula formation. The presence of a vascular ring may complicate battery ingestion if the battery lodges at the level of the ring and its important vascular structures. We report a 4-year-old boy with trisomy 21 who was diagnosed with a vascular ring at the time of button battery ingestion and died 9 days after presentation due to massive upper gastrointestinal bleeding from esophageal erosion and vasculoesophageal fistula formation. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Acute toxicity from baking soda ingestion.

    Science.gov (United States)

    Thomas, S H; Stone, C K

    1994-01-01

    Sodium bicarbonate is an extremely well-known agent that historically has been used for a variety of medical conditions. Despite the widespread use of oral bicarbonate, little documented toxicity has occurred, and the emergency medicine literature contains no reports of toxicity caused by the ingestion of baking soda. Risks of acute and chronic oral bicarbonate ingestion include metabolic alkalosis, hypernatremia, hypertension, gastric rupture, hyporeninemia, hypokalemia, hypochloremia, intravascular volume depletion, and urinary alkalinization. Abrupt cessation of chronic excessive bicarbonate ingestion may result in hyperkalemia, hypoaldosteronism, volume contraction, and disruption of calcium and phosphorus metabolism. The case of a patient with three hospital admissions in 4 months, all the result of excessive oral intake of bicarbonate for symptomatic relief of dyspepsia is reported. Evaluation and treatment of patients with acute bicarbonate ingestion is discussed.

  6. Prevention of ingestion injuries in children

    African Journals Online (AJOL)

    aspiration include attention-deficit hyperactivity syndrome,[9] low levels of parental ... the environment combined with inadequate caregiver supervision put children ... Increased primary prevention of ingestion through community awareness ...

  7. Potassium permanganate ingestion as a suicide attempt

    Directory of Open Access Journals (Sweden)

    Sebnem Eren Cevik

    2012-02-01

    Full Text Available Potassium permanganate is a highly corrosive, water-soluble oxidizing antiseptic. A 68- year-old female patient was admitted to our Emergency Department after ingestion of 3 tablets of 250 mg potassium permanganate as a suicide attempt. The physical exam revealed brown stained lesions in the oropharynx. Emergency endoscopy was performed by the gastroenterologist after the third hour of ingestion. Emergency endoscopy revealed multiple superficial (Grade I-II lesions on the esophagus and cardia, which were considered secondary to the caustic substance. The mainstay in the treatment of potassium permanganate is supportive and the immediate priority is to secure the airway. Emergency endoscopy is an important tool used to evaluate the location and severity of injury to the esophagus, stomach and duodenum after caustic ingestion. Patients with signs and symptoms of intentional ingestion should undergo endoscopy within 12 to 24 h to define the extent of the disease.

  8. Potassium permanganate ingestion as a suicide attempt

    Directory of Open Access Journals (Sweden)

    Tuba Cimilli Ozturk

    2012-01-01

    Full Text Available Potassium permanganate is a highly corrosive, water-soluble oxidizing antiseptic. A 68- year-old female patient was admitted to our Emergency Department after ingestion of 3 tablets of 250 mg potassium permanganate as a suicide attempt. The physical exam revealed brown stained lesions in the oropharynx. Emergency endoscopy was performed by the gastroenterologist after the third hour of ingestion. Emergency endoscopy revealed multiple superficial (Grade I-II lesions on the esophagus and cardia, which were considered secondary to the caustic substance. The mainstay in the treatment of potassium permanganate is supportive and the immediate priority is to secure the airway. Emergency endoscopy is an important tool used to evaluate the location and severity of injury to the esophagus, stomach and duodenum after caustic ingestion. Patients with signs and symptoms of intentional ingestion should undergo endoscopy within 12 to 24 h to define the extent of the disease.

  9. Fallout 3H ingestion in Akita, Japan

    International Nuclear Information System (INIS)

    Hisamatsu, S.; Takizawa, Y.; Abe, T.; Katsumata, T.

    1987-01-01

    To study fallout 3 H ingestion in Japan, 16 separate food group samples were collected from Akita during 1985. The 3 H concentration in free water and that in a tissue-bound form were determined separately. The average 3 H concentration in the tissue-bound form was 2.2 Bq L-1, 1.7 times higher than in the free water of the food. The ingestions of 3 H in the tissue-bound form and as free water in the diet were 0.60 Bq d-1 and 1.0 Bq d-1, respectively. Cereals represented the food group that contributed the most to the ingestion of tissue-bound 3 H. Total 3 H ingestion was estimated to be 4.1 Bq d-1. The contribution of the tissue-bound form to the total ingestion was 15%, considerably lower than reported for Italian diets. The ratio of 3 H ingestion in the tissue-bound form to the free water form in the diet was similar to the ratio reported for New York City

  10. Ingested foreign bodies in the paediatric patient.

    LENUS (Irish Health Repository)

    O'Brien, G C

    2012-02-03

    BACKGROUND: Paediatric foreign body (FB) ingestion is a common problem and while most can be managed conservatively, a sub-population require intervention. AIMS: To establish clear guidelines for management of paediatric FB ingestion. METHODS: A retrospective chart review analysing all paediatric admissions with FB ingestion over a 10-year period from 1990 to 1999. RESULTS: Of 339 patients presenting to the accident and emergency department with FB ingestion, 59 required admission. Ingestion was accidental in 93.0% of patients. The reasons for admission were as follows: large FBs; dangerous FBs; and living far from the hospital. Nineteen patients (32.2%) were discharged without intervention. Thirty-seven (62.7%) required endoscopic retrieval. In two, the FB was not identified at endoscopy. Only three (5%) required surgery. CONCLUSION: Conservative management of FB ingestion in the paediatric population is possible in the majority of cases. However, a minority require intervention. While guidelines for intervention are ill-defined, definitive indications include symptomatic patients, or dangerous objects.

  11. Extended-Release Guaifenesin/Pseudoephedrine Hydrochloride for Symptom Relief in Support of a Wait-and-See Approach for the Treatment of Acute Upper Respiratory Tract Infections: A Randomized, Double-Blind, Placebo-Controlled Study.

    Science.gov (United States)

    Septimus, Edward J; Albrecht, Helmut H; Solomon, Gail; Shea, Tim; Guenin, Eric P

    2017-01-01

    Despite the well-known fact that antibiotics (AB) are not effective against viruses, many patients ask for - and all too often doctors provide - AB for treating URTIs. Over-prescribing of AB is one of the key causes for the development of bacterial resistance, which the U.S. Centers for Disease Control and Prevention (CDC) calls "one of the world's most pressing public health problems". In addition to the CDC initiated "Get Smart About Antibiotics" campaign, focused on educating doctors the public about the importance of appropriate AB use, other programs tackling this problem include the development of new treatment paradigms. Data published at the Oregon Health & Science University demonstrated that a 'wait-and-see' approach, without an AB prescription for the treatment of acute childhood ear infections, was as quick, safe, and effective in resolving the infections as an AB prescription (Spiro DM, Tay KY, Arnold DH, Dziura JD, Baker MD, Shapiro ED. Wait-and-See Prescription for the Treatment of Acute Otitis Media. JAMA 2006; 296:1235-1241). To try and reduce inappropriate prescribing practices, a wait and see or delayed approach requires patients to return for a prescription if their symptoms persist or worsen. The aim of this study was to determine whether treatment with Mucinex D (Reckitt Benckiser LLC, Parsippany, New Jersey) lowers the use of antibiotics in the treatment of URTIs when compared with placebo. Patients aged 18 to 75 years with symptoms of acute URTIs were randomized to 1200 mg guaifenesin/120 mg pseudoephedrine hydrochloride extended-release, bilayer tablets or matching placebo for 7 consecutive days. Eligible patients met physician's criteria for antibiotic therapy but were considered suitable for a wait and see approach (withholding antibiotics for ≥48 hours). Patients recorded symptom ratings via an interactive voice response system. One thousand one hundred eighty-nine patients enrolled; data are presented for the modified intent

  12. Single- and multiple-dose pharmacokinetics of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155 compared with immediate-release hydrocodone bitartrate/ibuprofen and immediate-release tramadol HCl/acetaminophen

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2015-09-01

    Full Text Available Krishna Devarakonda,1 Kenneth Kostenbader,2 Michael J Giuliani,3 Jim L Young41Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, 2Mallinckrodt Pharmaceuticals, 3Research and Development, Mallinckrodt Pharmaceuticals, 4Department of Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USAObjective: To characterize the single-dose and steady-state pharmacokinetics (PK of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (IR/ER HB/APAP, IR HB/ibuprofen, and IR tramadol HCl/APAP.Methods: In this single-center, open-label, randomized, four-period crossover study, healthy participants received four treatments under fasted conditions: 1 a single dose of two IR/ER HB/APAP 7.5/325 mg tablets (15/650 mg total dose on day 1, followed by two tablets every 12 hours (q12h beginning on day 3; 2 a single dose of IR HB/ibuprofen 15/400 mg (divided as one 7.5/200 mg tablet at hour 0 and 6, followed by one tablet every 6 hours (q6h beginning on day 3; 3 a single dose of IR tramadol HCl/APAP 75/650 mg (divided as one 37.5/325 mg tablet at hour 0 and 6, followed by one tablet q6h beginning on day 3; and 4 a single dose of three IR/ER HB/APAP 7.5/325 mg tablets (22.5/975 mg total dose on day 1, a three-tablet initial dose at 48 hours followed by two-tablet doses q12h beginning on day 3. Hydrocodone and APAP single-dose and steady-state PK were assessed. Adverse events were monitored.Results: The PK analysis was carried out on 29 of 48 enrolled participants who completed all treatment periods. Single-dose hydrocodone exposure was similar for IR/ER HB/APAP 22.5/975 mg and IR HB/ibuprofen 15/400 mg; time to maximum observed plasma concentration was shorter and half-life was longer for IR/ER HB/APAP (22.5/975 mg and 15/650 mg vs IR HB/ibuprofen. Single-dose APAP exposure was similar for IR/ER HB/APAP 15/650 mg and IR tramadol HCl/APAP 75/650 mg. Steady-state hydrocodone and APAP exposures

  13. A randomized, rater-blinded, crossover study of the effects of oxymorphone extended release, fed versus fasting, on cognitive performance as tested with CANTAB in opioid-tolerant subjects.

    Science.gov (United States)

    Spierings, Egilius L H; Volkerts, Edmund R; Heitland, Ivo; Thomson, Heather

    2014-02-01

    The maximum plasma concentration (Cmax ) of oxymorphone extended release (ER) 20 mg and 40 mg is approximately 50% higher in fed than in fasted subjects, with most of the difference in area-under-the-curve (AUC) occurring in the first 4 hours post-dose. Hence, the US FDA recommends in the approved labeling that oxymorphone ER is taken at least 1 hour before or 2 hours after eating. In order to determine the potential impact on cognitive performance of the increased absorption of oxymorphone ER, fed versus fasting, we conducted a randomized, rater-blinded, crossover study in 30 opioid-tolerant subjects, using tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). The subjects randomly received 40 mg oxymorphone ER after a high-fat meal of approximately 1,010 kCal or after fasting for 8-12 hours, and were tested 1 hour and 3 hours post-dose. The CANTAB tests, Spatial Recognition Memory (SRM) and Spatial Working Memory (SWM), showed no statistically significant differences between the fed and fasting conditions. However, sustained attention, as measured by the Rapid Visual Information Processing (RVP) CANTAB test, showed a statistically significant interaction of fed versus fasting and post-dose time of testing (F[1,28] = 6.88, P = 0.01), suggesting that 40 mg oxymorphone ER after a high-fat meal versus fasting mitigates the learning effect in this particular cognition domain from 1 hour to 3 hours post-dose. Oxymorphone 40 mg ER affected cognitive performance similarly within 3 hours post-dose, whether given on an empty stomach or after a high-fat meal, suggesting that the effect of food on plasma concentration may not be relevant in the medication's impact on cognition. Wiley Periodicals, Inc.

  14. Comparison of extended-release epidural morphine with femoral nerve block to patient-controlled epidural analgesia for postoperative pain control of total knee arthroplasty: a case-controlled study.

    Science.gov (United States)

    Sugar, Scott L; Hutson, Larry R; Shannon, Patrick; Thomas, Leslie C; Nossaman, Bobby D

    2011-01-01

    Because newer anticoagulation strategies for total knee replacement present potentially increased risk of neuraxial analgesia, there is movement away from using patient-controlled epidural analgesia (PCEA) for pain control. This concern opens the door for other regional modalities in postoperative analgesia, including the use of extended-release epidural morphine (EREM) combined with a femoral nerve block (FNB). This study was a prospective observational chart review with the use of recent historical controls in patients undergoing unilateral total knee replacement. Outcomes of interest were 0-, 24-, and 48-hour postoperative pain scores using the visual analog scale (VAS); incidence of side effects; and time spent in the postanesthesia care unit (PACU). Postoperative pain scores at 24 and 48 hours in the EREM and FNB group (n  =  14; 2.6 ± 0.6 and 5.0 ± 0.9, respectively) were comparable to the PCEA group (n  =  14; 3.8 ± 0.6 and 4.2 ± 0.9). The PACU time was shorter in the EREM and FNB group (2.4 ± 0.3 hours) compared with PCEA (3.6 ± 0.3 hours, P  =  .02). No statistically significant difference was found in the incidence of side effects between the 2 groups. The VAS scores at 24 and 48 hours indicate that EREM and FNB provide comparable analgesia to PCEA. The trend toward shorter PACU times represents an opportunity for cost-identification analysis. The study data are limited by their observational nature and the small number of patients involved; nevertheless, this study demonstrates a therapeutic equivalence to PCEA that may be more cost effective.

  15. The impact of extended release exenatide as adjuvant therapy on hemoglobin A1C, weight, and total daily dose of insulin in patients with type 2 diabetes mellitus using U-500 insulin.

    Science.gov (United States)

    Farwig, Phillip A; Zielinski, Angela J; Accursi, Mallory L; Burant, Christopher J

    2017-12-01

    To evaluate the efficacy and safety of adjuvant exenatide extended release (ER) therapy in patients treated with regular U-500 insulin. In this retrospective chart review at an ambulatory care center in the Midwest, 18 patients with type 2 diabetes being treated with regular U-500 insulin and adjuvant exenatide ER were identified. These patients were evaluated for outcomes following the addition of exenatide ER. The primary outcome was change in HbA 1C from baseline to 3, 6, and 12months. Secondary outcomes included change in weight, total daily dose (TDD) of insulin, and hypoglycemia. Repeated measures ANOVA was performed to assess the differences in mean scores over four time periods. A total of 18 of 50 patients met inclusion criteria with sufficient data to be included in analysis. HbA 1C showed non-significant findings from baseline to 12months (8.08% vs. 8.23%; p=0.75). A non-significant, modest weight loss occurred (146.4kgvs. 144.2kg; -2.2kg; p=0.31). A significant decrease in TDD of insulin was observed (378 units vs. 326 units; p1). There was a trend towards hypoglycemia from baseline to month 3 post addition of exenatide ER (0.33 events vs. 1.33 events; p=0.055). In patients treated with regular U-500 insulin, adjuvant exenatide ER therapy showed no significant improvement in HbA 1C , but did show modest weight loss as well as decreased insulin requirements to achieve a HbA 1C that was comparable to baseline. Published by Elsevier B.V.

  16. Cost-utility analysis of memantine extended release added to cholinesterase inhibitors compared to cholinesterase inhibitor monotherapy for the treatment of moderate-to-severe dementia of the Alzheimer's type in the US.

    Science.gov (United States)

    Saint-Laurent Thibault, Catherine; Özer Stillman, Ipek; Chen, Stephanie; Getsios, Denis; Proskorovsky, Irina; Hernandez, Luis; Dixit, Shailja

    2015-01-01

    This study evaluates the cost-effectiveness of memantine extended release (ER) as an add-on therapy to acetylcholinesterase inhibitor (AChEI) [combination therapy] for treatment of patients with moderate-to-severe Alzheimer's disease (AD) from both a healthcare payer and a societal perspective over 3 years when compared to AChEI monotherapy in the US. A phase III trial evaluated the efficacy and safety of memantine ER for treatment of AD patients taking an AChEI. The analysis assessed the long-term costs and health outcomes using an individual patient simulation in which AD progression is modeled in terms of cognition, behavior, and functioning changes. Input parameters are based on patient-level trial data, published literature, and publicly available data sources. Changes in anti-psychotic medication use are incorporated based on a published retrospective cohort study. Costs include drug acquisition and monitoring, total AD-related medical care, and informal care associated with caregiver time. Incremental cost-utility ratio (ICUR), life years, care time for caregiver, time in community and institution, time on anti-psychotics, time by disease severity, and time without severe symptoms are reported. Costs and health outcomes are discounted at 3% per annum. Considering a societal perspective over 3 years, this analysis shows that memantine ER combined with an AChEI provides better clinical outcomes and lower costs than AChEI monotherapy. Discounted average savings were estimated at $18,355 and $20,947 per patient and quality-adjusted life-years (QALYs) increased by an average of 0.12 and 0.13 from a societal and healthcare payer perspective, respectively. Patients on combination therapy spent an average of 4 months longer living at home and spend less time in moderate-severe and severe stages of the disease. Combination therapy for patients with moderate-to-severe AD is a cost-effective treatment compared to AChEI monotherapy in the US.

  17. Synovial and systemic pharmacokinetics (PK) of triamcinolone acetonide (TA) following intra-articular (IA) injection of an extended-release microsphere-based formulation (FX006) or standard crystalline suspension in patients with knee osteoarthritis (OA).

    Science.gov (United States)

    Kraus, V B; Conaghan, P G; Aazami, H A; Mehra, P; Kivitz, A J; Lufkin, J; Hauben, J; Johnson, J R; Bodick, N

    2018-01-01

    Intra-articular (IA) corticosteroids relieve osteoarthritis (OA) pain, but rapid absorption into systemic circulation may limit efficacy and produce untoward effects. We compared the pharmacokinetics (PK) of IA triamcinolone acetonide (TA) delivered as an extended-release, microsphere-based formulation (FX006) vs a crystalline suspension (TAcs) in knee OA patients. This Phase 2 open-label study sequentially enrolled 81 patients who received a single IA injection of FX006 (5 mL, 32 mg delivered dose, N = 63) or TAcs (1 mL, 40 mg, N = 18). Synovial fluid (SF) aspiration was attempted in each patient at baseline and one post-IA-injection visit (FX006: Week 1, Week 6, Week 12, Week 16 or Week 20; TAcs: Week 6). Blood was collected at baseline and multiple post-injection times. TA concentrations (validated LC-MS/MS, geometric means (GMs)), PK (non-compartmental analysis models), and adverse events (AEs) were assessed. SF TA concentrations following FX006 were quantifiable through Week 12 (pg/mL: 231,328.9 at Week 1; 3590.0 at Week 6; 290.6 at Week 12); post-TAcs, only two of eight patients had quantifiable SF TA at Week 6 (7.7 pg/mL). Following FX006, plasma TA gradually increased to peak (836.4 pg/mL) over 24 h and slowly declined to IA injection prolonged SF joint residency, diminished peak plasma levels, and thus reduced systemic TA exposure relative to TAcs. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Short-term therapy with combination dipeptidyl peptidase-4 inhibitor saxagliptin/metformin extended release (XR) is superior to saxagliptin or metformin XR monotherapy in prediabetic women with polycystic ovary syndrome: a single-blind, randomized, pilot study.

    Science.gov (United States)

    Elkind-Hirsch, Karen E; Paterson, Martha S; Seidemann, Ericka L; Gutowski, Hanh C

    2017-01-01

    To evaluate efficacy with the dipeptidyl peptidase-4 inhibitor saxagliptin (SAXA), metformin extended release (MET), and combination (SAXA-MET) in patients with polycystic ovary syndrome (PCOS) and impaired glucose regulation. Prospective, randomized, single-blind drug study. Outpatient clinic. Patients (n = 38) with PCOS (aged 18-42 years) and prediabetic hyperglycemia determined by a 75-gram oral glucose tolerance test. Patients were randomized to SAXA-MET (5 mg/2,000 mg), SAXA (5 mg), or MET (2,000 mg) for 16 weeks. Fasting and mean blood glucose, insulin sensitivity, insulin secretion, and insulin secretion-sensitivity index (IS-SI) by oral glucose tolerance tests. Free androgen index and lipid levels, average menstrual interval, and anthropometric measurements (body mass index, waist circumference, and waist/height ratio). The study was completed by 34 patients. Nineteen patients had normal glucose tolerance: 3 of 12 (25%) on MET; 6 of 11 (55%) on SAXA; and 10 of 11 (91%) on SAXA-MET (SAXA-MET statistically superior to MET) at study completion. Body mass index, waist circumference, waist/height ratio, free androgen index, insulin sensitivity, IS-SI, and menses improved in all groups; however, IS-SI and menstrual regularity were significantly better with SAXA-MET vs. MET treatment. Triglyceride, triglyceride/high-density lipoprotein cholesterol ratio and mean blood glucose significantly declined in the SAXA-MET and SAXA groups only. This pilot work provides the first evidence regarding the effects of a dipeptidyl peptidase-4 inhibitor alone and in combination with MET in this patient population. Treatment with SAXA-MET was superior to either drug alone in terms of clinical and metabolic benefits in prediabetic patients with PCOS. NCT02022007. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  19. Evaluation of Quality of Life, Functioning, Disability, and Work/School Productivity Following Treatment with an Extended-Release Hydrocodone Tablet Formulated with Abuse-Deterrence Technology: A 12-month Open-label Study in Patients with Chronic Pain.

    Science.gov (United States)

    Hale, Martin E; Zimmerman, Thomas R; Ma, Yuju; Malamut, Richard

    2017-02-01

    This phase 3 study evaluated quality of life, functioning, and productivity after treatment with extended-release (ER) hydrocodone formulated with CIMA ® Abuse-Deterrence Technology platform. Patients with chronic pain were rolled over from a 12-week placebo-controlled hydrocodone ER study or were newly enrolled. Hydrocodone ER doses were titrated (15 to 90 mg every 12 hours) to an analgesic dose, and patients received up to 52 weeks of open-label treatment. Assessments included Clinician Assessment of Patient Function (CAPF), Patient Assessment of Function (PAF), Brief Pain Inventory-Short Form (BPI-SF), 36-item Short-Form Health Survey (SF-36), Sheehan Disability Scale (SDS), and World Health Organization Health and Work Performance Questionnaire-Short Form (HPQ-SF). Of 330 enrolled patients, 291 composed the full analysis population. By week 4, ≥ 50% of patients showed improvement from baseline in all 5 CAPF domains (general activities, walking, work/daily living, relationships, and enjoyment of life) and 6 of 7 PAF domains (work attendance, work performance, walking, exercise, socializing, and enjoying life). Mean decreases from baseline of 2 to 3 points were noted for BPI-SF pain interference questions from week 4 through endpoint. Mean improvements from baseline to endpoint in SF-36 subscales ranged from 3.3 to 22.3, and SDS scores improved from moderate (4.8 to 5.1) to mild (2.5 to 2.8) disruptions in work/school, social life, and family life. At endpoint, mean HPQ-SF absolute absenteeism scores decreased from 13.6 to 10.0 hours lost/month and absolute presenteeism scores improved from 67.0 to 77.1. Patients receiving hydrocodone ER showed early numeric improvements in functioning that continued throughout this 12-month study. © 2016 World Institute of Pain.

  20. A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol.

    Science.gov (United States)

    Currow, David; Watts, Gareth John; Johnson, Miriam; McDonald, Christine F; Miners, John O; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J; McCloud, Philip; Louw, Sandra; Lam, Lawrence; Greene, Aine; Fazekas, Belinda; Clark, Katherine C; Fong, Kwun; Agar, Meera R; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana; Ekström, Magnus

    2017-07-17

    Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. NCT02720822; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.

    Science.gov (United States)

    Rauck, Richard L; Hale, Martin E; Bass, Almasa; Bramson, Candace; Pixton, Glenn; Wilson, Jacquelyn G; Setnik, Beatrice; Meisner, Paul; Sommerville, Kenneth W; Malhotra, Bimal K; Wolfram, Gernot

    2015-09-01

    The objective of this multicenter, double-blind, placebo-controlled, randomized withdrawal study was to evaluate the efficacy and safety of ALO-02, an abuse-deterrent formulation containing pellets of extended-release oxycodone hydrochloride (HCl) surrounding sequestered naltrexone HCl, compared with placebo in the treatment of moderate-to-severe chronic low back pain. An open-label titration period in which all patients received ALO-02 was followed by a double-blind treatment period where patients meeting treatment response criteria were randomized to either a fixed dose of ALO-02 or placebo. Daily average low back pain was assessed using an 11-point numeric rating scale (NRS)-Pain. Of the 663 patients screened, 410 received ALO-02 during the open-label conversion and titration period and 281 patients were randomized to the double-blind treatment period (n = 134, placebo; n = 147, ALO-02). Change in the mean NRS-Pain score from randomization baseline to the final 2 weeks of the treatment period was significantly different favoring ALO-02 compared with placebo (P = 0.0114). Forty-four percent of patients treated with placebo and 57.5% of patients treated with ALO-02 reported ≥30% improvement in weekly average NRS-Pain scores from screening to the final 2 weeks of the treatment period (P = 0.0248). In the double-blind treatment period, 56.8% of patients in the ALO-02 group and 56.0% of patients in the placebo group experienced a treatment-emergent adverse event (TEAE). The most common treatment-related TEAEs for ALO-02 during the treatment period were nausea, vomiting, and constipation, consistent with opioid therapy. ALO-02 has been demonstrated to provide significant reduction of pain in patients with chronic low back pain and has a safety profile similar to other opioids.

  2. In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets via Drug Dissolution/Absorption Simulating System and pH Alteration.

    Science.gov (United States)

    Li, Zi-Qiang; Tian, Shuang; Gu, Hui; Wu, Zeng-Guang; Nyagblordzro, Makafui; Feng, Guo; He, Xin

    2018-05-01

    Each of dissolution and permeation may be a rate-limiting factor in the absorption of oral drug delivery. But the current dissolution test rarely took into consideration of the permeation property. Drug dissolution/absorption simulating system (DDASS) valuably gave an insight into the combination of drug dissolution and permeation processes happening in human gastrointestinal tract. The simulated gastric/intestinal fluid of DDASS was improved in this study to realize the influence of dynamic pH change on the complete oral dosage form. To assess the effectiveness of DDASS, six high-permeability drugs were chosen as model drugs, including theophylline (pK a1  = 3.50, pK a2  = 8.60), diclofenac (pK a  = 4.15), isosorbide 5-mononitrate (pK a  = 7.00), sinomenine (pK a  = 7.98), alfuzosin (pK a  = 8.13), and metoprolol (pK a  = 9.70). A general elution and permeation relationship of their commercially available extended-release tablets was assessed as well as the relationship between the cumulative permeation and the apparent permeability. The correlations between DDASS elution and USP apparatus 2 (USP2) dissolution and also between DDASS permeation and beagle dog absorption were developed to estimate the predictability of DDASS. As a result, the common elution-dissolution relationship was established regardless of some variance in the characteristic behavior between DDASS and USP2 for drugs dependent on the pH for dissolution. Level A in vitro-in vivo correlation between DDASS permeation and dog absorption was developed for drugs with different pKa. The improved DDASS will be a promising tool to provide a screening method on the predictive dissolution-permeation-absorption dynamics of solid drug dosage forms in the early-phase formulation development.

  3. A clinical trial to determine if corelease of morphine and naltrexone from crushed extended-release capsules induces withdrawal in opioid-dependent patients: a descriptive analysis of six patients.

    Science.gov (United States)

    Setnik, Beatrice; Roland, Carl L; Goli, Veeraindar; Sommerville, Kenneth; Webster, Lynn

    2013-01-01

    To evaluate whether intact or crushed doses of an extended-release formulation of morphine sulfate surrounding an inner core of sequestered naltrexone (MSN) induces signs and symptoms of withdrawal in opioid-dependent patients. Randomized, double-blind, two-way crossover study. Single center. Fourteen patients with chronic moderate-to-severe noncancer pain receiving opioids were enrolled into the study; six completed the maintenance and treatment phases prior to early study discontinuation for issues with manufacturing; eight discontinued: adverse effects (4), noncompliance (1), patient decision (1), study termination (2). Patients were titrated to a stable dose of MSN (ranging from 30/1.2 to 100/4.0 mg of morphine/naltrexone) that was used in the single-dose crossover evaluation of crushed and intact MSN. Clinical Opiate Withdrawal Scale (COWS). Clinically significant withdrawal (COWS ≥ 13) was observed with rapid onset (≤0.8 hours postdose) in three patients (50 percent) following treatment with crushed MSN at the highest doses administered of ≥60/2.4 mg. Although naltrexone exposure was negligible following exposure to intact MSN, increasing plasma levels of naltrexone and 6-β-naltrexol were associated with COWS score ≥13 in patients who received crushed MSN. COWS ≥ 13 was observed in one patient receiving intact MSN without quantifiable naltrexone concentrations. Crushing the MSN capsule may precipitate moderate-to-severe signs and symptoms of opioid withdrawal in opioid-dependent individuals. The negligible exposure to naltrexone following exposure to intact MSN supports that intact capsules may be taken safely without precipitating withdrawal in opioid-dependent individuals.

  4. Estimates of soil ingestion by wildlife

    Science.gov (United States)

    Beyer, W.N.; Connor, E.E.; Gerould, S.

    1994-01-01

    Many wildlife species ingest soil while feeding, but ingestion rates are known for only a few species. Knowing ingestion rates may be important for studies of environmental contaminants. Wildlife may ingest soil deliberately, or incidentally, when they ingest soil-laden forage or animals that contain soil. We fed white-footed mice (Peromyscus leucopus) diets containing 0-15% soil to relate the dietary soil content to the acid-insoluble ash content of scat collected from the mice. The relation was described by an equation that required estimates of the percent acid-insoluble ash content of the diet, digestibility of the diet, and mineral content of soil. We collected scat from 28 wildlife species by capturing animals, searching appropriate habitats for scat, or removing material from the intestines of animals collected for other purposes. We measured the acid-insoluble ash content of the scat and estimated the soil content of the diets by using the soil-ingestion equation. Soil ingestion estimates should be considered only approximate because they depend on estimated rather than measured digestibility values and because animals collected from local populations at one time of the year may not represent the species as a whole. Sandpipers (Calidris spp.), which probe or peck for invertebrates in mud or shallow water, consumed sediments at a rate of 7-30% of their diets. Nine-banded armadillo (Dasypus novemcinctus, soil = 17% of diet), American woodcock (Scolopax minor, 10%), and raccoon (Procyon lotor, 9%) had high rates of soil ingestion, presumably because they ate soil organisms. Bison (Bison bison, 7%), black-tailed prairie dog (Cynomys ludovicianus, 8%), and Canada geese (Branta canadensis, 8%) consumed soil at the highest rates among the herbivores studied, and various browsers studied consumed little soil. Box turtle (Terrapene carolina, 4%), opossum (Didelphis virginiana, 5%), red fox (Vulpes vulpes, 3%), and wild turkey (Meleagris gallopavo, 9%) consumed soil

  5. Randomized clinical trial assessing the side-effects of glyceryl trinitrate and diltiazem hydrochloride in the treatment of chronic anal fissure.

    Science.gov (United States)

    Kocher, H M; Steward, M; Leather, A J M; Cullen, P T

    2002-04-01

    Glyceryl trinitrate (GTN) ointment (0 small middle dot2 per cent) has an efficacy of up to 68 per cent in healing chronic anal fissure, but with headache as a major side-effect. Diltiazem hydrochloride (DTZ) cream (2 per cent) is expected to have fewer side-effects. A prospective double-blind randomized two-centre trial requiring at least 26 patients in each group (alpha = 0.05, beta = 0.9) was instituted after approval of the local ethics committee, to compare the incidence of side-effects (primary endpoint) with 0.2 per cent GTN ointment and 2 per cent DTZ cream in the treatment of chronic anal fissure. Treatments were applied perianally, twice daily for 6-8 weeks. All patients gave written informed consent. Both groups were comparable in patient demographics and clinical characteristics. Twelve patients violated the protocol, withdrew or did not attend follow-up. There were more side-effects with GTN (21 of 29 patients) than with DTZ (13 of 31) (relative risk (RR) 1.84 (95 per cent confidence interval (c.i.) 1.11 to 3.04), P = 0.01). In particular, more headaches occurred with GTN (17 of 29 patients) than with DTZ (eight of 31) (RR 2.06 (95 per cent c.i. 1.18 to 3.59), P = 0.01). There were no significant differences in healing and symptomatic improvement rates between patients receiving GTN (25 of 29) and DTZ (24 of 31). DTZ cream caused substantially fewer headaches than GTN ointment. There was no significant difference in the healing or improvement of chronic anal fissure between the treatments. DTZ may be the preferred first-line treatment for chronic anal fissure.

  6. Toxicological significance of soil ingestion by wild and domestic animals

    Science.gov (United States)

    Beyer, W. Nelson; Fries, George F.; Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

    2003-01-01

    Most wild and domestic animals ingest some soil or sediment, and some species may routinely, or under special circumstances, ingest considerable amounts. Ingested soil supplies nutrients, exposes animals to parasites and pathogens, and may play a role in developing immune systems.1 Soil ingestion is also sometimes the principal route of exposure to various environmental contaminants.2-7 Ingestion of soil and earthy material is defined as geophagy and may be either intentional or unintentional, occurring as an animal eats or grooms.

  7. Disc battery ingestion; a single event with different outcomes

    Directory of Open Access Journals (Sweden)

    E. Sindi

    2017-06-01

    Full Text Available Foreign body (FB ingestion is a common problem especially in children below the age of 5 years. This is fueled by their curiosity to explore their surroundings. The ingested foreign body finds its way out of the gastrointestinal tract without any serious consequences most of the time. On the other hand, disc battery ingestion has been reported to cause serious harm when ingested including death. We report two patients who had ingested disc batteries and their respective outcomes.

  8. Pharmacokinetics of hydrocodone extended-release tablets formulated with different levels of coating to achieve abuse deterrence compared with a hydrocodone immediate-release/acetaminophen tablet in healthy subjects.

    Science.gov (United States)

    Darwish, Mona; Bond, Mary; Tracewell, William; Robertson, Philmore; Yang, Ronghua

    2015-01-01

    A hydrocodone extended-release (ER) formulation employing the CIMA(®) Abuse-Deterrence Technology platform was developed to provide resistance against rapid release of hydrocodone when tablets are comminuted or taken with alcohol. This study evaluated the pharmacokinetics of three hydrocodone ER tablet prototypes with varying levels of polymer coating to identify the prototype expected to have the greatest abuse deterrence potential based on pharmacokinetic characteristics that maintain systemic exposure to hydrocodone comparable to that of a commercially available hydrocodone immediate-release (IR) product. In this four-period crossover study, healthy subjects aged 18-45 years were randomized to receive a single intact, oral 45-mg tablet of one of three hydrocodone ER prototypes (low-, intermediate-, or high-level coating) or an intact, oral tablet of hydrocodone IR/acetaminophen (APAP) 10/325 mg every 6 h until four tablets were administered, with each of the four treatments administered once over the four study periods. Dosing periods were separated by a minimum 5-day washout. Naltrexone 50 mg was administered to block opioid receptors. Blood samples for pharmacokinetic assessments were collected predose and through 72 h postdose. Parameters assessed included maximum observed plasma hydrocodone concentration (C(max)), time to C(max) (t(max)), and area under the concentration-time curve from time 0 to infinity (AUC(0-∞)). Mean C(max) values were 49.2, 32.6, and 28.4 ng/mL for the low-, intermediate-, and high-level coating hydrocodone ER tablet prototypes, respectively, and 37.3 ng/mL for the hydrocodone IR/APAP tablet; respective median t(max) values were 5.9, 8.0, 8.0, and 1.0 h. Total systemic exposure to hydrocodone (AUC(0-∞)) was comparable between hydrocodone ER tablet prototypes (640, 600, and 578 ng·h/mL, respectively) and hydrocodone IR/APAP (581 ng·h/mL). No serious adverse events or deaths were reported. The most common adverse events included

  9. The safety and effectiveness of open-label extended-release carbamazepine in the treatment of children and adolescents with bipolar I disorder suffering from a manic or mixed episode

    Directory of Open Access Journals (Sweden)

    Findling RL

    2014-08-01

    Full Text Available Robert L Findling,1,2 Lawrence D Ginsberg31Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, 2Kennedy Krieger Institute, Baltimore, MD, USA; 3Red Oak Psychiatry Associates, PA, Houston, TX, USAObjective: To assess the safety and effectiveness of open-label treatment with extended-release carbamazepine (ERC in pediatric subjects suffering from bipolar I disorder.Method: Medically healthy youths aged 10–17 years suffering from an acute manic or mixed episode were eligible. After screening for study eligibility, the youths began a 5-week titration period in which doses of ERC were adjusted in order to optimize benefit whilst minimizing adverse events, at doses between 200–1,200 mg/day. Thereafter, subjects could continue to receive treatment during a subsequent 21-week period. Safety measures included spontaneously reported adverse events (AEs and laboratory assessments. The primary efficacy measure was the Young Mania Rating Scale (YMRS.Results: A total of 60 children (ages 10–12 and 97 adolescents (ages 13–17, with an overall average age of 13.4 years (standard deviation [SD] 2.0 years received ERC. The mean duration of study participation was 109.6 days (SD 70.2 days, with 66 (42% completing the entire study. At end of study participation (end point, the most prevalent dose of ERC was 1,200 mg: 31.7% of children and 24.7% of adolescents reached the 1,200 mg dose. The YMRS decreased from a mean of 28.6 (SD 6.2 at baseline to a mean of 13.8 (SD 9.4 (P<0.0001 at end point. A total of 26 subjects discontinued study participation because of AEs, the most common of which were rash (n=6, white blood cell count decreased (n=5, nausea (n=3, and vomiting (n=3. No deaths were reported. The most commonly reported AEs were headache (n=41, somnolence (n=30, nausea (n=22, dizziness (n=21, and fatigue (n=19.Conclusions: Open-label administration of ERC might be a safe

  10. Is adjunctive pharmacotherapy in attention-deficit/hyperactivity disorder cost-effective in Canada: a cost-effectiveness assessment of guanfacine extended-release as an adjunctive therapy to a long-acting stimulant for the treatment of ADHD.

    Science.gov (United States)

    Lachaine, Jean; Sikirica, Vanja; Mathurin, Karine

    2016-01-16

    Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in children, with worldwide prevalence of ADHD varying from 5.9 to 7.1 %, depending on the reporter. In case of inadequate response to stimulants, combination therapy of stimulants and an adjunctive medication may improve the control of ADHD symptoms, reduce the dose-limiting adverse events, and help control comorbidities. To date, the only medication to be used for adjunctive therapy to psychostimulants is guanfacine extended release (GXR). The aim of this study was to assess the economic impact of GXR as an adjunct therapy with long-acting stimulants (GXR + stimulant) compared to long-acting stimulant monotherapy (stimulant alone) in the treatment of children and adolescents with ADHD in Canada. A Markov model was developed using health states defined based on the clinician-reported Clinical Global Impression-Severity (CGI-S) score (normal, mild, moderate, severe). Transition probabilities were calculated based on patient-level data from a published study. Long-acting stimulants available in Canada were considered in the base-case model: amphetamine mixed salts, methylphenidate HCl formulations, and lisdexamfetamine dimesylate. Analyses were conducted from a Canadian Ministry of Health (MoH; Ontario) and a societal perspective over a 1-year time horizon with weekly cycles. Over a 1-year time horizon, GXR + stimulant was associated with 0.655 quality-adjusted life year (QALY), compared to 0.627 QALY with stimulant alone, for a gain of 0.028 QALY. From a MoH perspective, GXR+ stimulant and stimulant alone were associated with total costs of $CA1,617 and $CA949, respectively (difference of $CA668), which resulted in an incremental cost-effectiveness ratio (ICER) of $CA23,720/QALY. From a societal perspective, GXR + stimulant and stimulant alone were associated with total costs of $CA3,915 and $CA3,582, respectively (difference of $CA334), which resulted in an ICER of $CA11

  11. Efficacy and tolerability of a hydrocodone extended-release tablet formulated with abuse-deterrence technology for the treatment of moderate-to-severe chronic pain in patients with osteoarthritis or low back pain

    Directory of Open Access Journals (Sweden)

    Hale ME

    2015-09-01

    Full Text Available Martin E Hale,1 Charles Laudadio,2 Ronghua Yang,2 Arvind Narayana,2 Richard Malamut2 1Gold Coast Research, LLC, Plantation, FL, 2Teva Branded Pharmaceutical Products R & D, Inc., Frazer, PA, USA Abstract: This double-blind, placebo-controlled study evaluated the efficacy and safety of hydrocodone extended release (ER developed with abuse-deterrence technology to provide sustained pain relief and limit effects of alcohol and tablet manipulation on drug release. Eligible patients with chronic moderate-to-severe low back or osteoarthritis pain were titrated to an analgesic dose of hydrocodone ER (15–90 mg and randomized to placebo or hydrocodone ER every 12 hours. The primary efficacy measure was change from baseline to week 12 in weekly average pain intensity (API; 0=no pain, 10=worst pain imaginable. Secondary measures included percentage of patients with >33% and >50% increases from baseline in weekly API, change from baseline in weekly worst pain intensity, supplemental opioid usage, aberrant drug-use behaviors, and adverse events. Overall, 294 patients were randomized and received ≥1 dose of placebo (n=148 or hydrocodone ER (n=146. Weekly API did not differ significantly between hydrocodone ER and placebo at week 12 (P=0.134; although, in post hoc analyses, the change in weekly API was significantly lower with hydrocodone ER when excluding the lowest dose (15 mg; least squares mean, –0.20 vs 0.40; P=0.032. Significantly more patients had .33% and .50% increase in weekly API with placebo (P<0.05, and mean weekly worst pain intensity was significantly lower with hydrocodone ER at week 12 (P=0.026. Supplemental medication usage was higher with placebo (86% than hydrocodone ER (79%. Incidence of aberrant drug-use behaviors was low, and adverse events were similar between groups. This study did not meet the primary endpoint, although results support the effectiveness of this hydrocodone ER formulation in managing chronic low back or

  12. The cost-effectiveness of solifenacin vs fesoterodine, oxybutynin immediate-release, propiverine, tolterodine extended-release and tolterodine immediate-release in the treatment of patients with overactive bladder in the UK National Health Service.

    Science.gov (United States)

    Cardozo, Linda; Thorpe, Andrew; Warner, Juliet; Sidhu, Manpreet

    2010-08-01

    To assess the cost-effectiveness of solifenacin vs other antimuscarinic strategies commonly used in UK clinical practice, based on the results of a recent published review. Overactive bladder (OAB) syndrome is characterized by symptoms of urgency, frequency, incontinence and nocturia. Pharmacological treatment comprises oral antimuscarinic agents, which are divided into older-generation treatments, including oxybutynin, and new-generation treatments, comprising solifenacin, tolterodine, darifenacin and fesoterodine. The latter have reduced central nervous system penetration and have better selectivity for the M3 subclass of acetylcholine receptors, resulting in improved tolerability. A recent systematic review and meta-analysis of the efficacy and safety of antimuscarinics provided an opportunity for an economic evaluation of these agents using a rigorous assessment of efficacy. A cost-utility analysis was undertaken using a 1-year decision-tree model. Treatment success was defined separately for urgency, frequency and incontinence, with efficacy data taken from the recent review. Treatment persistence rates were taken from the Information Management System database. Utility values for the calculation of quality-adjusted life-years (QALYs) were taken from published sources. The analysis included costs directly associated with treatment for OAB, i.e. antimuscarinic therapy, consultations with general practitioners, and outpatient contacts. Resource use was based on expert opinion. Costs were reported at 2007/2008 prices. Extensive deterministic and probabilistic analyses were conducted to test the robustness of the base-case results. Solifenacin was associated with the highest QALY gains (per 1000 patients) for all three outcomes of interest, i.e. urgency (712.3), frequency (723.1) and incontinence (695.0). Solifenacin was dominant relative to fesoterodine, tolterodine extended-release (ER) and tolterodine immediate-release (IR), and cost-effective relative to

  13. Quality measure attainment with dapagliflozin plus metformin extended-release as initial combination therapy in patients with type 2 diabetes: a post hoc pooled analysis of two clinical studies

    Directory of Open Access Journals (Sweden)

    Bell KF

    2016-10-01

    Full Text Available Kelly F Bell, Arie Katz, John J Sheehan AstraZeneca, Wilmington, DE, USA Background: The use of quality measures attempts to improve safety and health outcomes and to reduce costs. In two Phase III trials in treatment-naive patients with type 2 diabetes, dapagliflozin 5 or 10 mg/d as initial combination therapy with metformin extended-release (XR significantly reduced glycated hemoglobin (A1C from baseline to 24 weeks and allowed higher proportions of patients to achieve A1C <7% vs dapagliflozin or metformin monotherapy. Objective: A pooled analysis of data from these two studies assessed the effect of dapagliflozin 5 or 10 mg/d plus metformin XR (combination therapy compared with placebo plus metformin XR (metformin monotherapy on diabetes quality measures. Quality measures include laboratory measures of A1C and low-density lipoprotein cholesterol (LDL-C as well as vital status measures of blood pressure (BP and body mass index (BMI. The proportion of patients achieving A1C, BP, and LDL-C individual and composite measures was assessed, as was the proportion with baseline BMI ≥25 kg/m2 who lost ≥4.5 kg. Subgroup analyses by baseline BMI were also performed. Results: A total of 194 and 211 patients were treated with dapagliflozin 5- or 10-mg/d combination therapy, respectively, and 409 with metformin monotherapy. Significantly higher proportions of patients achieved A1C ≤6.5%, <7%, or <8% with combination therapy vs metformin monotherapy (P<0.02. Significantly higher proportions of patients achieved BP <140/90 mmHg (P<0.02 for each dapagliflozin dose and BP <130/80 mmHg (P<0.02 with dapagliflozin 5 mg/d only with combination therapy vs metformin monotherapy. Similar proportions (29%–33% of patients had LDL-C <100 mg/dL across treatment groups. A higher proportion of patients with baseline BMI ≥25 kg/m2 lost ≥4.5 kg with combination therapy. Combination therapy had a more robust effect on patients with higher baseline BMI. Conclusion

  14. Does switching from oral extended-release methylphenidate to the methylphenidate transdermal system affect health-related quality-of-life and medication satisfaction for children with attention-deficit/hyperactivity disorder?

    Directory of Open Access Journals (Sweden)

    Landgraf Jeanne M

    2009-12-01

    Full Text Available Abstract Background To evaluate health-related quality of life (HRQL and medication satisfaction after switching from a stable dose of oral extended-release methylphenidate (ER-MPH to methylphenidate transdermal system (MTS via a dose-transition schedule in children with attention-deficit/hyperactivity disorder (ADHD. Methods In a 4-week, multisite, open-label study, 171 children (164 in the intent-to-treat [ITT] population aged 6-12 years diagnosed with ADHD abruptly switched from a stable dose of oral ER-MPH to MTS nominal dosages of 10, 15, 20, and 30 mg using a predefined dose-transition schedule. Subjects remained on the scheduled dose for the first week, after which the dose was then titrated to an optimal effect. The ADHD Impact Module-Children (AIM-C, a disease-specific validated HRQL survey instrument measuring child and family impact, was used to assess the impact of ADHD symptoms on the lives of children and their families at baseline and study endpoint. Satisfaction with MTS use was assessed via a Medication Satisfaction Survey (MSS at study endpoint. Both the AIM-C and MSS were completed by a caregiver (parent/legally authorized representative. Tolerability was monitored by spontaneous adverse event (AE reporting. Results AIM-C child and family HRQL mean scores were above the median possible score at baseline and were further improved at endpoint across all MTS doses. Similar improvements were noted for behavior, missed doses, worry, and economic impact AIM-C item scores. Overall, 93.8% of caregivers indicated a high level of satisfaction with their child's use of the study medication. The majority of treatment-emergent AEs (> 98% were mild to moderate in intensity, and the most commonly reported AEs included headache, decreased appetite, insomnia, and abdominal pain. Seven subjects discontinued the study due to intolerable AEs (n = 3 and application site reactions (n = 4. Conclusion This study demonstrates that MTS, when carefully

  15. Long-term safety and effectiveness of once-daily, single-entity, extended-release hydrocodone over 76 weeks of an open-label study in patients with chronic noncancer and nonneuropathic pain.

    Science.gov (United States)

    Taber, Louise; Lynch, Shau Yu; He, Ellie; Ripa, Steven R

    2016-01-01

    To evaluate long-term use of Hysingla(®) ER (HYD), a single-entity, extended-release, once-daily hydrocodone bitartrate tablet with abuse-deterrent properties in patients with moderate-to-severe chronic noncancer and nonneuropathic pain. This open-label study consisted of a dose-titration period (up to 45 days), a 52-week maintenance period and a 24-week extension period. Opioid-naïve or opioid-experienced patients with controlled or uncontrolled chronic pain conditions were treated with HYD 20-120 mg daily. Supplemental nonopioid and short-acting opioid analgesics were permitted. This paper presents the results of 106 patients who continued HYD treatment for up to 76 weeks. Primary safety measures included the incidence of adverse events, as well as audiologic, clinical laboratory and electrocardiogram measurements. Effectiveness was measured by the change between baseline and the overall 76-week treatment period in "average pain over the last 24 h" (0 = no pain, 10 = pain as bad as you can imagine), Brief Pain Inventory-Short Form survey, Medical Outcomes Study 36-Item Short Form Health Survey, Medical Outcomes Study Sleep Scale-Revised and concomitant nonstudy opioid analgesic use. Among 410 patients who completed the maintenance period, 106 continued into the extension. Of these, 83 (78%) completed the entire 76-week treatment period. Treatment-emergent adverse events were typical of those observed with μ-opioid agonists. No study drug abuse or diversion was reported. Clinically important analgesia and functional improvement were achieved during the dose-titration period and were maintained in most patients throughout 76 weeks without the need for continued HYD dose increases or changes in concomitant nonstudy opioid analgesics. The mean pain score was 6.1 at baseline, 3.8 at the end of the dose titration period and 3.8 through 76 weeks. HYD was generally well tolerated. No unexpected safety concerns emerged. Pain control was sustained throughout 76 weeks of

  16. Metabolism of ingested uranium and radium

    International Nuclear Information System (INIS)

    Wrenn, M.D.; Durbin, P.W.; Howard, B.; Lipsztein, J.; Rundo, J.; Still, E.T.; Willis, D.L.

    1983-01-01

    Metabolic models for U and Ra are described to estimate the risks to human health from ingesting these elements in drinking water. Chemical toxicity, which is relevant to U in its natural, depleted or slightly enriched state, is addressed, as are the radiotoxicity and the radiobiological effects of the important alpha-emitting isotopes of Ra, including 224 Ra, 226 Ra, and 228 Ra. This paper estimates the kinetics of skeletal U deposition, so that risk coefficients for bone cancer induction can be applied. Skeletal cancer is regarded as the major potential radiobiological effect of ingested alpha-emitting radioisotopes of Ra and the presumed radiobiological effect of U, if any. Best estimates of normal U metabolism are used, because even in extreme cases the amounts of U or Ra ingested in potable water are not great enough to chemically or radiobiologically modify their metabolic behavior

  17. Metabolism of ingested uranium and radium

    Energy Technology Data Exchange (ETDEWEB)

    Wrenn, M.D.; Durbin, P.W.; Howard, B.; Lipsztein, J.; Rundo, J.; Still, E.T.; Willis, D.L.

    1983-01-01

    Metabolic models for U and Ra are described to estimate the risks to human health from ingesting these elements in drinking water. Chemical toxicity, which is relevant to U in its natural, depleted or slightly enriched state, is addressed, as are the radiotoxicity and the radiobiological effects of the important alpha-emitting isotopes of Ra, including /sup 224/Ra, /sup 226/Ra, and /sup 228/Ra. This paper estimates the kinetics of skeletal U deposition, so that risk coefficients for bone cancer induction can be applied. Skeletal cancer is regarded as the major potential radiobiological effect of ingested alpha-emitting radioisotopes of Ra and the presumed radiobiological effect of U, if any. Best estimates of normal U metabolism are used, because even in extreme cases the amounts of U or Ra ingested in potable water are not great enough to chemically or radiobiologically modify their metabolic behavior.

  18. Global analysis of anthropogenic debris ingestion by sea turtles.

    Science.gov (United States)

    Schuyler, Qamar; Hardesty, Britta Denise; Wilcox, Chris; Townsend, Kathy

    2014-02-01

    Ingestion of marine debris can have lethal and sublethal effects on sea turtles and other wildlife. Although researchers have reported on ingestion of anthropogenic debris by marine turtles and implied incidences of debris ingestion have increased over time, there has not been a global synthesis of the phenomenon since 1985. Thus, we analyzed 37 studies published from 1985 to 2012 that report on data collected from before 1900 through 2011. Specifically, we investigated whether ingestion prevalence has changed over time, what types of debris are most commonly ingested, the geographic distribution of debris ingestion by marine turtles relative to global debris distribution, and which species and life-history stages are most likely to ingest debris. The probability of green (Chelonia mydas) and leatherback turtles (Dermochelys coriacea) ingesting debris increased significantly over time, and plastic was the most commonly ingested debris. Turtles in nearly all regions studied ingest debris, but the probability of ingestion was not related to modeled debris densities. Furthermore, smaller, oceanic-stage turtles were more likely to ingest debris than coastal foragers, whereas carnivorous species were less likely to ingest debris than herbivores or gelatinovores. Our results indicate oceanic leatherback turtles and green turtles are at the greatest risk of both lethal and sublethal effects from ingested marine debris. To reduce this risk, anthropogenic debris must be managed at a global level. © 2013 The Authors. Conservation Biology published by Wiley Periodicals, Inc., on behalf of the Society for Conservation Biology.

  19. Intestinal perforation by an ingested foreign body*

    Science.gov (United States)

    Nicolodi, Gabriel Cleve; Trippia, Cesar Rodrigo; Caboclo, Maria Fernanda F. S.; de Castro, Francisco Gomes; Miller, Wagner Peitl; de Lima, Raphael Rodrigues; Tazima, Leandro; Geraldo, Jamylle

    2016-01-01

    Objective To identify the computed tomography findings suggestive of intestinal perforation by an ingested foreign body. Materials and Methods This was a retrospective study of four cases of surgically proven intestinal perforation by a foreign body, comparing the computed tomography findings with those described in the literature. Results None of the patients reported having ingested a foreign body, all were over 60 years of age, three of the four patients used a dental prosthesis, and all of the foreign bodies were elongated and sharp. In all four patients, there were findings indicative of acute abdomen. None of the foreign bodies were identified on conventional X-rays. The computed tomography findings suggestive of perforation were thickening of the intestinal walls (in all four cases), increased density of mesenteric fat (in all four cases), identification of the foreign body passing through the intestinal wall (in three cases), and gas in the peritoneal cavity (in one case). Conclusion In cases of foreign body ingestion, intestinal perforation is more common when the foreign body is elongated and sharp. Although patients typically do not report having ingested such foreign bodies, the scenario should be suspected in elderly individuals who use dental prostheses. A computed tomography scan can detect foreign bodies, locate perforations, and guide treatment. The findings that suggest perforation are thickening of the intestinal walls, increased mesenteric fat density, and, less frequently, gas in the peritoneal cavity, often restricted to the point of perforation. PMID:27818542

  20. Intestinal perforation by an ingested foreign body

    International Nuclear Information System (INIS)

    Nicolodi, Gabriel Cleve; Trippia, Cesar Rodrigo; Caboclo, Maria Fernanda F.S.; Castro, Francisco Gomes de; Miller, Wagner Peitl; Lima, Raphael Rodrigues de; Tazima, Leandro; Geraldo, Jamylle

    2016-01-01

    Objective: To identify the computed tomography findings suggestive of intestinal perforation by an ingested foreign body. Materials and Methods: This was a retrospective study of four cases of surgically proven intestinal perforation by a foreign body, comparing the computed tomography findings with those described in the literature. Results: None of the patients reported having ingested a foreign body, all were over 60 years of age, three of the four patients used a dental prosthesis, and all of the foreign bodies were elongated and sharp. In all four patients, there were findings indicative of acute abdomen. None of the foreign bodies were identified on conventional X-rays. The computed tomography findings suggestive of perforation were thickening of the intestinal walls (in all four cases), increased density of mesenteric fat (in all four cases), identification of the foreign body passing through the intestinal wall (in three cases), and gas in the peritoneal cavity (in one case). Conclusion: In cases of foreign body ingestion, intestinal perforation is more common when the foreign body is elongated and sharp. Although patients typically do not report having ingested such foreign bodies, the scenario should be suspected in elderly individuals who use dental prostheses. A computed tomography scan can detect foreign bodies, locate perforations, and guide treatment. The findings that suggest perforation are thickening of the intestinal walls, increased mesenteric fat density, and, less frequently, gas in the peritoneal cavity, often restricted to the point of perforation. (author)

  1. Intestinal perforation by an ingested foreign body.

    Science.gov (United States)

    Nicolodi, Gabriel Cleve; Trippia, Cesar Rodrigo; Caboclo, Maria Fernanda F S; de Castro, Francisco Gomes; Miller, Wagner Peitl; de Lima, Raphael Rodrigues; Tazima, Leandro; Geraldo, Jamylle

    2016-01-01

    To identify the computed tomography findings suggestive of intestinal perforation by an ingested foreign body. This was a retrospective study of four cases of surgically proven intestinal perforation by a foreign body, comparing the computed tomography findings with those described in the literature. None of the patients reported having ingested a foreign body, all were over 60 years of age, three of the four patients used a dental prosthesis, and all of the foreign bodies were elongated and sharp. In all four patients, there were findings indicative of acute abdomen. None of the foreign bodies were identified on conventional X-rays. The computed tomography findings suggestive of perforation were thickening of the intestinal walls (in all four cases), increased density of mesenteric fat (in all four cases), identification of the foreign body passing through the intestinal wall (in three cases), and gas in the peritoneal cavity (in one case). In cases of foreign body ingestion, intestinal perforation is more common when the foreign body is elongated and sharp. Although patients typically do not report having ingested such foreign bodies, the scenario should be suspected in elderly individuals who use dental prostheses. A computed tomography scan can detect foreign bodies, locate perforations, and guide treatment. The findings that suggest perforation are thickening of the intestinal walls, increased mesenteric fat density, and, less frequently, gas in the peritoneal cavity, often restricted to the point of perforation.

  2. Measuring water ingestion from spray exposures.

    Science.gov (United States)

    Sinclair, Martha; Roddick, Felicity; Nguyen, Thang; O'Toole, Joanne; Leder, Karin

    2016-08-01

    Characterisation of exposure levels is an essential requirement of health risk assessment; however for water exposures other than drinking, few quantitative exposure data exist. Thus, regulatory agencies must use estimates to formulate policy on treatment requirements for non-potable recycled water. We adapted the use of the swimming pool chemical cyanuric acid as a tracer of recreational water ingestion to permit detection of small water volumes inadvertently ingested from spray exposures. By using solutions of 700-1000 mg/L cyanuric acid in an experimental spray exposure scenario, we were able to quantify inadvertent water ingestion in almost 70% of participants undertaking a 10 min car wash activity using a high pressure spray device. Skin absorption was demonstrated to be negligible under the experimental conditions, and the measured ingestion volumes ranged from 0.06 to 3.79 mL. This method could be applied to a range of non-potable water use activities to generate exposure data for risk assessment processes. The availability of such empirical measurements will provide greater assurance to regulatory agencies and industry that potential health risks from exposure to non-potable water supplies are well understood and adequately managed to protect public health. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Intestinal perforation by an ingested foreign body

    Energy Technology Data Exchange (ETDEWEB)

    Nicolodi, Gabriel Cleve; Trippia, Cesar Rodrigo; Caboclo, Maria Fernanda F.S.; Castro, Francisco Gomes de; Miller, Wagner Peitl; Lima, Raphael Rodrigues de; Tazima, Leandro; Geraldo, Jamylle, E-mail: gabrielnicolodi@gmail.com [Hospital Sao Vicente - Funef, Curitiba, PR (Brazil)

    2016-09-15

    Objective: To identify the computed tomography findings suggestive of intestinal perforation by an ingested foreign body. Materials and Methods: This was a retrospective study of four cases of surgically proven intestinal perforation by a foreign body, comparing the computed tomography findings with those described in the literature. Results: None of the patients reported having ingested a foreign body, all were over 60 years of age, three of the four patients used a dental prosthesis, and all of the foreign bodies were elongated and sharp. In all four patients, there were findings indicative of acute abdomen. None of the foreign bodies were identified on conventional X-rays. The computed tomography findings suggestive of perforation were thickening of the intestinal walls (in all four cases), increased density of mesenteric fat (in all four cases), identification of the foreign body passing through the intestinal wall (in three cases), and gas in the peritoneal cavity (in one case). Conclusion: In cases of foreign body ingestion, intestinal perforation is more common when the foreign body is elongated and sharp. Although patients typically do not report having ingested such foreign bodies, the scenario should be suspected in elderly individuals who use dental prostheses. A computed tomography scan can detect foreign bodies, locate perforations, and guide treatment. The findings that suggest perforation are thickening of the intestinal walls, increased mesenteric fat density, and, less frequently, gas in the peritoneal cavity, often restricted to the point of perforation. (author)

  4. Data ingestion and assimilation in ionospheric models

    Czech Academy of Sciences Publication Activity Database

    Burešová, Dalia; Nava, B.; Galkin, I.; Angling, M.; Stankov, S. M.; Coisson, P.

    2009-01-01

    Roč. 52, 3/4 (2009), s. 235-253 ISSN 1593-5213 R&D Projects: GA ČR GA205/08/1356; GA MŠk OC 091 Institutional research plan: CEZ:AV0Z30420517 Keywords : ionosphere * models * data assimilation * data ingestion Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 0.548, year: 2009

  5. Appetite influences the responses to meal ingestion.

    Science.gov (United States)

    Pribic, T; Nieto, A; Hernandez, L; Malagelada, C; Accarino, A; Azpiroz, F

    2017-08-01

    We have previously shown that the postprandial experience includes cognitive sensations, such as satiety and fullness, with a hedonic dimension involving digestive well-being and mood. Preload conditioning has been shown to modulate appetite and food consumption under certain conditions, but its effects on the responses to meal ingestion are not clear. We hypothesized that appetite modulation by preload conditioning has differential effects on the cognitive and the emotive responses to meal ingestion. The effects of preload conditioning (ingestion of a low- vs a high-calorie breakfast) on appetite and on the cognitive and emotive responses to a comfort probe meal ingested 2 hours later (ham and cheese sandwich with orange juice; 300 mL, 425 Kcal) was tested in healthy subjects (n=12) in a cross-over design. Sensations were measured at regular intervals 15 minutes before and 60 minutes after the probe meal. As compared to the low-calorie breakfast, the high-calorie breakfast reduced basal hunger sensation and influenced the responses to the subsequent probe meal: it increased satiety (4.3±0.2 score vs 2.7±0.2 score; PAppetite modulation by preload conditioning has differential effects on the cognitive and emotive responses to a meal. Preload conditioning of the postprandial experience may be applicable to dietary planning and prevention of postprandial symptoms. © 2017 John Wiley & Sons Ltd.

  6. 14 CFR 33.76 - Bird ingestion.

    Science.gov (United States)

    2010-01-01

    ... single bird, the single largest medium bird which can enter the inlet, and the large flocking bird must...) (d) Large flocking bird. An engine test will be performed as follows: (1) Large flocking bird engine.... (4) Ingestion of a large flocking bird under the conditions prescribed in this paragraph must not...

  7. Intestinal perforation by an ingested foreign body

    Directory of Open Access Journals (Sweden)

    Gabriel Cleve Nicolodi

    Full Text Available Abstract Objective: To identify the computed tomography findings suggestive of intestinal perforation by an ingested foreign body. Materials and Methods: This was a retrospective study of four cases of surgically proven intestinal perforation by a foreign body, comparing the computed tomography findings with those described in the literature. Results: None of the patients reported having ingested a foreign body, all were over 60 years of age, three of the four patients used a dental prosthesis, and all of the foreign bodies were elongated and sharp. In all four patients, there were findings indicative of acute abdomen. None of the foreign bodies were identified on conventional X-rays. The computed tomography findings suggestive of perforation were thickening of the intestinal walls (in all four cases, increased density of mesenteric fat (in all four cases, identification of the foreign body passing through the intestinal wall (in three cases, and gas in the peritoneal cavity (in one case. Conclusion: In cases of foreign body ingestion, intestinal perforation is more common when the foreign body is elongated and sharp. Although patients typically do not report having ingested such foreign bodies, the scenario should be suspected in elderly individuals who use dental prostheses. A computed tomography scan can detect foreign bodies, locate perforations, and guide treatment. The findings that suggest perforation are thickening of the intestinal walls, increased mesenteric fat density, and, less frequently, gas in the peritoneal cavity, often restricted to the point of perforation.

  8. A randomized study to compare the efficacy and safety of extended-release and immediate-release tramadol HCl/acetaminophen in patients with acute pain following total knee replacement.

    Science.gov (United States)

    Park, Yong-Beom; Ha, Chul-Won; Cho, Sung-Do; Lee, Myung-Chul; Lee, Ju-Hong; Seo, Seung-Suk; Kang, Seung-Baik; Kyung, Hee-Soo; Choi, Choong-Hyeok; Chang, NaYoon; Rhim, Hyou Young Helen; Bin, Seong-Il

    2015-01-01

    To evaluate the relative efficacy and safety of extended-release tramadol HCl 75 mg/acetaminophen 650 mg (TA-ER) and immediate-release tramadol HCl 37.5 mg/acetaminophen 325 mg (TA-IR) for the treatment of moderate to severe acute pain following total knee replacement. This phase III, double-blind, placebo-controlled, parallel-group study randomized 320 patients with moderate to severe pain (≥4 intensity on an 11 point numeric rating scale) following total knee replacement arthroplasty to receive oral TA-ER (every 12 hours) or TA-IR (every 6 hours) over a period of 48 hours. In the primary analysis, TA-ER was evaluated for efficacy non-inferior to that of TA-IR based on the sum of pain intensity difference (SPID) at 48 hours after the first dose of study drug (SPID48). Secondary endpoints included SPID at additional time points, total pain relief at all on-therapy time points (TOTPAR), sum of SPID and TOTPAR at all on-therapy time points (SPID + TOTPAR), use of rescue medication, subjective pain assessment (PGIC, Patient Global Impression of Change), and adverse events (AEs). Analysis of the primary efficacy endpoint (SPID48) could not establish the non-inferiority of TA-ER to TA-IR. However, a post hoc analysis with a re-defined non-inferiority margin did demonstrate the non-inferiority of TA-ER to TA-IR. No statistically significant difference in SPID at 6, 12, or 24 hours was observed between the TA-ER and TA-IR groups. Similarly, analysis of TOTPAR showed that there were no significant differences between groups at any on-therapy time point, and SPID + TOTPAR at 6 and 48 hours were similar among groups. There was no difference in the mean frequency or dosage of rescue medication required by both groups, and the majority of patients in both the TA-ER and TA-IR groups rated their pain improvement as 'much' or 'somewhat better'. The overall incidence of ≥1 AEs was similar among the TA-ER (88.8%) and TA-IR (89.5%) groups. The most commonly

  9. Evaluation of Patient Migration Patterns and Related Health Care Costs Within a National Medicare Advantage Prescription Drug Plan After Implementation of an Oxycodone HCl Extended-Release Access Restriction.

    Science.gov (United States)

    Chen, Chi-Chang; De, Ajita P; Sweet, Brian; Wade, Rolin L

    2017-08-01

    Health plans use formulary restrictions (e.g., prior authorization, step therapy, tier change, nonformulary status) in an effort to control cost and promote quality, safety, and appropriate prescription utilization. Some Medicare payers perceive that the inclusion of certain agents, such as branded oxycodone HCl extended-release tablets (OERs), on their formularies is associated with attracting high-cost members to the plan. To evaluate disenrollment rates, patient migration, and subsequent health care costs among OER users who disenrolled from a national Medicare Advantage Prescription Drug plan (study-MAPD) in the plan year following OER nonformulary restriction. A retrospective, longitudinal cohort study using IMS pharmacy and medical claims data between July 1, 2011, and December 31, 2014, was conducted. In the study-MAPD, adults aged ≥ 18 years who were chronic OER users with ≥ 2 OER claims 6 months before the nonformulary restriction date on January 1, 2013 (index date) and with continuous activity in pharmacy and medical claims for 6 months pre- and post-index were included in the study. Comparison years of 2012 and 2014 prerestriction/postrestriction were selected. All groups were followed for 6 months postindex. Year-to-year disenrollment rates of OER patients and the overall plan, as well as patient characteristics and costs of those who disenrolled from and those who remained with the plan, were measured. Costs were compared using a difference-in-differences approach. This study identified 2,935 eligible OER users from the study-MAPD population after imposing nonformulary restrictions on OERs on January 1, 2013. Mean age was 62.1 years, and 59.8% were female. The mean Charlson Comorbidity Index score was 1.83 for those 1,001 patients with medical claims data. For comparison years 2012 (prerestriction) and 2014 (postrestriction), 2,248 and 2,222 OER patients were identified, respectively. Patient characteristics were similar across patient cohorts in

  10. Prediction of complications following caustic ingestion in adults

    DEFF Research Database (Denmark)

    Christesen, H B

    1995-01-01

    The records of 86 adults admitted to hospital following caustic ingestion were reviewed. Eighteen patients (21%) developed complications; of these, six were fatal. Patients without symptoms or signs did not develop complications. Complications occurred only following lye ingestion, or intentional...

  11. Intestinal perforation caused by multiple magnet ingestion | Corduk ...

    African Journals Online (AJOL)

    Multiple magnet ingestion is rare, but can cause serious gastrointestinal complications. We report a case of 7-year-old girl with multiple intestinal perforations caused by multiple magnet ingestion. The aim of this report is to draw attention to magnetic toys, results of magnet ingestion and the importance of timing of operation.

  12. Gastric Perforation by Ingested Rabbit Bone Fragment

    Directory of Open Access Journals (Sweden)

    Giulio Gambaracci

    2016-04-01

    Full Text Available The majority of accidentally ingested foreign bodies is excreted from the gastrointestinal (GI tract without any complications. Sometimes sharp foreign bodies – like chicken and fish bones – can lead to intestinal perforation and may present insidiously with a wide range of symptoms and, consequently, different diagnoses. We report the case of a 59-year-old woman presenting with fever and a 1-month history of vague abdominal pain. Computed tomography (CT showed the presence of a hyperdense linear image close to the gastric antrum surrounded by a fluid collection and free peritoneal air. At laparotomy, a 4-cm rabbit bone fragment covered in inflamed tissue was detected next to a gastric wall perforation. Rabbit bone fragment ingestion, even if rarely reported, should not be underestimated as a possible cause of GI tract perforation.

  13. Propylene Glycol Poisoning From Excess Whiskey Ingestion

    Directory of Open Access Journals (Sweden)

    Courtney A. Cunningham MD

    2015-09-01

    Full Text Available In this report, we describe a case of high anion gap metabolic acidosis with a significant osmolal gap attributed to the ingestion of liquor containing propylene glycol. Recently, several reports have characterized severe lactic acidosis occurring in the setting of iatrogenic unintentional overdosing of medications that use propylene glycol as a diluent, including lorazepam and diazepam. To date, no studies have explored potential effects of excess propylene glycol in the setting of alcohol intoxication. Our patient endorsed drinking large volumes of cinnamon flavored whiskey, which was likely Fireball Cinnamon Whisky. To our knowledge, this is the first case of propylene glycol toxicity from an intentional ingestion of liquor containing propylene glycol.

  14. Evaluation of skin and ingestion exposure pathways

    International Nuclear Information System (INIS)

    Aaberg, Rosanne; Logsdon, Joe E.

    1989-06-01

    After a nuclear accident when there has been a release of radionuclides into the atmosphere with consequential deposition on the ground, decisions are necessary on whether protective action guides should be implemented. In order to do this, several pathways for radiation exposure must be evaluated to determine the projected dose to individuals. The objective of this study, conducted by Pacific Northwest Laboratories for the U.S. Environmental Protection Agency, is to provide background information on exposure pathways for use in the development of Protective Action Guides. The relative importance of three exposure pathways that are usually considered to be unimportant compared to other pathways expected to control relocation decisions following a nuclear power plant accident is evaluated. The three pathways are the skin dose from contact with radionuclides transferred from the ground, the skin dose from radionuclides on the ground surface, and ingestion of radionuclides transferred directly to the mouth from the hands or other contaminated surfaces. Ingestion of contaminated food is not included in this evaluation, except for situations where the food is contaminated as a result of actions by the person who consumes the food (e.g., transfer of contamination from hands to food). Estimates of skin and ingestion doses are based on a source term with a radionuclide mix predicted for an SST2-type nuclear accident in an area where the first year reference whole-body dose equivalent from whole body external exposure to gamma radiation plus the committed effective dose equivalent from inhalation of resuspended radionuclides is 1 rem. Appendixes have been included to allow the reader to examine dose factor calculations, source-term data, and quantification of contact and ingestion parameters in more detail

  15. Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion

    OpenAIRE

    Hughes, Adrienne; Brown, Alisha; Valento, Matthew

    2016-01-01

    Baking soda is a readily available household product composed of sodium bicarbonate. It can be used asa home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to causea variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagicencephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers ofbaking soda misuse and the associated adverse effects. [West J Emerg Med. 2016;17(5)619...

  16. Evaluation of skin and ingestion exposure pathways

    Energy Technology Data Exchange (ETDEWEB)

    Aaberg, Rosanne [Pacific Northwest Laboratory, Richland, WA (United States); Logsdon, Joe E [United States Environmental Protection Agency, Office of Radiation Programs, Washington, DC (United States)

    1989-06-01

    After a nuclear accident when there has been a release of radionuclides into the atmosphere with consequential deposition on the ground, decisions are necessary on whether protective action guides should be implemented. In order to do this, several pathways for radiation exposure must be evaluated to determine the projected dose to individuals. The objective of this study, conducted by Pacific Northwest Laboratories for the U.S. Environmental Protection Agency, is to provide background information on exposure pathways for use in the development of Protective Action Guides. The relative importance of three exposure pathways that are usually considered to be unimportant compared to other pathways expected to control relocation decisions following a nuclear power plant accident is evaluated. The three pathways are the skin dose from contact with radionuclides transferred from the ground, the skin dose from radionuclides on the ground surface, and ingestion of radionuclides transferred directly to the mouth from the hands or other contaminated surfaces. Ingestion of contaminated food is not included in this evaluation, except for situations where the food is contaminated as a result of actions by the person who consumes the food (e.g., transfer of contamination from hands to food). Estimates of skin and ingestion doses are based on a source term with a radionuclide mix predicted for an SST2-type nuclear accident in an area where the first year reference whole-body dose equivalent from whole body external exposure to gamma radiation plus the committed effective dose equivalent from inhalation of resuspended radionuclides is 1 rem. Appendixes have been included to allow the reader to examine dose factor calculations, source-term data, and quantification of contact and ingestion parameters in more detail.

  17. Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion.

    Science.gov (United States)

    Hughes, Adrienne; Brown, Alisha; Valento, Matthew

    2016-09-01

    Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects.

  18. Hemorrhagic Encephalopathy From Acute Baking Soda Ingestion

    Directory of Open Access Journals (Sweden)

    Adrienne Hughes

    2016-09-01

    Full Text Available Baking soda is a readily available household product composed of sodium bicarbonate. It can be used as a home remedy to treat dyspepsia. If used in excessive amounts, baking soda has the potential to cause a variety of serious metabolic abnormalities. We believe this is the first reported case of hemorrhagic encephalopathy induced by baking soda ingestion. Healthcare providers should be aware of the dangers of baking soda misuse and the associated adverse effects.

  19. Severe Neurotoxicity Following Ingestion of Tetraethyl Lead

    OpenAIRE

    Wills, Brandon K.; Christensen, Jason; Mazzoncini, Joe; Miller, Michael

    2010-01-01

    Organic lead compounds are potent neurotoxins which can result in death even from small exposures. Traditionally, these compounds are found in fuel stabilizers, anti-knock agents, and leaded gasoline. Cases of acute organic lead intoxication have not been reported for several decades. We report a case of a 13-year-old Iraqi male who unintentionally ingested a fuel stabilizer containing 80–90% tetraethyl lead, managed at our combat support hospital. The patient developed severe neurologic symp...

  20. An Unusual Neck Mass: Ingested Chicken Bone

    OpenAIRE

    Demirhan, Erhan; İber, Metin; Yağız, Özlem; Kandoğan, Tolga; Çukurova, İbrahim

    2016-01-01

    Background: Foreign bodies in the upper aerodigestive tract are frequently seen in otolaryngological practice, but migration of an ingested foreign body to the neck is a very rare condition. Case Report: We present a 66-year-old woman admitted to our outpatient department with a painful neck mass. She had a history of emergency department admission 4 months prior with odynophagia after eating chicken meal. A physical examination revealed a painful and hyperemic mass on the left neck. Ant...

  1. Quantification of Soil Ingested by Children

    Energy Technology Data Exchange (ETDEWEB)

    Bothe, M.; Boden, W. [Nuclear Engineering and Analytics Inc., Dresden (Germany)

    2006-07-01

    Direct ingestion of soil is a possible essential exposition path for radionuclides and toxic substances, in particular for playing children. To quantify the soil ingested by children 22 test persons in 4 age groups (< 1 year, 1 to 2 years, 2 to 7 years, 7 to 12 years) were investigated for 12 days. We used some chemical elements as tracers. For the investigation purpose tracer elements should comply following conditions as best as possible: high concentration in soil, low intake by food, low gastrointestinal resorption. So we selected the elements Al, Si, Sc, Ti, Ga, Y, Zr, Nb, La, Ce and Nd. To determine the amount of ingested soil we sampled diet and stool of all 22 children for 12 days in summer 2002. We also sampled soil of the main playgrounds and house dust of thildren homes. The behaviour of the children was recorded by the parents or childminders, particularly diet, defecation and outdoor playing. The mean values for all test persons are for the grain size fraction < 500 {mu}m 53 mg/d or 19 mg/h playing time and for the grain size fraction < 63 {mu}m 31 mg/d or 12 mg/ h playing time.The combined standard uncertainty is about 50 % for the data in mg/d and about 60 % for the data in mg/h playing time.The results are presented in tables and curves. (N.C.)

  2. Quantification of Soil Ingested by Children

    International Nuclear Information System (INIS)

    Bothe, M.; Boden, W.

    2006-01-01

    Direct ingestion of soil is a possible essential exposition path for radionuclides and toxic substances, in particular for playing children. To quantify the soil ingested by children 22 test persons in 4 age groups (< 1 year, 1 to 2 years, 2 to 7 years, 7 to 12 years) were investigated for 12 days. We used some chemical elements as tracers. For the investigation purpose tracer elements should comply following conditions as best as possible: high concentration in soil, low intake by food, low gastrointestinal resorption. So we selected the elements Al, Si, Sc, Ti, Ga, Y, Zr, Nb, La, Ce and Nd. To determine the amount of ingested soil we sampled diet and stool of all 22 children for 12 days in summer 2002. We also sampled soil of the main playgrounds and house dust of the children homes. The behaviour of the children was recorded by the parents or childminders, particularly diet, defecation and outdoor playing. The mean values for all test persons are for the grain size fraction < 500 μm 53 mg/d or 19 mg/h playing time and for the grain size fraction < 63 μm 31 mg/d or 12 mg/ h playing time.The combined standard uncertainty is about 50 % for the data in mg/d and about 60 % for the data in mg/h playing time.The results are presented in tables and curves. (N.C.)

  3. Trichloroacetic Acid Ingestion: Self-Harm Attempt

    Directory of Open Access Journals (Sweden)

    E. R. Black

    2017-01-01

    Full Text Available Objective. Trichloroacetic acid (TCAA, or trichloroethanoic acid, is a chemical analogue of acetic acid where three methyl group hydrogen atoms are replaced by chlorine. TCAAs are also abbreviated and referred to as TCAs, causing confusion with the psychiatric antidepressant drug class, especially among patients. TCAAs exist in dermatological treatments such as chemical peels or wart chemoablation medication. TCAA ingestion or overdose can cause gastric irritation symptoms including vomiting, diarrhea, or lassitude. This symptomatology is less severe than TCA overdose, where symptoms may include elevated body temperature, blurred vision, dilated pupils, sleepiness, confusion, seizures, rapid heart rate, and cardiac arrest. Owing to the vast difference in symptoms, the need for clinical intervention differs greatly. While overdose of either in a self-harm attempt can warrant psychiatric hospital admission, the risk of death in TCAA ingestion is far less. Case Report. A patient ingested TCAA in the form of a commercially available dermatological chemical peel as a self-harm attempt, thinking that it was a more injurious TCA. Conclusion. Awareness among physicians, particularly psychiatrists, regarding this relatively obscure chemical compound (TCAA and its use by suicidal patients mistakenly believing it to be a substance that can be significantly more lethal (TCA, is imperative.

  4. Severe neurotoxicity following ingestion of tetraethyl lead.

    Science.gov (United States)

    Wills, Brandon K; Christensen, Jason; Mazzoncini, Joe; Miller, Michael

    2010-03-01

    Organic lead compounds are potent neurotoxins which can result in death even from small exposures. Traditionally, these compounds are found in fuel stabilizers, anti-knock agents, and leaded gasoline. Cases of acute organic lead intoxication have not been reported for several decades. We report a case of a 13-year-old Iraqi male who unintentionally ingested a fuel stabilizer containing 80-90% tetraethyl lead, managed at our combat support hospital. The patient developed severe neurologic symptoms including agitation, hallucinations, weakness, and tremor. These symptoms were refractory to escalating doses of benzodiazepines and ultimately required endotracheal intubation and a propofol infusion. Adjunctive therapies included chelation, baclofen, and nutrition provided through a gastrostomy tube. The patient slowly recovered and was discharged in a wheelchair 20 days after ingestion, still requiring tube feeding. Follow-up at 62 days post-ingestion revealed near-resolution of symptoms with residual slurred speech and slight limp. This case highlights the profound neurotoxic manifestations of acute organic lead compounds.

  5. Soil ingestion: a concern for acute toxicity in children.

    OpenAIRE

    Calabrese, E J; Stanek, E J; James, R C; Roberts, S M

    1997-01-01

    Several soil ingestion studies have indicated that some children ingest substantial amounts of soil on given days. Although the EPA has assumed that 95% of children ingest 200 mg soil/day or less for exposure assessment purposes, some children have been observed to ingest up to 25-60 g soil during a single day. In light of the potential for children to ingest such large amounts of soil, an assessment was made of the possibility for soil pica episodes to result in acute intoxication from conta...

  6. Comparison of the fates of ingested leucine and ingested 2-ketoisocaproate in rats

    Energy Technology Data Exchange (ETDEWEB)

    Imura, K.; Walser, M. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1990-05-01

    We previously reported that the ratio, R, of 14C to 3H in the leucine of whole body protein, measured 6 h after ingestion of (3H)leucine and (1-14C)2-ketoisocaproate is equal to ratio of the dose of leucine to the dose of 2-ketoisocaproate (KIC) (on a leucine-free diet) required to achieve the same rate of growth. To determine whether R is dependent on the interval between injection and sampling, R was measured at intervals in purified whole body protein after oral injection of these isotopes in groups of rats; it was constant from 1 h onward for 1 wk, averaging 0.64 +/- 0.01 (means +/- SEM). Thus, the extent of incorporation into the leucine of whole body protein of ingested KIC remains close to 64% of the incorporation of ingested leucine administered as such simultaneously, from 1 h onward for at least 1 wk.

  7. Hemorrhagic shock secondary to button battery ingestion

    Directory of Open Access Journals (Sweden)

    Naomi Andreia Takesaki

    Full Text Available CONTEXT:Button battery ingestion is a frequent pediatric complaint. The serious complications resulting from accidental ingestion have increased significantly over the last two decades due to easy access to gadgets and electronic toys. Over recent years, the increasing use of lithium batteries of diameter 20 mm has brought new challenges, because these are more detrimental to the mucosa, compared with other types, with high morbidity and mortality. The clinical complaints, which are often nonspecific, may lead to delayed diagnosis, thereby increasing the risk of severe complications.CASE REPORT:A five-year-old boy who had been complaining of abdominal pain for ten days, was brought to the emergency service with a clinical condition of hematemesis that started two hours earlier. On admission, he presented pallor, tachycardia and hypotension. A plain abdominal x-ray produced an image suggestive of a button battery. Digestive endoscopy showed a deep ulcerated lesion in the esophagus without active bleeding. After this procedure, the patient presented profuse hematemesis and severe hypotension, followed by cardiorespiratory arrest, which was reversed. He then underwent emergency exploratory laparotomy and presented a new episode of cardiorespiratory arrest, which he did not survive. The battery was removed through rectal exploration.CONCLUSION:This case describes a fatal evolution of button battery ingestion with late diagnosis and severe associated injury of the digestive mucosa. A high level of clinical suspicion is essential for preventing this evolution. Preventive strategies are required, as well as health education, with warnings to parents, caregivers and healthcare professionals.

  8. Automatic ingestion monitor: a novel wearable device for monitoring of ingestive behavior.

    Science.gov (United States)

    Fontana, Juan M; Farooq, Muhammad; Sazonov, Edward

    2014-06-01

    Objective monitoring of food intake and ingestive behavior in a free-living environment remains an open problem that has significant implications in study and treatment of obesity and eating disorders. In this paper, a novel wearable sensor system (automatic ingestion monitor, AIM) is presented for objective monitoring of ingestive behavior in free living. The proposed device integrates three sensor modalities that wirelessly interface to a smartphone: a jaw motion sensor, a hand gesture sensor, and an accelerometer. A novel sensor fusion and pattern recognition method was developed for subject-independent food intake recognition. The device and the methodology were validated with data collected from 12 subjects wearing AIM during the course of 24 h in which both the daily activities and the food intake of the subjects were not restricted in any way. Results showed that the system was able to detect food intake with an average accuracy of 89.8%, which suggests that AIM can potentially be used as an instrument to monitor ingestive behavior in free-living individuals.

  9. Development of an Ingestion Pathway Model for AXAIRQ

    Energy Technology Data Exchange (ETDEWEB)

    Simpkins, A.A.

    1999-01-13

    AXAIRQ is a dose mode code used for prospective accident assessment at the Savannah River Site and is primarily used to show regulatory compliance. For completeness of pathway analysis, an ingestion model, AXINGST, has been developed for use with, and incorporation in, AXAIRQ. Currently available ingestion models were referenced as a basis for AXINGST. AXINGST calculates a conservative ingestion dose following an atmospheric release of radionuclides and includes site specific variables where applicable.

  10. Too attractive: the growing problem of magnet ingestions in children.

    Science.gov (United States)

    Brown, Julie C; Otjen, Jeffrey P; Drugas, George T

    2013-11-01

    Small, powerful magnets are increasingly available in toys and other products and pose a health risk. Small spherical neodymium magnets marketed since 2008 are of particular concern. The objective of this study was to determine the incidence, characteristics, and management of single and multiple-magnet ingestions over time. Magnet ingestion cases at a tertiary children's hospital were identified using radiology reports from June 2002 to December 2012. Cases were verified by chart and imaging review. Relative risk regressions were used to determine changes in the incidence of ingestions and interventions over time. Of 56 cases of magnet ingestion, 98% occurred in 2006 or later, and 57% involved multiple magnets. Median age was 8 years (range, 0-18 years). Overall, 21% of single and 88% of multiple ingestions had 2 or more imaging series obtained, whereas no single and 56.3% of multiple ingestions required intervention (25.0% endoscopy, 18.8% surgery, 12.5% both). Magnet ingestions increased in 2010 to 2012 compared with 2007 to 2009 (relative risk, 1.9; 95% confidence interval, 1.2-3.0). Small, spherical magnets likely from magnet sets comprised 27% of ingestions, all ingested 2010 or later: 86% involved multiple magnets, 50% of which required intervention. Excluding these cases, ingestions of other magnets did not increase in 2010 to 2012 compared with 2007 to 2009 (relative risk, 0.94; 95% confidence interval, 0.6-1.4). The incidence of pediatric magnet ingestions and subsequent interventions has increased over time. Multiple-magnet ingestions result in high utilization of radiological imaging and surgical interventions. Recent increases parallel the increased availability of small, spherical magnet sets. Young and at-risk children should not have access to these and other small magnets. Improved regulation and magnet safety standards are needed.

  11. A review of soil and dust ingestion studies for children.

    Science.gov (United States)

    Moya, Jacqueline; Phillips, Linda

    2014-11-01

    Soil and dust ingestion by children may be important pathways of exposure to environmental contaminants. Contaminated soil and dust may end up on children's hands and objects, because they play close to the ground. These contaminants can be ingested by children, because they have a tendency to place objects, including their fingers, in their mouths. Assessing exposure through this pathway requires information about the amount of soil and dust ingested by children. Estimates of soil and dust ingestion and information on the prevalence of the behavior have been published in the literature, but research in this area is generally limited. Three methodologies have been used to quantify soil and dust ingestion rates. In this paper, these are referred to as the tracer element method, the biokinetic model comparison method, and the activity pattern method. This paper discusses the information available on the prevalence of soil and dust ingestion behavior, summarizes the three methodologies for quantifying soil and dust ingestion, and discusses their limitations. Soil ingestion data derived from studies that use these methodologies are also summarized. Although they are based on different estimation approaches, the central tendency estimates of soil and dust ingestion derived from the three methodologies are generally comparable.

  12. Button battery ingestion in children: An emerging hazard

    Directory of Open Access Journals (Sweden)

    Mayank Jain

    2013-01-01

    Full Text Available Button battery ingestion is an emerging hazard. In this retrospective study, we report six cases of lithium button battery ingestion in pediatric age group (mean age 2.8 years. Three button batteries were removed from stomach and three from esophagus. Esophageal site was associated with significant local injury, and one button battery was impacted in the esophagus, requiring rigid esophagoscopy for removal. Small battery size, used batteries, and early removal (<12 h after ingestion were associated with lesser mucosal injury. No long-term complications were noted. Our study emphasizes that early diagnosis and urgent removal of ingested button battery are the only measures which prevent complications.

  13. Suicidal ingestion of potassium permanganate crystals: a rare encounter.

    Science.gov (United States)

    Karthik, Ravikanti; Veerendranath, Hari Prasad Kanakapura; Wali, Siddraj; Mohan, Murali N T; Kumar, Praveen A C; Trimurty, Gaganam

    2014-01-01

    Potassium permanganate poisoning is not common. Although Symptoms of potassium permanganate ingestion are gastrointestinal and Complications due to ingestion of potassium permanganate include cardiovascular depression, hepatic and renal damage, upper airway obstruction, bleeding tendency and methemoglobinemia. Gastric damage due to potassium permanganate has rarely been reported previously. We are reporting a 34-year old female patient who presented to our Emergency Department after suicidal ingestion of potassium permanganate crystals. After treatment, the patient was discharged home on the 8(th) day after admission. So we conclude that Emergency endoscopy has a significant role in diagnosis and management of potassium permanganate ingestion.

  14. Existing ingestion guidance: Problems and recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Mooney, Robert R; Ziegler, Gordon L; Peterson, Donald S [Environmental Radiation Section, Division of Radiation Protection, WA (United States)

    1989-09-01

    Washington State has been developing plans and procedures for responding to nuclear accidents since the early 1970s. A key part of this process has been formulating a method for calculating ingestion pathway concentration guides (CGs). Such a method must be both technically sound and easy to use. This process has been slow and frustrating. However, much technical headway has been made in recent years, and hopefully the experience of the State of Washington will provide useful insight to problems with the existing guidance. Several recommendations are offered on ways to deal with these problems. In January 1986, the state held an ingestion pathway exercise which required the determination of allowed concentrations of isotopes for various foods, based upon reactor source term and field data. Objectives of the exercise were not met because of the complexity of the necessary calculations. A major problem was that the allowed concentrations had to be computed for each isotope and each food group, given assumptions on the average diet. To solve problems identified during that exercise, Washington developed, by March 1986, partitioned CGs. These CGs apportioned doses from each food group for an assumed mix of radionuclides expected to result from a reactor accident. This effort was therefore in place just in time for actual use during the Chernobyl fallout episode in May 1986. This technique was refined and described in a later report and presented at the 1987 annual meeting of the Health Physics Society. Realizing the technical weaknesses which still existed and a need to simplify the numbers for decision makers, Washington State has been developing computer methods to quickly calculate, from an accident specific relative mix of isotopes, CGs which allow a single radionuclide concentration for all food groups. This latest approach allows constant CGs for different periods of time following the accident, instead of peak CGs, which are good only for a short time after the

  15. Existing ingestion guidance: Problems and recommendations

    International Nuclear Information System (INIS)

    Mooney, Robert R.; Ziegler, Gordon L.; Peterson, Donald S.

    1989-01-01

    Washington State has been developing plans and procedures for responding to nuclear accidents since the early 1970s. A key part of this process has been formulating a method for calculating ingestion pathway concentration guides (CGs). Such a method must be both technically sound and easy to use. This process has been slow and frustrating. However, much technical headway has been made in recent years, and hopefully the experience of the State of Washington will provide useful insight to problems with the existing guidance. Several recommendations are offered on ways to deal with these problems. In January 1986, the state held an ingestion pathway exercise which required the determination of allowed concentrations of isotopes for various foods, based upon reactor source term and field data. Objectives of the exercise were not met because of the complexity of the necessary calculations. A major problem was that the allowed concentrations had to be computed for each isotope and each food group, given assumptions on the average diet. To solve problems identified during that exercise, Washington developed, by March 1986, partitioned CGs. These CGs apportioned doses from each food group for an assumed mix of radionuclides expected to result from a reactor accident. This effort was therefore in place just in time for actual use during the Chernobyl fallout episode in May 1986. This technique was refined and described in a later report and presented at the 1987 annual meeting of the Health Physics Society. Realizing the technical weaknesses which still existed and a need to simplify the numbers for decision makers, Washington State has been developing computer methods to quickly calculate, from an accident specific relative mix of isotopes, CGs which allow a single radionuclide concentration for all food groups. This latest approach allows constant CGs for different periods of time following the accident, instead of peak CGs, which are good only for a short time after the

  16. Data, Meet Compute: NASA's Cumulus Ingest Architecture

    Science.gov (United States)

    Quinn, Patrick

    2018-01-01

    NASA's Earth Observing System Data and Information System (EOSDIS) houses nearly 30PBs of critical Earth Science data and with upcoming missions is expected to balloon to between 200PBs-300PBs over the next seven years. In addition to the massive increase in data collected, researchers and application developers want more and faster access - enabling complex visualizations, long time-series analysis, and cross dataset research without needing to copy and manage massive amounts of data locally. NASA has looked to the cloud to address these needs, building its Cumulus system to manage the ingest of diverse data in a wide variety of formats into the cloud. In this talk, we look at what Cumulus is from a high level and then take a deep dive into how it manages complexity and versioning associated with multiple AWS Lambda and ECS microservices communicating through AWS Step Functions across several disparate installations

  17. Endurance exercise after orange ingestion anaphylaxis

    Directory of Open Access Journals (Sweden)

    Manu Gupta

    2016-01-01

    Full Text Available Endurance exercise after orange ingestion cause anaphylaxis which is food-dependent exercise-induced anaphylaxis (FDEIA which is a form of exercise-induced anaphylaxis. In this article, an individual develops symptoms such as flushing, itching, urticaria, angioedema, and wheezing after eating a food allergen and proceeds to exercise. Neither the food alone nor exercise alone is sufficient to induce a reaction. This case report describes a 36-year-old asthmatic male athlete who experienced nausea, vomiting, flushing, urticaria, and facial swelling while exercising in a gymnasium after eating oranges. Neither oranges alone nor exercise alone induced the reaction. Total avoidance of suspected food allergens would be ideal. Persons with FDEIA should keep at hand an emergency kit with antihistamines, injectable rapid action corticoids, and adrenaline.

  18. Cancer risks from ingestion of radiostrontium

    Energy Technology Data Exchange (ETDEWEB)

    Raabe, O. G.

    2004-07-01

    Studies have been conducted of the lifetime effects in 403 beagles of the skeletal uptake in seven logarithmically increasing dosage groups of ingested Sr-90. The Sr-90 was fed during skeletal developmental from mid-gestation to adulthood at age 540 days resulting in lifetime protracted beta radiation exposure of the skeleton and some adjacent tissues. Statistical analysis of all types of cancer deaths in the 403 exposed beagles and in 162 unexposed controls indicated that deaths caused by five types of cancer were significantly elevated by high level exposure to Sr-90; these were (1) myeloid leukemia, (2) bone sarcoma, (3) squamous cell carcinoma of periodontal origin, (4) nasal carcinoma, and (5) oral carcinoma. Dose response analysis of these radiation-induced cancer deaths showed non-linear relationships with marked thresholds. A mean lifetime skeletal absorbed dose of 22.5 +/-5.7 Gy SD (22.5 +/-5.7 Sv SD) was associated with the lowest dosage group in which any radiation induced cancer deaths were observed. Three-dimensional models of the observed dose-rate/time/response relationships were fir with maximum likelihood regression methods to describe the risks of death associated with the different types of radiation-induced cancer. The models show that a life-time virtual threshold for cancer risk occurs because the time required to induce cancer is longer at lower radiation dose rates and may exceed the natural life span. Scaling these results to predict human cancer risks from ingestion of Sr-90 shows negligible risks for people whose lifetime cumulative skeletal dose is less than 10 Sv. (Author)

  19. Ingestion and transfer of microplastics in the planktonic food web

    International Nuclear Information System (INIS)

    Setälä, Outi; Fleming-Lehtinen, Vivi; Lehtiniemi, Maiju

    2014-01-01

    Experiments were carried out with different Baltic Sea zooplankton taxa to scan their potential to ingest plastics. Mysid shrimps, copepods, cladocerans, rotifers, polychaete larvae and ciliates were exposed to 10 μm fluorescent polystyrene microspheres. These experiments showed ingestion of microspheres in all taxa studied. The highest percentage of individuals with ingested spheres was found in pelagic polychaete larvae, Marenzelleria spp. Experiments with the copepod Eurytemora affinis and the mysid shrimp Neomysis integer showed egestion of microspheres within 12 h. Food web transfer experiments were done by offering zooplankton labelled with ingested microspheres to mysid shrimps. Microscopy observations of mysid intestine showed the presence of zooplankton prey and microspheres after 3 h incubation. This study shows for the first time the potential of plastic microparticle transfer via planktonic organisms from one trophic level (mesozooplankton) to a higher level (macrozooplankton). The impacts of plastic transfer and possible accumulation in the food web need further investigations. -- Highlights: • Experiments show the potential of ingestion of plastics by various zooplankton taxa. • This ingestion of plastics can be indirect via other zooplankton organisms. • There may be several alternate routes for microplastic transfer in the food webs. -- Experiments with zooplankton and microspheres showed ingestion of spheres by zpl and the transfer of ingested microspheres to higher trophic level organisms via labelled zooplankton

  20. Sharp foreign body ingestion by a young girl

    African Journals Online (AJOL)

    Riyadh Mohamad Hasan

    2017-06-09

    Jun 9, 2017 ... Sharp foreign body ingestion by a young girl. Riyadh Mohamad Hasan. University of Baghdad ... ray imaging and retrieved with the aid of C-arm fluoroscope at a laparotomy. Her postoperative period ... In our patient the foreign bodies were long sharp ones (sewing needles). Foreign body ingestion can be ...

  1. The anesthetic management of button battery ingestion in children.

    Science.gov (United States)

    Ing, Richard J; Hoagland, Monica; Mayes, Lena; Twite, Mark

    2018-03-01

    Injuries related to button battery ingestion are common in children. This review provides an outline of the epidemiology, pathophysiology, management, and anesthetic implications in children who have ingested a button battery. A literature search was conducted in the United States National Library of Medicine PubMed database using the terms "button battery ingestion" and "children' and "removal" and "surgery" and "anesthesia". Ninety-six articles published in English were found from 1983-2017, and 62 of these articles were incorporated into this review. Additionally, the Internet was searched with the terms "button battery ingestion and children" to identify further entities, organizations, and resources affiliated with button battery ingestion in children. These additional sources were studied and included in this review. Button batteries are ubiquitous in homes and electronic devices. Since 2006, larger-diameter and higher-voltage batteries have become available. These are more likely to become impacted in the esophagus after ingestion and lead to an increase in severe morbidity and mortality due to caustic tissue injury. Children at the highest risk for complications are those under six years of age who have ingested batteries > 20 mm in diameter and sustain prolonged esophageal impaction at the level of the aortic arch with the negative pole oriented anteriorly. Anesthesiologists need to know about the epidemiology, pathophysiology, complications, and anesthetic management of children who have ingested button batteries.

  2. Suicidal Ingestion of Potassium Permanganate Crystals: A Rare Encounter

    OpenAIRE

    Karthik, Ravikanti; Veerendranath, Hari Prasad Kanakapura; Wali, Siddraj; Mohan, Murali N T; Kumar, Praveen A. C.; Trimurty, Gaganam

    2014-01-01

    Potassium permanganate poisoning is not common. Although Symptoms of potassium permanganate ingestion are gastrointestinal and Complications due to ingestion of potassium permanganate include cardiovascular depression, hepatic and renal damage, upper airway obstruction, bleeding tendency and methemoglobinemia. Gastric damage due to potassium permanganate has rarely been reported previously. We are reporting a 34-year old female patient who presented to our Emergency Department after suicidal ...

  3. Ingestion of six cylindrical and four button batteries

    DEFF Research Database (Denmark)

    Nielsen, Simon U; Rasmussen, Morten; Hoegberg, Lotte C G

    2010-01-01

    We report a suicidal ingestion of six cylindrical and four button batteries, in combination with overdosed prescription medicine and smoking of cannabis.......We report a suicidal ingestion of six cylindrical and four button batteries, in combination with overdosed prescription medicine and smoking of cannabis....

  4. Pediatric magnet ingestions: the dark side of the force.

    Science.gov (United States)

    Brown, Julie C; Otjen, Jeffrey P; Drugas, George T

    2014-05-01

    Pediatric magnet ingestions are increasing. Commercial availability of rare-earth magnets poses a serious health risk. This study defines incidence, characteristics, and management of ingestions over time. Cases were identified by searching radiology reports from June 2002 to December 2012 at a children's hospital and verified by chart and imaging review. Relative risk (RR) regressions determined changes in incidence and interventions over time. In all, 98% of ingestions occurred since 2006; 57% involved multiple magnets. Median age was 8 years (range 0 to 18); 0% of single and 56% of multiple ingestions required intervention. Compared with 2007 to 2009, ingestions increased from 2010 to 2012 (RR = 1.9, 95% confidence interval 1.2 to 3.0). Intervention proportion was unchanged (RR = .94, 95% confidence interval .4 to 2.2). Small spherical magnets comprised 26.8% of ingestions since 2010; 86% involved multiple magnets and 47% required intervention. Pediatric magnet ingestions and interventions have increased. Multiple ingestions prompt more imaging and surgical interventions. Magnet safety standards are needed to decrease risk to children. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Esophageal perforation following foreign body ingestion in children ...

    African Journals Online (AJOL)

    Esophageal perforation following foreign body ingestion in children: report of three cases. O Abdelhadi, AE Ali, O Taha, A Abdalla, F Nugud. Abstract. We report three cases of foreign body esophagus, in two of them the foreign body was a coin, and the third child ingested a disc battery. In all three cases the foreign body ...

  6. Influence of Sensor Ingestion Timing on Consistency of Temperature Measures

    Science.gov (United States)

    2009-01-01

    volunteers orally ingested an ITS (VitalSense Jonah Ingestible Capsule ; Minimitter Inc.). From 1300 to 1700 h, volunteers per- formed structured...emptying and gastrointes- tinal transit. Clin Investig. 1992;70(6):487–91. 24. Rao SS, Welcher K, Zimmerman B, Stumbo P. Is coffee a colonic stimulant? Eur J

  7. Ingestible capsule for remote controlled release of a substance

    DEFF Research Database (Denmark)

    2014-01-01

    The application relates to an ingestible capsule (102) for delivery of a substance e.g. a pharmaceutical drug, to a human or animal. The ingestible capsule comprises a capsule wall structure (202) forming a substantially sealed reservoir or lumen holding the substance (204). An electrical resonance...

  8. Imaging pediatric magnet ingestion with surgical-pathological correlation

    International Nuclear Information System (INIS)

    Otjen, Jeffrey P.; Iyer, Ramesh S.; Rohrmann, Charles A.

    2013-01-01

    Foreign body ingestion is a common problem in the pediatric population and a frequent cause for emergency room visits. Magnets are common household objects that when ingested can bring about severe, possibly fatal gastrointestinal complications. Radiography is an integral component of the management of these children. Pediatric and emergency radiologists alike must be aware of imaging manifestations of magnet ingestion, as their identification drives decision-making for consulting surgeons and gastroenterologists. Radiology can thus substantially augment the clinical history and physical exam, facilitating appropriate management. This manuscript sequentially presents cases of magnet ingestion featuring imaging findings coupled with surgical and pathological correlation. Each case is presented to highlight ways in which the radiologist can make impactful contributions to diagnosis and management. Clinical overview with pitfalls of magnet ingestion imaging and an imaging decision tree will also be presented. (orig.)

  9. Imaging pediatric magnet ingestion with surgical-pathological correlation.

    Science.gov (United States)

    Otjen, Jeffrey P; Rohrmann, Charles A; Iyer, Ramesh S

    2013-07-01

    Foreign body ingestion is a common problem in the pediatric population and a frequent cause for emergency room visits. Magnets are common household objects that when ingested can bring about severe, possibly fatal gastrointestinal complications. Radiography is an integral component of the management of these children. Pediatric and emergency radiologists alike must be aware of imaging manifestations of magnet ingestion, as their identification drives decision-making for consulting surgeons and gastroenterologists. Radiology can thus substantially augment the clinical history and physical exam, facilitating appropriate management. This manuscript sequentially presents cases of magnet ingestion featuring imaging findings coupled with surgical and pathological correlation. Each case is presented to highlight ways in which the radiologist can make impactful contributions to diagnosis and management. Clinical overview with pitfalls of magnet ingestion imaging and an imaging decision tree will also be presented.

  10. Aging of microplastics promotes their ingestion by marine zooplankton.

    Science.gov (United States)

    Vroom, Renske J E; Koelmans, Albert A; Besseling, Ellen; Halsband, Claudia

    2017-12-01

    Microplastics (microplastics to test their impacts, while aging processes such as weathering and biofouling alter the characteristics of plastic particles in the marine environment. We investigated zooplankton ingestion of polystyrene beads (15 and 30 μm) and fragments (≤30 μm), and tested the hypothesis that microplastics previously exposed to marine conditions (aged) are ingested at higher rates than pristine microplastics. Polystyrene beads were aged by soaking in natural local seawater for three weeks. Three zooplankton taxa ingested microplastics, excluding the copepod Pseudocalanus spp., but the proportions of individuals ingesting plastic and the number of particles ingested were taxon and life stage specific and dependent on plastic size. All stages of Calanus finmarchicus ingested polystyrene fragments. Aged microbeads were preferred over pristine ones by females of Acartia longiremis as well as juvenile copepodites CV and adults of Calanus finmarchicus. The preference for aged microplastics may be attributed to the formation of a biofilm. Such a coating, made up of natural microbes, may contain similar prey as the copepods feed on in the water column and secrete chemical exudates that aid chemodetection and thus increase the attractiveness of the particles as food items. Much of the ingested plastic was, however, egested within a short time period (2-4 h) and the survival of adult Calanus females was not affected in an 11-day exposure. Negative effects of microplastics ingestion were thus limited. Our findings emphasize, however, that aging plays an important role in the transformation of microplastics at sea and ingestion by grazers, and should thus be considered in future microplastics ingestion studies and estimates of microplastics transfer into the marine food web. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Safety evaluation on irradiated food ingestion

    International Nuclear Information System (INIS)

    1986-01-01

    This paper reports double-blind observations of volunteers who took 35 kinds of irradiated foods as their main diet for 90 days. The subjects consisted of 70 medical students and 8 staff members in the Shanghai Medical University. They were randomly divided into two groups. One group was supplied with irradiated foods, the other acted as controls eating the same food but non-irradiated. The 35 kinds of irradiated foods were grain, meat products, vegetables, fruits, dried fruits etc. The absorbed dose of irradiation from the processed foods varied from 0.1 to 8.0 kGy. The irradiated foods made up 60.3% of the total food intake by weight. Observations during 90 days indicated that the subjects were all pleased with their diets and no adverse effects on their health were seen. Clinical and laboratory examinations included routine blood and urine tests, blood biochemical examinations, hepatic and renal function tests, endocrinological assays, cellular immunity tests, and mutagenetic studies (such as the incidence of polyploid cells, chromosomal structural aberration, rates of sister chromatid-exchanges, micronuclei test, urine Ames' test). These studies showed that the ingestion of these foods are safe for humans

  12. Radiographic identification of ingested disc batteries

    International Nuclear Information System (INIS)

    Maves, M.D.

    1986-01-01

    Recently, the hazards by posed the accidental ingestion and impaction of small disc batteries have been widely publicized in the medical and lay press. These foreign bodies, when lodged in the esophagus, leak a caustic solution of 26 to 45% sodium or potassium hydroxide which can cause a burn injury to the esophagus in a very short period of time. Because of the considerable clinical morbidity and mortality from this foreign body, it becomes imperative for the radiologist to quickly and accurately identify disc batteries on plain radiographs. This communication offers a series of radiologic signs important in the identification of disc batteries demonstrate a double density shadow due to the bilaminar structure of the battery. On lateral view, the edges of most disc batteries are round and again present a step-off at the junction of the cathode and anode. These findings are differentiated from the more common esophageal foreign body of a coin which does not have a double density on frontal projection, has a much sharper edge and no visible stepoff. (orig.)

  13. Ingestion of microplastics by commercial fish off the Portuguese coast.

    Science.gov (United States)

    Neves, Diogo; Sobral, Paula; Ferreira, Joana Lia; Pereira, Tânia

    2015-12-15

    The digestive tract contents of 263 individuals from 26 species of commercial fish were examined for microplastics. These were found in 17 species, corresponding to 19.8% of the fish of which 32.7% had ingested more than one microplastic. Of all the fish that ingested microplastics, 63.5% was benthic and 36.5% pelagic species. A total of 73 microplastics were recorded, 48 (65.8%) being fibres and 25 (34.2%) being fragments. Polymers were polypropylene, polyethylene, alkyd resin, rayon, polyester, nylon and acrylic. The mean of ingested microplastics was 0.27 ± 0.63 per fish, (n=263). Pelagic fish ingested more particles and benthic fish ingested more fibres, but no significant differences were found. Fish with the highest number of microplastics were from the mouth of the Tagus river. Scomber japonicus registered the highest mean of ingested microplastics, suggesting its potential as indicator species to monitor and investigate trends in ingested litter, in the MSFD marine regions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Surgical management and morbidity of pediatric magnet ingestions.

    Science.gov (United States)

    Waters, Alicia M; Teitelbaum, Daniel H; Thorne, Vivian; Bousvaros, Athos; Noel, R Adam; Beierle, Elizabeth A

    2015-11-01

    Foreign body ingestion remains a common reason for emergency room visits and operative interventions in the pediatric population. Rare earth magnet ingestion represents a low percentage of all foreign bodies swallowed by children; however, magnets swallowed in multiplicity can result in severe injuries. Pediatric surgeons with membership in the Surgical Section of the American Academy of Pediatrics were surveyed to determine the magnitude and consequences of magnet ingestions in the pediatric population. About 100 (16%) participant responses reported on 99 magnet ingestions. The median age at ingestion was 3.7 y, and the majority of ingestions (71%) occurred after year 2010. Thirty-two children underwent endoscopy with successful removal in 70% of cases, and multiple magnets were found in 65% of these patients. Seventy-three children required either laparotomy (51) or laparoscopy (22) for magnet removal, and 90% of these children were discovered to have ingested more than one magnet. In addition, 17% of the children were found to have at least one perforation or fistula, and 34% of the children had multiple perforations or fistulae. Nine children required long-term care for their injuries including repeat endoscopies. One child died after hemorrhage from an esophago-aortic fistula. These results demonstrated the increasing need for magnet regulations and public awareness to prevent potentially serious complications. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Serious complications after button battery ingestion in children.

    Science.gov (United States)

    Krom, Hilde; Visser, Margot; Hulst, Jessie M; Wolters, Victorien M; Van den Neucker, Anita M; de Meij, Tim; van der Doef, Hubert P J; Norbruis, Obbe F; Benninga, Marc A; Smit, Margot J M; Kindermann, Angelika

    2018-05-02

    Serious and fatal complications after button battery ingestion are increasing worldwide. The aim of this study is to describe serious complications after battery ingestion in children in the Netherlands.All pediatric gastroenterologists in the Netherlands performing upper endoscopies were asked to report all serious complications after battery ingestion in children (0-18 years) between 2008 and 2016 retrospectively.Sixteen serious complications were reported: death after massive bleeding through esophageal-aortal fistula (n = 1), esophageal-tracheal fistula (n = 5), stenosis after (suspected) perforation and mediastinitis (n = 5), (suspected) perforation and mediastinitis (n = 3), vocal cord paralysis (n = 1), and required reintubation for dyspnea and stridor (n = 1). The median time interval between ingestion and presentation was 5 (IQR 2-258) h. All children were ≤ 5 (median 1.4; IQR 0.9-2.1) years. Vomiting (31.3%), swallowing/feeding problems (31.3%), and fever (31.3%) were the most common presenting symptoms; however, 18.8% of the patients were asymptomatic (n = 1 missing). All batteries were button batteries (75% ≥ 20 mm; 18.8% batteries were removed by esophagogastroduodenoscopy (50%) and rigid endoscopy (37.5%) or surgically (12.5%). Sixteen serious complications occurred after small and large button batteries ingestion between 2008 and 2016 in both symptomatic and asymptomatic children in the Netherlands. Therefore, immediate intervention after (suspected) button battery ingestion is required. What is Known: • Button battery ingestion may result in serious and fatal complications. • Serious and fatal complications after button battery ingestion are increasing worldwide. What is New: • Sixteen serious complications after button battery ingestion occurred during 2008-2016 in children in the Netherlands. • Serious complications were also caused by small batteries (< 20 mm) in the Netherlands and also occurred

  16. Gastric Perforation and Phlegmon Formation by Foreign Body Ingestion

    Directory of Open Access Journals (Sweden)

    Albert Alejandro Avila Alvarez

    2014-08-01

    Full Text Available This is a case report of foreign body ingestion in a suicide attempt resulting in gastric perforation and phlegmon formation during a subsequent 6 month period that eventually required surgical intervention. The patient had a prolonged course because she did not report a history of foreign body ingestion and the initial evaluating physicians had no suspicion about possible foreign body ingestion and may have missed important findings on physical examination. Gastric perforation by a foreign object  may have a slow course rather than presenting acute abdomen. The realization of a proper physical examination in the emergency department is key to an accurate diagnosis.

  17. The ingestion of plutonium and americium by range cattle

    International Nuclear Information System (INIS)

    Blincoe, C.; Bohman, V.R.; Smith, D.D.

    1981-01-01

    The intake of plutonium and americium in the diet of cattle grazing on plutonium contaminated desert range was determined. Daily feed intake of the grazing animals was also determined so that the amount of nuclides ingested daily could be ascertained. Soil ingested by range cattle constituted the principal and possibly only source of ingested plutonium and americium and resulted in a daily intake of 3600-6600 pCi 238 Pu, 85,000-400,000 pCi 239 Pu, and 11,000-31,000 pCi 241 Am daily. Determining transuranic intake by direct measurement and from the composition and contamination of the diet gave identical results. (author)

  18. Oxycodone Ingestion Patterns in Acute Fracture Pain With Digital Pills.

    Science.gov (United States)

    Chai, Peter R; Carreiro, Stephanie; Innes, Brendan J; Chapman, Brittany; Schreiber, Kristin L; Edwards, Robert R; Carrico, Adam W; Boyer, Edward W

    2017-12-01

    Opioid analgesics are commonly prescribed on an as-needed (PRN) basis for acute painful conditions. Uncertainty of how patients actually take PRN opioids, coupled with a desire to completely cover pain, leads to variable and overly generous opioid prescribing practices, resulting in a surplus of opioids. This opioid surplus becomes a source for diversion and nonmedical opioid use. Understanding patterns of actual opioid ingestion after acute painful conditions can help clinicians counsel patients on safe opioid use, and allow timely recognition and intervention when escalating opioid self-dosing occurs, to prevent tolerance and addiction. We used a novel oxycodone digital pill system (ingestible biosensor within a standard gelatin capsule combined with 5-mg oxycodone) that when ingested, is activated by the chloride ion gradient in the stomach thereby emitting a radiofrequency signal captured by a wearable reader. The reader relays ingestion data to a cloud-based server that displays ingestion events to the study team. We deployed the oxycodone digital pill among opioid-naive individuals discharged from the emergency department with acute fracture pain. Participants were trained on digital pill operation and discharged with twenty-one 5-mg oxycodone digital pills. They were instructed to take digital pills PRN for pain on discharge. We conducted a brief interview 7 days after study enrollment, at which point participants returned the digital pill system. We identified oxycodone ingestion events in real time by data from the digital pill system and performed pill counts at the return visit to validate digital pill reporting of medication ingestion. In this study, 26 individuals were approached; 16 enrolled with 15 completing the study. Participants ingested a median of 6 (3-9.5) oxycodone digital pills over the course of 7 days, with 82% of the oxycodone dose ingested in the first 3 days. In individuals who required operative repair, 86% (N = 6) continued to ingest

  19. The relative importance of ingestion for multiple pathway dose assessments

    International Nuclear Information System (INIS)

    Wicker, W.; Grogan, H.; Bergstroem, U.; Hoffman, O.

    1991-01-01

    The general purpose of this report is to examine the relative importance of ingestion pathways, and particularly food chain transport in overall dose assessment. The importance of ingestion pathways is examined for various release scenarios and radionuclides because the findings are expected to differ with circumstances. The degree to which contaminated food products contribute to the total dose will affect the importance of accuracy and uncertainty of food chain model predictions, which is the main thrust of the Biospheric Model Validation Study (BIOMOVS). This analysis requires that all modes of radiation exposure be examined, including inhalation, external exposure, and the various ingestion pathways. (2 figs., 2 tabs.)

  20. The ingestion pathway comments and issues

    International Nuclear Information System (INIS)

    McDonnell, Lawrence J.

    1989-01-01

    Full text: The Ingestion Pathway and its recent emphasis on planning for nuclear power plant emergencies has created activity at all levels of government. Federal Emergency Management Agency (FEMA) guidelines have been developed and there has been an urgency placed on implementing these guides and planning standards at all levels of government. This global approach has led to confusion and in some cases rapid development of public brochures at the state level. These brochures are meant to educate the public in the need for protective action in the ingestion pathway. Some forethought on the planning process and the integration of the protective action guidelines seems in order. Some issues that should be addressed are listed below: Suggested consideration of issues to facilitate the planning process: - Review existing technical specifications of nuclear power plants requiring environmental monitoring. This should provide at least the baseline sampling of food products for site specific plants; - Review state monitoring/analysis of sampling programs and NRC contracts to states for radiological monitoring of nuclear power facilities; - Encourage each state to involve food producers at an early date in the planning development. Such producer associations as the Daily Associations, Marketing Boards, and Cooperatives are valuable resources in implementing plans because they represent the affected economic impacted parties; - Involve and educate the agricultural extension agencies in the planning process so they can inform the public through their usual points of contact; - Set up principle agency responsibilities in existing state specific framework. For example, the farm or food producers normally are familiar with their extension agents. Use this relationship to help the affected producers understand the protective actions that will be implemented in case of severe nuclear power plant accidents; - Recognize that the disaster services agencies are lead agencies for

  1. Sodium bicarbonate ingestion and boxing performance.

    Science.gov (United States)

    Siegler, Jason C; Hirscher, Kristian

    2010-01-01

    Boxing is a sport that consists of multiple high-intensity bouts separated by minimal recovery time and may benefit from a pre-exercise alkalotic state. The purpose of this study was to observe the ergogenic potential of sodium bicarbonate (NaHCO3) ingestion on boxing performance. Ten amateur boxers volunteered to participate in 2 competitive sparring bouts. The boxers were prematched for weight and boxing ability and consumed either 0.3 g.kg(-1) body weight (BW) of NaHCO3 (BICARB) or 0.045 g.kg(-1) BW of NaCl placebo (PLAC) mixed in diluted low calorie-flavored cordial. The sparring bouts consisted of four 3-minute rounds, each separated by 1-minute seated recovery. Blood acid-base (pH, bicarbonate [HCO3(-)], base excess [BE]), and performance (rates of perceived exertion [RPE], heart rate [HR] [HR(ave) and HR(max)], total punches landed successfully) profiles were analyzed before (where applicable) and after sparring. The results indicated a significant interaction effect for HCO3(-) (p < or = 0.001) and BE (p < 0.001), but not for pH (p = 0.48). Post hoc analysis revealed higher presparring HCO3(-) and BE for the BICARB condition, but no differences between the BICARB and PLAC conditions postsparring. There was a significant increase in punches landed during the BICARB condition (p < 0.001); however, no significant interaction effects for HRave (p = 0.15), HRmax (p = 0.32), or RPE (p = 0.38). The metabolic alkalosis induced by the NaHCO3 loading elevated before and after sparring blood buffering capacity. In practical application, the findings suggest that a standard NaHCO3 loading dose (0.3 g.kg(-1)) improves punch efficacy during 4 rounds of sparring performance.

  2. Contribution of inhalation by food animals to man's ingestion dose

    International Nuclear Information System (INIS)

    Zach, R.

    1985-01-01

    Animals' inhalation (AI) pathway was evaluated for 57 radionuclides using infant dose predictions from the food-chain model LIMCAL. With ingestion transfer coefficients fMi to define transfer from the respiratory tract to milk, the AI pathway appeared to be insignificant compared to animals' plant ingestion, as implicitly assumed in most environmental assessment models for nuclear installations. Using ICRP Publication 30 respiratory clearance models for man to adjust ingestion transfer coefficients, animals' inhalation appeared to be important, particularly for some actinide radionuclides. The AI pathway also appeared to be significant relative to man's inhalation, especially for infants. The importance of the AI pathway varied greatly between radionuclides, and results strongly suggest that it cannot be ignored in environmental assessments. Until better data become available to implement this pathway fully, adjusted ingestion transfer coefficient values can be used for transfer from animals' respiratory tract to milk and other food products

  3. Cow Dung Ingestion and Inhalation Dependence: A Case Report

    Science.gov (United States)

    Khairkar, Praveen; Tiple, Prashant; Bang, Govind

    2009-01-01

    Although abuse of several unusual inhalants had been documented, addiction to cow dung fumes or their ashes has not been reported in medical literature as yet. We are reporting a case of cow dung dependence in ingestion and inhalational form.

  4. Linking plastic ingestion research with marine wildlife conservation.

    Science.gov (United States)

    Avery-Gomm, Stephanie; Borrelle, Stephanie B; Provencher, Jennifer F

    2018-05-16

    Plastic is an increasingly pervasive marine pollutant. Concomitantly, the number of studies documenting plastic ingestion in wildlife is accelerating. Many of these studies aim to provide a baseline against which future levels of plastic ingestion can be compared, and are motivated by an underlying interest in the conservation of their study species and ecosystems. Although this research has helped to raise the profile of plastic as a pollutant of emerging concern, there is a disconnect between research examining plastic pollution and wildlife conservation. We present ideas to further discussion about how plastic ingestion research could benefit wildlife conservation by prioritising studies that elucidates the significance of plastic pollution as a population-level threat, identifies vulnerable populations, and evaluates strategies for mitigating impacts. The benefit of plastic ingestion research to marine wildlife can be improved by establishing a clearer understanding of how discoveries will be integrated into conservation and policy actions. Copyright © 2018. Published by Elsevier B.V.

  5. Ocular Dynamics of Bolus Ingestion of Eleis guineensis Sap (Palm ...

    African Journals Online (AJOL)

    Elaeis guineensis), and is widely consumed among the various ethnic nationalities in Nigeria. The effect of bolus ingestion of 600ml, palm wine was undertaken so as to determine its ocular dynamics in healthy volunteers. Results showed that ...

  6. The Report of Suicide by Ingestion of Lidocaine Topical Spray

    Directory of Open Access Journals (Sweden)

    Hossein Hassanian-Moghaddam

    2014-09-01

    Full Text Available Background: Lidocaine is a local anesthetic and antiarrhythmic agent. There are reports on accidental and intentional cases of poisoning following injection of lidocaine while rare are the fatal cases realized after oral ingestion of lidocaine. Suicidal poisoning with lidocaine pharmaceutical formulations is rare since no pharmaceutical dosage forms for oral use are available except gels and sprays used as local anesthetics in dentistry. Cases: Three cases of suicidal poisoning by ingestion of the content of lidocaine topical spray are reported in the present study. The cases developed episodes of seizure requiring diazepam and other therapeutic modalities upon admission. Eventually, one of the cases expired. Conclusion: To the best of our knowledge, this study is the first reported case of suicidal poisoning after ingestion of this formulation which highlights the fact that lidocaine topical spray formulation may be used for committing suicide. Ingestion of lidocaine present in topical spray can induce varying levels of toxicity that can even be fatal.

  7. Predictors of Recurrent Ingestion of Gastrointestinal Foreign Bodies

    Directory of Open Access Journals (Sweden)

    Ian C Grimes

    2013-01-01

    Full Text Available BACKGROUND: Gastrointestinal foreign bodies are commonly encountered; however, little knowledge exists as to the causes of foreign body ingestions and why they occur repeatedly in some patients.

  8. Rare-earth magnet ingestion: a childhood danger reaches adolescence.

    Science.gov (United States)

    Agha, Beesan Shalabi; Sturm, Jesse J; Costello, Brian E

    2013-10-01

    Ingestion of multiple magnets may cause serious gastrointestinal morbidity, such as pressure necrosis, perforation, fistula formation, or intestinal obstruction due to forceful attraction across bowel wall. Although the consequences of multiple magnet ingestion are well documented in young children, the current popularity of small, powerful rare-earth magnets marketed as "desk toys" has heightened this safety concern in all pediatric age groups. A recent US Consumer Product Safety Commission product-wide warning additionally reports the adolescent practice of using toy high-powered, ball-bearing magnets to simulate tongue and lip piercings, a behavior that may increase risk of inadvertent ingestion. We describe 2 cases of older children (male; aged 10 and 13 years, respectively) with unintentional ingestion of multiple rare-earth magnets. Health care providers should be alerted to the potential for misuse of these high-powered, ball-bearing magnets among older children and adolescents.

  9. Post-exercise ingestion of a carbohydrate and casein hydrolysate ...

    African Journals Online (AJOL)

    an isocaloric carbohydrate and protein supplement and ingested the assigned ..... week, and day showed that the 4-way interaction with “condition” ..... on markers of muscle recovery following soccer training: a randomized cross-over study.

  10. Ingested metallic foreign body lodged in the appendix

    Directory of Open Access Journals (Sweden)

    R R Sarkar

    2011-01-01

    Full Text Available An 8-year-old child ingested a metallic screw 3 months prior to admission. At laparotomy, the foreign body was found to be lodged inside the vermiform appendix, and was removed by appendicectomy.

  11. Influence of Sensor Ingestion Timing on Consistency of Temperature Measures

    National Research Council Canada - National Science Library

    Goodman, Daniel A; Kenefick, Robert W; Cadarette, Bruce S; Cheuvront, Samuel N

    2009-01-01

    ... (ITS) to measure core body temperature have been demonstrated. However, the effect of elapsed time between ITS ingestion and Tint measurement has not been thoroughly studied. Methods: Eight volunteers...

  12. Building scalable digital library ingestion pipelines using microservices

    OpenAIRE

    Cancellieri, Matteo; Pontika, Nancy; Pearce, Samuel; Anastasiou, Lucas; Knoth, Petr

    2017-01-01

    CORE, a harvesting service offering access to millions of open access research papers from around the world, has shifted its harvesting process from following a monolithic approach to the adoption of a microservices infrastructure. In this paper, we explain how we rearranged and re-scheduled our old ingestion pipeline, present CORE's move to managing microservices and outline the tools we use in a new and optimised ingestion system. In addition, we discuss the ineffciencies of our old harvest...

  13. Food control concept: Food safety/ingestion issues

    International Nuclear Information System (INIS)

    Armstrong, B.

    1995-01-01

    This talk outlines the issues in food safety/ingestion in the case of radiation accidents at nuclear power plants and how emergency preparedness plans can/should be tailored. The major topics are as follows: In Washington: food safety/ingestion issues exist at transition between response and regulatory worlds; agricultural concerns; customer concerns; Three Mile Island: detailed maps; development of response procedures; development of tools; legal issues

  14. Clinical evaluation of disc battery ingestion in children.

    Science.gov (United States)

    Mirshemirani, AliReza; Khaleghnejad-Tabari, Ahmad; Kouranloo, Jaefar; Sadeghian, Naser; Rouzrokh, Mohsen; Roshanzamir, Fatolah; Razavi, Sajad; Sayary, Ali Akbar; Imanzadeh, Farid

    2012-04-01

    BACKGROUND The purpose of this study was to evaluate the characteristics, management, and outcomes of disc battery ingestion in children. METHODS We reviewed the medical records of children admitted to Mofid Children's Hospital due to disc battery ingestion from January 2006 to January 2010. Clear history, clinical symptoms and results of imaging studies revealed diagnosis of disc battery ingestion in suspected patients. The clinical data reviewed included age, gender, clinical manifestation, radiologic findings, location of disc battery, duration of ingestion, endoscopic results and surgical treatment. RESULTS We found 22 cases (11 males and 11 females) of disc battery ingestion with a mean age of 4.3 years (range: 9 months to 12 years). Common symptoms were vomiting, cough, dysphagia, and dyspnea. The mean duration of ingestion was 2.7 days (4 hours to 1.5 months). A total of 19 patients had histories of disc battery ingestion, but three cases referred with the above symptoms, and the batteries were accidentally found by x-ray. Only three cases had batteries impacted in the esophagus. Twelve batteries were removed endoscopically, 6 batteries spontaneously passed through the gastrointestinal (GI) tract within 5 to 7 days, and 4 patients underwent surgery due to complications: 3 due to tracheo-esophageal fistula (TEF) and 1 due to intestinal perforation. There was no mortality in our study. CONCLUSION Most cases of disc battery ingestion run uneventful courses, but some may be complicated. If the battery lodges in the esophagus, emergency endoscopic management is necessary. However, once in the stomach, it will usually pass through the GI tract.

  15. Acute abdomen caused by ingested chicken wishbone: a case report

    OpenAIRE

    Hoxha, Faton T; Hashani, Shemsedin I; Komoni, Driton S; Gashi-Luci, Lumturije H; Kurshumliu, Fisnik I; Hashimi, Medita SH; Krasniqi, Avdyl S

    2009-01-01

    Introduction An ingested foreign body often passes the gastrointestinal tract without any complications. Foreign bodies, such as dentures, fish bones, chicken bones, and toothpicks, have been known to cause perforation of the GI tract. Case presentation We are presenting a case of a fifty-year-old male with acute abdomen; diffuse fibro purulent peritonitis, i.e. ileum perforation, caused by accidentally ingesting a chicken wishbone. He was treated surgically with ileum resection, and temporar...

  16. Heartburn and regurgitation in pregnancy: the effect of fat ingestion.

    Science.gov (United States)

    Dall'Alba, Valesca; Fornari, Fernando; Krahe, Cláudio; Callegari-Jacques, Sidia Maria; Silva de Barros, Sérgio Gabriel

    2010-06-01

    Reflux symptoms are common in pregnancy, but their association with fat ingestion is unclear. To investigate an association of dietary fats with heartburn and regurgitation in pregnancy. This is a prospective study in which 89 pregnant women (gestational age 34 +/- 4 weeks) attending a low-risk prenatal outpatient clinic were asked to provide information on the frequency they experienced heartburn and regurgitation. Fat ingestion was estimated by means of a 24-h diet record. Symptomatic patients were compared with those with no reflux symptoms (n = 20). Heartburn once a week or more often occurred in 56 of the 89 patients (63%). The ingested amount of polyunsaturated fatty acids was higher in patients with heartburn (11.2 +/- 6.4 vs. 7.7 +/- 3.5 mg; P = 0.022) than in controls after adjusting for age, gain weight during pregnancy, ingestion of caffeine and vitamin C, and total energetic intake. The ingestion of monounsaturated fatty acids was higher in patients with heartburn, but with a borderline statistical significance (16.1 +/- 11 vs. 11.8 +/- 6.5 mg; P = 0.061). No association was observed between the consumption of fats and regurgitation. This study suggests that heartburn in the third trimester of pregnancy is associated with the ingestion of polyunsaturated fatty acids.

  17. Ingested razor blades within the appendix: A rare case report

    Directory of Open Access Journals (Sweden)

    Jason Cui

    Full Text Available Introduction: Foreign body ingestion is a common clinical presentation with less than 1% of the cases requiring surgical intervention. In this report, we present a rare case of razor blades lodged in the appendix as a result of intentional ingestion. Presentation of case: A 25 year old male prisoner presented to our hospital with persistent right iliac fossa pain after razor blade ingestion. After 5 days of conservative management, there was no sign of transition on serial X-Rays. Laparoscopy with intraoperative image intensification confirmed the presence of the razor blades in the appendix and appendicectomy was subsequently performed without complications. Discussion: Most ingested objected with diameter less than 2.5 cm and length less than 6 cm can pass through the gastrointestinal tract spontaneously in less than one week. The entry of foreign objects into the appendix is thought to be due to relative low motility of the caecum, the dependent position of the appendix and the size of the appendiceal orifice. Radiographic localisation to the appendiceal lumen was complicated by metallic artefact, but was consistent with failure to transit. Appendicectomy was felt to be the safest mode of retrieval. Conclusion: Ingested foreign body lodged in the appendix is a rare event. Once the exact location is confirmed, a simple laparoscopic appendicectomy can be performed to facilitate the removal. Keywords: Appendicitis, Laparoscopy, Appendicectomy, Foreign body ingestion, Razor blades, Case report

  18. Energy intake and obesity: ingestive frequency outweighs portion size.

    Science.gov (United States)

    Mattes, Richard

    2014-07-01

    Energy intake is a function of the quantity of energy consumed per ingestive event and the number of these events. The marked increase of energy intake and body weight over the past 35 years indicates that there has been poor precision in the reciprocity of these two facets of intake. With recent study of the associations between gut "satiation" peptides and energy intake, there has been an emphasis on the contribution of portion size to positive energy balance. However, this orientation may not appropriately weight the contribution of ingestive frequency. Gut peptides are not purely satiation factors and metabolic and environmental cues may more strongly guide the onset and number of ingestive events. Evidence is presented that while both portion size and ingestive frequency have increased in the population, the latter may be more problematic for weight gain. The magnitude and time course of increments in ingestive frequency map better onto energy intake and BMI trends than changes of portion size. This may occur, in part, because dietary compensation and thermogenic effects are weaker for increases in ingestive frequency than portion size. Though not to the exclusion of consideration of portion size effects, improved weight management may be achieved with greater attention to the drivers of eating and drinking frequency. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. [Adaptation of food ingestion to energy expenditure].

    Science.gov (United States)

    Louis-Sylvestre, J

    1987-01-01

    Body energy balance is regulated in adults. The accuracy of the phenomenon is particularly evident in laboratory animals under steady conditions. Moreover, it has been repeatedly demonstrated that this balance is maintained in spite of fluctuations in food intake or energy expenditure. When animals such as rats, dogs or rabbits are presented with a diluted or concentrated version of familiar food, they compensate rapidly by increasing or decreasing their ponderal intake. This is achieved first by a change in meal frequency, then meal size adapts to the new caloric content and meal frequency returns to the original pattern. This adaptation is based on the learning of post-ingestive cues. Hypo or hyperphagia leads to reduced or increased energy expenditure, as the case may be; the basal metabolic rate is modulated by thyroid hormones and diet-induced thermogenesis by the sympathetic system. These variations are partly regulatory. In a cold environment, the increase in energy expenditure caused by increased thermogenesis is rapidly compensated by increased caloric intake. Physical activity activates the sympathetic system responsible for numerous hormonal changes, the most important of which is insulin hyposecretion. In animals or humans, moderate aerobic exercise induces a small weight loss; afterwards, weight gain is normalized and increased caloric intake compensates for energy expenditures such as exercise, increased basal metabolic rate and diet-induced thermogenesis. Extreme changes in body weight and fat are produced by gestation and lactation; they are satisfactorily explained by concomitant hormonal changes. Especially during lactation, food intake is regulated so that it allows body weight to return to pregestation level. Studies on the mechanisms implicated in the regulation of body energy balance are still in progress. Friedman and Ramirez (1985) suggest that the way fatty acids are utilized is important. Kasser et al. (1985) show a striking difference in

  20. Bilayer tablets of Paliperidone for Extended release osmotic drug delivery

    Science.gov (United States)

    Chowdary, K. Sunil; Napoleon, A. A.

    2017-11-01

    The purpose of this study is to develop and optimize the formulation of paliperidone bilayer tablet core and coating which should meet in vitro performance of trilayered Innovator sample Invega. Optimization of core formulations prepared by different ratio of polyox grades and optimization of coating of (i) sub-coating build-up with hydroxy ethyl cellulose (HEC) and (ii).enteric coating build-up with cellulose acetate (CA). Some important influence factors such as different core tablet compositions and different coating solution ingredients involved in the formulation procedure were investigated. The optimization of formulation and process was conducted by comparing different in vitro release behaviours of Paliperidone. In vitro dissolution studies of Innovator sample (Invega) with formulations of different release rate which ever close release pattern during the whole 24 h test is finalized.

  1. Formulation of Extended-Release Metformin Hydrochloride Matrix ...

    African Journals Online (AJOL)

    Erah

    ... of diclofenac sodium by non-solvent addition technique. Trop J Pharm. Res 2010; 9(2): 187-195. 17. Hadjiioannou TP, Christian GD, Koupparis MA,. Macheras PE. Quantitative Calculations in. Pharmaceutical Practice and Research, VCH. Publishers Inc, New York: 1993; p 345-348. 18. Bourne DWA. Pharmacokinetics.

  2. Extended-release hydrocodone – gift or curse?

    Directory of Open Access Journals (Sweden)

    Krashin D

    2013-01-01

    Full Text Available Daniel Krashin,1 Natalia Murinova,2 Andrea M Trescot31Department of Anesthesiology and Pain Medicine, 2Department of Neurology University of Washington, Seattle, WA, USA 3Algone Pain Center, Wasilla, AK, USAAbstract: Hydrocodone is a semisynthetic opioid, which has been used for decades as a short-acting analgesic combined with acetaminophen (or less commonly ibuprofen. Several long-acting, non-acetaminophen-containing hydrocodone formulations are undergoing trials in the US under the auspices of the US Food and Drug Administration, and may be available shortly. This article reviews some of the advantages (including drug familiarity and lack of acetaminophen toxicity and potential disadvantages (including altered use patterns and high morphine equivalent dosing of such a medication formulation. We also discuss the abuse potential of long-acting versus short-acting opioids in general and hydrocodone specifically, as well as the metabolism of hydrocodone.Keywords: hydrocodone, long-acting opioids, opioid abuse, acetaminophen toxicity, tamper-resistant opioids

  3. Locomotor therapy with extended-release crystalline glucocorticoids

    Directory of Open Access Journals (Sweden)

    Vladimir Vasilyevich Badokin

    2013-01-01

    Full Text Available Topical glucocorticoid (GC therapy for locomotor diseases is an extremely important component of a comprehensive program to treat inflammatory and, to a lesser extent, degenerative diseases. It reduces the time of hospitalization by 5—10 days in this category of patients, has a prompt and potent anti-inflammatory effect, and shows predictable efficiency. This therapy shows good tolerability and high safety and prevents serious adverse reactions to GC treatment.

  4. Development of extended-release formulation of domperidone using ...

    African Journals Online (AJOL)

    Raphia hookeri (Family: Palmae) is the largest palm in ... previous work of Majekodunmi and Makper [7]. All other ... individually using an analytical balance (Mettler, .... Also, the retention of all the ... assessed to ensure acceptable mechanical.

  5. Formulation of Extended-Release Metformin Hydrochloride Matrix ...

    African Journals Online (AJOL)

    Methods: Various metformin hydrochloride formulations containing a hydrophobic carrier (stearic acid) and a hydrophilic polymer (polyethylene oxide) were prepared using a 32 factorial design. ... The release data were subjected to various release kinetic models and also compared with those of a commercial brand.

  6. Global Analysis of Anthropogenic Debris Ingestion by Sea Turtles

    Science.gov (United States)

    Schuyler, Qamar; Hardesty, Britta Denise; Wilcox, Chris; Townsend, Kathy

    2014-01-01

    Ingestion of marine debris can have lethal and sublethal effects on sea turtles and other wildlife. Although researchers have reported on ingestion of anthropogenic debris by marine turtles and implied incidences of debris ingestion have increased over time, there has not been a global synthesis of the phenomenon since 1985. Thus, we analyzed 37 studies published from 1985 to 2012 that report on data collected from before 1900 through 2011. Specifically, we investigated whether ingestion prevalence has changed over time, what types of debris are most commonly ingested, the geographic distribution of debris ingestion by marine turtles relative to global debris distribution, and which species and life-history stages are most likely to ingest debris. The probability of green (Chelonia mydas) and leatherback turtles (Dermochelys coriacea) ingesting debris increased significantly over time, and plastic was the most commonly ingested debris. Turtles in nearly all regions studied ingest debris, but the probability of ingestion was not related to modeled debris densities. Furthermore, smaller, oceanic-stage turtles were more likely to ingest debris than coastal foragers, whereas carnivorous species were less likely to ingest debris than herbivores or gelatinovores. Our results indicate oceanic leatherback turtles and green turtles are at the greatest risk of both lethal and sublethal effects from ingested marine debris. To reduce this risk, anthropogenic debris must be managed at a global level. Análisis Global de la Ingesta de Residuos Antropogénicos por Tortugas Marinas La ingesta de residuos marinos puede tener efectos letales y subletales sobre las tortugas marinas y otros animales. Aunque hay investigadores que han reportado la ingesta de residuos antropogénicos por tortugas marinas y la incidencia de la ingesta de residuos ha incrementado con el tiempo, no ha habido una síntesis global del fenómeno desde 1985. Por esto analizamos 37 estudios publicados, desde

  7. Microplastic ingestion in fish larvae in the western English Channel.

    Science.gov (United States)

    Steer, Madeleine; Cole, Matthew; Thompson, Richard C; Lindeque, Penelope K

    2017-07-01

    Microplastics have been documented in marine environments worldwide, where they pose a potential risk to biota. Environmental interactions between microplastics and lower trophic organisms are poorly understood. Coastal shelf seas are rich in productivity but also experience high levels of microplastic pollution. In these habitats, fish have an important ecological and economic role. In their early life stages, planktonic fish larvae are vulnerable to pollution, environmental stress and predation. Here we assess the occurrence of microplastic ingestion in wild fish larvae. Fish larvae and water samples were taken across three sites (10, 19 and 35 km from shore) in the western English Channel from April to June 2016. We identified 2.9% of fish larvae (n = 347) had ingested microplastics, of which 66% were blue fibres; ingested microfibers closely resembled those identified within water samples. With distance from the coast, larval fish density increased significantly (P < 0.05), while waterborne microplastic concentrations (P < 0.01) and incidence of ingestion decreased. This study provides baseline ecological data illustrating the correlation between waterborne microplastics and the incidence of ingestion in fish larvae. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Polyuria, acidosis, and coma following massive ibuprofen ingestion.

    Science.gov (United States)

    Levine, Michael; Khurana, Amandeep; Ruha, Anne-Michelle

    2010-09-01

    Ibuprofen was the first over-the-counter nonsteroidal anti-inflammatory drug available in the United States. Despite being a common agent of ingestion, significant toxicity in overdose is rare. We report a case of a massive ibuprofen ingestion who developed polyuria, acidosis, and coma but survived, despite having a serum ibuprofen concentration greater than previous fatal cases. A 19-year-old man ingested 90 g (1,200 mg/kg) ibuprofen. He was initially awake and alert, but his level of consciousness deteriorated over several hours. Seven hours following the ingestion, he was intubated and mechanically ventilated secondary to loss of airway reflexes. He developed a lactic acidosis and polyuria, which lasted for nearly 24 h. His serum creatinine peaked at 1.12 mg/dL. An ibuprofen level drawn 7 h postingestion was 739.2 mg/L (therapeutic 5-49 mg/L). We describe a case of a massive ibuprofen overdose characterized by metabolic acidosis, coma, and a state of high urine output who survived with aggressive supportive care. This case is unique in several ways. First, ibuprofen levels this high have only rarely been described. Second, polyuria is very poorly described following ibuprofen ingestions.

  9. Magnet foreign body ingestion: rare occurrence but big consequences.

    Science.gov (United States)

    Sola, Richard; Rosenfeld, Eric H; Yu, Yangyang R; St Peter, Shawn D; Shah, Sohail R

    2017-08-24

    To review the outcomes of magnet ingestions from two children's hospitals and develop a clinical management pathway. Children magnet were reviewed from 1/2011 to 6/2016 from two tertiary center children's hospitals. Demographics, symptoms, management and outcomes were analyzed. From 2011 to 2016, there were 89 magnet ingestions (50 from hospital 1 and 39 from hospital 2); 50 (56%) were males. Median age was 7.9 (4.0-12.0) years; 60 (67%) presented with multiple magnets or a magnet and a second metallic co-ingestion. Suspected locations found on imaging were: stomach (53%), small bowel (38%), colon (23%) and esophagus (3%). Only 35 patients (39%) presented with symptoms and the most common symptom was abdominal pain (33%). 42 (47%) patients underwent an intervention, in which 20 (23%) had an abdominal operation. For those undergoing abdominal surgery, an exact logistic regression model identified multiple magnets or a magnet and a second metallic object co-ingestion (OR 12.9; 95% CI, 2.4 - Infinity) and abdominal pain (OR 13.0; 95% CI, 3.2-67.8) as independent risk factors. Magnets have a high risk of requiring surgical intervention for removal. Therefore, we developed a management algorithm for magnet ingestion. Level III. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. [Magnet ingestions in children: a French multicenter study].

    Science.gov (United States)

    Talvard, M; Mouttalib, S; Flaum, V; Viala, J; Galinier, P; Olives, J-P; Mas, E

    2015-01-01

    Digestive complications related to the ingestion of magnetic foreign bodies in children are increasing, especially in Asia and North America. In France, several case reports have been reported since 2008. We conducted a retrospective multicentric study to evaluate the frequency of ingestion of magnet foreign bodies and to describe the complicated cases that have occurred in France over the last 5 years. We report 40 cases of which 60% were multiple magnet ingestions. Eighty-eight percent of the children of the group who had swallowed multiple magnets needed interventional management by endoscopy (33%) or surgery (58%). Only two children (12.5%) of the group who swallowed one magnet required removal. This problem is not uncommon in France (2% of the 1132 foreign bodies investigated in the Toulouse center over 5 years), which justifies clear information for healthcare professionals and caregivers in order to avoid potential intestinal complications. We suggest interventional management or very close monitoring in the cases of multiple magnet ingestion. Meanwhile, in the majority of confirmed cases of simple magnet ingestions, we propose home monitoring. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. Prediction of complications following unintentional caustic ingestion in children. Is endoscopy always necessary?

    DEFF Research Database (Denmark)

    Christesen, H B

    1995-01-01

    The records of 115 children hospitalized following caustic ingestion over an 18.5-year period from 1976 to 1994 were reviewed. The relationship between types of product ingested, signs and symptoms, degree of esophageal injury and complications was analyzed. All complications were the result...... of strong alkali ingestion (sensitivity = 1.0). Among the 102 incident patients, 36.8% of lye ingestions resulted in complications, whereas only 2.7% (one) of automatic dishwasher detergent (ADD) ingestions caused any complications (p

  12. An ingested foreign body: two sides of the same coin?

    Science.gov (United States)

    Varadharajan, Kiran; Magill, Jennifer; Patel, Kalpesh

    2014-04-09

    A 2-year-old child presented to the emergency department with an acute onset of dysphagia and stertor. A plain anteroposterior chest X-ray revealed a single circular opacity in the middle third of the oesophagus consistent with an ingested coin. The child was taken to the theatre for rigid pharyngo-oesophagoscopy and removal of the coin. After the first coin was removed subsequent endoscopic examination revealed a second coin at the same location. This extremely rare case of two ingested coins becoming impacted with perfect radiological alignment emphasises the importance of thorough examination on endoscopy and the potential limitations of an X-ray in initial assessment of an ingested foreign body.

  13. An Ingested Orthodontic Wire Fragment: A Case Report.

    Science.gov (United States)

    Puryer, James; McNamara, Catherine; Sandy, Jonathan; Ireland, Tony

    2016-08-01

    Accidental ingestion or inhalation of foreign bodies has been widely documented, including incidents which occur whilst undertaking dental treatment. Most ingested objects pass through the gastrointestinal tract (GIT) spontaneously, but approximately 10%-20% need to be removed endoscopically and 1% require surgery. This case reports a complication arising from the accidental loss of an archwire fragment during maxillary archwire placement. It describes the immediate and subsequent management, including the use of radiographs to track the passage of the fragment through the gastro-intestinal tract. This case stresses the vigilance that dentists must take to prevent inhalation or ingestion of foreign bodies and the consequences of time-delays when management decisions are needed.

  14. Microplastics ingestion by a common tropical freshwater fishing resource.

    Science.gov (United States)

    Silva-Cavalcanti, Jacqueline Santos; Silva, José Diego B; França, Elton José de; Araújo, Maria Christina Barbosa de; Gusmão, Felipe

    2017-02-01

    Microplastics pollution is widespread in marine ecosystems and a major threat to biodiversity. Nevertheless, our knowledge of the impacts of microplastics in freshwater environments and biota is still very limited. The interaction of microplastics with freshwater organisms and the risks associated with the human consumption of organisms that ingested microplastics remain major knowledge gaps. In this study, we assessed the ingestion of microplastics by Hoplosternum littorale, a common freshwater fish heavily consumed by humans in semi-arid regions of South America. We assessed the abundance and diversity of both plastic debris and other food items found in the gut of fishes caught by local fishermen. We observed that 83% of the fish had plastic debris inside the gut, the highest frequency reported for a fish species so far. Most of the plastic debris (88.6%) recovered from the guts of fish were microplastics (microplastics at the urbanized sections of the river, and that the ingestion of microplastics was negatively correlated with the diversity of other food items in the gut of individual fish. Nevertheless, microplastics ingestion appears to have a limited impact on H. littorale, and the consequences of human consumption of this fish were not assessed. Our results suggest freshwater biota are vulnerable to microplastics pollution and that urbanization is a major factor contributing to the pollution of freshwater environments with microplastics. We suggest the gut content of fish could be used as a tool for the qualitative assessment of microplastics pollution in freshwater ecosystems. Further research is needed to determine the processes responsible for the high incidence of microplastics ingestion by H. littorale, and to evaluate the risk posed to humans by the consumption of freshwater fish that ingested microplastics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. When do we eat? Ingestive behavior, survival, and reproductive success.

    Science.gov (United States)

    Schneider, Jill E; Wise, Justina D; Benton, Noah A; Brozek, Jeremy M; Keen-Rhinehart, Erin

    2013-09-01

    The neuroendocrinology of ingestive behavior is a topic central to human health, particularly in light of the prevalence of obesity, eating disorders, and diabetes. The study of food intake in laboratory rats and mice has yielded some useful hypotheses, but there are still many gaps in our knowledge. Ingestive behavior is more complex than the consummatory act of eating, and decisions about when and how much to eat usually take place in the context of potential mating partners, competitors, predators, and environmental fluctuations that are not present in the laboratory. We emphasize appetitive behaviors, actions that bring animals in contact with a goal object, precede consummatory behaviors, and provide a window into motivation. Appetitive ingestive behaviors are under the control of neural circuits and neuropeptide systems that control appetitive sex behaviors and differ from those that control consummatory ingestive behaviors. Decreases in the availability of oxidizable metabolic fuels enhance the stimulatory effects of peripheral hormones on appetitive ingestive behavior and the inhibitory effects on appetitive sex behavior, putting a new twist on the notion of leptin, insulin, and ghrelin "resistance." The ratio of hormone concentrations to the availability of oxidizable metabolic fuels may generate a critical signal that schedules conflicting behaviors, e.g., mate searching vs. foraging, food hoarding vs. courtship, and fat accumulation vs. parental care. In species representing every vertebrate taxa and even in some invertebrates, many putative "satiety" or "hunger" hormones function to schedule ingestive behavior in order to optimize reproductive success in environments where energy availability fluctuates. © 2013. Published by Elsevier Inc. All rights reserved.

  16. Ballpoint pen ingestion in a 2-year-old child.

    Science.gov (United States)

    Rameau, Anaïs; Anand, Sumeet M; Nguyen, Lily H

    2011-07-01

    A 2-year-old girl ingested a ballpoint pen, which was found on chest x-ray to have lodged in the lower esophagus and stomach. The pen, which measured nearly 15 cm in length, was removed via rigid esophagoscopy without complication. To the best of our knowledge, this is the longest nonflexible foreign body ingested by a young child ever reported in the English-language literature. We describe the presentation of this case and the current guidelines for safety as enumerated in the Small Parts Regulations established by the U.S. Consumer Product Safety Commission.

  17. Glucose ingestion during endurance training does not alter adaptation

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Fischer, Christian P; Plomgaard, Peter

    2009-01-01

    , 2) lower citrate synthase (CS) and beta-hydroxyacyl-CoA dehydrogenase (beta-HAD) activity and glycogen content in skeletal muscle, and 3) attenuated endurance performance enhancement in the trained state. To investigate this we studied nine male subjects who performed 10 wk of one-legged knee...... extensor training. They trained one leg while ingesting a 6% glucose solution (Glc) and ingested a sweetened placebo while training the other leg (Plc). The subjects trained their respective legs 2 h at a time on alternate days 5 days a week. Endurance training increased peak power (P(max)) and time...

  18. A case of acute hepatitis following mad honey ingestion

    Directory of Open Access Journals (Sweden)

    Fatma Sari Dogan

    2015-12-01

    Full Text Available Acute hepatitis is characterized by liver inflammation and liver cell necrosis. The most frequently observed underlying cause thereof is viruses, but various other causes, such as alcohol, medication, or toxins may also lead thereto.In this paper, a case of acute hepatitis presenting with bradycardia, hypotension, and a prominent increase in liver enzymes following mad honey ingestion is discussed. Since there are only few cases of acute hepatitis following mad honey ingestion in the literature, we want to present this subject matter. Keywords: Mad honey poisoning, Mad honey intoxication, Bradycardia, Hypotension, Acute hepatitis

  19. Dose construction for vegetable ingestion exposure in Hong Kong

    International Nuclear Information System (INIS)

    Lui, W.S.; Walton, A.; Yeung, M.R.

    1997-01-01

    The author presents the mathematical model TERRA used for the construction of ingestion doses resulting from the consumption of contaminated vegetables during a nuclear accident in Hong Kong. Using the ground surface deposited radionuclide densities as input, TERRA calculates the concentrations of 54 radionuclides on the surfaces and within the tissue of vegetables as a function of time and the radiation doses delivered to the various vital organs following their consumption by humans. The present model provides a convenient tool to determine the time histories of 54 radionuclides in vegetables and to back track or project the ingestion dose after a major accident such that more appropriate and timely countermeasures can be implemented

  20. An investigation of the ingestion exposure pathways in Hong Kong

    International Nuclear Information System (INIS)

    Yeung, Mankit Ray; Lui, Wai Sing

    1995-01-01

    An investigation of the food supply and the dietetic pattern of Hong Kong was conducted and some of the important factors affecting the ingestion exposure pathways following a severe nuclear accident were examined. It was found that the nuclide concentrations in the vegetables are very sensitive to time and substantial saving in effective dose resulted from ingesting contaminated vegetables can be achieved by appropriate imposition of restriction on the consumption of local produce. The consumption of locally grown vegetables in large quantity and the proximity of the Hong Kong vegetable farms to the Guangdong Nuclear Power Station suggests that the vegetable-human pathway is important and warrants special attention

  1. Acute neurotoxicity after yohimbine ingestion by a body builder.

    Science.gov (United States)

    Giampreti, Andrea; Lonati, Davide; Locatelli, Carlo; Rocchi, Loretta; Campailla, Maria Teresa

    2009-09-01

    Yohimbine is an alkaloid obtained from the Corynanthe yohimbe tree and other biological sources. Yohimbine is currently approved in the United States for erectile dysfunction and has undergone resurgence in street use as an aphrodisiac and mild hallucinogen. In recent years yohimbine use has become common in body-building communities for its presumed lipolytic and sympathomimetic effects. We describe a 37-year-old bodybuilder in which severe acute neurotoxic effects occurred in 2 h after yohimbine ingestion. The patient presented with malaise, vomiting, loss of consciousness, and repeated seizures after ingestion of 5 g of yohimbine during a body-building competition in a gymnasium. His Glasgow Coma Score was 3, requiring orotracheal intubation. Two hours after admission, vital signs were blood pressure 259/107 mmHg and heart rate 140 beats/min. Treatment with furosemide, labetalol, clonidine, and urapidil and gastrointestinal decontamination were performed. Twelve hours later the patient was extubated with normal hemodynamic parameters and neurological examination. The yohimbine blood levels at 3, 6, 14, and 22 h after ingestion were 5,240; 2,250; 1,530; and 865 ng/mL, respectively, with a mean half-life of 2 h. Few data are available about yohimbine toxicity and the related blood levels. This is a case of a large ingestion of yohimbine in which severe hemodynamic and neurological manifestations occurred and elevated blood levels of yohimbine were detected.

  2. Glucose ingestion stimulates atherothrombotic inflammation in polycystic ovary syndrome

    Science.gov (United States)

    Kirwan, John P.; Rote, Neal S.; Minium, Judi

    2013-01-01

    Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation that can increase the risk of atherothrombosis. We performed a cross-sectional study to examine the effect of glucose ingestion on markers of atherothrombotic inflammation in mononuclear cells (MNC) of 16 women with PCOS (8 lean, 8 obese) and 16 weight-matched controls. Activator protein-1 (AP-1) activation and the protein content of early growth response-1 (EGR-1), matrix matalloproteinases-2 (MMP2), and tissue factor (TF) were quantified from MNC obtained from blood drawn fasting and 2 h after glucose ingestion. Plasma MMP9 and C-reactive protein (CRP) were measured from fasting blood samples. Truncal fat was determined by DEXA. Lean women with PCOS exhibited greater AP-1 activation and MMP2 protein content after glucose ingestion and higher plasma MMP9 and CRP levels than lean controls. Obese women with PCOS exhibited greater EGR-1 and TF protein content after glucose ingestion, and plasma CRP levels were even higher compared with lean subjects regardless of PCOS status. Truncal fat correlated with MMP9 and CRP levels and glucose-stimulated increases in AP-1 activation and EGR-1 and TF protein content. Testosterone correlated with glucose-stimulated AP-1 activation, and androstenedione correlated with MMP9 and CRP levels and glucose-stimulated AP-1 activation. Thus, both PCOS and obesity contribute to an atherothrombotic state in which excess abdominal adiposity and hyperandrogenism may be specific risk factors for developing atherothrombosis. PMID:23249695

  3. Foreign body ingestion in children: case report and literature review ...

    African Journals Online (AJOL)

    Foreign body (FB) ingestion is a common occurrence in children. In most cases these foreign bodies pass through the gastrointestinal tract uneventfully. The important considerations for intervention include size, shape, and composition of the FB. Also, the site of lodgement and underlying pathology in the patient with the ...

  4. Foreign body ingestion in a neonate | Ugwu | Port Harcourt Medical ...

    African Journals Online (AJOL)

    She had an emergency tracheostomy and subsequent extraction of the foreign body. She was extubated after four days and was discharged on the eighth day in good clinical condition. Conclusion: Foreign body ingestion in the neonate although very uncommon is possible. Paediatricians should therefore remember that ...

  5. Maternal ethanol ingestion: effect on maternal and neonatal glucose balance

    International Nuclear Information System (INIS)

    Witek-Janusek, L.

    1986-01-01

    Liver glycogen availability in the newborn is of major importance for the maintenance of postnatal blood glucose levels. This study examined the effect of maternal ethanol ingestion on maternal and neonatal glucose balance in the rate. Female rats were placed on 1) the Lieber-DeCarli liquid ethanol diet, 2) an isocaloric liquid pair-diet, or 3) an ad libitum rat chow diet at 3 wk before mating and throughout gestation. Blood and livers were obtained from dams and rat pups on gestational days 21 and 22. The pups were studied up to 6 h in the fasted state and up to 24 h in the fed state. Maternal ethanol ingestion significantly decreased litter size, birth weight, and growth. A significantly higher mortality during the early postnatal period was seen in the prenatal ethanol exposed pups. Ethanol significantly decreased fed maternal liver glycogen stores but not maternal plasma glucose levels. The newborn rats from ethanol ingesting dams also had significantly decreased liver glycogen stores. Despite mobilizing their available glycogen, these prenatal ethanol exposed pups became hypoglycemic by 6 h postnatal. This was more marked in the fasted pups. Ethanol did not affect maternal nor neonatal plasma insulin levels. Thus maternal ethanol ingestion reduces maternal and neonatal liver glycogen stores and leads to postnatal hypoglycemia in the newborn rat

  6. Caustic ingestion injuries-at military hospital rawalpindi

    International Nuclear Information System (INIS)

    Ahsan, O.; Razzaq, K.; Abbas, W.; Zarrin, F.

    2015-01-01

    To study the pattern and endoscopic severity of caustic ingestion injuries presenting at Military Hospital Rawalpindi. Study Design: Descriptive study. Place and Duration of Study: The study was conducted at Medical and Gastroenterology Department Military Hospital Rawalpindi from August 2012 to April 2013. Material and Methods: Patients were selected from those who presented with caustic ingestion history in Medical OPD, ER and in medical wards. After informed consent the patient underwent upper gastrointestinal (GI) Endoscopy. Endoscopic findings were recorded. Results: Out of 50 patients, 21(42%) were males and 29 (58%) were females. Ingestion was accidental in 19 (38%) and was with intent of suicide or self-harm in 31(62%) patients. Mean age was 33.2 years (SD ± 13.2). All the patients were subjected to upper GI endoscopy and findings were recorded. Endoscopic findings were grade 0 in 4 (8%), Grade 1 in 6 (12%), grade 2a in 7 (14%), grade 2b in 10 (20%), grade 3a in 6 (12%) and grade 3b in 17 (34%) patients. Conclusion: Caustic ingestion injuries were seen more in younger females with predominant cause as suicidal intent. On endoscopic examination severe corrosive injuries were more frequent. (author)

  7. The relationship between sward structure, ingestive behavior and ...

    African Journals Online (AJOL)

    Animals adjusted biting rates to compensate for changes in bite size and thus maintained rates of intake. Bite size and dietary CP were negatively correlated. It was argued that, in the present study, leaf table height, stemminess, leaf density and leaf % were the main determinants of dietary CP and ingestive behaviour.

  8. Plastic ingestion by harbour seal (Phoca vitulina) in the Netherlands

    NARCIS (Netherlands)

    Bravo Rebolledo, E.; Franeker, van J.A.; Jansen, O.E.; Brasseur, S.M.J.M.

    2013-01-01

    Abundance of ingested debris by seals has been mentioned as a potential indicator of marine litter in the European Marine Strategy Framework Directive (MSFD). A sample of 107 stomachs, 100 intestines and 125 scats of harbour seals from the Netherlands was analysed for the presence of plastics.

  9. Aging of microplastics promotes their ingestion by marine zooplankton

    NARCIS (Netherlands)

    Vroom, Renske J.E.; Koelmans, Bart; Besseling, Ellen

    2017-01-01

    Microplastics (<5 mm) are ubiquitous in the marine environment and are ingested by zooplankton with possible negative effects on survival, feeding, and fecundity. The majority of laboratory studies has used new and pristine microplastics to test their impacts, while aging processes such as

  10. Benign hepatic portal venous gas following caustic ingestion

    International Nuclear Information System (INIS)

    Lewin, Maite; Tubiana, Jean-Michel; Pocard, Marc; Caplin, Scott; Parc, Rolland; Blain, Antoine

    2002-01-01

    Hepatic portal vein gas has been documented in numerous conditions and is traditionally regarded as a poor prognostic sign. There are, however, several reports of portal vein gas with a benign course. We report the first case of transient hepatic portal vein gas secondary to the ingestion of a caustic substance. The literature of hepatic portal vein gas in benign disease is reviewed. (orig.)

  11. Severe hypokalaemic paralysis and rhabdomyolysis due to ingestion of liquorice

    NARCIS (Netherlands)

    A.E. van den Bosch (Annemien); J.M. van der Klooster; D.M. Zuidgeest; R.J.T. Ouwendijk (Rob); A. Dees

    2005-01-01

    textabstractChronic ingestion of liquorice induces a syndrome with findings similar to those in primary hyperaldosteronism. We describe a patient who, with a plasma K+ of 1.8 mmol/l, showed a paralysis and severe rhabdomyolysis after the habitual consumption of natural liquorice.

  12. Thermal Esophageal Injury following Ingestion of Boiling Mushroom Water

    Directory of Open Access Journals (Sweden)

    Allison Prevost

    2017-01-01

    Full Text Available Thermal esophageal and gastric damage from ingestion of hot liquids is poorly studied in pediatrics. Limited case reports exist in the literature. Many cases presented with chest pain, dysphagia, and odynophagia. Variable histologic findings were reported. No definitive management guidelines exist for such injuries. We provide a report of the acute assessment and management of an obvious thermal esophageal injury and contribute to what is known about this presentation. A 16-year-old male presented with odynophagia, dysphagia, and hematemesis following ingestion of “nearly boiling” mushroom water. Ondansetron, pantoprazole, ketorolac, maintenance intravenous fluids, and a clear liquid diet were started. At sixty hours after ingestion, an esophagogastroduodenoscopy (EGD revealed blistering and edema of the soft palate and epiglottis, circumferential erythema of the entire esophagus with an exudate likely to be desquamated mucosa, and linear erythema of the body and fundus of the stomach. An EGD one month after ingestion showed no residual effects from the injury. The pantoprazole was weaned and restrictions to his diet were lifted. To better standardize care in these rare esophageal injuries, the development of a clinical care algorithm may be beneficial to provide clinicians with a guide for management based on outcomes of previously reported cases.

  13. [Intestinal perforation due to multiple magnet ingestion: a case report].

    Science.gov (United States)

    Cevizci, Mehmet Nuri; Karadağ, Cetin Ali; Demir, Mesut; Dokucu, Ali Ihsan

    2012-03-01

    Multiple magnet ingestion during childhood may result in emergency situations. A single magnet may be discharged with intestinal peristalsis, but multiple magnets may stick together and cause significant intestinal complications. Here we present a case with intestinal perforation due to ingestion of multiple magnets and metal pieces. An eight-year-old girl presented with abdominal pain and vomiting. She had abdominal tenderness and defense on the physical examination. Abdominal X-ray showed air and fluid levels. Metallic images were not considered at first as important in the diagnosis. Abdominal ultrasonography was reported as acute appendicitis. During the abdominal exploration, the appendix was normal, but there were dense adherences around the ileum and cecum. After adhesiolysis, intestinal perforations were seen in the cecum and 15 and 45 cm proximal to the cecum. Magnet and metal pieces were present in the perforated segments. Wedge resection and primary repair was performed. There were no postoperative complications, and she was discharged on the postoperative fifth day. Pediatric surgeons should be aware of the complications of multiple magnet ingestion. If the patient has a history of multiple magnet ingestion, follow-up with daily abdominal X-rays should be done, and in cases where magnets seem to cluster together or if acute abdominal signs develop, surgical exploration should be considered.

  14. Foreign body ingestions in a schizophrenic patient | Alao | West ...

    African Journals Online (AJOL)

    Here, we report a case of ingestion of a rolled, metal tuna can lid in a male prison inmate previously diagnosed with depression and paranoid schizophrenia. Following evaluation by the surgical team, the foreign body was removed by laparotomy and the patient was discharged back to the prison without complication.

  15. Effects of kale ingestion on pharmacokinetics of acetaminophen in rats.

    Science.gov (United States)

    Yamasaki, Izumi; Uotsu, Nobuo; Yamaguchi, Kohji; Takayanagi, Risa; Yamada, Yasuhiko

    2011-12-01

    Kale is a cruciferous vegetable (Brassicaceae) that contains a large amount of health-promoting phytochemicals. The chronic ingestion of cabbage of the same family is known to accelerate conjugating acetaminophen (AA) and decrease the plasma AA level. Therefore, we examined to clarify the effects of kale on the pharmacokinetics of AA, its glucuronide (AA-G) and sulfate (AA-S). AA was orally administered to rats pre-treated with kale or cabbage (2000 mg/kg/day) for one week. Blood samples were collected from the jugular vein, and the concentrations of AA, AA-G and AA-S were determined. In results, kale ingestion induced an increase in the area under the concentration-time curve (AUC) and a decrease in the clearance of AA, whereas cabbage had almost no influence. In addition, there were significant differences in the AUC of AA-G between the control and kale groups. mRNA expression levels of UDP-glucuronosyltransferases, the enzymes involved in glucuronidation, in the kale group were significantly higher than those in the control group. In conclusion, kale ingestion increased the plasma concentrations of both AA and AA-G. The results suggest that kale ingestion accelerates the glucuronidation of AA, but an increase of plasma AA levels has a different cause than the cause of glucuronidation.

  16. Colloidal silver ingestion with copper and caeruloplasmin deficiency.

    Science.gov (United States)

    Stepien, Karolina M; Taylor, Andrew

    2012-05-01

    The copper concentration in serum can be affected by the presence of other trace elements such as silver. Low serum copper may result in decreased caeruloplasmin synthesis. We report the case of a 59-year-old woman, who was admitted to hospital with acute psychosis and who had been ingesting chronically, colloidal silver.

  17. Sharp foreign body ingestion by a young girl | Hasan | Alexandria ...

    African Journals Online (AJOL)

    A 16 year old patient had ingested two sewing needles about 4.5 cm long accidentally that eventually resided in extra intestinal tract position, and being asymptomatic, she ignored the problem for a long period about 2 years. She only consulted the hospital after having symptoms. The needles were located by Xray imaging ...

  18. Effect of Carbohydrate and Caffeine Ingestion on Badminton Performance.

    Science.gov (United States)

    Clarke, Neil D; Duncan, Michael J

    2016-01-01

    To investigate the effect of ingesting carbohydrate and caffeine solutions on measures that are central to success in badminton. Twelve male badminton players performed a badminton serve-accuracy test, coincidence-anticipation timing (CAT), and a choice reaction-time sprint test 60 min before exercise. Participants then consumed 7 mL/kg body mass of either water (PLA), 6.4% carbohydrate solution (CHO), a solution containing a caffeine dose of 4 mg/kg, or 6.4% carbohydrate and 4 mg/kg caffeine (C+C). All solutions were flavored with orange-flavored concentrate. During the 33-min fatigue protocol, participants were provided with an additional 3 mL/kg body mass of solution, which was ingested before the end of the protocol. As soon as the 33-min fatigue protocol was completed, all measures were recorded again. Short-serve accuracy was improved after the ingestion of CHO and C+C compared with PLA (P = .001, η(p)(2) = .50). Long-serve accuracy was improved after the ingestion of C+C compared with PLA (P badminton match can maintain serve accuracy, anticipation timing, and sprinting actions around the court.

  19. Miniature ingestible telemeter devices to measure deep-body temperature

    Science.gov (United States)

    Pope, J. M.; Fryer, T. B. (Inventor)

    1976-01-01

    A telemetry device comprised of a pill-size ingestible transmitter developed to obtain deep body temperature measurements of a human is described. The device has particular utility in the medical field where deep body temperatures provide an indication of general health.

  20. Effect of varying concentrations of orally ingested glucose on platelet ...

    African Journals Online (AJOL)

    The physiologic basis of bleeding is a function of normal platelets and coagulation factors. This study is aimed at ascertaining the effect of varying concentrations of orally ingested glucose on platelet count and hemoglobin concentration during menstruation. Forty menstruating students between the ages of 18 and 25 from ...

  1. Caffeine ingestion enhances Wingate performance: a meta-analysis.

    Science.gov (United States)

    Grgic, Jozo

    2018-03-01

    The positive effects of caffeine ingestion on aerobic performance are well-established; however, recent findings are suggesting that caffeine ingestion might also enhance components of anaerobic performance. A commonly used test of anaerobic performance and power output is the 30-second Wingate test. Several studies explored the effects of caffeine ingestion on Wingate performance, with equivocal findings. To elucidate this topic, this paper aims to determine the effects of caffeine ingestion on Wingate performance using meta-analytic statistical techniques. Following a search through PubMed/MEDLINE, Scopus, and SportDiscus ® , 16 studies were found meeting the inclusion criteria (pooled number of participants = 246). Random-effects meta-analysis of standardized mean differences (SMD) for peak power output and mean power output was performed. Study quality was assessed using the modified version of the PEDro checklist. Results of the meta-analysis indicated a significant difference (p = .005) between the placebo and caffeine trials on mean power output with SMD values of small magnitude (0.18; 95% confidence interval: 0.05, 0.31; +3%). The meta-analysis performed for peak power output indicated a significant difference (p = .006) between the placebo and caffeine trials (SMD = 0.27; 95% confidence interval: 0.08, 0.47 [moderate magnitude]; +4%). The results from the PEDro checklist indicated that, in general, studies are of good and excellent methodological quality. This meta-analysis adds on to the current body of evidence showing that caffeine ingestion can also enhance components of anaerobic performance. The results presented herein may be helpful for developing more efficient evidence-based recommendations regarding caffeine supplementation.

  2. Food Ingestion Factors of the Korean Exposure Factors Handbook

    Directory of Open Access Journals (Sweden)

    Jae-Yeon Jang

    2014-01-01

    Full Text Available The purpose of this study was to establish food ingestion factors needed to assess exposure to contaminants through food ingestion. The study reclassified the raw data of the Korean National Health and Nutrition Examination Survey in 2001 into 12 subcategories including grain products, meat products, fish and shellfish, and vegetables for international comparability of exposure evaluation. The criteria for food intake calculation were unified according to the characteristics of food groups, and recommended values for food ingestion factors were calculated through moisture correction and recategorization of cooked, processed, and mixed foods for each group. The average intake rate for grain and grain products was 6.25 g/kg-d per capita and the men's intake rate was approximately 8% higher than that of the women. The average intake rate of meat and meat products was 1.62 g/kg-d per capita and the men's intake rate was 30% higher than that of the women, on average. The average intake rate of fish and shellfish was 1.53 g/kg-d per capita, and the age groups of 1 to 2 and 3 to 6 recorded higher capita intake rates than other age groups, 2.62 g/kg-d and 2.25 g/kg-d, respectively. The average intake rate of vegetables was 6.47 g/kg-d per capita, with the age group of 1 to 2 recording the highest per capita intake rate of 9.79 g/kg-d and that of 13 to 19 recording the lowest mean. The study also offers recommended values for food ingestion factors of other food groups by gender, age, and region. The food ingestion exposure factors will need future updates in consideration of ongoing changes in food consumption behavior.

  3. Arsenic metabolites in humans after ingestion of wakame seaweed

    Directory of Open Access Journals (Sweden)

    Hata A.

    2013-04-01

    Full Text Available Seaweed contains large amounts of various arsenic compounds such as arsenosugars (AsSugs, but their relative toxicities have not yet been fully evaluated. A risk evaluation of dietary arsenic would be necessary. After developing an arsenic speciation analysis of wakame seaweed (Undaria pinnatifida, we conducted a wakame ingestion experiment using volunteers. Five volunteers ingested 300 g of commercial wakame after refraining from seafood for 5 days. Arsenic metabolites in the urine were monitored over a 5-day period after ingestion. Total arsenic concentration of the wakame seaweed was 34.3 ± 2.1 mg arsenic/kg (dry weight, n = 3. Two AsSugs, 3-[5′-deoxy-5′-(dimethyl-arsinoyl-β-ribofuranosyloxy]-propylene glycol (AsSug328 and 3-[5′-deoxy-5′-(dimethyl-arsinoyl-β- ribofuranosyl-oxy]-2-hydroxypropyl-2,3-dihydroxy-propyl phosphate (AsSug482 were detected, but arsenobetaine, dimethylarsinic acid (DMA, monomethylarsonic acid, and inorganic arsenics (iAs were not detected. The major peak was AsSug328, which comprised 89% of the total arsenic. Approximately 30% of the total arsenic ingested was excreted in the urine during the 5-day observation. Five arsenic compounds were detected in the urine after ingestion, the major one being DMA, which comprised 58.1 ± 5.0% of the total urinary arsenic excreted over the 5 days. DMA was believed to be metabolized not from iAs but from AsSugs, and its biological half-time was approximately 13 h.

  4. Food ingestion factors of the Korean exposure factors handbook.

    Science.gov (United States)

    Jang, Jae-Yeon; Jo, Soo-Nam; Kim, Sun-Ja; Myung, Hyung-Nam; Kim, Cho-Il

    2014-01-01

    The purpose of this study was to establish food ingestion factors needed to assess exposure to contaminants through food ingestion. The study reclassified the raw data of the Korean National Health and Nutrition Examination Survey in 2001 into 12 subcategories including grain products, meat products, fish and shellfish, and vegetables for international comparability of exposure evaluation. The criteria for food intake calculation were unified according to the characteristics of food groups, and recommended values for food ingestion factors were calculated through moisture correction and recategorization of cooked, processed, and mixed foods for each group. The average intake rate for grain and grain products was 6.25 g/kg-d per capita and the men's intake rate was approximately 8% higher than that of the women. The average intake rate of meat and meat products was 1.62 g/kg-d per capita and the men's intake rate was 30% higher than that of the women, on average. The average intake rate of fish and shellfish was 1.53 g/kg-d per capita, and the age groups of 1 to 2 and 3 to 6 recorded higher capita intake rates than other age groups, 2.62 g/kg-d and 2.25 g/kg-d, respectively. The average intake rate of vegetables was 6.47 g/kg-d per capita, with the age group of 1 to 2 recording the highest per capita intake rate of 9.79 g/kg-d and that of 13 to 19 recording the lowest mean. The study also offers recommended values for food ingestion factors of other food groups by gender, age, and region. The food ingestion exposure factors will need future updates in consideration of ongoing changes in food consumption behavior.

  5. A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide.

    Science.gov (United States)

    Setnik, Beatrice; Roland, Carl L; Sommerville, Kenneth W; Pixton, Glenn C; Berke, Robert; Calkins, Anne; Goli, Veeraindar

    2015-01-01

    To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN) using a standardized conversion guide. This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility. Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%). The mean (standard deviation) number of days to stable dose was 20 (8.94), and number of titration steps to stable dose was 2.4 (1.37). The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again. Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of opioid-experienced patients with chronic moderate-to-severe pain. Investigators found the guide to be a useful tool to assist conversion of opioid-experienced patients to MSN.

  6. Relative oral bioavailability of morphine and naltrexone derived from crushed morphine sulfate and naltrexone hydrochloride extended-release capsules versus intact product and versus naltrexone solution: a single-dose, randomized-sequence, open-label, three-way crossover trial in healthy volunteers.

    Science.gov (United States)

    Johnson, Franklin K; Stark, Jeffrey G; Bieberdorf, Frederick A; Stauffer, Joe

    2010-06-01

    Morphine sulfate/sequestered naltrexone hydrochloride (HCl) (MS-sNT) extended-release fixed-dose combination capsules, approved by the US Food and Drug Administration (FDA) in August 2009 for chronic moderate to severe pain, contain extended-release morphine pellets with a sequestered core of the opioid antagonist naltrexone. MS-sNT was designed so that if the product is tampered with by crushing, the naltrexone becomes bioavailable to mitigate morphine-induced subjective effects, rendering the product less attractive for tampering. The primary aim of this study was to compare the oral bioavailability of naltrexone and its metabolite 6-beta-naltrexol, derived from crushed pellets from MS-sNT capsules, to naltrexone solution. This study also assessed the relative bioavailability of morphine from crushed pellets from MS-sNT capsules and that from the whole, intact product. This single-dose, randomized-sequence, open-label, 3-period, 3-treatment crossover trial was conducted in healthy volunteers. Adults admitted to the study center underwent a 10-hour overnight fast before study drug administration. Each subject received all 3 of the following treatments, 1 per session, separated by a 14-day washout: tampered pellets (crushed for >or=2 minutes with a mortar and pestle) from a 60-mg MS-sNT capsule (60 mg morphine/2.4 mg naltrexone); 60-mg whole, intact MS-sNT capsule; and oral naltrexone HCl (2.4 mg) solution. Plasma concentrations of naltrexone and 6-beta-naltrexol were measured 0 to 168 hours after administration. Morphine pharmaco-kinetics of crushed and whole pellets were determined 0 to 72 hours after administration. The analysis of relative bioavailability was based on conventional FDA criteria for assuming bioequivalence; that is, 90% CIs for ratios of geometric means (natural logarithm [In]-transformed C(max) and AUC) fell within the range of 80% to 125%. Subjects underwent physical examinations, clinical laboratory tests, and ECG at screening and study

  7. Evaluation of new polysaccharides networks for extended-release purposes: mesquite seed gum (MSG, xanthan gum and chitosan Estudo da utilização de polissacarídeos no desenvolvimento de formulações de liberação prolongada: goma de semente de algaroba, goma xantana e quitosano

    Directory of Open Access Journals (Sweden)

    Carlos César dos Santos Nogueira

    2003-09-01

    Full Text Available The aim of this work was to design new hydrophilic matrix (HM systems by cross-linking Mesquite Seed Gum (MSG, a galactomannan that occurs in the endosperm layer of the seeds of a Brazilian tree,Prosopis juliflora DC, with two well-known polysaccharides with the ability of retarding drug release, chitosan and xanthan gum. This had in mind the idea of using these new compounds in the preparation of extended-release dosage oral forms. The first part of this study was dedicated to the evaluation of MSG in terms of its functionality as a hydrophilic matrix (HM system for extended-release purposes. Next, we started the study of water uptake profile of all polymers of interest (MSG, Xanthan Gum and Chitosan, in the following media: water, SGF and SIF. Following, we searched for the best cross-linking agent between Glutharaldehyde (GA and Hexamethylenediisocyanate (HMDI, which turned out to be the GA. Next step we begun to prepare new hydrophilic matrices of MSG_Chitosan and MSG_Xanthan Gum, with different ratios, 1:1, 1:2 and 2:1. Finally, after deciding which new HM system presented best results, by using statistics tools, we investigated the mechanism controlling the rate release of the model drug, from tablets made with this new matrix. As a final result we concluded that the best combination of polysaccharides was achieved with MSG and Xanthan Gum, with mass ratio of 1:2, using glutharaldehyde aqueous solution as cross-linking agent. It presented a prevalent zero order kinetics, which is a very important feature when thinking about an extended-release oral dosage.O objetivo deste trabalho foi o desenvolvimento de novos sistemas de matrizes hidrofílicas através da formação de ligações cruzadas (cross-linking entre a Goma da Semente da Algaroba (GSA, uma galactomanana que ocorre no endosperma das sementes de uma árvore nativa do Brasil, a Prosopis juliflora DC, e dois polissacarídeos bem conhecidos pela sua habilidade de retardar a libera

  8. Breath Hydrogen Produced by Ingestion of Commercial Hydrogen Water and Milk

    OpenAIRE

    Shimouchi, Akito; Nose, Kazutoshi; Yamaguchi, Makoto; Ishiguro, Hiroshi; Kondo, Takaharu

    2009-01-01

    Objective: To compare how and to what extent ingestion of hydrogen water and milk increase breath hydrogen in adults.Methods: Five subjects without specific diseases, ingested distilled or hydrogen water and milk as a reference material that could increase breath hydrogen. Their end-alveolar breath hydrogen was measured.Results: Ingestion of hydrogen water rapidly increased breath hydrogen to the maximal level of approximately 40 ppm 10–15 min after ingestion and thereafter rapidly decrease...

  9. Ingestion of Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli by human peritoneal mesothelial cells

    NARCIS (Netherlands)

    Visser, C. E.; Brouwer-Steenbergen, J. J.; Schadee-Eestermans, I. L.; Meijer, S.; Krediet, R. T.; Beelen, R. H.

    1996-01-01

    In the present study we examined whether mesothelial cells can ingest and digest bacteria. The results showed that all strains were ingested. Ingested staphylococci proliferated abundantly, and only a few were digested. Escherichia coli, however, was digested during the first 8 h, whereafter the

  10. Physiologic Conditions Affect Toxicity of Ingested Industrial Fluoride

    Directory of Open Access Journals (Sweden)

    Richard Sauerheber

    2013-01-01

    Full Text Available The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings.

  11. Physiologic conditions affect toxicity of ingested industrial fluoride.

    Science.gov (United States)

    Sauerheber, Richard

    2013-01-01

    The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings.

  12. Attempted Suicide by Massive Warfarin Ingestion Conservatively Managed Using Phytonadione

    Directory of Open Access Journals (Sweden)

    Katherine L. March

    2016-01-01

    Full Text Available Treatment strategies for acute toxicity following massive ingestion of warfarin are not well described in the literature. Warfarin is the primary oral anticoagulation agent used in the treatment of thromboembolic disease, and patients with acute toxicity are at risk for life-threatening hemorrhages. Treatment options include phytonadione (vitamin K1, fresh frozen plasma (FFP, and prothrombin complex concentrates (PCCs used alone or in combination. FFP and PCC can be associated with volume complications, undesirable thromboembolic events, and increased costs. We describe the case of a 63-year-old female with acute warfarin toxicity following a massive ingestion of warfarin (420 mg–450 mg in an attempt to commit suicide. Upon arrival to the emergency department, serial INR checks were initiated to help guide dosing strategy and later adjusted based on INR response to treatment using only phytonadione.

  13. Acute renal failure after ingestion of guaifenesin and dextromethorphan.

    Science.gov (United States)

    Small, Evan; Sandefur, Benjamin J

    2014-07-01

    Guaifenesin is a common nonprescription medication that has been implicated in drug-induced nephrolithiasis. Dextromethorphan, a nonprescription antitussive found in some guaifenesin-containing preparations, is increasingly recognized as a substance of abuse by many youth and young adults. Renally excreted medications known to have poor solubility in urine have the potential to precipitate when ingested in large quantity, leading to acute obstruction of the ureters and renal failure. We describe the case of a 22-year-old male who developed severe bilateral flank pain, hematuria, and oliguria after an isolated recreational ingestion of guaifenesin and dextromethorphan. The patient was found to have bilateral ureteral obstruction and acute renal failure, suspected to be secondary to precipitation of medication metabolites in the urine. This case highlights the potential for acute renal failure secondary to guaifenesin and dextromethorphan abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Methodology for Estimating Ingestion Dose for Emergency Response at SRS

    CERN Document Server

    Simpkins, A A

    2002-01-01

    At the Savannah River Site (SRS), emergency response models estimate dose for inhalation and ground shine pathways. A methodology has been developed to incorporate ingestion doses into the emergency response models. The methodology follows a two-phase approach. The first phase estimates site-specific derived response levels (DRLs) which can be compared with predicted ground-level concentrations to determine if intervention is needed to protect the public. This phase uses accepted methods with little deviation from recommended guidance. The second phase uses site-specific data to estimate a 'best estimate' dose to offsite individuals from ingestion of foodstuffs. While this method deviates from recommended guidance, it is technically defensibly and more realistic. As guidance is updated, these methods also will need to be updated.

  15. Plastic microfibre ingestion by deep-sea organisms

    Science.gov (United States)

    Taylor, M. L.; Gwinnett, C.; Robinson, L. F.; Woodall, L. C.

    2016-09-01

    Plastic waste is a distinctive indicator of the world-wide impact of anthropogenic activities. Both macro- and micro-plastics are found in the ocean, but as yet little is known about their ultimate fate and their impact on marine ecosystems. In this study we present the first evidence that microplastics are already becoming integrated into deep-water organisms. By examining organisms that live on the deep-sea floor we show that plastic microfibres are ingested and internalised by members of at least three major phyla with different feeding mechanisms. These results demonstrate that, despite its remote location, the deep sea and its fragile habitats are already being exposed to human waste to the extent that diverse organisms are ingesting microplastics.

  16. Ingestive behavior of lambs fed diets containing castor seed meal.

    Science.gov (United States)

    Nicory, Isis Miranda Carvalho; de Carvalho, Gleidson Giordano Pinto; Ribeiro, Ossival Lolato; Silva, Robério Rodrigues; Tosto, Manuela Silva Libanio; Costa-Lopes, Lívia Santos; Souza, Fábio Nicory Costa; de Oliveira Nascimento, Camila

    2015-06-01

    The objective of this study was to evaluate the substitution of soybean meal for castor seed meal (CSM) in diets for feedlot lambs and the effects of these diets on their ingestive behavior. Fifty male Santa Inês lambs were used. The diets were composed of Tifton 85 hay and a concentrate containing detoxified CSM substituting 0, 25, 50, 75, or 100 % of the soybean meal. There was no effect (P > 0.05) of the CSM levels on the feeding, rumination, idle times, chews and time spent chewing per bolus, total chewing time, number of boli chewed, and number of chews per day. The dry matter (DM) intake decreased linearly (P  0.05) the numbers of feeding, rumination, and idle periods, but had a quadratic effect (P ingestive behavior.

  17. Refractory priapism associated with ingestion of yohimbe extract

    OpenAIRE

    Myers, Amy; Barrueto, Fermin

    2009-01-01

    Extracts of the bark of the central African treePausinystalia yohimbe contain yohimbine, an indole alkaloid, which is used to treat erectile dysfunction. The reported side effects of over-the-counter preparations of yohimbine include gastrointestinal upset, anxiety, increased blood pressure, headache, agitation, rash, tachycardia, and frequent urination. In this report, we describe a severe case of intractable priapism associated with the ingestion of yohimbe extract. Management required inse...

  18. Refractory priapism associated with ingestion of yohimbe extract.

    Science.gov (United States)

    Myers, Amy; Barrueto, Fermin

    2009-12-01

    Extracts of the bark of the central African tree Pausinystalia yohimbe contain yohimbine, an indole alkaloid, which is used to treat erectile dysfunction. The reported side effects of over-the-counter preparations of yohimbine include gastrointestinal upset, anxiety, increased blood pressure, headache, agitation, rash, tachycardia, and frequent urination. In this report, we describe a severe case of intractable priapism associated with the ingestion of yohimbe extract. Management required insertion of a proximal cavernosal spongiosum shunt (Quackles shunt) in the operating room.

  19. The muscle protein synthetic response to food ingestion.

    Science.gov (United States)

    Gorissen, Stefan H M; Rémond, Didier; van Loon, Luc J C

    2015-11-01

    Preservation of skeletal muscle mass is of great importance for maintaining both metabolic health and functional capacity. Muscle mass maintenance is regulated by the balance between muscle protein breakdown and synthesis rates. Both muscle protein breakdown and synthesis rates have been shown to be highly responsive to physical activity and food intake. Food intake, and protein ingestion in particular, directly stimulates muscle protein synthesis rates. The postprandial muscle protein synthetic response to feeding is regulated on a number of levels, including dietary protein digestion and amino acid absorption, splanchnic amino acid retention, postprandial insulin release, skeletal muscle tissue perfusion, amino acid uptake by muscle, and intramyocellular signaling. The postprandial muscle protein synthetic response to feeding is blunted in many conditions characterized by skeletal muscle loss, such as aging and muscle disuse. Therefore, it is important to define food characteristics that modulate postprandial muscle protein synthesis. Previous work has shown that the muscle protein synthetic response to feeding can be modulated by changing the amount of protein ingested, the source of dietary protein, as well as the timing of protein consumption. Most of this work has studied the postprandial response to the ingestion of isolated protein sources. Only few studies have investigated the postprandial muscle protein synthetic response to the ingestion of protein dense foods, such as dairy and meat. The current review will focus on the capacity of proteins and protein dense food products to stimulate postprandial muscle protein synthesis and identifies food characteristics that may modulate the anabolic properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Pattern of corrosive ingestion in southwestern Saudi Arabia

    International Nuclear Information System (INIS)

    AlBinali Ali M; AlShehri, Mohammed A; AlFifi, Suliman H; Abdelmoneim, Ismail; Shomrani, Ali S

    2009-01-01

    Ingested corrosive material is a major pediatric emergency all over the world. The corrosive material can cause damage to the digestive tract, ranging from minor injury to strictures, and sometimes even death. We aimed to review the pattern of corrosive ingestion in children who had been admitted to Aseer Central Hospital in the Southwestern region of Saudi Arabia. This is a retrospective study of all children who had been admitted with a history of corrosive ingestion to Aseer Central Hospital over a period of five years period from 1990 to 1995. The records of 72 patients (38 males and 34 females) were reviewed. The data included age, sex, time lapse till admission, action taken by parents, presenting symptoms, general management given to the child, barium study, endoscopy, and the postcorrosive ingestion outcome of the child. The mean age of the pediatric patients was 28 + - 20 months. Different types of corrosives were encountered. The most common type was 5.25% hypochlorite in 36 patients (50%), kerosene in 12 patients (16.7%), caustic soda in nine patients (12.5%), hydrogen chloride and N-alkyl dimethyl benzyl ammonium chloride (HC and ADB) in eight patients (11.1%), and other material in seven patients (9.7%). Endoscopy was done in 30 patients (31.7%), 14 of whom were abnormal. Barium swallow was performed in 11 patients; five of them showed strictures that required frequent dilatation whereas one needed interposition surgery. Corrosive injury is still a major pediatric emergency among young children. It carries a major risk of complications (mainly stricture) and requires standardized management based on evidence-based medicine. (author)

  1. Unintentional Cannabis Ingestion in Children: A Systematic Review.

    Science.gov (United States)

    Richards, John R; Smith, Nishelle E; Moulin, Aimee K

    2017-11-01

    To analyze published reports of unintentional cannabis ingestions in children to determine presenting signs and symptoms, route of exposure, treatment, and outcome. PubMed, OpenGrey, and Google Scholar were systematically searched. Articles were selected, reviewed, and graded using Oxford Center for Evidence-Based Medicine guidelines. Of 3316 articles, 44 were included (3582 children age ≤12 years). We found no high quality (Oxford Center for Evidence-Based Medicine level I or II) studies and 10 level III studies documenting lethargy as the most common presenting sign and confirming increasing incidence of unintentional ingestion in states having decriminalized medical and recreational cannabis. We identified 16 level IV case series, and 28 level V case reports with 114 children, mean age 25.2 ± 18.7 months, range 8 months to 12 years, and 50 female children (44%). The most common ingestion (n = 43, 38%) was cannabis resin, followed by cookies and joints (both n = 15, 13%). Other exposures included passive smoke, medical cannabis, candies, beverages, and hemp oil. Lethargy was the most common presenting sign (n = 81, 71%) followed by ataxia (n = 16, 14%). Tachycardia, mydriasis, and hypotonia were also commonly observed. All cases were cared for in the emergency department or admitted, and mean length of stay was 27.1 ± 27.0 hours. Twenty (18%) were admitted to the pediatric intensive care unit, and 7 (6%) were intubated. Unintentional cannabis ingestion by children is a serious public health concern and is well-documented in numerous studies and case reports. Clinicians should consider cannabis toxicity in any child with sudden onset of lethargy or ataxia. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Ingestion Pathway Transfer Factors for Plutonium and Americium

    International Nuclear Information System (INIS)

    Blanchard, A.

    1999-01-01

    Overall transfer factors for major ingestion pathways are derived for plutonium and americium. These transfer factors relate the radionuclide concentration in a given foodstuff to deposition on the soil. Equations describing basic relationships consistent with Regulatory Guide 1.109 are followed. Updated values and coefficients from IAEA Technical Reports Series No. 364 are used when a available. Preference is given to using factors specific to the Savannah River Site

  3. Insulin binding to erythrocytes after acute 16-methyleneprednisolone ingestion.

    Science.gov (United States)

    Dwenger, A; Holle, W; Zick, R; Trautschold, I

    1982-10-01

    The binding of [125I]insulin to erythrocytes, glucose and insulin were determined before and 1, 7 and 35 days after ingestion of 2 X 60-methyleneprednisolone. None of two groups of volunteers (7 males, 4 females showed clear alterations of the insulin binding parameters (Ka and R0), or of the fasting cortisol, glucose and insulin concentrations. These results exclude the possibility that the diabetogenic effect of glucocorticoides is accompanied by an alteration of the insulin receptor characteristics of erythrocytes.

  4. Acute Hepatic Failure in a Dog after Xylitol Ingestion.

    Science.gov (United States)

    Schmid, Renee D; Hovda, Lynn R

    2016-06-01

    Xylitol is a five-carbon sugar alcohol produced from natural resources frequently used as a sugar substitute for humans. We report the development and successful treatment of acute hepatic failure and coagulopathy in a dog after xylitol ingestion. A 9-year-old 4.95 kg (10.9 lb) neutered male Chihuahua was evaluated at a veterinary clinic for vomiting after ingesting 224 g (45 g/kg, 20.5 g/lb) of granulated xylitol. Hypoglycemia developed within 1-2 h, elevated liver values, suggesting the development of acute hepatic failure, within 12 h and coagulopathy less than 24 h after ingestion. Treatment included maropitant, intravenous dextrose, phytonadione, metronidazole, and fresh frozen plasma. N-acetylcysteine (NAC) and S-adensoyl-L-methionine (SAMe) provided hepatic detoxification and support. The dog survived and liver values returned to normal within 1 month post ingestion. No adverse effects to hepatic function have been identified 2 years after acute xylitol toxicity. This paper is one of the few reports of successful management of a dog with hypoglycemia, hepatic failure, and coagulopathy caused by xylitol toxicity. To date, this is the highest published xylitol dose survived by a dog, as well as the only reported case that documents laboratory changes throughout the course of toxicity and includes normal hepatic indices for 7 months following xylitol toxicity. The rapidly expanding use of xylitol in a variety of products intended for human consumption has led to a rise in xylitol toxicity cases reported in dogs, and clinicians should be aware that more dogs may potentially be exposed and develop similar manifestations.

  5. Homespun remedy, homespun toxicity: baking soda ingestion for dyspepsia.

    Science.gov (United States)

    Ajbani, Keyur; Chansky, Michael E; Baumann, Brigitte M

    2011-04-01

    A 68-year-old man presented to the Emergency Department with a severe metabolic alkalosis after ingesting large quantities of baking soda to treat his dyspepsia. His underlying pulmonary disease and a progressively worsening mental status necessitated intubation for respiratory failure. Laboratory studies revealed a hyponatremic, hypochloremic, hypokalemic metabolic alkalosis. The patient was successfully treated after cessation of the oral bicarbonate, initiation of intravenous hydration, and correction of electrolyte abnormalities. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Fate of ingested Clostridium difficile spores in mice.

    Directory of Open Access Journals (Sweden)

    Amber Howerton

    Full Text Available Clostridium difficile infection (CDI is a leading cause of antibiotic-associated diarrhea, a major nosocomial complication. The infective form of C. difficile is the spore, a dormant and resistant structure that forms under stress. Although spore germination is the first committed step in CDI onset, the temporal and spatial distribution of ingested C. difficile spores is not clearly understood. We recently reported that CamSA, a synthetic bile salt analog, inhibits C. difficile spore germination in vitro and in vivo. In this study, we took advantage of the anti-germination activity of bile salts to determine the fate of ingested C. difficile spores. We tested four different bile salts for efficacy in preventing CDI. Since CamSA was the only anti-germinant tested able to prevent signs of CDI, we characterized CamSa's in vitro stability, distribution, and cytotoxicity. We report that CamSA is stable to simulated gastrointestinal (GI environments, but will be degraded by members of the natural microbiota found in a healthy gut. Our data suggest that CamSA will not be systemically available, but instead will be localized to the GI tract. Since in vitro pharmacological parameters were acceptable, CamSA was used to probe the mouse model of CDI. By varying the timing of CamSA dosage, we estimated that C. difficile spores germinated and established infection less than 10 hours after ingestion. We also showed that ingested C. difficile spores rapidly transited through the GI tract and accumulated in the colon and cecum of CamSA-treated mice. From there, C. difficile spores were slowly shed over a 96-hour period. To our knowledge, this is the first report of using molecular probes to obtain disease progression information for C. difficile infection.

  7. Efficacy of Carbohydrate Ingestion on CrossFit Exercise Performance

    Science.gov (United States)

    Rountree, Jaden A.; Krings, Ben M.; Peterson, Timothy J.; Thigpen, Adam G.; McAllister, Matthew J.; Holmes, Megan E.

    2017-01-01

    The efficacy of carbohydrate (CHO) ingestion during high-intensity strength and conditioning type exercise has yield mixed results. However, little is known about shorter duration high-intensity exercise such as CrossFit. The purpose of this study was to investigate the performance impact of CHO ingestion during high-intensity exercise sessions lasting approximately 30 min. Eight healthy males participated in a total of four trials; two familiarizations, a CHO trial, and a similarly flavored, non-caloric placebo (PLA) trial. CrossFit’s “Fight Gone Bad Five” (FGBF) workout of the day was the exercise model which incorporated five rounds of maximal repetition exercises, wall throw, box jump, sumo deadlift high pull, push press, and rowing, followed by one minute of rest. Total repetitions and calories expended were summated from each round to quantify total work (FGBF score). No difference was found for the total work between CHO (321 ± 51) or PLA (314 ± 52) trials (p = 0.38). There were also no main effects (p > 0.05) for treatment comparing exercise performance across rounds. Based on the findings of this study, it does not appear that ingestion of CHO during short duration, high-intensity CrossFit exercise will provide a beneficial performance effect.

  8. Epidemiology and prevention of caustic ingestion in children

    DEFF Research Database (Denmark)

    Christesen, H B

    1994-01-01

    A total of 102 children less than 16 years of age admitted for caustic ingestion in the period 1976-1991 were registered. The annual incidence rate of hospitalization was 10.8:100,000 for the city of Aarhus, Denmark. Esophageal burns occurred with a frequency of 5.0:100,000 per year. Ninety-four ...... of toddlers is recommended. Information material should stress that caustics should always be inaccessible to children and stored separately, and should never be decanted.......A total of 102 children less than 16 years of age admitted for caustic ingestion in the period 1976-1991 were registered. The annual incidence rate of hospitalization was 10.8:100,000 for the city of Aarhus, Denmark. Esophageal burns occurred with a frequency of 5.0:100,000 per year. Ninety......-four percent of the children were less than 5 years old. For this age group, the incidence rates of admission and esophageal burns were 34.6:100,000 and 15.8:100,000, respectively. All ingestions were accidental. The incidence rates of esophageal burns in children 0-4 years old (p = 0.019) decreased...

  9. Lead shot pellets dispersed by hunters: ingested by ducks

    Energy Technology Data Exchange (ETDEWEB)

    Danell, K [Univ. of Umea, Sweden; Andersson, A; Marcstrom, V

    1977-01-01

    Many of the lead pellets shot by waterfowl hunters over shores and waters fall on the feeding grounds of ducks and geese. These pellets, picked up and ingested by the birds, can remain in the gizzard where they are eroded by mechanical and chemical action. In some cases the bird absorbs enough lead to cause lead poisoning. This report describes the incidence of ingested lead shot pellets found in 928 ducks collected in Sweden during hunting season. Pellets were found in both dabbling and diving ducks and were present in birds from six of the eight localities sampled. Usually one or two pellets were found but some ducks contained up to 62 pellets. As the incidence of ingested pellets in the present study is approximately the same as that found in North America, where the annual duck loss due to lead poisoning is estimated to be 2 to 3 percent of the population, it may be assumed that lead poisoning is a mortality factor for Swedish ducks also.

  10. Safety-pin ingestion in children: a cultural fact.

    Science.gov (United States)

    Gün, Feryal; Salman, Tansu; Abbasoglu, Latif; Celik, Rüya; Celik, Alaaddin

    2003-08-01

    Pediatric foreign-body (FB) ingestion is a common problem. Many of these FBs are sharp objects such as needles, toothpicks and safety pins (SP). This report reviews the management of SP ingestion in children. During a 16-year period, we recorded 49 pediatric cases of witnessed SP ingestion. In all children, SPs were used to attach the blue beads to the child's suits with the belief of averting the evil eye. The mean age was 8 months ranging from 4 months to 2 years, and 30 patients were males and 19 were females. SPs were most commonly sited in esophagus (37%) and stomach (37%). In the remainder, the SPs have already reached the duodenum and intestine. In this series, 20 (41%) children passed SPs spontaneously, 14 (28.5%) required endoscopic removal and 15 (30.5%) underwent surgery. The outcome of all patients was uneventful. All of the esophageal SPs require endoscopic intervention, however, after passing into stomach the patients can be observed with keeping the surgical intervention in mind if the SP displays a fixed position for more than three days.

  11. Ingestion of Nevada Test Site Fallout: Internal dose estimates

    International Nuclear Information System (INIS)

    Whicker, F.W.; Kirchner, T.B.; Anspaugh, L.R.

    1996-01-01

    This paper summarizes individual and collective dose estimates for the internal organs of hypothetical yet representative residents of selected communities that received measurable fallout from nuclear detonations at the Nevada Test Site. The doses, which resulted from ingestion of local and regional food products contaminated with over 20 radionuclides, were estimated with use of the PATHWAY food-chain-transport model to provide estimates of central tendency and uncertainty. The thyroid gland received much higher doses than other internal organs and tissues. In a avery few cases, infants might have received thyroid doses in excess of 1 Gy, depending on location, diet, and timing of fallout. 131 I was the primary thyroid dose contributor, and fresh milk was the main exposure pathway. With the exception of the thyroid, organ doses from the ingestion pathway were much smaller (<3%) than those from external gamma exposure to deposited fallout. Doses to residents living closest to the Nevada Test Site were contributed mainly by a few fallout events; doses to more distantly located people were generally smaller, but a greater number of events provided measurable contributions. The effectiveness of different fallout events in producing internal organ doses through ingestion varied dramatically with seasonal timing of the test, with maximum dose per unit fallout occurring for early summer depositions when milk cows were on pasture and fresh, local vegetables were used. Within specific communities, internal doses differed by age, sex, and lifestyle. Collective internal dose estimates for specific geographic areas are provided

  12. Feeding type affects microplastic ingestion in a coastal invertebrate community.

    Science.gov (United States)

    Setälä, Outi; Norkko, Joanna; Lehtiniemi, Maiju

    2016-01-15

    Marine litter is one of the problems marine ecosystems face at present, coastal habitats and food webs being the most vulnerable as they are closest to the sources of litter. A range of animals (bivalves, free swimming crustaceans and benthic, deposit-feeding animals), of a coastal community of the northern Baltic Sea were exposed to relatively low concentrations of 10 μm microbeads. The experiment was carried out as a small scale mesocosm study to mimic natural habitat. The beads were ingested by all animals in all experimental concentrations (5, 50 and 250 beads mL(-1)). Bivalves (Mytilus trossulus, Macoma balthica) contained significantly higher amounts of beads compared with the other groups. Free-swimming crustaceans ingested more beads compared with the benthic animals that were feeding only on the sediment surface. Ingestion of the beads was concluded to be the result of particle concentration, feeding mode and the encounter rate in a patchy environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. POSTFUNDOPLICATION DYSPHAGIA CAUSES SIMILAR WATER INGESTION DYNAMICS AS ACHALASIA.

    Science.gov (United States)

    Dantas, Roberto Oliveira; Santos, Carla Manfredi; Cassiani, Rachel Aguiar; Alves, Leda Maria Tavares; Nascimento, Weslania Viviane

    2016-01-01

    - After surgical treatment of gastroesophageal reflux disease dysphagia is a symptom in the majority of patients, with decrease in intensity over time. However, some patients may have persistent dysphagia. - The objective of this investigation was to evaluate the dynamics of water ingestion in patients with postfundoplication dysphagia compared with patients with dysphagia caused by achalasia, idiopathic or consequent to Chagas' disease, and controls. - Thirty-three patients with postfundoplication dysphagia, assessed more than one year after surgery, together with 50 patients with Chagas' disease, 27 patients with idiopathic achalasia and 88 controls were all evaluated by the water swallow test. They drunk, in triplicate, 50 mL of water without breaks while being precisely timed and the number of swallows counted. Also measured was: (a) inter-swallows interval - the time to complete the task, divided by the number of swallows during the task; (b) swallowing flow - volume drunk divided by the time taken; (c) volume of each swallow - volume drunk divided by the number of swallows. - Patients with postfundoplication dysphagia, Chagas' disease and idiopathic achalasia took longer to ingest all the volume, had an increased number of swallows, an increase in interval between swallows, a decrease in swallowing flow and a decrease in water volume of each swallow compared with the controls. There was no difference between the three groups of patients. There was no correlation between postfundoplication time and the results. - It was concluded that patients with postfundoplication dysphagia have similar water ingestion dynamics as patients with achalasia.

  14. Metabolic and exercise endurance effects of coffee and caffeine ingestion.

    Science.gov (United States)

    Graham, T E; Hibbert, E; Sathasivam, P

    1998-09-01

    Caffeine (Caf) ingestion increases plasma epinephrine (Epi) and exercise endurance; these results are frequently transferred to coffee (Cof) consumption. We examined the impact of ingestion of the same dose of Caf in Cof or in water. Nine healthy, fit, young adults performed five trials after ingesting (double blind) either a capsule (Caf or placebo) with water or Cof (decaffeinated Cof, decaffeinated with Caf added, or regular Cof). In all three Caf trials, the Caf dose was 4.45 mg/kg body wt and the volume of liquid was 7.15 ml/kg. After 1 h of rest, the subject ran at 85% of maximal O2 consumption until voluntary exhaustion (approximately 32 min in the placebo and decaffeinated Cof tests). In the three Caf trials, the plasma Caf and paraxanthine concentrations were very similar. After 1 h of rest, the plasma Epi was increased (P capsules than with Cof. During the exercise there were no differences in Epi among the three Caf trials, and the Epi values were all greater (P capsule trial; there were no differences among the other four tests. One cannot extrapolate the effects of Caf to Cof; there must be a component(s) of Cof that moderates the actions of Caf.

  15. Acute Caffeine Ingestion on Performance in Young Judo Athletes.

    Science.gov (United States)

    Astley, Camilla; Souza, Diego; Polito, Marcos

    2017-08-01

    To compare the acute effect of caffeine ingestion on performance in young judo athletes. In a randomized double-blind design, eighteen judo athletes (16.1 ± 1.4 yrs.) were evaluated on three nonconsecutive days. On the first day, the special judo fitness test (SJFT) was used as a control session. On the second day, the sample was randomly divided into two equal groups. One group received 4 mg.kg -1 of caffeine (capsule) and the other group received a placebo. After resting for 60 min, the sample performed the SJFT. On the final day of testing, the same procedure was performed but the substance ingested was exchanged between the groups. Heart rate (HR) and rating of perceived exertion (RPE) were recorded throughout the applications of the SJFTs. Caffeine ingestion did not induce changes in HR, but reduced the RPE compared with the placebo session (7.0 ± 1.1 vs 8.2 ± 2.0; p performance on SJFT in young judo athletes and reduced the RPE.

  16. A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide

    Directory of Open Access Journals (Sweden)

    Setnik B

    2015-07-01

    Full Text Available Beatrice Setnik,1 Carl L Roland,1 Kenneth W Sommerville,1,2 Glenn C Pixton,1 Robert Berke,3,4 Anne Calkins,5 Veeraindar Goli1,2 1Pfizer Inc, 2Duke University Medical Center, Durham, NC, USA; 3Family Health Medical Services PLLC, Mayville, 4Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, 5New York Spine & Wellness Center, Syracuse, NY, USA Objective: To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN using a standardized conversion guide. Methods: This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility. Results: Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%. The mean (standard deviation number of days to stable dose was 20 (8.94, and number of titration steps to stable dose was 2.4 (1.37. The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again. Conclusion: Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of

  17. Modeling Commercial Turbofan Engine Icing Risk With Ice Crystal Ingestion

    Science.gov (United States)

    Jorgenson, Philip C. E.; Veres, Joseph P.

    2013-01-01

    The occurrence of ice accretion within commercial high bypass aircraft turbine engines has been reported under certain atmospheric conditions. Engine anomalies have taken place at high altitudes that have been attributed to ice crystal ingestion, partially melting, and ice accretion on the compression system components. The result was degraded engine performance, and one or more of the following: loss of thrust control (roll back), compressor surge or stall, and flameout of the combustor. As ice crystals are ingested into the fan and low pressure compression system, the increase in air temperature causes a portion of the ice crystals to melt. It is hypothesized that this allows the ice-water mixture to cover the metal surfaces of the compressor stationary components which leads to ice accretion through evaporative cooling. Ice accretion causes a blockage which subsequently results in the deterioration in performance of the compressor and engine. The focus of this research is to apply an engine icing computational tool to simulate the flow through a turbofan engine and assess the risk of ice accretion. The tool is comprised of an engine system thermodynamic cycle code, a compressor flow analysis code, and an ice particle melt code that has the capability of determining the rate of sublimation, melting, and evaporation through the compressor flow path, without modeling the actual ice accretion. A commercial turbofan engine which has previously experienced icing events during operation in a high altitude ice crystal environment has been tested in the Propulsion Systems Laboratory (PSL) altitude test facility at NASA Glenn Research Center. The PSL has the capability to produce a continuous ice cloud which are ingested by the engine during operation over a range of altitude conditions. The PSL test results confirmed that there was ice accretion in the engine due to ice crystal ingestion, at the same simulated altitude operating conditions as experienced previously in

  18. Bolus Ingestion of Whey Protein Immediately Post-Exercise Does Not Influence Rehydration Compared to Energy-Matched Carbohydrate Ingestion

    Directory of Open Access Journals (Sweden)

    Gethin H. Evans

    2018-06-01

    Full Text Available Whey protein is a commonly ingested nutritional supplement amongst athletes and regular exercisers; however, its role in post-exercise rehydration remains unclear. Eight healthy male and female participants completed two experimental trials involving the ingestion of 35 g of whey protein (WP or maltodextrin (MD at the onset of a rehydration period, followed by ingestion of water to a volume equivalent to 150% of the amount of body mass lost during exercise in the heat. The gastric emptying rates of the solutions were measured using 13C breath tests. Recovery was monitored for a further 3 h by the collection of blood and urine samples. The time taken to empty half of the initial solution (T1/2 was different between the trials (WP = 65.5 ± 11.4 min; MD = 56.7 ± 6.3 min; p = 0.05; however, there was no difference in cumulative urine volume throughout the recovery period (WP = 1306 ± 306 mL; MD = 1428 ± 443 mL; p = 0.314. Participants returned to net negative fluid balance 2 h after the recovery period with MD and 3 h with WP. The results of this study suggest that whey protein empties from the stomach at a slower rate than MD; however, this does not seem to exert any positive or negative effects on the maintenance of fluid balance in the post-exercise period.

  19. ACIDIC AND NEUTRAL LIQUID INGESTION IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE

    Directory of Open Access Journals (Sweden)

    Dafne Calsoni GOMES

    2014-09-01

    Full Text Available Context Sour acidic liquid has a slower distal esophageal transit than a neutral liquid. Our hypothesis was that an acidic sour bolus has a different ingestion dynamic than a neutral bolus. Method In 50 healthy volunteers and 29 patients with gastroesophageal reflux disease (GERD, we evaluated the ingestion dynamics of 100 mL of acidic sour liquid (concentrated lemon juice, pH: 3.0 and 100 mL of water (pH: 6.8. The time to ingest the total volume, the number of swallows to ingest the volume, the interval between swallows, the flux of ingestion and the volume ingested in each swallow was measured. Results In both groups, healthy volunteers and patients in treatment for GERD, the acidic liquid took longer to be ingested, a higher number of swallows, a slower flux of ingestion and a smaller volume in each swallow than the neutral bolus. There was no difference between healthy volunteers and patients with GERD. The ingestion in women was longer than in men for acidic and neutral liquids. Conclusion Acidic liquid has a different dynamic of ingestion than the neutral liquid, which may be consequence of the slower transit through the distal esophageal body or an anticipation to drink a sour bolus. Patients with GERD have the same prolonged ingestion of the acidic liquid bolus as seen in healthy volunteers.

  20. Acidic and neutral liquid ingestion in patients with gastroesophageal reflux disease.

    Science.gov (United States)

    Gomes, Dafne Calsoni; Dantas, Roberto Oliveira

    2014-01-01

    Sour acidic liquid has a slower distal esophageal transit than a neutral liquid. Our hypothesis was that an acidic sour bolus has a different ingestion dynamic than a neutral bolus. In 50 healthy volunteers and 29 patients with gastroesophageal reflux disease (GERD), we evaluated the ingestion dynamics of 100 mL of acidic sour liquid (concentrated lemon juice, pH: 3.0) and 100 mL of water (pH: 6.8). The time to ingest the total volume, the number of swallows to ingest the volume, the interval between swallows, the flux of ingestion and the volume ingested in each swallow was measured. In both groups, healthy volunteers and patients in treatment for GERD, the acidic liquid took longer to be ingested, a higher number of swallows, a slower flux of ingestion and a smaller volume in each swallow than the neutral bolus. There was no difference between healthy volunteers and patients with GERD. The ingestion in women was longer than in men for acidic and neutral liquids. Acidic liquid has a different dynamic of ingestion than the neutral liquid, which may be consequence of the slower transit through the distal esophageal body or an anticipation to drink a sour bolus. Patients with GERD have the same prolonged ingestion of the acidic liquid bolus as seen in healthy volunteers.

  1. POSTFUNDOPLICATION DYSPHAGIA CAUSES SIMILAR WATER INGESTION DYNAMICS AS ACHALASIA

    Directory of Open Access Journals (Sweden)

    Roberto Oliveira DANTAS

    Full Text Available ABSTRACT Background - After surgical treatment of gastroesophageal reflux disease dysphagia is a symptom in the majority of patients, with decrease in intensity over time. However, some patients may have persistent dysphagia. Objective - The objective of this investigation was to evaluate the dynamics of water ingestion in patients with postfundoplication dysphagia compared with patients with dysphagia caused by achalasia, idiopathic or consequent to Chagas' disease, and controls. Methods - Thirty-three patients with postfundoplication dysphagia, assessed more than one year after surgery, together with 50 patients with Chagas' disease, 27 patients with idiopathic achalasia and 88 controls were all evaluated by the water swallow test. They drunk, in triplicate, 50 mL of water without breaks while being precisely timed and the number of swallows counted. Also measured was: (a inter-swallows interval - the time to complete the task, divided by the number of swallows during the task; (b swallowing flow - volume drunk divided by the time taken; (c volume of each swallow - volume drunk divided by the number of swallows. Results - Patients with postfundoplication dysphagia, Chagas' disease and idiopathic achalasia took longer to ingest all the volume, had an increased number of swallows, an increase in interval between swallows, a decrease in swallowing flow and a decrease in water volume of each swallow compared with the controls. There was no difference between the three groups of patients. There was no correlation between postfundoplication time and the results. Conclusion - It was concluded that patients with postfundoplication dysphagia have similar water ingestion dynamics as patients with achalasia.

  2. Microplastic ingestion decreases energy reserves in marine worms.

    Science.gov (United States)

    Wright, Stephanie L; Rowe, Darren; Thompson, Richard C; Galloway, Tamara S

    2013-12-02

    The indiscriminate disposal of plastic to the environment is of concern. Microscopic plastic litter (environment, originating from the fragmentation of plastic items and from industry and personal-care products [1]. On highly impacted beaches, microplastic concentrations (impacts remain understudied [1]. Here, we show that deposit-feeding marine worms maintained in sediments spiked with microscopic unplasticised polyvinylchloride (UPVC) at concentrations overlapping those in the environment had significantly depleted energy reserves by up to 50% (Figure 1). Our results suggest that depleted energy reserves arise from a combination of reduced feeding activity, longer gut residence times of ingested material and inflammation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion.

    Science.gov (United States)

    Thurlow, John S; Little, Dustin J; Baker, Thomas P; Yuan, Christina M

    2013-06-01

    We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ∼5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose chronic exposure. This case represents possible sequelae of chronic potassium chlorate ingestion.

  4. Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion*

    Science.gov (United States)

    Thurlow, John S.; Little, Dustin J.; Baker, Thomas P.; Yuan, Christina M.

    2013-01-01

    We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ∼5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose chronic exposure. This case represents possible sequelae of chronic potassium chlorate ingestion. PMID:26064493

  5. Pathophysiology of esophageal impairment due to button battery ingestion.

    Science.gov (United States)

    Völker, Johannes; Völker, Christine; Schendzielorz, Philipp; Schraven, Sebastian P; Radeloff, Andreas; Mlynski, Robert; Hagen, Rudolf; Rak, Kristen

    2017-09-01

    The increased use of button batteries with high energy densities in devices of daily life presents a high risk of injury, especially for toddlers and young children. If an accidental ingestion of a button battery occurs, this foreign body can become caught in the constrictions of the esophagus and cause serious damage to the adjacent tissue layers. The consequences can be ulcerations, perforations with fistula formation and damage to the surrounding anatomical structures. In order to gain a better understanding of the pathophysiology after ingestion, we carried out systematic studies on fresh preparations of porcine esophagi. The lithium button battery type CR2032, used most frequently in daily life, was exposed in preparations of porcine esophagi and incubated under the addition of artificial saliva at 37 °C. A total of eight esophagi were analysed by different methods. Measurements of the pH value around the battery electrodes and histological studies of the tissue damage were carried out after 0.5-24 h exposure time. In addition, macroscopic time-lapse images were recorded. Measurements of the battery voltage and the course of the electric current supplemented the experiments. The investigations showed that the batteries caused an electrolysis reaction in the moist environment. The positive electrode formed an acidic and the negative electrode a basic medium. Consequently, a coagulation necrosis at the positive pole, and a deep colliquation necrosis at the minus pole occurred. After an exposure time of 12 h, tissue damage caused by the lye corrosion was observed on the side of the negative electrode up to the lamina muscularis. The corrosion progressed up to the final exposure time of 24 h, but the batteries still had sufficient residual voltage, such that further advancing damage would be expected. Button battery ingestion in humans poses an acute life-threatening danger and immediate endoscopic removal of the foreign body is essential. After only 2

  6. [Methaemoglobinaemia induced by ingestion of alkyl nitrite, "poppers"].

    Science.gov (United States)

    Kragsfeldt, Celina Thelberg; Nissen, Christoffer B; Brandt, Frans

    2016-08-22

    We present a case report of an 18-year-old male who was referred to the emergency department with evidence of methaemoglobinaemia. He presented with classic symptoms with peripheral cyanosis and hypoxia. Arterial blood gas showed a methaemoglobin level of 36%. This was caused by ingestion of alkyl nitrate, a widespread party drug called "poppers". When inhaled it causes euphoria, reduced pain and relaxation of the anal sphincter, but oral use may induce life-threatening methaemoglobinaemia. The treatment of choice is the antidote methylene blue. After treatment the patient regained full recovery and was discharged on the following day. We discuss classic symptoms, diagnosis and treatment of intoxication with methylene blue.

  7. Orally ingestion of krokodil in Spain: report of a case.

    Science.gov (United States)

    Baquero Escribano, Abel; Beltrán Negre, María Teresa; Calvo Orenga, Gema; Carratalá Monfort, Sonia; Arnau Peiró, Francisco; Meca Zapatero, Sara; Haro Cortés, Gonzalo

    2016-06-14

    The krokodil use disorder is an addictive pathology with quite severe organic effects, especially at the skin level, that causes severe and degenerative necrosis of blood and muscle tissue. Though this disorder has a low prevalence in Spain, compared to the large number of consumers in other countries such as Ukraine or Russia, its consumption is slowly but gradually expanding in countries of the European Union and America. The simplicity of the process of obtaining the substance from desomorphine, together with its high availability and low cost, contribute toward consumers' self-sufficiency. This article presents the case of a user of krokodil and reviews the clinical symptoms of oral ingestion.

  8. Acute ingestion dosimetry using the ICRP 30 gastrointestinal tract model

    International Nuclear Information System (INIS)

    Cassels, B.M.

    1987-01-01

    This paper examines the gastrointestinal (GI) tract model used for dosimetry as outlined in ICRP30, to allow quick calculations of effective dose equivalents for acute radionuclide ingestion. A computer program has been developed to emulate the GI tract model. The program and associated data files are structured so that the GI tract model parameters can be varied, while the file structure and algorithm for the GI tract model should require minimal modification to allow the same theories that apply in this model to be used for other dosimetric models

  9. Congenital goiter due to maternal ingestion of iodide

    International Nuclear Information System (INIS)

    Iancu, T.; Boyanower, Y.; Laurian, N.

    1974-01-01

    A newborn infant with large bilateral cervical masses developed respiratory difficulties three days after birth. A congenital goiter was suspected and a biopsy was performed. Later information pointed to the ingestion of large amounts of inorganic iodine, during the pregnancy, by the asthmatic mother. Further investigation proved the goiter to be due to transient depression of peroxidase activity by the exogenous iodine. Within several days after birth, the infant's thyroid regained its full activity, the goiter disappeared, and the few signs of hypothyroidism subsided. (U.S.)

  10. A Case of Argyria Following Colloidal Silver Ingestion

    OpenAIRE

    Kwon, Hyok Bu; Lee, Joon Ho; Lee, Seung Ho; Lee, Ai Young; Choi, Jong Sun; Ahn, Yeon Soon

    2009-01-01

    Argyria is a rare cutaneous discoloration caused by the intake of silver or various compounds containing silver. We report a case of argyria in a 73-year-old male following ingestion of colloidal silver as an alternative medicine over 5 years. He had a diffuse, slate gray discoloration of his face and hands. A biopsy specimen from the face revealed brown-black extracellular granules in the upper dermis and between collagen bundles. We also found silver particles in the mucous of the colon. Th...

  11. Effects of lifetime ingestion of 90Sr in beagle dogs

    International Nuclear Information System (INIS)

    Book, S.A.; Spangler, W.L.; Swartz, L.A.

    1982-01-01

    To investigate the effects of lifetime 90 Sr ingestion, fifteen beagle dogs were fed the equivalent of 1.3, 4.0, and 12.0 μCi 90 Sr. Exposures prior to weaning were made by maternal administration of one of the same 90 Sr levels, begining at 21 days of gestation. Median survival was 12.5 years for the 1.3 μCi/day group, 6.5 years for the 4 μCi/day group, and 5.2 years of the 12 μCi/day group, compared to unirradiated control values of 14.5 to 15 years. The normal life span of more than half of the 1.3 μCi/day group is remarkable, considering they ingested 5900 to 7500 μCi 90 Sr during their lifetimes. One of seven 1.3 μCi/day dogs died of mycloproliferative syndrome (MPS), while one of four 4 μCi/day and one of four 12 μCi/day dogs died from MPS. In addition, another 12 μCi/day dog died of osteosarcoma and two others in the same group showed skeletal changes related to 90 Sr exposure. Other deaths were as could be expected in normal canine populations. Lifetime skeletal doses, determined by periodic whole-body counting, were 1990-3750, 1880-9230, and 6360-14,680 rad for the 1.3, 4, and 12 μCi/day groups, respectively. Comparison of these values with those from the large 90 Sr toxicity study at Davis in which 90 Sr feeding ended at 18 months of age indicates similar average skeletal doses from the two types of feeding regimens. The similarity of the skeletal doses may relate to the inability of 90 Sr to be incorporated to any great extent into a mature skeleton that no longer has the high calcium turnover associated with early life. As a result, deaths from lifetime 90 Sr ingestion appeared no earlier than when 90 Sr ingestion ended in early adulthood

  12. Salicylate toxicity from ingestion of traditional massage oil

    Science.gov (United States)

    Muniandy, Rajesh Kumar; Sinnathamby, Vellan

    2012-01-01

    A 16-month-old child developed a brief generalised tonic–clonic fitting episode and vomiting at home, after accidental ingestion of traditional massage oil. As the patient presented with clinical features of salicylate toxicity, appropriate management was instituted. He was admitted to the intensive care unit for multiorgan support. The child was discharged well 1 week after the incident. Methyl-salicylate is a common component of massage oils which are used for topical treatment of joint and muscular pains. However, these massage oils may be toxic when taken orally. Early recognition of the salicylate toxicity is very important in producing a good patient outcome. PMID:22922924

  13. Characteristics of hand sanitizer ingestions by adolescents reported to poison centers.

    Science.gov (United States)

    Forrester, Mathias B

    2015-02-01

    There had been reports of adolescents using hand sanitizers to obtain alcohol and ending up in emergency departments with alcohol poisoning. This study aimed to describe the pattern of adolescent ingestions of hand sanitizers reported to a statewide poison center system. Our study subjects included patients aged 13-19 years who reported hand sanitizer ingestions as reported to Texas poison centers during 2000-2013. The distribution of the ingestions was determined for various demographic and clinical factors. Of 385 total cases, 61% of the patients were male, and the mean age was 15.3 years. The ingestion reason was unintentional (61%), intentional abuse/misuse (18%), and malicious (10%). Ingestion site was most frequently reported to be the patient's own residence (53%), followed by school (35%). About 77% of the patients were managed on site. The medical outcome was serious (moderate effect or unable to follow-potentially toxic) in 5% of the cases. The most frequently reported adverse clinical effects were vomiting (5%), abdominal pain (4%), nausea (4%), throat irritation (4%), and drowsiness (2%). Adolescents who ingested hand sanitizers were more likely to be male and younger. One-third of the ingestions occurred at school, suggesting that school personnel might be made aware of the potential problem of hand sanitizer ingestions by adolescents. Nevertheless, despite the potential for serious outcomes from adolescent hand sanitizer ingestion, most of the ingestions reported to poison centers are not likely to be serious and can be successfully managed outside of a healthcare facility.

  14. Transmesocolic double gastro-enteric fistulas due to ingestion of 28 magnets

    Directory of Open Access Journals (Sweden)

    Adrian Surd

    2018-05-01

    Full Text Available Introduction: Accidental ingestion of magnetic foreign bodies has become more common due to increased availability of objects and toys with magnetic elements. The majority of them traverse the gastrointestinal system spontaneously without complication. However, ingestion of multiple magnets may require surgical resolution. Magnet ingestion usually does not cause serious complications, but in case of multiple magnet ingestion or ingestion of magnet and a metal object, it could cause intestinal obstruction, fistula formation or even perforation. Case report: We report case of a transmesocolic double gastro-enteric fistula formation following ingestion of 28 small magnets in a 17 months old boy. No history of foreign body ingestion could be obtained from parents therefore the patient was treated conservatively in a pediatric clinic for vomiting, dehydration, upper respiratory tract infection and suspicion of upper digestive tract bleeding. After 48 h he was sent in our clinic for surgical evaluation. Intraoperatively double transmesocolic gastro-enteric fistula was found. After separation of de gastric and enteral walls, resection of gastric wall and intestinal segment containing the two perforations was performed, followed by gastric suture in two layers and entero-enteric anastomosis. A total of 28 magnets were removed from the stomach and small intestine. Conclusion: Single magnet ingestion is treated as non-magnetic foreign body. Multiple magnet ingestion should be closely monitored and surgical approach could be the best option to prevent or to cure its complications. Keywords: Ingestion, Magnetic foreign body, Multiple magnets, Intestinal fistula, Children

  15. Ingestion of Caustic Substances in Adults: A Review Article

    Directory of Open Access Journals (Sweden)

    Andon Chibishev

    2013-02-01

    Full Text Available Background: Ingestion of caustic agents can cause serious damages of the upper gastrointestinal tract and in some cases this kind of poisoning may have fatal outcomes. Acute caustic intoxications are one of the main problems in the modern clinical toxicology since they mainly affect young people with psychic disorders, suicidal intent, and alcohol addiction. Text: In diagnostic evaluation of this kind of poisoning, different procedures are used. Today’s golden standard for determination of the grade and extent of the lesion is esophagogastroduodenoscopy (EGD performed in the first 12-24 hours following corrosive ingestion. In some patients, some late complications, such as esophageal stenosis and gastric stenosis, which are the most common, as well as carcinoma of the upper gastrointestinal tract, which is rarely seen, can be detected. Acute caustic poisonings are treated with specific kinds of protocols. According to them, first, an attempt is made to neutralize the poison. Combinations of antibiotics, anti-secretory drugs, and collagen synthesis inhibitors are used. As a support therapy, nutritional liquids can be utilized, and in the most unmanageable cases, esophageal dilatation, stent placement and surgery are used. Conclusion: In the future, caustic poisonings will remain a serious socio-medical issue, due to the difficult clinical presentation, expensive diagnostic protocol, extended hospitalization, and possible permanent disability.

  16. Preliminary evidence that glucose ingestion facilitates prospective memory performance.

    Science.gov (United States)

    Riby, Leigh M; Law, Anna S; McLaughlin, Jennifer; Murray, Jennifer

    2011-05-01

    Previous research has found that the ingestion of glucose boosts task performance in the memory domain (including tasks tapping episodic, semantic, and working memory). The present pilot study tested the hypothesis that glucose ingestion would enhance performance on a test of prospective memory. In a between-subjects design, 56 adults ranging from 17 to 80 years of age performed a computerized prospective memory task and an attention (filler) task after 25 g of glucose or a sweetness-matched placebo. Blood glucose measurements were also taken to assess the impact of individual differences on glucose regulation. After the drink containing glucose, cognitive facilitation was observed on the prospective memory task after excluding subjects with impaired fasting glucose level. Specifically, subjects receiving glucose were 19% more accurate than subjects receiving a placebo, a trend that was marginally nonsignificant, F₁,₄₁ = 3.4, P = .07, but that had a medium effect size, d = 0.58. Subjects receiving glucose were also significantly faster on the prospective memory task, F₁,₃₅ = 4.8, P glucose (indicative of poor glucose regulation) was associated with slower prospective memory responding, F₁,₃₅ = 4.4, P memory and executive functioning can benefit from the increased provision of glucose to the brain. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Ingestion of Fireworks: Rare Cause of Poisoning in Children.

    Science.gov (United States)

    Yuksekkaya, Hasan; Gumus, Meltem; Yucel, Aylin; Energin, Meltem; Demirci, Serafettin

    2018-03-12

    Mistaken ingestion of all manner of toxic matter is common in childhood, but poisoning with fireworks and matchsticks is rare. Fireworks usually contain 10% yellow phosphorus and 50% potassium chlorate. Potassium chlorate is an extremely reactive and toxic agent that is used in fireworks and matchstick heads. Eleven cases (7 females and 5 males; median age, 36 months [ranging from 24 to 48 months]) of poisoning after ingestion of fireworks and matchstick(s), between February 2008 and June 2014, were reviewed. The most common initial symptom was vomiting except for 2 cases in this group. Biochemical tests indicated that hyperphosphatemia was present in all patients, 8 patients (72.7%) had subclinical hepatic injury, 1 (9%) had acute hepatic failure, and 2 patients had no clinical or biochemical evidence of hepatic damage. Three patients had renal impairment, but none of them required dialysis. All of the patients recovered with supportive therapy except for 2 cases. One patient underwent cadaveric liver transplantation, whereas the other died because of circulatory dysfunction and respiratory failure due to pulmonary alveolar hemorrhage. Without prompt intervention, poisoning with fireworks carries high morbidity and mortality in children. It can cause pulmonary hemorrhage, in addition to other organ damage, including liver and kidney. Hyperphosphatemia is common, as it was seen in all of the study patients.

  18. Biogastronomy: Factors that determine the biological response to meal ingestion.

    Science.gov (United States)

    Pribic, T; Azpiroz, F

    2018-02-02

    The biological response to a meal includes physiological changes, primarily related to the digestive process, and a sensory experience, involving sensations related to the homeostatic control of food consumption, eg, satiety and fullness, with a hedonic dimension, ie associated with changes in digestive well-being and mood. The responses to a meal include a series of events before, during and after ingestion. While much attention has been paid to the events before and during ingestion, relatively little is known about the postprandial sensations, which are key to the gastronomical experience. The aim of this narrative review is to provide a comprehensive overview and to define the framework to investigate the factors that determine the postprandial experience. Based on a series of proof-of-concept studies and related information, we propose that the biological responses to a meal depend on the characteristics of the meal, primarily its palatability and composition, and the responsiveness of the guest, which may be influenced by multiple previous and concurrent conditioning factors. This information provides the scientific backbone to the development of personalized gastronomy. © 2018 John Wiley & Sons Ltd.

  19. Effects of fluid, electrolyte and substrate ingestion on endurance capacity.

    Science.gov (United States)

    Maughan, R J; Fenn, C E; Leiper, J B

    1989-01-01

    The availability of carbohydrate (CHO) as a substrate for the exercising muscles is known to be a limiting factor in the performance of prolonged cycle exercise, and provision of exogenous CHO in the form of glucose can increase endurance capacity. The present study examined the effects of ingestion of fluids and of CHO in different forms on exercise performance. Six male volunteers exercised to exhaustion on a cycle ergometer at a workload which required approximately 70% of Vo2max. After one preliminary trial, subjects performed this exercise test on six occasions, one week apart. Immediately before exercise, and at 10-min intervals throughout, subjects ingested 100 ml of one of the following: control (no drink), water, glucose syrup, fructose syrup, glucose-fructose syrup or a dilute glucose-electrolyte solution. Each of the syrup solutions contained approximately 36 g CHO per 100 ml; the isotonic glucose-electrolyte solution contained 4 g glucose per 100 ml. A randomised Latin square order of administration of trials was employed. Expired air samples for determination of Vo2, respiratory exchange ratio and rate of CHO oxidation were collected at 15-min intervals. Venous blood samples were obtained before and after exercise. Subjects drinking the isotonic glucose-electrolyte solution exercised longer (90.8 (12.4) min, mean (SEM] than on the control test (70.2 (8.3) min; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Aeromechanics Analysis of a Boundary Layer Ingesting Fan

    Science.gov (United States)

    Bakhle, Milind A.; Reddy, T. S. R.; Herrick, Gregory P.; Shabbir, Aamir; Florea, Razvan V.

    2013-01-01

    Boundary layer ingesting propulsion systems have the potential to significantly reduce fuel burn but these systems must overcome the challe nges related to aeromechanics-fan flutter stability and forced response dynamic stresses. High-fidelity computational analysis of the fan a eromechanics is integral to the ongoing effort to design a boundary layer ingesting inlet and fan for fabrication and wind-tunnel test. A t hree-dimensional, time-accurate, Reynolds-averaged Navier Stokes computational fluid dynamics code is used to study aerothermodynamic and a eromechanical behavior of the fan in response to both clean and distorted inflows. The computational aeromechanics analyses performed in th is study show an intermediate design iteration of the fan to be flutter-free at the design conditions analyzed with both clean and distorte d in-flows. Dynamic stresses from forced response have been calculated for the design rotational speed. Additional work is ongoing to expan d the analyses to off-design conditions, and for on-resonance conditions.

  1. Plastic debris ingestion by marine catfish: an unexpected fisheries impact.

    Science.gov (United States)

    Possatto, Fernanda E; Barletta, Mário; Costa, Monica F; do Sul, Juliana A Ivar; Dantas, David V

    2011-05-01

    Plastic marine debris is a pervasive type of pollution. River basins and estuaries are a source of plastics pollution for coastal waters and oceans. Estuarine fauna is therefore exposed to chronic plastic pollution. Three important catfish species [Cathorops spixii (N=60), Cathorops agassizii (N=60) and Sciades herzbergii (N=62)] from South Western Atlantic estuaries were investigated in a tropical estuary of the Brazilian Northeast in relation to their accidental ingestion of plastic marine debris. Individuals from all three species had ingested plastics. In C. spixii and C. agassizii, 18% and 33% of individuals had plastic debris in their stomachs, respectively. S. herzbergii showed 18% of individuals were contaminated. All ontogenetic phases (juveniles, sub-adults and adults) were contaminated. Nylon fragments from cables used in fishery activities (subsistence, artisanal and commercial) played a major role in this contamination. These catfish spend their entire life cycles within the estuary and are an important feeding resource for larger, economically important, species. It is not yet possible to quantify the scale and depth of the consequences of this type of pollution. However, plastics are well known threat to living resources in this and other estuaries. Conservation actions will need to from now onto take plastics pollution into consideration. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Changes in mouse gastrointestinal microbial ecology with ingestion of kale.

    Science.gov (United States)

    Uyeno, Y; Katayama, S; Nakamura, S

    2014-09-01

    Kale, a cultivar of Brassica oleracea, has attracted a great deal of attention because of its health-promoting effects, which are thought to be exerted through modulation of the intestinal microbiota. The present study was performed to investigate the effects of kale ingestion on the gastrointestinal microbial ecology of mice. 21 male C57BL/6J mice were divided into three groups and housed in a specific pathogen-free facility. The animals were fed either a control diet or experimental diets supplemented with different commercial kale products for 12 weeks. Contents of the caecum and colon of the mice were processed for the determination of active bacterial populations by a bacterial rRNA-based quantification method and short-chain fatty acids by HPLC. rRNAs of Bacteroides-Prevotella, the Clostridium coccoides-Eubacterium rectale group, and Clostridium leptum subgroup constituted the major fraction of microbiota regardless of the composition of the diet. The ratio of Firmicutes to Bacteroidetes was higher in the colon samples of one of the kale diet groups than in the control. The colonic butyrate level was also higher with the kale-supplemented diet. Overall, the ingestion of kale tended to either increase or decrease the activity of specific bacterial groups in the mouse gastrointestinal tract, however, the effect might vary depending on the nutritional composition.

  3. Acute oxalate nephropathy after ingestion of star fruit.

    Science.gov (United States)

    Chen, C L; Fang, H C; Chou, K J; Wang, J S; Chung, H M

    2001-02-01

    Acute oxalate nephropathy associated with ingestion of star fruit (carambola) has not been reported before. We report the first two cases. These patients developed nausea, vomiting, abdominal pain, and backache within hours of ingesting large quantities of sour carambola juice; then acute renal failure followed. Both patients needed hemodialysis for oliguric acute renal failure, and pathologic examinations showed typical changes of acute oxalate nephropathy. The renal function recovered 4 weeks later without specific treatment. Sour carambola juice is a popular beverage in Taiwan. The popularity of star fruit juice is not compatible with the rare discovery of star fruit-associated acute oxalate nephropathy. Commercial carambola juice usually is prepared by pickling and dilution processes that reduce oxalate content markedly, whereas pure fresh juice or mild diluted postpickled juice for traditional remedies, as used in our cases, contain high quantities of oxalate. An empty stomach and dehydrated state may pose an additional risk for development of renal injury. To avoid acute oxalate nephropathy, pure sour carambola juice or mild diluted postpickled juice should not be consumed in large amounts, especially on an empty stomach or in a dehydrated state.

  4. Effect of Coffee and Caffeine Ingestion on Resistance Exercise Performance.

    Science.gov (United States)

    Richardson, Darren L; Clarke, Neil D

    2016-10-01

    Richardson, DL and Clarke, ND. Effect of coffee and caffeine ingestion on resistance exercise performance. J Strength Cond Res 30(10): 2892-2900, 2016-The aim of the present study was to determine the effect of ingesting caffeine dose-matched anhydrous caffeine, coffee, or decaffeinated coffee plus anhydrous caffeine during resistance exercise on performance. Nine resistance-trained men (mean ± SD: age, 24 ± 2 years; weight, 84 ± 8 kg; height, 180 ± 8 cm) completed a squat and bench press exercise protocol at 60% 1 repetition maximum until failure on 5 occasions consuming 0.15 g·kg caffeinated coffee (COF), 0.15 g·kg decaffeinated coffee (DEC), 0.15 g·kg decaffeinated coffee plus 5 mg·kg anhydrous caffeine (D + C), 5 mg·kg anhydrous caffeine (CAF), or a placebo (PLA). Felt arousal and rating of perceived exertion (RPE) were used to assess perceptual variables and heart rate (HR) to assess physiological responses between trials. There were significant differences in total weight lifted for the squat between conditions (p caffeine have the ability to improve performance during a resistance exercise protocol, although possibly not over multiple bouts.

  5. Plastic ingestion by fish in the Southern Hemisphere: A baseline study and review of methods.

    Science.gov (United States)

    Cannon, Seon M E; Lavers, Jennifer L; Figueiredo, Bianca

    2016-06-15

    Plastic ingestion is well documented among marine birds and sea turtles but fewer studies have investigated ingestion in fish, particularly in the Southern Hemisphere. We investigated the frequency of plastic ingestion in 21 species of fish and one species of cephalopod. The overall occurrence of plastic ingestion was 0.3%. Two micro-plastic items were recovered from the gastrointestinal tract of a single Antarctic toothfish (Dissostichus mawsoni). Ingestion rates were similar to other studies of fish conducted in both the Northern and Southern Hemispheres, however comparisons across species and locations are challenging due to the lack of consistency in the identification and classification of plastic debris. In response, we propose a standardised sampling protocol based on the available literature to provide a stronger basis for comparisons among existing and future studies of plastic ingestion in fish. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Intestinal volvulus and perforation caused by multiple magnet ingestion: report of a case.

    Science.gov (United States)

    Ilçe, Zekeriya; Samsum, Hakan; Mammadov, Emil; Celayir, Sinan

    2007-01-01

    Ingested magnets can cause intestinal fistulas, perforation, and obstruction. There have been reports of magnet ingestion causing intestinal volvulus, but multiple magnet ingestion causing perforation and intestinal volvulus in a child is very unusual. We report the case of a 4-year-old girl, who ingested four magnets she acquired as toys, which caused intestinal volvulus and perforation as a result of pressure necrosis, several days after ingestion. At surgery we repaired two perforations, but additional bowel resection was not required. The patient was discharged on postoperative day 10. If multiple magnet ingestion is suspected in a child, the child must be monitored carefully. If there are signs of obstruction, emergency surgery is mandatory.

  7. Prevalence, clinical features and management of pediatric magnetic foreign body ingestions.

    Science.gov (United States)

    Tavarez, Melissa M; Saladino, Richard A; Gaines, Barbara A; Manole, Mioara D

    2013-01-01

    Foreign body (FB) ingestions are frequent in children. Whereas the majority of FBs pass spontaneously through the gastrointestinal tract, ingestion of magnetic FBs pose a particular risk for obstruction due to proximate attraction through the intestinal wall. We aimed to identify the prevalence, clinical presentation, and management of magnetic FB ingestions at our tertiary care institution. We performed a retrospective chart review of medical records of patients presenting to the pediatric Emergency Department (ED) or admitted to the hospital with FB ingestions from June 2003-July 2009. From those cases, patients with magnetic FB ingestions were identified. During the study period, 337,839 patients presented to the ED; 38 cases of magnetic FB ingestion were identified (prevalence 0.01%). Abdominal radiography was obtained in all cases. Ingestion of a single magnet occurred in 30 of 38 cases (79%). Of those, 4 patients underwent endoscopic removal due to signs of FB impaction in the esophagus or pylorus; no complications were noted. Ingestion of multiple magnets (range 2-6) occurred in 8 of 38 cases. Four of the 8 patients with multiple magnetic FBs (50%) presented with signs of peritonitis and required operative repair of multiple intestinal perforations. No deaths were identified. Although ingestion of a single magnetic FB may, in most cases, be managed as a simple FB ingestion, the ingestion of multiple magnetic FB is associated with a high risk of complication and requires aggressive management. We propose an algorithm for management of children with magnetic FB ingestions. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Feeding behaviour of sheep fed lucerne v. grass hays with controlled post-ingestive consequences

    OpenAIRE

    Favreau, Angelique; Ginane, Cécile; Baumont, Rene

    2010-01-01

    Understanding what determines feeding behaviour in herbivores is essential to optimise the use of forages in breeding systems. Herbivores can evaluate foods by associative learning of their pre-ingestive characteristics (taste, odour, etc.) and their postingestive consequences. Post-ingestive consequences are acknowledged as influencing intake and food choices, but the role of pre-ingestive characteristics is still being debated. Our experiment was designed to test their separate effects on d...

  9. After the Recall: Reexamining Multiple Magnet Ingestion at a Large Pediatric Hospital.

    Science.gov (United States)

    Rosenfield, Daniel; Strickland, Matt; Hepburn, Charlotte Moore

    2017-07-01

    To evaluate the effectiveness of a mandatory product recall on the frequency of multiple mini-magnet ingestion at a large tertiary pediatric hospital, and to examine the morbidity and mortality associated with these ingestions. In this retrospective chart review, we searched our institution's electronic patient record for patients aged magnetic foreign bodies between 2002 and 2015, a period that included the mandatory product recall. We compared the frequency and character of ingestions before and after the recall. Comparing the postrecall years (January 1, 2014, to December 31, 2015) with the 2 years immediately preceding the recall year (January 1, 2011, to December 31, 2012) yields an incidence rate ratio of 0.34 (95% CI, 0.18-0.64) for all magnet ingestions and 0.20 (95% CI, 0.08-0.53) for ingestion of multiple magnets. Based on the Fisher exact test, the incidence of both magnet ingestion (P magnet ingestion (P magnet ingestion decreased. There were no deaths in either study period. There was a significant decrease in multiple mini-magnet ingestion following a mandatory product recall. This study supports the effectiveness of the recall, which should bolster efforts to keep it in place in jurisdictions where it is being appealed. More broadly, the result provides general evidence of a recall helping decrease further harm from a product that carries a potential hazard. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. [Psychotic Acute Episode and Rhabdomyolysis after Lovastatin Ingestion].

    Science.gov (United States)

    Caamaño, Beatriz H; Díaz, Jairo M González; Bracho, Daniel Guerrero; Herrera, Harold; Samur, Manuel Castro

    2012-09-01

    Statins are the most prescribed drugs worldwide given the benefit and security they offer. However, they can cause severe neurological, gastrointestinal, renal and muscular side effects. To describe the clinical course of a female patient with adverse drug reaction to Lovastatin. Case report and literature review. 52-year old woman with sudden psychosis and rhabdomyolysis secondary to Lovastatin and ending after the drug suspension. The causal relationship was corroborated with a score of 6 (probable ADR) on Naranjo's Scale. The simultaneous manifestation of psychosis and rhabdomiolysis represents an atypical and unique case following Lovastatin ingestion. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  11. Selection of Models for Ingestion Pathway and Relocation

    International Nuclear Information System (INIS)

    Blanchard, A.; Thompson, J.M.

    1998-01-01

    The area in which intermediate phase protective actions (such as food interdiction and relocation) may be needed following postulated accidents at three Savannah River Site nonreactor nuclear facilities will be determined by modeling. The criteria used to select dispersion/deposition models are presented. Several models are considered, including ARAC, MACCS, HOTSPOT, WINDS (coupled with PUFF-PLUME), and UFOTRI. Although ARAC and WINDS are expected to provide more accurate modeling of atmospheric transport following an actual release, analyses consistent with regulatory guidance for planning purposes may be accomplished with comparatively simple dispersion models such as HOTSPOT and UFOTRI. A recommendation is made to use HOTSPOT for non-tritium facilities and UFOTRI for tritium facilities. The most recent Food and Drug Administration Derived Intervention Levels (August 1998) are adopted as evaluation guidelines for ingestion pathways

  12. Selection of Models for Ingestion Pathway and Relocation

    International Nuclear Information System (INIS)

    Blanchard, A.; Thompson, J.M.

    1999-01-01

    The area in which intermediate phase protective actions (such as food interdiction and relocation) may be needed following postulated accidents at three Savannah River Site nonreactor nuclear facilities will be determined by modeling. The criteria used to select dispersion/deposition models are presented. Several models are considered, including ARAC, MACCS, HOTSPOT, WINDS (coupled with PUFF-PLUME), and UFOTRI. Although ARAC and WINDS are expected to provide more accurate modeling of atmospheric transport following an actual release, analyses consistent with regulatory guidance for planning purposes may be accomplished with comparatively simple dispersion models such as HOTSPOT and UFOTRI. A recommendation is made to use HOTSPOT for non-tritium facilities and UFOTRI for tritium facilities. The most recent Food and Drug Administration Derived Intervention Levels (August 1998) are adopted as evaluation guidelines for ingestion pathways

  13. Radionuclides in food and the radiation exposure due to ingestion

    International Nuclear Information System (INIS)

    Michel, Rolf

    2015-01-01

    As a consequence of the reactor accidents in Fukushima Daiichi high amounts of radioactive iodine and cesium isotopes were released into the terrestrial and marine Japanese environment. The largest release occurred on March 15, 2011 as a consequence of the containment failure of unit 2. Due to the meteorological conditions large area fallout occurred in the district of Fukushima. Other prefectures in the north of Japan were also contaminated. As a consequence of the high surface contamination the dose limits for drinking water, milk and milky products and food were increased to 200 Bq/kg.It turned out that the contamination of rice was marginal, the contamination of predatory fish higher than that of non-predatory fish. A systematic investigation of food samples could allow a better estimation of ingestion induced exposure.

  14. A crisis management decision support system to reduce ingestion dose

    International Nuclear Information System (INIS)

    Schenker-Wicki, A.; Gibbert, R.

    1993-01-01

    Environmental accidents such as extensive radioactive or chemical contamination can have more serious consequences for a population than any other kind of accidents known before. Owing to the serious consequences and the high number of people who may be affected, the selection of the best countermeasures to ameliorate the imminent impact is very difficult and the political responsibility is enormous. To help overcome such problems the National Emergency Operations Center in Zurich (Switzerland) has developed a decision support system to evaluate acceptable countermeasures for reducing ingestion dose after an accidental release of radioactive material. The system involves all the necessary modules and techniques for efficient decision making, based on the most recent developments in decision theory as well as the necessary structuring of the decision-making process. The decision-making concept comprehends decision making on two different levels, a technical and a political one. (author)

  15. Recurrent lactic acidosis secondary to hand sanitizer ingestion.

    Science.gov (United States)

    Wilson, M E; Guru, P K; Park, J G

    2015-01-01

    Due to their ability to decrease the spread of infection, hand sanitizers are now ubiquitous in health care settings. We present the case of a 50-year-old woman who was admitted with acute alcohol intoxication and had near complete recovery in 12 hrs. Subsequently, she was found unresponsive on the floor of her hospital room on two separate occasions. Evaluations revealed repeatedly elevated levels of ethanol, acetone, and lactate as well as increased anion gap and hypotension, requiring intensive care unit evaluation and intubation for airway protection. During the second episode, she was found next to an empty bottle of ethanol-based hospital hand sanitizer. She confirmed ingesting hand sanitizer in order to become intoxicated.

  16. Recurrent lactic acidosis secondary to hand sanitizer ingestion

    Directory of Open Access Journals (Sweden)

    M E Wilson

    2015-01-01

    Full Text Available Due to their ability to decrease the spread of infection, hand sanitizers are now ubiquitous in health care settings. We present the case of a 50-year-old woman who was admitted with acute alcohol intoxication and had near complete recovery in 12 hrs. Subsequently, she was found unresponsive on the floor of her hospital room on two separate occasions. Evaluations revealed repeatedly elevated levels of ethanol, acetone, and lactate as well as increased anion gap and hypotension, requiring intensive care unit evaluation and intubation for airway protection. During the second episode, she was found next to an empty bottle of ethanol-based hospital hand sanitizer. She confirmed ingesting hand sanitizer in order to become intoxicated.

  17. Rhinocerebral Mucor circinelloides infection in immunocompromised patient following yogurt ingestion.

    Science.gov (United States)

    Lazar, Stephen P; Lukaszewicz, Jennifer M; Persad, Kamleish A; Reinhardt, John F

    2014-08-01

    The purpose of this case report is to illustrate the cause of this patient's headache and sinus pain in the setting of a unique environmental exposure: the patient ingested yogurt only days before presentation. This particular brand of yogurt caused controversy in early September 2013 when the manufacturer voluntarily recalled all flavors. The yogurt was found to be contaminated with Mucor circinelloides. The recall was triggered by the FDA, after receiving many complaints from consumers affected by temporary gastrointestinal symptoms such as abdominal cramping, diarrhea, and nausea. This patient was diagnosed with Rhinocerebral mucormycosis through fungal culture of the affected area. He was specifically colonized with Mucor circinelloides, a variant that rarely causes disease in humans. According to a literature review, only eight cases of mucormycosis in adults caused by this strain were documented before 2009.

  18. A lethal cocktail: gastric perforation following liquid nitrogen ingestion.

    Science.gov (United States)

    Pollard, James Scott; Simpson, Joanne Elizabeth; Bukhari, Moatasiem Idris

    2013-01-07

    We report a case of gastric perforation in an 18-year-old girl as a result of ingesting an alcoholic drink containing liquid nitrogen. The drink was purchased in licensed premises. The extent of the injury necessitated total gastrectomy with Roux-en Y reconstruction. We review the literature, discuss the mechanism of injury and consider the implications for medical services. The authors believe this case is of educational interest to professionals working in emergency medicine, general surgery and public health fields. It raises awareness of a rare injury, but one that may be more commonly encountered because of developing social trends. It informs surgeons confronted with this type of injury that trauma to the gastrointestinal tract can be extensive and preoperative contact with oesophago-gastric colleagues is advisable. Public health bodies must be aware of, and monitor, the use of liquid nitrogen in this way and consider regulation to prevent further injuries.

  19. Ultrastructural apoptotic lesions induced in rat thymocytes after borax ingestion.

    Science.gov (United States)

    Sylvain, I C; Berry, J P; Galle, P

    1998-01-01

    Apoptosis has gained increasing attention in recent years. Several chemical compounds induce apoptotic lesions in the thymus. Male Wistar rats received 2000 ppm of borax (Na2B4O7.10H2O) in their food for 16 days. The rats were sacrificed 2, 5, 9, 12, 19, 21, 26 and 28 days after the beginning of treatment. Thymus samples of all rats were taken. A Philips EM 300 electron microscopy was used to study the ultrastructural morphology. Serious nuclear and cytoplasmic lesions were observed. Moreover, numerous macrophages containing apoptotic cells were present in the thymus. The alterations were observed from the 2nd to the 28th day. The extent of damage was much more important in the rats sacrificed 21, 26 and 28 days after borax ingestion.

  20. Development of internal dose calculation programing via food ingestion

    International Nuclear Information System (INIS)

    Kim, H. J.; Lee, W. K.; Lee, M. S.

    1998-01-01

    Most of dose for public via ingestion pathway is calculating for considering several pathways; which start from radioactive material released from a nuclear power plant to diffusion and migration. But in order to model these complicate pathways mathematically, some assumptions are essential and lots of input data related with pathways are demanded. Since there is uncertainty related with environment in these assumptions and input data, the accuracy of dose calculating result is not reliable. To reduce, therefore, these uncertain assumptions and inputs, this paper presents exposure dose calculating method using the activity of environmental sample detected in any pathway. Application of dose calculation is aim at peoples around KORI nuclear power plant and the value that is used to dose conversion factor recommended in ICRP Publ. 60

  1. Incretin effect after oral amino Acid ingestion in humans

    DEFF Research Database (Denmark)

    Lindgren, Ola; Pacini, Giovanni; Tura, Andrea

    2015-01-01

    is also present after amino acid ingestion is not known. OBJECTIVE: The objective of the study was to explore insulin secretion and incretin hormones after oral and iv amino acid administration at matched total amino acid concentrations in healthy subjects. DESIGN: An amino acid mixture (Vaminolac......) was administered orally or iv at a rate resulting in matching total amino acid concentrations to 12 male volunteers with age 22.5 ± 1.4 years and a body mass index 22.4 ± 1.4 kg/m(2), who had no history of diabetes. MAIN OUTCOME MEASURES: Main outcome measures were area under the 120-minute curve for insulin, C...... after oral than after iv amino acid challenges (P = .006), whereas there was no significant difference in the glucagon response. Intact and total GIP rose after oral but not after iv amino acid administration, whereas intact and total GLP-1 levels did not change significantly in either test. CONCLUSION...

  2. Sparkle lamp ingestion: a rare cause of death.

    Science.gov (United States)

    Grundlingh, Johann; Dargan, Paul; Gokmen, Refik; Nair, Rajesh

    2010-10-01

    A 51-year-old man was brought to the emergency department after he had drunk 200 mL of fluid from a decorative sparkle lamp. His calcium level was 4.99 mmol/L with a blood gas pH of 7.21. His calcium levels were corrected and his acidosis improved, but his stay in the intensive care department was complicated on day 10 by upper gastrointestinal hemorrhage because of caustic erosions in his stomach. Ten days after admission, he had an emergency right hemicolectomy during which residual luminescent particles were found to have eroded through his cecal mucosa. He eventually died 15 days after admission because of disseminated intravascular coagulopathy and refractory septic shock. This case demonstrates the potential for fatal toxicity associated with ingestion of a common household item.

  3. Hepatic veno-occlusive disease associated with comfrey ingestion.

    Science.gov (United States)

    Yeong, M L; Swinburn, B; Kennedy, M; Nicholson, G

    1990-01-01

    A 23 year old man presented with hepatic veno-occlusive disease and severe portal hypertension and subsequently died from liver failure. Light microscopy and hepatic angiography showed occlusion of sublobular veins and small venous radicles of the liver, associated with widespread haemorrhagic necrosis of hepatocytes. The patient had been on a predominantly vegetarian diet and, prior to his illness, took comfrey leaves which are known to contain hepatotoxic pyrrolizidine alkaloids. Comfrey is widely used as a herbal remedy, but so far has only been implicated in two other documented cases of human hepatic veno-occlusive disease. A possible causal association of comfrey and this patient's veno-occlusive disease is suggested by the temporal relationship of the ingestion of comfrey to his presentation, the histological changes in the liver and the exclusion of other known causes of the disease.

  4. Radionuclides in food and the radiation exposure due to ingestion; Radionuklide in Lebensmitteln und die Strahlenexposition durch Ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Michel, Rolf

    2015-06-01

    As a consequence of the reactor accidents in Fukushima Daiichi high amounts of radioactive iodine and cesium isotopes were released into the terrestrial and marine Japanese environment. The largest release occurred on March 15, 2011 as a consequence of the containment failure of unit 2. Due to the meteorological conditions large area fallout occurred in the district of Fukushima. Other prefectures in the north of Japan were also contaminated. As a consequence of the high surface contamination the dose limits for drinking water, milk and milky products and food were increased to 200 Bq/kg.It turned out that the contamination of rice was marginal, the contamination of predatory fish higher than that of non-predatory fish. A systematic investigation of food samples could allow a better estimation of ingestion induced exposure.

  5. Haff disease associated with the ingestion of the freshwater fish Mylossoma duriventre (pacu-manteiga).

    Science.gov (United States)

    Tolesani Júnior, Oswaldo; Roderjan, Christian Nejm; do Carmo Neto, Edgard; Ponte, Micheli Mikaeli; Seabra, Mariana Cristina Pelli; Knibel, Marcos Freitas

    2013-01-01

    Haff disease associated rhabdomyolysis is correlated with the ingestion of certain freshwater fish and shellfish and is caused by an unidentified toxin. We report the case of a patient who experienced rhabdomyolysis approximately 2 hours after ingestion of the freshwater fish Mylossoma duriventre (pacu-manteiga) approximately 3 years after an outbreak had been reported in Manaus, Brazilian Amazon.

  6. Increasing frequency of plastic particles ingested by seabirds in the subarctic North Pacific

    Science.gov (United States)

    Robards, Martin D.; Piatt, John F.; Wohl, Kenton D.

    1995-01-01

    We examined gut contents of 1799 seabirds comprising 24 species collected in 1988-1990 to assess the types and quantities of plastic particles ingested by seabirds in the subarctic waters of Alaska. Of the 15 species found to ingest plastic, most were surface-feeders (shearwaters, petrels, gulls) or plankton-feeding divers (auklets, puffins). Of 4417 plastic particles examined, 76% were industrial pellets and 21% were fragments of ‘user’ plastic. Ingestion rates varied geographically, but no trends were evident and rates of plastic ingestion varied far more among species within areas than within species among areas. Comparison with similar data from 1968 seabirds comprising 37 species collected in 1969-1977 revealed that plastic ingestion by seabirds has increased significantly during the 10–15-year interval between studies. This was demonstrated by: (i) an increase in the total number of species ingesting plastic; (ii) an increase in the frequency of occurrence of plastic particles within species that ingested plastic; and, (iii) an increase in the mean number of plastic particles ingested by individuals of those species.

  7. Ingestion of an orthodontic archwire resulting in a perforated bowel: A case report.

    Science.gov (United States)

    Jauhar, Preeti; Machesney, Michael Robert; Sharma, Pratik K

    2016-09-01

    Accidentally, ingesting components of an orthodontic appliance can result in serious consequences for the patient. This paper presents one such complication, not previously reported, where the patient needed emergency surgery to retrieve part of an orthodontic appliance. This case report highlights the consequences of and possible solutions to prevent patients inhaling or ingesting parts of their appliance.

  8. Presentation of an ingested foreign body as a vesical calculus: a ...

    African Journals Online (AJOL)

    Vesical calculus is a common entity in children of developing countries. Foreign body ingestion is a common occurrence in the pediatric population. An ingested foreign body eroding into the urinary bladder and leading to the formation of a vesical calculus is an extremely rare condition. We encountered a 14-year-old girl ...

  9. Presentation of an ingested foreign body as a vesical calculus: a ...

    African Journals Online (AJOL)

    Presentation of an ingested foreign body as a vesical calculus: a common condition, but uncommon presentation. Shailendra Pal Singh a. , Anand Pandey a. , Vipin Gupta a. , Jigyasa Pandey b and. Rajesh Verma a. Vesical calculus is a common entity in children of developing countries. Foreign body ingestion is a common.

  10. Glucose ingestion during endurance training in men attenuates expression of myokine receptor

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Krogh-Madsen, Rikke; Petersen, Anne Marie Winther

    2009-01-01

    -leg) while ingesting a glucose solution (Glc) and ingested a placebo (Plc) while training the other leg (Plc-leg). Endurance training increased peak power by 14% and reduced the exercise-induced gene expression of IL-6 and IL-6Ralpha in skeletal muscle and IL-6 plasma concentration. The IL-6Ralpha density...

  11. Ingestive Skill Difficulties are Frequent Among Acutely-Hospitalized Frail Elderly Patients, and Predict Hospital Outcomes

    DEFF Research Database (Denmark)

    Hansen, Tina; Lambert, Heather; Faber, Jens

    2012-01-01

    Purpose : To examine the relationship between ingestive skill performance while eating and drinking and frailty status in acutely-hospitalized elderly patients and to examine whether there is a relationship between the proportion of ingestive skill difficulties and Length of Hospital Stay (LOS) a...

  12. Soil ingestion rates for children under 3 years old in Taiwan

    Science.gov (United States)

    Soil and dust ingestion rates by children are among the most critical exposure factors in determining risks to children from exposures to environmental contaminants in soil and dust. This is the first published soil ingestion study for children in Taiwan using tracer element meth...

  13. Widespread microplastic ingestion by fish assemblages in tropical estuaries subjected to anthropogenic pressures

    International Nuclear Information System (INIS)

    Vendel, A.L.; Bessa, F.; Alves, V.E.N.; Amorim, A.L.A.; Patrício, J.; Palma, A.R.T.

    2017-01-01

    Our aim was to quantify microplastic ingestion by fish assemblages in two tropical Brazilian estuaries and to evaluate whether biological and ecological factors influence the ingestion of microplastics by fish species. Of 2233 fish from both estuaries (from 69 species) examined in this study, 9% of the individuals (24 species) had microplastics in their gut contents. Microplastic ingestion occurred irrespective of fish size and functional group. The diet of fish species was analyzed based on prey items identified in the fish's full stomach contents and five feeding guilds were defined. Microplastics were common throughout all feeding guilds. Low (average ingestion values 1.06 ± 0.30 items/total fish) but widespread occurrence among estuaries also indicates proliferation of microplastic pollution. Our findings highlight the need to focus on assemblage level studies to understand the real magnitude of the problem and emphasize the urgency of mitigation measures directed at microplastic pollution in estuarine ecosystems. - Highlights: • We analyzed microplastic ingestion in 69 fish species collected along two estuaries. • Microplastic ingestion was widespread in fish assemblages in two tropical estuaries. • Microplastic ingestion was independent of fish size and fish functional groups. • Microplastics were observed in fish from five different feeding guilds. • The level of anthropogenic pressures did not influence microplastic ingestion.

  14. Marine debris ingestion and Thayer's law - The importance of plastic color.

    Science.gov (United States)

    Santos, Robson G; Andrades, Ryan; Fardim, Lorena M; Martins, Agnaldo Silva

    2016-07-01

    In recent years marine plastic pollution has gained considerable attention as a significant threat to marine animals. Despite the abundant literature related to marine debris ingestion, only a few studies attempted to understand the factors involved in debris ingestion. Plastic ingestion is commonly attributed to visual similarities of plastic fragments to animal's prey items, such as plastic bags and jellyfish. However, this simple explanation is not always coherent with the variety of debris items ingested and with the species' main prey items. We assess differences in the conspicuousness of plastic debris related to their color using Thayer's law to infer the likelihood that visual foragers detect plastic fragments. We hypothesize that marine animals that perceive floating plastic from below should preferentially ingest dark plastic fragments, whereas animals that perceive floating plastic from above should select for paler plastic fragments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Hunger and thirst interact to regulate ingestive behavior in flies and mammals.

    Science.gov (United States)

    Jourjine, Nicholas

    2017-05-01

    In animals, nervous systems regulate the ingestion of food and water in a manner that reflects internal metabolic need. While the coordination of these two ingestive behaviors is essential for homeostasis, it has been unclear how internal signals of hunger and thirst interact to effectively coordinate food and water ingestion. In the last year, work in insects and mammals has begun to elucidate some of these interactions. As reviewed here, these studies have identified novel molecular and neural mechanisms that coordinate the regulation of food and water ingestion behaviors. These mechanisms include peptide signals that modulate neural circuits for both thirst and hunger, neurons that regulate both food and water ingestion, and neurons that integrate sensory information about both food and water in the external world. These studies argue that a deeper understanding of hunger and thirst will require closer examination of how these two biological drives interact. © 2017 WILEY Periodicals, Inc.

  16. Impact of Decontamination Therapy on Ultrasound Visualization of Ingested Pills

    Directory of Open Access Journals (Sweden)

    Jason Bothwell

    2014-03-01

    Full Text Available Introduction: Acute toxic ingestion is a common cause of morbidity and mortality. Emergency physicians (EP caring for overdose (OD patients are often required to make critical decisions with incomplete information. Point of care ultrasound (POCUS may have a role in assisting EPs manage OD patients. We evaluated the impact of different liquid adjuncts used for gastric decontamination on examiners’ ability to identify the presence of tablets using POCUS, and assessed examiners’ ability to quantify the numbers of tablets in a simulated massive OD. Methods: This prospective, blinded, pilot study was performed at an academic emergency department. Study participants were volunteer resident and staff EPs trained in POCUS. Five non-transparent, sealed bags were prepared with the following contents: 1 liter (L of water, 1 L of water with 50 regular aspirin (ASA tablets, 1 L of water with 50 enteric-coated aspirin tablets (ECA, 1 L of polyethylene glycol (PEG with 50 ECA, and 1 L of activated charcoal (AC with 50 ECA. After performing POCUS on each of the bags using a 10-5 MHz linear array transducer, participants completed a standardized questionnaire composed of the following questions: (1 Were pills present? YES/NO; (2 If tablets were identified, estimate the number (1-10, 11-25, >25. We used a single test on proportions using the binomial distribution to determine if the number of EPs who identified tablets differed from 50% chance. For those tablets identified in the different solutions, another test on proportions was used to determine whether the type of solution made a difference. Since 3 options were available, we used a probability of 33.3%. Results: Thirty-seven EPs completed the study. All (37/37 EP’s correctly identified the absence of tablets in the bag containing only water, and the presence of ECA in the bags containing water and PEG. For Part 2 of the study, most participants - 25/37 (67.5% using water, 23/37 (62.1% using PEG, and

  17. Acute renal failure by ingestion of Euphorbia paralias

    Directory of Open Access Journals (Sweden)

    Karima Boubaker

    2013-01-01

    Full Text Available Euphorbia paralias is known in traditional medicine as an anti-inflammatory agent, a purgative and for its local anesthetic property. To the best our knowledge, renal toxicity of this substance has not been previously reported. In this paper, we report the case of a 29-year-old male who developed renal damage following ingestion of Euphorbia paralias. He had been on follow-up for nephrotic syndrome since 1986, although irregularly, with several relapses but each responding well to steroid therapy. A kidney biopsy had not been performed earlier due to refusal by the patient. He was off steroids since April 2008 because the patient developed osteoporosis. He was admitted with general malaise and oliguria to our department in May 2009, following repeated vomiting and watery diarrhea for three days. On examination, he was edematous but had normal vital signs except for a pulse rate of 120/min. Hemoglobin was only 5.5 g/dL but with normal white cell and platelet counts. Blood biochemistry showed evidence of advanced renal failure with a serum creatinine level of 1835 μmol/L and urea at 44.6 mmol/L, sodium of 132 μmol/L and potassium at 4.3 mmol/L. He had features of nephrotic syndrome with severe hypoproteinamia and 24-h urinary protein of 10.45 g. Ultrasonography revealed enlarged kidneys with a reduced echogenecity of the medulla and the papillae. Subsequently, after hemodialysis with blood transfusion, a kidney biopsy was performed that showed focal segmental glomerulosclerosis associated with an acute tubular injury. On intensive interrogation, the patient gave a history of ingesting boiled Euphorbia paralias as a native treatment for edema, ten days prior to the onset of the current illness. A diagnosis of acute renal failure (ARF resulting from the possible nephrotoxic effect of Euphorbia paralias poisoning was made. He was treated with intermittent hemodialysis and corticosteroids. Serum creatinine values improved after 48 days. At six

  18. Do polymorphisms in chemosensory genes matter for human ingestive behavior?

    Science.gov (United States)

    Hayes, John E; Feeney, Emma L; Allen, Alissa L

    2013-12-01

    In the last decade, basic research in chemoreceptor genetics and neurobiology have revolutionized our understanding of individual differences in chemosensation. From an evolutionary perspective, chemosensory variations appear to have arisen in response to different living environments, generally in the avoidance of toxins and to better detect vital food sources. Today, it is often assumed that these differences may drive variable food preferences and choices, with downstream effects on health and wellness. A growing body of evidence indicates chemosensory variation is far more complex than previously believed. However, just because a genetic polymorphism results in altered receptor function in cultured cells or even behavioral phenotypes in the laboratory, this variation may not be sufficient to influence food choice in free living humans. Still, there is ample evidence to indicate allelic variation in TAS2R38 predicts variation in bitterness of synthetic pharmaceuticals (e.g., propylthiouracil) and natural plant compounds (e.g., goitrin), and this variation associates with differential intake of alcohol and vegetables. Further, this is only one of 25 unique bitter taste genes ( TAS2Rs ) in humans, and emerging evidence suggests other TAS2Rs may also contain polymorphisms that a functional with respect to ingestive behavior. For example, TAS2R16 polymorphisms are linked to the bitterness of naturally occurring plant compounds and alcoholic beverage intake, a TAS2R19 polymorphism predicts differences in quinine bitterness and grapefruit bitterness and liking, and TAS2R31 polymorphisms associate with differential bitterness of plant compounds like aristolochic acid and the sulfonyl amide sweeteners saccharin and acesulfame-K. More critically with respect to food choices, these polymorphisms may vary independently from each other within and across individuals, meaning a monolithic one-size-fits-all approach to bitterness needs to be abandoned. Nor are genetic

  19. Sublethal effects of cadmium ingestion on mallard ducks. [Anas platyrhynchos

    Energy Technology Data Exchange (ETDEWEB)

    Di Giulio, R T; Scanlon, P F

    1984-11-01

    Juvenile mallard (Anas platyrhynchos) drakes were fed diets containing 0, 50, 150, or 450 ppM cadmium for 42 +/- 1 days in order to assess the impacts of cadmium ingestion on energy metabolism and tissue metal concentrations in this species. Most significant effects on energy metabolism were observed only in the 450 ppM group which displayed reduced body and liver weights, increased kidney weights, reduced liver aldolase activity, increased plasma concentrations of uric acid, decreased plasma triiodothyronine concentrations, and elevated adrenal weights and adrenal corticosterone concentrations. Ducks in the 150 ppM group displayed increased adrenal and kidney weights and elevated plasma nonesterified fatty acid concentrations. Among all treatments, increased cadmium and zinc concentrations in both livers and kidneys were dose-related; a similar trend was observed for copper concentrations in kidneys but not livers. Cadmium interference with carbohydrate metabolism in similar studies with mammals was more severe than that observed in mallards in the present study. 52 references, 6 tables.

  20. Ingestion Exposure to Nitrosamines in Chlorinated Drinking Water

    Science.gov (United States)

    Han, Kichan

    2011-01-01

    Objectives N-Nitrosodimethylamine (NDMA) is classified as a probable human carcinogen by the United States Environmental Protection Agency (US EPA) and is formed during the chlorination of municipal drinking water. In this study, selected nitrosamines were measured in chlorinated drinking water collected from Chuncheon, Kangwon-do, Republic of Korea, and a risk assessment for NDMA was conducted. Methods Twelve water samples were collected from 2 treatment plants and 10 household taps. Samples were analyzed for 6 nitrosamines via solid-phase extraction cleanup followed by conversion to dansyl derivatives and high-performance liquid chromatography-fluorescence detection (HPLC-FLD). Considering the dietary patterns of Korean people and the concentration change of NDMA by boiling, a carcinogenic risk assessment from ingestion exposure was conducted following the US EPA guidelines. Results NDMA concentrations ranged between 26.1 and 112.0 ng/L. NDMA in water was found to be thermally stable, and thus its concentration at the end of boiling was greater than before thermal treatment owing to the decrease in water volume. The estimated excess lifetime carcinogenic risk exceeded the regulatory baseline risk of 10-5. Conclusions This result suggests that more extensive studies need to be conducted on nitrosamine concentration distributions over the country and the source of relatively high nitrosamine concentrations. PMID:22125764