TREATMENT THYROID HORMON IN PREMATURE INFANTS

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Int. J. Med. Sci. 2008, 5 87International Journal of Medical Sciences ISSN 1449-1907 www.medsci.org 2008 5(2):87-91 © Ivyspring International Publisher. All rights reserved Research Paper TPO, but not soluble-IL-6 receptor, levels increase after anagrelide treat-ment of thrombocythemia in chronic myeloproliferative disorders Jan Palmblad1, Magnus Björkholm2, Jack Kutti3, Gerd Lärfars4, Eva Löfvenberg1, Berit Markevärn5, Mats Merup1, Nils Mauritzson6, Jan Westin6, Jan Samuelsson4 and Gunnar Birgegård7 1. Hematology Center, Karolinska University Hospital Huddinge, Stockholm 2. Hematology Center, Karolinska University Hospital Solna, Stockholm 3. Dept of Hematology, Sahlgrenska University Hospital, Göteborg 4. Dept of Medicine, Stockholm South Hospital, Stockholm 5. Dept of Medicine, University Hospital, Umeå 6. Dept of Hematology, University Hospital, Lund, Sweden 7. Dept of Medicine, University Hospital, Uppsala, for the Swedish MPD Study Group. Correspondence to: Jan Palmblad, MD, PhD, Professor of Medicine, Dept. of Medicine, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden. Tel +46 8 5858 2693, fax +46 8 711 7684, e-mail address jan.palmblad@ki.se Received: 2008.02.06; Accepted: 2008.04.13; Published: 2008.04.13 Anagrelide is often used in the treatment of thrombocythemia in myeloproliferative disease (MPD), but infor-mation concerning effects of treatment on cytokines involved in regulation of blood platelet levels is limited. Here, we investigated serum levels of thrombopoietin (TPO) and soluble IL-6 receptor (sIL-6R) in relation to re-sponse to treatment with and plasma concentrations of anagrelide. Samples from 45 patients with thrombo-cythemia due to MPD (ET=31, PV=14), being treated with anagrelide for 6 months, were analyzed for TPO, sIL-6R and anagrelide levels. The mean baseline platelet count was 983x109/L. A reduction of platelets to <600 in asymptomatic or <400 x 109/L in symptomatic patients was defined as a complete remission (CR), a reduction with >50% of baseline as partial remission, and <50% reduction as failure. At 6 months, 35 patients were in CR, 1 had a partial remission and 9 were treatment failures. For all patients, there was an increase in TPO of 44% from baseline; this change was more pronounced for patients with partial remission and failure. sIL-6R levels did not change significantly. There was no correlation between levels of anagrelide and cytokine levels at 6 months, and changes of cytokine levels did not relate to changes of platelet counts. Thus, a pronounced increase of TPO levels after 6 months of anagrelide treatment indicated that this treatment affected a major regulatory mechanism for megakaryocyte and platelet formation in MPD. Key words: thrombocythemia, anagrelide, thrombopoietin, IL-6, soluble receptors Introduction One of the clinical challenges in chronic mye-loproliferative disorders (MPD) is thrombocythemia, always present in essential thrombocythemia (ET) and often in polycythemia vera (PV), myelofibrosis (MF) and chronic myelogenous leukemia. The risks associ-ated with thrombocythemia are thromboembolic events and bleeding, risks that may be reduced with appropriate therapy. Anagrelide hydroxide is a platelet reducing compound, often used as an alternative to hydroxy-urea, interferon-α and alkylating agents for the treat-ment of thrombocytosis in MPD [1-4]. Anagrelide ex-erts TREATMENT OF THYROID HORMON IN PREMATURES DR.THI NGAI NGO Nephrology and Endocrinology Department Children’s Hospital INTRODUCTION: Function of thyroid hormon • Increase the basal metabolic rate, • Affect protein synthesis, • synergy with growth hormone, and neural maturation • Increase the body's sensitivity to catecholamines (such as adrenaline) by permissiveness • Regulate protein, fat, and carbohydrate metabolism • Inhibit neuronal activity • Severe drop in body temperature Fetal thyroid function: 8-10 weeks Second trimester and then T4 steadily increase 24 - 34 weeks, serum T4levels plateau STUDIES: 105 premature infants (28-34 weeks) TSH (TSH 10-30 µU/mL) with normal fT4 levels after : week of postnatal life(12%) weeks of postnatal life(32%) weeks of postnatal life(54%) Repeated thyroid function tests are necessary for preterm infants Treatment thyroid hormon in premature infants is unnecessery P&S Journal: Fall 1996, Vol.16, No.3 Research Reports Premature Babies, Thyroid Hormone, and CP Premature infants with low levels of thyroid hormones are significantly more likely to develop cerebral palsy (CP) than are infants with normal hormone The stimulatory and suppressive effects of antenatal TRH treatment observed at birth are transient and not affect pituitary-thyroid responsiveness at 28 d of age Nine studies were identified that compared thyroid hormone treatment and nontreatment This review does not support the use of thyroid hormones in preterm infants to reduce neonatal mortality, improve neurodevelopmental There is insufficient evidence to determine whether use of thyroid hormones for treatment of preterm infants with transient hypothyroxinaemia results in changes in neonatal morbidity and mortality, or reductions in neurodevelopmental impairments Further research is required Developmental data revealed no significant differences in the mental, motor, or gross neurologic outcome in the treated and nontreated infants after year of follow-up Severe hypothyroxinemia in preterm infants may be NOT an important cause of problems in neurologic and mental development detected at the age of two years CONCLUSIONS: • Should follow up thyroid hormon in premature infants • Treatment thyroid hormon in premature infants is unnecessery Introduction  Humanimmunodeciencyvirus(HIV)associated tuberculosis(TB)remainsamajorglobalpublichealth challenge. By the end of 2009, an estimated 33.3 millionpeoplewerelivingwithHIV,thevastmajority in sub-Saharan Africa and Asia. An estimated 2.6 million individuals had become newly infected with HIV and 1.8 million had died of AIDS in that year alone 1 .TBisthemostcommonopportunisticinfection (OI)amongHIV-infectedindividuals,andco-infected individuals are at high risk of death 2,3 .Theestimates oftheglobalburdenofdiseasecausedbyTBin2009 Review Article Diagnosis&treatmentoftuberculosisinHIVco-infectedpatients C.Padmapriyadarsini,G.Narendran&SoumyaSwaminathan National Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, India ReceivedOctober31,2011 Human immunodeciency virus (HIV) associated tuberculosis (TB) remains a major global public health challenge, with an estimated 1.4 million patients worldwide. Co-infection with HIV leads to challenges in both the diagnosis and treatment of tuberculosis. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDR-TB) and extensively drug resistant TB (XDRTB), which are difcult to treat and contribute to increased mortality. Because of the poor performance of sputum smear microscopy in HIV-infected patients, newer diagnostic tests are urgently required that are not only sensitive and specic but easy to use in remote and resource-constrained settings. The treatment of co-infected patients requires antituberculosis and antiretroviral drugs to be administered concomitantly; challenges include pill burden and patient compliance, drug interactions, overlapping toxic effects, and immune reconstitution inammatory syndrome. Also important questions about the duration and schedule of anti-TB drug regimens and timing of antiretroviral therapy remain unanswered. From a programmatic point of view, screening of all HIV-infected persons for TB and vice- versa requires good co-ordination and communication between the TB and AIDS control programmes. Linkage of co-infected patients to antiretroviral treatment centres is critical if early mortality is to be prevented. We present here an overview of existing diagnostic strategies, new tests in the pipeline and recommendations for treatment of patients with HIV-TB dual infection. Key words Co-infection-diagnosis-drugresistance-HIV-IRIS-treatment-tuberculosis wereasfollows:9.4millionincidentcases(range8.9- 9.9 million), 1.3million deaths amongHIV-negative TB patients (range 1.2-1.5 million) and 0.38 million deaths among HIV-positiveTB patients (range 0.32- 0.45million).MostTBcaseswereintheSouth-East Asia, African and Western Pacic regions (35, 30 and 20%, respectively).Anestimated 11-13 per cent of incident cases were HIV-positive 4 . TB may occur atanystageofHIVdiseaseandisfrequentlytherst recognizedpresentationofunderlyingHIVinfection 5,6 . AscomparedtopeoplewithoutHIV,peoplelivingwith HIV(PLWH)havea20-foldhigherriskofdeveloping 850 IndianJMedRes134,December2011,pp850-865 TB 7  and the risk continues to increase as CD4 cell countsprogressivelydecline 5 .  AsaresultofWHO’s3by5campaign,>6million HIV-infected individuals in resource limited settings havehadaccesstoantiretroviraltherapy(ART)since 2004 8 ,thoughthisisstillfarshortoftheactualneed. AlthoughART can reduce the incidence of TB both at the individual and population level, 1616 P St. NW Washington, DC 20036 202-328-5000 www.rff.org February 2010  RFF DP 10-04 The Treatment of Uncertainty in EPA’s Analysis of Air Pollution Rules A Status Report Arthur G. Fraas DISCUSSION PAPER © 2010 Resources for the Future. All rights reserved. No portion of this paper may be reproduced without permission of the authors. Discussion papers are research materials circulated by their authors for purposes of information and discussion. They have not necessarily undergone formal peer review. The Treatment of Uncertainty in EPA’s Analysis of Air Pollution Rules: A Status Report Arthur G. Fraas Abstract An understanding of the uncertainty in benefit and cost estimates is a critical part of a benefit– cost analysis. Without a quantitative treatment of uncertainty, it is difficult to know how much confidence to place in these estimates. In 2002, an NRC report recommended that EPA move toward conducting probabilistic, multiple-source uncertainty analyses in its RIAs with the specification of probability distributions for major sources of uncertainty in the benefit estimates. In 2006, reports by GAO and RFF found that EPA had begun to address the NRC recommendations, but that much remained to be done to meet the NRC concerns. This paper provides a further review of EPA’s progress in developing a quantitative assessment of the uncertainties in its health benefits analyses for the RIAs for four recent NAAQS rulemakings. In conclusion, EPA’s recent RIAs present the results of its uncertainty analyses in piecemeal fashion rather than providing an overall, comprehensive statement of the uncertainty in its estimates. In addition, its recent RIAs continue to focus on the concentration-response relationship and largely fail to address the uncertainty associated with the other key elements of the benefits analysis. Key Words: benefit–cost analysis, uncertainty analysis JEL Classification Numbers: B41, D61, D80, I18, Q50 Contents Introduction 1  Background 2 EPA’s Approach to Uncertainty Analysis at the Time of the NRC Review 2 NRC Committee: Estimating the Public Health Benefits of Proposed Air Pollution Regulations 3 OMB’ Circular A-4 5 GAO’s Report to Congress 5 2006 RFF Study 6 Status of EPA Uncertainty Analysis in Recent RIA’s 7 Alternate Concentration-Response Functions for PM Mortality (Expert Elicitation Study)8 EPA’s “Primary” Analysis for Health Effects with Monte Carlo Methods 9 Sensitivity Analysis 11 Qualitative Discussion of Other Areas of Uncertainty 12 Summary 13 Tables 16 References 20 Resources for the Future Fraas 1 The Treatment of Uncertainty in EPA’s Analysis of Air Pollution Rules: A Status Report Arthur G. Fraas ∗ Introduction In a 2002 report titled Estimating the Public Health Benefits of Proposed Air Pollution Regulations, the National Research Council (NRC) of the National Academy of Sciences raised specific and detailed concerns with the U.S. Environmental Protection Agency’s (EPA) treatment of uncertainty in its health benefits analysis. 1 , 2 While previous recommendations 2003;111;e590Pediatrics Turner, Boaz Karmazyn and Lea Sirota Nehama Linder, Orli Haskin, Orli Levit, Gil Klinger, Tal Prince, Nora Naor, Pol Premature Infants: A Retrospective Case-Control Study Risk Factors for Intraventricular Hemorrhage in Very Low Birth Weight http://pediatrics.aappublications.org/content/111/5/e590.full.html located on the World Wide Web at: The online version of this article, along with updated information and services, is of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2003 by the American Academy published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point publication, it has been published continuously since 1948. PEDIATRICS is owned, PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly at Viet Nam:AAP Sponsored on February 10, 2014pediatrics.aappublications.orgDownloaded from at Viet Nam:AAP Sponsored on February 10, 2014pediatrics.aappublications.orgDownloaded from Risk Factors for Intraventricular Hemorrhage in Very Low Birth Weight Premature Infants: A Retrospective Case-Control Study Nehama Linder, MD*§; Orli Haskin, MD*§; Orli Levit, MD*§; Gil Klinger, MD*§; Tal Prince, MD*§; Nora Naor, MD*§; Pol Turner, MD*§; Boaz Karmazyn, MD‡§; and Lea Sirota, MD*§ ABSTRACT. Objective. High-grade intraventricular hemorrhage (IVH) is an important cause of severe cogni- tive and motor neurologic impairment in very low birth weight infants and is associated with a high mortality rate. The risk of IVH is inversely related to gestational age and birth weight. Previous studies have proposed a number of risk factors for IVH; however, lack of ade- quate matching for gestational age and birth weight may have confounded the results. The purpose of this study was to identify variables that affect the risk of high-grade IVH, using a retrospective and case-control clinical study. Methods. From a cohort of 641 consecutive preterm infants with a birth weight of <1500 g, 36 infants with IVH grade 3 and/or 4 were identified. A control group of 69 infants, closely matched for gestational age and birth weight, was selected. Maternal factors, labor and delivery characteristics, and neonatal parameters were collected in both groups. Results of cranial ultrasound examinations, whether routine or performed in presence of clinical suspicion, were also collected. Univariate analysis and multivariate logistic regression analysis were performed. Results. High fraction of inspired oxygen in the first 24 hours, pneumothorax, fertility treatment (mostly in vitro fertilization), and early sepsis were associated with an increased risk of IVH. A higher number of suctioning procedures, a higher first hematocrit, and a relatively low arterial pressure of carbon dioxide during the first 24 hours of life were associated with a lower occurrence. In the multivariate logistic regression model, early sepsis (odds ratio [OR]: 8.19; 95% confidence interval [CI]: 1.55– 43.1) and fertility treatment (OR: 4.34; 95% CI: 1.42–13.3) were associated with a greater risk of high-grade IVH, whereas for every dose of antenatal steroid treatment there was a lower risk of high-grade IVH (OR: 0.52; 95% CI: 0.30–0.90) and each decrease in a mmHg unit of arterial pressure of carbon dioxide during the first 24 hours was associated with a lower risk of IVH (OR: 0.91; 95% CI: 0.83–0.98). This multivariate model had a sensi- tivity of 77%, a specificity of 75%, and a positive predic- tive value of 76%. The area under the curve derived from the receiver operator characteristic plots is 0.82. Conclusions. Our results confirm that the develop- ment of IVH is associated with early sepsis and failure to give antenatal steroid treatment. We propose that fertility treatment (and especially in vitro fertilization) may be a new risk factor, and more research is needed to assess its role. Pediatrics 2003;111:e590 Dr NGUYỄN THÚC BỘI NGỌC DICH VU  Copyright 2012 by ESPGHAN and NASPGHAN European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition  JPGN Volume 55, Number 1, July 2012 BACKGROUND  Gastroesophageal reflux (GER) is defined as the retrograde passage of gastric contents into the esophagus or extraesophageal regions, which affects approximately 50% of healthy infants ages to months  In a study involving 948 healthy infants 13 months or younger, 50% of those ages to months, 67% of those ages months, and 21% of those ages to months regurgitated at least once daily  In most infants, regurgitation decreases in frequency or resolves completely by 12 months of age  Simple physiological reflux can lead to pathologic gastroesophageal reflux disease (GERD) when reflux produces adverse symptoms or characteristic histologic and/or endoscopically visible changes (eg, esophageal erosions)  Clinical symptoms of GERD in infants include recurrent vomiting, poor weight gain, irritability, dysphagia, discomfort, esophagitis and respiratory disorders  One of the primary goals of acid suppressive therapy is to relieve symptoms that may be associated with esophageal inflammation and prevent other complications (eg, esophageal strictures, respiratory involvement)  Esomeprazole is the only PPI approved by the US Food and Drug Administration (FDA) for treating children to 11 months old for erosive esophagitis caused by acidmediated GERD and is available in oral and intravenous formulations  Treatment of GERD in infants younger than year has not been studied as extensively as in older children or adolescents, and the few clinical studies that have been conducted yielded conflicting findings  The objective of the present study is to evaluate the efficacy and safety of esomeprazole in infants ages to 11 months with signs and symptoms of GERD METHODS Study Design and Patients  This was a multicenter randomized, double-blind, placebo-controlled, parallel-group, treatmentwithdrawal study conducted in 33 centers in the United States, France, Germany, and Poland  The study followed guidelines established by the FDA SELECT CRITERIA  Infants ages to 11 months: They had a clinical diagnosis of suspected GERD based on symptoms, endoscopically proven GERD, laboratory test results, diagnostic tests  Patients were required to have at least of the symptoms of GERD - Vomiting/regurgitation, irritability - Cough, wheezing and/or stridor, labored breathing, - Respiratory symptoms triggered by feeding, feeding difficulties (food refusal, choking, hiccups for >1 hour/day) at least times per week in a 4-week period  During the 2-week open-label phase, all of the patients received esomeprazole (Nexium) once daily orally according to body weight  After the open-label phase, infants were randomized 1:1 to double-blind treatment with esomeprazole (at the openlabel dose) or placebo for up to weeks  The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician Adverse events were recorded RESULTS:  Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment  During the double-blind phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P=0.28)  The time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P=0.01)  Numerical increase in the incidence of upper respiratory infection in patients treated with esomeprazole (6/39 patients) compared with placebo (4/41 patients) DISCUSSION  A majority (83%) of patients showed improvement in GERD symptoms within weeks of starting openlabel esomeprazole therapy  The downward trend ... problems in neurologic and mental development detected at the age of two years CONCLUSIONS: • Should follow up thyroid hormon in premature infants • Treatment thyroid hormon in premature infants. .. Repeated thyroid function tests are necessary for preterm infants Treatment thyroid hormon in premature infants is unnecessery P&S Journal: Fall 1996, Vol.16, No.3 Research Reports Premature. .. the use of thyroid hormones in preterm infants to reduce neonatal mortality, improve neurodevelopmental There is insufficient evidence to determine whether use of thyroid hormones for treatment