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Timing of default from tuberculosis treatment: a systematic review Margaret E. Kruk 1 , Nina R. Schwalbe 2 and Christine A. Aguiar 1 1 Department of Health Management and Policy, University of Michigan School of Public Health, Ann Arbor, MI, USA 2 Global Alliance for TB Drug Development, TB Alliance, New York, NY, USA Summary objectives To provide a systematic assessment of the timing of default from tuberculosis (TB) treatment which could help to quantify the potential contribution of new shorter duration TB drugs to global TB control. methods We performed a systematic review following QUOROM guidelines. MEDLINE was searched from 1998 to the present using the terms TB and default or drop-out or compliance or adherence and therapy. A total of 840 articles were returned. A further detailed manual review selected 15 randomized trials and observational studies that reported timing of drop-out and focused on developing countries. results The selected studies comprised randomized controlled trials, retrospective record reviews, and qualitative assessments and spanned 10 countries. Both directly observed treatment (DOT) and non-DOT programs were represented. Thus results were highly heterogeneous and not statistically aggregated. Data suggest, but do not conclude, that the majority of defaulters across the studies completed the 2-month intensive phase of treatment. conclusions There is insufficient high-quality comparable information on the timing of default from TB treatment to permit any firm conclusions on trends in default. However, a substantial pro- portion of defaulters appear to leave treatment in the later stages of the current 6-month regimen, suggesting that new TB chemotherapeutic agents which can reduce the length of treatment have the potential to improve global TB treatment success rates. keywords tuberculosis therapy, directly observed treatment, default, time of default, temporal trends Introduction Tuberculosis (TB) is a global health emergency, killing nearly 1.6 million people each year, mostly in low- and middle-income countries (Stop-TB Partnership 2006). TB cases in Africa have more than quadrupled since 1990, as a result of co-infection with HIV (WHO 2005). The World Health Organization (WHO) – recommended treatment strategy, directly observed treatment or direct observation (DOT), which forms the basis of the Stop TB Strategy, is a 6- to 8-month regimen with a combination of anti-TB agents (Lienhardt & Ogden 2004). This regimen is also known as short-course chemotherapy (SCC). The first 2 months of SCC, known as the intensive phase, generally involve a combination of four drugs and the 4- to 6-month follow-up period, known as the continuation phase, involves two drugs. Both the drugs used in treatment and the duration of the intensive phase may vary within SCC programs. While cure rates with this combination under optimal conditions approach 95%, actual global treatment success in 2005 was 84% (Borgdorff et al. 2002; WHO 2007). This figure is much lower in some regions: In Africa, the overall cure rate for smear-positive TB was 74% and as low as 54% in some areas (WHO 2007.) Further, Mycobacterium tuberculosis resistant to both isoniazid and rifampicin, or multi-drug resistant TB, is now diagnosed in an estimated 4.3% of all new and previously treated TB patients (Zignol et al. 2006). A major contributor to both treatment failure and the rise of multidrug-resistant TB is inadequate and incomplete treatment (Borgdorff et al. 2002; Sharma & Mohan 2006). While structural factors such as interruptions in drug supply play a role, patient default ESPGHAN Committee on NEW EVIDENCE IN PARAQUAT POISONING Emergency Department – Children’s Hospital CONTENT  Introduction  Management Gastrointestinal decontamination  Specific treatment and antidotal therapy  Extracorporeal therapies  Anti-inflammatory and immunosuppressive therapy   Conclusion INTRODUCTION  Paraquat ingestion is a leading cause of fatal poisoning in many parts of Asia, Pacific nations, and the Americas  Rapidly-acting, effective, nonselective and relatively inexpensive  widespread use in much of the developing countries  Self-poisoning, suicide INTRODUCTION  Swallowing of 20 to 24 % paraquat concentrate > 30 mL (a mouthful or two)  lethal  10 mL  significant illness   The time of ingestion MANAGEMENT INITIAL MANAGEMENT GASTROINTESTINAL DECONTAMINATION TOPICAL AND INHALATION MONITORING SPECIFIC TREATMENTS AND ANTIDOTAL THERAPIES ONGOING MANAGEMENT GASTROINTESTINAL DECONTAMINATION Paraquat Poisoning – UpToDate 14.0 Gastrointestinal decontamination is recommended to limit sytemic exposure Grade 2C GASTROINTESTINAL DECONTAMINATION  Activated charcoal (1 g/kg in water; water maximum dose 50 g) or Fuller’s Earth (2 g/kg in water; maximum 150 g in water) should be given as soon as possible per oral or via a nasogastric tube to patients who present within approximately two hours of ingestion  Treatment should not be delayed for confirmatory testing  “… both activated charcoal and Fuller’s Earth adsorb paraquat in vitro and thus may be beneficial in minor exposures …” UpToDate14.0 GASTROINTESTINAL DECONTAMINATION  Decontamination is not useful with delayed presentations due to the rapid absorption and high toxicity of paraquat  Gastric lavage and forced emesis are contraindicated due to paraquat-induced caustic injury  In cases that present early, a nasogastric tube should be inserted and the stomach contents aspirated prior to administration of charcoal UpToDate14.0 MANAGEMENT INITIAL MANAGEMENT GASTROINTESTINAL DECONTAMINATION TOPICAL AND INHALATION MONITORING SPECIFIC TREATMENTS AND ANTIDOTAL THERAPIES ONGOING MANAGEMENT SPECIFIC TREATMENTS AND ANTIDOTAL THERAPY Extracorporeal therapies Anti inflammatory Anti and immunosuppressive therapy Anti-oxidant therapy EXTRACORPOREAL THERAPIES Paraquat Poisoning – UpToDate14.0 Indications for extracorporeal therapies: Treatment with hemoperfusion for four hours if it can be initiated within four hours of ingestion Grade 2C ANTI-INFLAMMATORY AND ANTIIMMUNOSUPPRESSIVE THERAPY The Cochrane Collaboration Glucocorticoid with cyclophosphamide for paraquat paraquat-induced lung fibrosis (Review) Li LR, Sydenham E, Chaudhary B, Beecher D, You C GLUCOCORTICOID WITH CYCLOPHOSPHAMIDE FOR PARAQUATPARAQUAT-INDUCED LUNG FIBROSIS  Types of studies: Randomised controlled trials (RCTs)  Types of participants: Any person with paraquat poisoning GLUCOCORTICOID WITH CYCLOPHOSPHAMIDE FOR PARAQUATPARAQUAT-INDUCED LUNG FIBROSIS  Types of interventions: All patients were to receive standard care plus either the intervention or control Intervention: glucocorticoid with cyclophosphamide in combination  Control: placebo, standard care alone or any other therapy in addition to standard care   Studies that focused on any single immunosuppressant or other combinations of therapies were excluded GLUCOCORTICOID WITH CYCLOPHOSPHAMIDE FOR PARAQUATPARAQUAT-INDUCED LUNG FIBROSIS GLUCOCORTICOID WITH CYCLOPHOSPHAMIDE FOR PARAQUATPARAQUAT-INDUCED LUNG FIBROSIS  This systematic review includes three trials with a combined total of 164 participants who had moderate to severe paraquat poisoning  All three trials reported death at the end of the follow-up period GLUCOCORTICOID WITH CYCLOPHOSPHAMIDE FOR PARAQUATPARAQUAT-INDUCED LUNG FIBROSIS Patients who received glucocorticoid with cyclophosphamide in addition to standard care had a lower risk of death than those receiving standard care alone (RR 0.72; 95% CI 59 to 0.89) GLUCOCORTICOID WITH CYCLOPHOSPHAMIDE FOR PARAQUATPARAQUAT-INDUCED LUNG FIBROSIS Based on the findings of three small RCTs of moderate to severely poisoned patients, glucocorticoid with cyclophosphamide in addition to standard care may be a beneficial treatment for patients with paraquat induced lung fibrosis paraquat CONCLUSION  Standard care for removing paraquat from the body involves gastrointestinal decontamination and hemoperfusion  Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination may be beneficial THANK YOU FOR YOUR ATTENTION ORIGINAL RESEARCH Open AccessEmergency intraosseous access in a helicopteremergency medical service: a retrospective studyGeir A Sunde1,2*, Bård E Heradstveit1,2, Bjarne H Vikenes1,2, Jon K Heltne1,2,3AbstractBackground: Intraosseous access (IO) is a method for providing vascular access in out-of-hospital resuscitation ofcritically ill and injured patients when traditional intravenous access is difficult or impossible. Different intraosseoustechniques have been used by our Helicopter Emergency Medical Services (HEMS) since 2003. Few articlesdocument IO use by HEMS physicians. The aim of this study was to evaluate the use of intraosseous access in pre-hospital emergency situations handled by our HEMS.Methods: We reviewed all medical records from the period May 2003 to April 2010, and compared three differenttechniques: Bone Injection Gun (B.I.G® - Waismed), manual bone marrow aspiration needle (Inter V - Medical DeviceTechnologies) and EZ-IO® (Vidacare), used on both adults and paediatric patients.Results: During this seven-year period, 78 insertion attempts were made on 70 patients. Overall success rates were50% using the manual needle, 55% using the Bone Injection Gun, and 96% using the EZ-IO®. Rates of success onfirst attempt were significantly higher using the EZ-IO® compared to the manual needle/Bone Injection Gun (p <0.01/p < 0.001). Fifteen failures were due to insertion-related problems (19.2%), with four technical problems (5.1%)and three extravasations (3.8%) being the most frequent causes. Intraosseous access was primarily used inconnection with 53 patients in cardiac arrest (75.7%), including traumatic arrest, drowning and SIDS. Otherdiagnoses were seven patients with multi-trauma (10.0%), five with seizures/epilepsy (7.1%), three with respiratoryfailure (4.3%) and two others (2.9%). Nearly one third of all insertions (n = 22) were made in patients younger thantwo years. No cases of osteomyelitis or other serious complications were documented on the follow-up.Conclusions: Newer intraosseous techniques may enable faster and more reliable vascular access, and this canlower the threshold for intraosseous access on both adult and paediatric patients in critical situations. We believethat all emergency services that handle critically ill or injured paediatric and adult patients should be familiar withintraosseous techniques.BackgroundVascular access is important in the resuscitation of criti-cally ill or injured adult and paediatric patients [1,2]. Itcan be challenging to obtain vascular access, especiallyin the resuscitation of small children in emergencysituations [3-5]. The European Resuscitation Council2005 guidelines [6] and International Liaison Committeeon Resuscitation guidelines [4] recommend intraosseousaccess during resuscitation if intravenous access provesto be difficult or impossible. Despite these recommenda-tions, intraosseous techniques appear to be rarely used[7]. While numerous reports have been published aboutthe use of different intraosseous devices in emergencypatients, they are primarily from paramedic-basedambulance services [2,8]. Few comparisons have beenpublished of different IO techniques used by physiciansin emergency departments [7] or in HEMS servicesmanned by physicians/nurses [9,10].Typical HEMS operating conditions make specialdemands on medical equipment such as IO devices.Rain, cold, darkness and non-sterile conditions meanthat such equipment must be durable and simple to usein all conditions. User friendliness is important for res-cuers, both on-scene and in-flight [10].Intravenous access is traditionally regarded as theoptimal route for medication and fluids, and the* Oral Ondansetron for Gastroenteritis in a Pediatric Emergency Department Background BỘ GIÁO DỤC VÀ ĐÀO TẠO TRƯỜNG ĐẠI HỌC DÂN LẬP HẢI PHÒNG ------------------------------- ISO 9001 : 2008 KHÓA LUẬN TỐT NGHIỆP NGÀNH: NGOẠI NGỮ HẢI PHÒNG - 2010 2 HAIPHONG PRIVATE UNIVESITY FOREIGN LANGUAGES DEPARTMENT ----------------------------------- GRADUATION PAPER A STUDY ON TRANSLATION OF ENGLISH - RELATED TERMS IN FINANCE AND BANKING INTO VIETNAMESE By: BUI THI THOM Class: NA 1004 Supervisor: DAO THI LAN HUONG, M.A HAI PHONG - 2010 3 BỘ GIÁO DỤC VÀ ĐÀO TẠO TRƯỜNG ĐẠI HỌC DÂN LẬP HẢI PHÒNG -------------------------------------- Nhiệm vụ đề tài tốt nghiệp Sinh viên: .Mã Số: Lớp: Ngành: Tên đề tài: . . 4 Nhiệm vụ đề tài 1. Nội dung và các yêu cầu cần giải quyết trong nhiệm vụ đề tài tốt nghiệp ( về lý luận, thực tiễn, các số liệu cần tính toán và các bản vẽ). …………………………………………………………………………… …………………………………………………………………………… …………………………………………………………………………… …………………………………………………………………………… …………………………………………………………………………… …………………………………………………………………………… …………………………………………………………………………… …………………………………………………………………………… 2. Các số liệu cần thiết để thiết kế, tính toán. …………………………………………………………………………… …………………………………………………………………………… …………………………………………………………………………… …………………………………………………………………………… Update on mangement of patent ductus arteriosus in preterm infants Dr Trinh Thi Thu Ha Outline Overview of PDA Timing of screening PDA? When to treat PDA? Timing of ductal closure Prenatal MgSO4, tocolytic Postnatal surfactant  Early, severe pulmonary hemorrhage is associated with ductal patency at 12 to 18 hours of age, but later pulmonary hemorrhage (after the first week) is not related to persistent ductal patency (Workbook in Practical Neonatology 5th Edition 2015)  Diagnosis: In most cases, the clinically silent PDA during the first few days goes undetected unless an echocardiogram is performed  Signs of bounding pulses, active precordium, and systolic murmur were of reasonable specificity but very low sensitivity in the first to days of birth for diagnosis of an echocardiographically defined significant PDA  Relying on clinical signs alone led to a mean diagnostic delay of days (A blinded comparison of clinical and echocardiographic evaluation of the preterm infant for patent ductus arteriosus.Skelton R1, Evans N, Smythe J JPaediatr Child Health 1994 Oct;30(5):406-11) Ibuprofen Prophylaxis  No significant differences in mortality, IVH, or BPD  No reduction in IVH, PAL in the treated group  Increased risk of gastrointestinal bleeding  Prophylactic ibuprofen exposes many infants to renal and gastrointestinal side effects without any important short-term benefits and is not recommended Pre-symptomatic Pharmacologic Treatment  No effect on the rate of mortality, BPD, IVH, ROP, or length of ventilation, death, IVH, NEC,…  More renal side effect  Presymptomatic indomethacin or ibuprofen therapy for PDA in preterm infants is not recommended Conservative Management       Fluid restriction Diuretics, avoidance of loop diuretics Maintaining a hematocrit of 35 to 40 percent Increased positive airway pressure Correction of alkalosis Avoidance of pulmonary vasodilators: oxygen or NO  Asymptomatic infants with PDAs generally not require medical management or surgical ligation These infants should be monitored for evidence of CHF, failure or renal PEDIATRIC OBSTRUCTIVE SLEEP APNEA (OSA) DEFINITION OSA • Inspiratory airflow is either partly (hypopnea) or completely (apnea) occluded during sleep The combination of sleep-disordered breathing with daytime sleepiness is referred to as the OSA syndrome • Obstructive apnea occurs when there is complete cessation of airflow for ≥ 10 s PATHOPHYSIOLOGY major predisposing factors for upper airway obstruction: • Anatomic narrowing • Abnormal mechanical linkage between airway dilating muscles and airway walls • Muscle weakness • Abnormal neural regulation PATHOPHYSIOLOGY • • • • Sleep fragmentation Increased work of breathing Alveolar hypoventilation Intermittent hypoxemia COMPLICATIONS • • • • • Neurobehavioral disturbances, ADHD Diminished learning capabilities Failure to thrive Pulmonary hypertension Cor pulmonale CONDITION ASSOCIATED-CAUSES • • • • • • • • Tonsillar and adenoid hypertrophy Neuromuscular disorders Myelomeningocele Obesity Pierre Robin sequence Cerebral palsy Down syndrome Hypothyroidism EPIDEMIOLOGY • United States: Affecting 2–3% of all children (snoring: 8-27%) • 2-8 years (adenotonsillar lymphatic tissue growth) • Sex: prepubertal children: male = female, older adolescents: male > female • Races: black children > white children, high frequency of OSA / adult Asia: craniofacial structures HISTORY • Nonspecific • Interview: speciality, sensity # 50-60% • Family: snoring, allergies, exposure to tobacco smoke • History of loud snoring >=3 nights/week: increase suspicion of OSA • Breathing difficulties during sleep, unusual sleeping positions, morning headaches, daytime fatigue, irritability, poor growth, behavioral problems PHYSICAL • • • • • • • • Growth chart, height, weight, obesity Nasal passenge Palate Tonsillar hypertrophy, uvula Malformation: cleft, chin, maxilla Compression Cardiac examination Conditions in cause POLYSOMNOGRAPHY • • • • Sleep state (>2 EEG leads) Electrooculogram (right and left) Electromyelogram (EMG) Airflow at nose and mouth (thermistor, capnography, or mask and pneumotachygraph) • Chest and abdominal wall motion • Electrocardiogram (preferably with R-R interval derivation technology) POLYSOMNOGRAPHY • Pulse oximetry (including a pulse waveform channel) • End-tidal carbon dioxide (sidestream or mainstream infrared sensor) • Video camera monitor with sound montage • Transcutaneous oxygen and carbon dioxide tensions (in infants and children 10 minutes • Total sleep time (TST) > 5.5 hours • Rapid eye movement (REM) sleep >15% of TST • Percentage of stage 3-4 non-REM sleep > 25% of TST • Respiratory arousal index (number per hour of TST) < • Periodic leg movements (number per hour of TST) < • Apnea index (number per hour of TST) 95% • Desaturation index (>4% for s; number / hour of TST) < • Highest CO2 52 mm Hg • CO2 > 45 mm Hg < 20% of TST TREATMENT Medical therapy: limited value • Antihistamine or antimuscarinic: nasal congestion, benefit is uncertain • Leukotriene modifier: eliminate residual OSA following surgery, improve clinical outcomes without surgery • Budesonide for weeks: sustained improvement in mild OSA TREATMENT Positive-pressure ventilation: safe, efficient, alternative to further surgery or tracheotomy in children and infants with unresolved OSA after tonsillectomy and adenoidectomy • CPAP • BiPAP TREATMENT Surgery: • Tonsillectomy and adenoidectomy • Tracheotomy • Uvulopharyngopalatoplasty, epiglottoplasty • Bariatric surgery Pediatric obstructive sleep apnea (OSA): A potential late consequence of respiratory syncitial virus (RSV) bronchiolitis Ayelet Snow, MD,1 Ehab Dayyat, MD,1 Hawley E MANAGEMENT OF SUSPECTED VIRAL ENCEPHALITIS IN CHILDREN OVERVIEW • 1980s: dramatically improved by aciclovir HSV encephalitis in adults • Delays treatment(> 48h after hospital admission): associated with a worse prognosis OVERVIEW • Syndrome of neurological dysfunction: inflammation of the brain parenchyma • Many causes: Infectious: viruses, bacteria, parasites and fungi Non- infectious: antibody-mediated RECOMMENDATION • Which clinical features should lead to a suspicion of encephalitis in children? RECOMMENDATION • Current or recent febrile illness: altered behaviour, personality, cognition or consciousness, seizures or new focal neurological signs (A, II) • The differential diagnosis: metabolic, toxic, autoimmune causes or sepsis outside the CNS (B, III), past history is very important • Sub-acute (weeks to months) encephalitis: autoimmune, paraneoplastic, metabolic aetiologies (C, III) • Priority of the investigations: determined by clinical history and clinical presentation (C, III) RECOMMENDATION • Diagnostic features for specific aetiologies? Age  Immunocompetence  Geography Exposure HSV encephalitis RECOMMENDATION • Symptom: non – specific • Children: labial – herpes is diagnostic specific (develop encephalitis with primary HSV infection) • Acute opercular syndrome (disturbance of voluntary control of the facio-linguo-glossopharyngeal muscles leading to oro-facial palsy, dysarthria and dysphagia) • Sexual abuse RECOMMENDATION • MRI: as soon as possible on all patients with suspected encephalitis/ diagnosis is uncertain, 24 hrs – 48 hrs after hospital admission (B, II) • MRI: chosen appropriately should be interpreted by an experienced paediatric neuroradiologist • SPECT and PET are not indicated in the assessment of suspected acute viral encephalitis (B, II) • For which patients should aciclovir treatment be started empirically? RECOMMENDATIO • Initial CSF and/or imaging suspected encephalitis: start acyclovir within hours of admission if these results are awaited (A, II) • First CSF/imaging: normal, clinical suspicion of HSV or VZV encephalitis: start acyclovir within hours of admission whilst further diagnostic investigations are awaited (A, II) RECOMMENDATION • Dose? 3 months-12 years 500mg/m2 hourly  >12 years 10mg/kg hourly reduced in patients with pre-existing renal impairment (A, II) If meningitis is also suspected, should also be treated (A, II) • How long should acyclovir be continued in proven HSV encephalitis, and is there a role for oral treatment? RECOMMENDATION • Proven: continued for 14-21 days (A, II), repeat LP • CSF PCR is still positive for HSV: aciclovir should continue, with weekly CSF PCR until it is negative (B, II) • months-12 years a minimum of 21 days of aciclovir should be given before repeating the LP (B, III) • When can presumptive treatment with aciclovir be safely stopped, in patients that are HSV PCR negative? RECOMMENDATION • An alternative diagnosis has been made, or • HSV PCR in the CSF is negative on two occasions 24-48 hours apart, and MRI imaging (performed >72 hours after symptom onset), is not characteristic for HSV encephalitis, or • HSV PCR in the CSF is negative once >72 hours after neurological symptom onset, with normal level of consciousness, normal MRI, CSF white cell count of less than 106/L (B, III) • What is the role of corticosteroids in HSVB encephalitis? RECOMMENDATION • Corticosteroids should not be used routinely in patients with HSV encephalitis (B, III) • Corticosteroids may have a role in patients with HSV encephalitis under specialist supervision (study results are awaited (C, III)) • What should be the specific management of VZV encephalitis? RECOMMENDATION • No specific treatment for VZV cerebellitis (B, II) • ... DECONTAMINATION Paraquat Poisoning – UpToDate 14.0 Gastrointestinal decontamination is recommended to limit sytemic exposure Grade 2C GASTROINTESTINAL DECONTAMINATION  Activated charcoal (1 g/kg in. .. and relatively inexpensive  widespread use in much of the developing countries  Self -poisoning, suicide INTRODUCTION  Swallowing of 20 to 24 % paraquat concentrate > 30 mL (a mouthful or two)... time of ingestion MANAGEMENT INITIAL MANAGEMENT GASTROINTESTINAL DECONTAMINATION TOPICAL AND INHALATION MONITORING SPECIFIC TREATMENTS AND ANTIDOTAL THERAPIES ONGOING MANAGEMENT GASTROINTESTINAL