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They are not able to reach the hospital by if you can offer fistula surgery in order to let as public transport because they are sent off the many women profit as possible diltiazem 60mg. They have to eat buy diltiazem 180 mg fast delivery, and they lose income as International Society of Obstetric Fistula surgeons buy discount diltiazem 60 mg on line. It cannot be stressed enough that primary preven- Addis Ababa Fistula Hospital. Health personnel from hos- org pitals and remote healthcare facilities should receive International Federation of Gynaecologists (FIGO). Surgery Training Manual can be accessed under pub- In many regions of the world less than 50% of lications, miscellaneous, on this site. Traditional birth attendants must be aware of the causes, early signs Teaching Aids at Low Cost. Available from Teaching Aids at Low Cost (TALC), Box 49, St Albans Global Library of Women’s Medicine. Practical Obstetric Fistula Sur- this website there is a link to the complete contents gery. Global Competency Based Fistula Surgery Training Manual. First steps in Vesico-Vaginal Fistula Repair, and also a Published by the International Federation of Gynae- film of four operations performed at the Addis cology and Obstetrics. May be downloaded from the Ababa Fistula Hospital in 1999. Obstetric labour in- jury complex: obstetric fistula formation and the multi- faceted morbidity of maternal birth trauma in the developing world. The immediate management of fresh obstetric fistulas. Br J Obstet Gynaecol 2009;116:1265–7 272 Vesico-vaginal and Recto-vaginal Fistula APPENDIX 2: CLASSIFICATION Thus, there may be considerable interobserver variation; however, if a surgeon applies the same Goh’s classification criteria in all cases, this will enable a meaningful This is based on three variables: audit to be done. For example, this classification has been used to confirm the suspicion that the • The length of the urethra (types 1–4) worst fistulae occur in primiparous patients and • The size of the fistula (a–c) those having a vaginal delivery. This system of grading from type 1aI to type 4cIII does indicate an increasingly poor prognosis, Urethral length although it is not always an indication of difficulty Type 1: Distal edge of fistula >3. Type 1aI cases have the best prognosis ternal urethral orifice (EUO), i. An additional refinement is to Fistula size measure functional bladder capacity during dye testing. No or mild fibrosis around fistula/vagina, and/ Fistulae not involving the closing mechanism (5 cm or vaginal length >6cm or normal capacity. Moderate or severe fibrosis around fistula and/ or vagina, and/or reduced vaginal length and/ Type II or capacity. This is a popular system and used by many fistula b. It is based on the variables of involve- • There may be lack of agreement as to what con- ment of the closing mechanism, circumferential stitutes a circumferential fistula. It is used by the juxta-urethral fistulae may be slightly detached many surgeons whom he has trained, although from the bladder, although some surgeons re- others find it difficult to understand the cut-off serve the term ‘circumferential’ for cases where between A and B fistulas. In other countries similar headlights may often be found in resources for dental surgeons. Scope of the problem The prevalence of FGM is illustrated in Figure 11. Female circumcision or genital mutilation is still widely practiced in over 30 countries in the world. WHO estimates that over 120 million women have been circumcised and several thousand more are circumcised each day. Due to population move- Figure 1 Prevalence of female genital mutilation in ments women and girls living in western nations Africa. The practice has become an issue for most healthcare providers, particularly History and practice midwives and obstetricians who may, however, not be aware of the consequences. All health workers Female sexuality has been repressed in a variety of who are involved in caring for the mutilated ways in all parts of the world throughout history up patient have an important role to play: they to the present time. Female slaves in ancient Rome must recognize the sensitive nature and com- had one or more rings put through their labia to plexity of the issues related to FGM, and should prevent them from becoming pregnant. Chastity have knowledge on the possible complications in belts were brought to Europe by the crusaders dur- childbirth. Caregivers should avoid becoming ing the 12th century. In the 19th century the re- tion particularly the sexual problems and the moval of the clitoris was performed as a surgical possible serious gynecological and obstetric remedy against masturbation in Europe and in the complications. FGM may be viewed upon as one of the 275 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS extreme forms of female oppression seen across • Type III: excision of part or all of the external centuries. FGM is found across many African coun- genitalia and stitching/narrowing of the vaginal tries (Figure 1) and some countries in Asia and the opening, or infibulation (may be known as Middle East such as Malaysia, Indonesia and the pharaonic circumcision of infibulation). It is traditional in many • Type IV: pricking, piercing or incising of the different groups and faiths, including Christians and clitoris and/or labia; stretching of the clitoris Muslims. Although there is no clear obligatory and/or labia; cauterization by burning of the statement in the Qur’an for this practice, it is still clitoris and surrounding tissue; scraping of tissue carried out in the name of religion, although the surrounding the vaginal orifice (angurya cuts) or practice is not exclusive to Muslims. It varies from a few days’ old baby to cause bleeding, or for the purpose of tighten- (e. Mali, the Jewish Flashas in Ethiopia and the ing or narrowing it – and any other procedure Nomads of the Sudan) to about 7 years old (as in that falls under the definition given above. Egypt and many countries of Central Africa), or to adolescents (among the Ibo of Nigeria) where exci- Cultural issues sion takes place shortly before marriage or before the first child (as among the Ahols in mid-Western Several theories exist about its origin: Nigeria). Most experts agree, however, that the age • To control women’s sexuality or an attempt to of mutilation is becoming younger and has less and obtain control of women’s magic power.

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Comparison of evidence and practice in the treatment of constipation cheap diltiazem 60mg overnight delivery. Lack of objective evidence of efficacy of laxatives in chronic constipation cheap 60mg diltiazem with mastercard. Lubiprostone diltiazem 180mg on line, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety. Polyethylene glycol for constipation in children younger than eighteen months old. Constipation Drugs Page 79 of 141 Final Report Drug Effectiveness Review Project Appendix A. Search Strategies #1 Search "Constipation"[MeSH] OR "Irritable Bowel Syndrome"[MeSH] 8148 #3 Search "tegaserod"[Substance Name] OR zelnorm OR 27912 "lubiprostone"[Substance Name] OR mitina OR mitina OR "Dioctyl Sulfosuccinic Acid"[MeSH] OR "Psyllium"[MeSH] OR "Polyethylene Glycols"[MeSH] OR "Lactulose"[MeSH] #4 Search "Cathartics"[MeSH] OR laxative OR "fecal softener" OR "stool 15769 softener" OR "Dioctyl Sulfosuccinic Acid"[MeSH] OR colace OR surfak OR "docusate sodium" OR "docusate calcium" #5 Search #3 OR #4 41964 #6 Search #1 AND #5 1327 #7 Search #1 AND #5 Limits: Publication Date from 1985, Humans 829 #8 Search #1 AND #5 Limits: All Child: 0-18 years, Publication Date from 230 1985, Humans #9 Search #1 AND #5 Limits: All Adult: 19+ years, Publication Date from 414 1985, Humans #13 Search ("Randomized Controlled Trial"[Publication Type] OR 327612 "Randomized Controlled Trials"[MeSH]) OR "Single-Blind Method"[MeSH] OR "Double-Blind Method"[MeSH] OR "Random Allocation"[MeSH] #14 Search #8 AND #13 51 #15 Search #9 AND #13 108 #17 Search ("Review Literature"[MeSH] OR "Review"[Publication Type]) 1242191 #18 Search #8 AND #17 49 #19 Search #9 AND #17 57 #20 Search #1 AND #5 Limits: All Child: 0-18 years, Publication Date from 2 1985, Meta-Analysis, Humans #21 Search #1 AND #5 Limits: All Adult: 19+ years, Publication Date from 7 1985, Meta-Analysis, Humans #23 Search longitudinal studies [mh] OR cohort studies [mh] OR case- 857524 control studies [mh] OR comparative study [mh] OR "observational studies" [tw] #24 Search #8 AND #23 68 #25 Search #9 AND #23 97 Cochrane Reviews = 14 EMBASE = 75 IPA = 70 Constipation Drugs Page 80 of 141 Final Report Drug Effectiveness Review Project TOTAL UNDUPLICATE DATABASE = 405 #10 Search "Constipation"[MeSH] OR "Irritable Bowel Syndrome"[MeSH] 8315 #11 Search "tegaserod"[Substance Name] OR zelnorm OR 28468 "lubiprostone"[Substance Name] OR mitina OR mitina OR "Dioctyl Sulfosuccinic Acid"[MeSH] OR "Psyllium"[MeSH] OR "Polyethylene Glycols"[MeSH] OR "Lactulose"[MeSH] #12 Search "Cathartics"[MeSH] OR laxative OR "fecal softener" OR "stool 15906 softener" OR "Dioctyl Sulfosuccinic Acid"[MeSH] OR colace OR surfak OR "docusate sodium" OR "docusate calcium" #13 Search #11 OR #12 42634 #14 Search #10 AND #13 1348 #15 Search #10 AND #13 Limits: added to PubMed in the last 180 days, 24 Humans PUBMED = 20 new records Cochrane Reviews = 2 = 0 new EMBASE = 10 = 2 new IPA = 14 = 10 new TOTAL = 32 new Constipation Drugs Page 81 of 141 Final Report Drug Effectiveness Review Project Appendix B. Comparison of polyethylene glycol 3350, NF powder and lactulose and lactulose for treatment of chronic constipation in children. J Pediatr Gastroenterol Nutr 2000;31(Supplement 2):S131. Titration regimen indicates partial 5-HT4 agonist HTF 919 improves symptoms of constipation predominant irritable bowel syndrome (C-IBS). Johanson JF, Gargano MA, Holland PC, Patchen ML, Ueno R. Phase III efficacy and safety of RU- 0211, a novel chloride channel activator, for the treatment of constipation [Abstract 372]. Johanson JF, Gargano MA, Holland PC, Patchen ML, Ueno R. Phase III, randomized withdrawal study of RU-0211, a novel chloride channel activator for the treatment of constipation [Abstract 749]. Johanson JF, Gargano MA, Holland PC, Patchen ML, Ueno R. Initial and sustained effects of lubiprostone, a chloride channel-2 (CIC-2) activator for the treatment of constipation: data from a 4-week phase III study [Abstract 884]. Johanson JF, Gargano MA, Holland PC, Patchen ML, Ueno R. Multicenter open-label study of oral lubiprostone for the treatment of chronic constipation. Johanson JF, Gargano MA, Holland PC, Patchen ML, Ueno R. Multicenter open-label study of oral lubiprostone for the treatment of chronic constipation [Abstract 903]. Johanson JF, Gargano MA, Holland PC, Patchen ML, Ueno R. Phase III efficacy and safety of lubiprostone, a novel chloride channel activator, for the treatment of constipation. Presentation at: World Congress of Gastroenterology. Johanson JF, Gargano MA, Holland PC, Patchen ML, Ueno R. Phase III patient assessments of the effects of lubiprostone, a chloride channel-2 (CIC-2) activator, for the treatment of constipation [Abstract 899]. Johanson JF, Gargano MA, Holland PC, Patchen ML, Ueno R. Phase III study of lubiprostone, a chloride channel-2 (CIC-2) activator for the treatment of constipation: safety and primary efficacy [Abstract 896]. Efficacy and safety of a novel compound,RU- 0211, for the treatment of constipation [Abstract M1511]. A dose-ranging, double-blind, placebo-controlled study of lubiprostone in subjects with irritable bowel syndrome and constipation (c-ibs) [Abstract 131]. Long-term efficacy of lubiprostone for the treatment of chronic constipation [Abstract M1171]. Tegaserod is effective and well tolerated in chronic constipation: Findings from a randomized, double-blind, placebo-controlled trial. Krumholz S, Tanghe J, Schmitt C, Heggland J, Shi Y, Rüega PC. The 5HT4 partial agonist, tegaserod, improves abdominal bloating and altered stool consistency in irritable bowel syndrome (IBS). Tegaserod provides relief of symptoms in female patients with irritable bowel syndrome (IBS) suffering from abdominal pain and discomfort, bloating and constipation. Constipation Drugs Page 82 of 141 Final Report Drug Effectiveness Review Project 17. The 5-HT4 partial agonist, tegaserod, improves abdominal discomfort/pain and normalizes altered bowel function in irritable bowel syndrome. Relief of overall GI symptoms and abdominal pain and discomfort as outcome measures in a clinical trial of irritable bowel syndrome with HTF 919. Tegaserod provides rapid, effective relief of abdominal pain/discomfort, bloating and constipation in Chinese patients with irritable bowel syndrome with constipation (IBS-C). Tegaserod, a 5HT4 receptor partial agonist, relieves key symptoms of irritable bowel syndrome (IBS) [Abstract 1000]. Relapse of symptoms following withdrawal of tegaserod treatment in irritable bowel syndrom with constipation (IBS-C). Tegaserod is an effective and safe therapy for irritable bowel syndrome in a Nordic population. Schmitt C, Krumholz S, Tanghe J, Heggland J, Shi Y, Lefkowitz M.

In the vast majority of stable treated children treatment with intra- venous immunoglobulins and PCP prophylaxis is no longer required (Nachman 2005) order diltiazem 180 mg without a prescription. However 180mg diltiazem overnight delivery, there are still life-threatening infections and deaths from HIV if perinatal HIV infection is unrecognized or ART has not led to immune reconstitu- tion purchase diltiazem 60 mg with visa. A description of such infections in adults is given in other chapters of this book. An excellent and detailed guide for treatment of children with OIs can be found at http://www. Conclusion In many aspects HIV infection in children is different from HIV infection in adults. The ongoing growth and development of children, their viral dynamics and imma- turity of the immune system result in a different response to HIV compared to adults. This has important consequences for the diagnosis and treatment of HIV in chil- dren. The aim of therapy is to achieve maximum efficacy while avoiding long-term side effects. Sustained success in the treatment of children with HIV infection depends on: •a multidisciplinary approach; •standardized treatment protocols; •participation in multicenter trials; •appropriate formulations and treatment strategies for children & introduction of new classes of ART (e. In developed countries the clinical picture of HIV infection in children has now changed from an often fatal to a treatable chronic infection, allowing children to lead a largely normal life. This picture is still different in developing countries but prevention of mother-to-child transmission and broader coverage with ART is getting better and the number of deaths from HIV infection in children estimated by UNAIDS is decreasing (2006: 380,000; 2014: 150,000). Antiretroviral Therapy in Children 569 References Arpadi S, Shiau, S, Strehlau, R, et al. Metabolic abnormalities and body composition of HIV-infected children on Lopinavir or Nevirapine-based antiretroviral therapy. Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV-1 infection 2015: optimizing health in preparation for adult life. Performance of HIV-1 DNA or HIV-1 RNA tests for early diagnosis of peri- natal HIV-1 infection during anti-retroviral prophylaxis. Long-term therapeutic efficacy of lamivudine compared with interferon-alpha in children with chronic hepatitis B: the younger the better. Predictors of suboptimal virologic response to highly active antiretrovi- ral therapy among hiv-infected adolescents: analyses of the reaching for excellence in adolescent care and health (REACH) project. The sensitivity of HIV-1 DNA polymerase chain reaction in the neonatal period and the relative contributions of intra-uterine and intra-partum transmission. Pediatric underdosing of efavirenz: a pharmacokinetic study in Uganda. Antiretroviral drug-drug interaction considerations for HIV-infected children. Pharmacokinetics and 48-week safety and antiviral activity of fosam- prenavir-containing regimens in HIV-infected 2- to 18-year-old children. Safety and efficacy of a NRTI-sparing HAART regimen of efavirenz and lopinavir/ritonavir in HIV-1-infected children. Immunologic changes during unplanned treatment interruptions of highly active antiretroviral therapy in children with human immunodeficiency virus type 1 infection. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. Clinical management and follow-up of hypercholesterolemia among perinatally HIV-infected children enrolled in the PACTG 219C study. Cushing syndrome with secondary adrenal insufficiency from con- comitant therapy with ritonavir and fluticasone. Prevalence of lipodystrophy in HIV-infected children in Tanzania on highly active antiretroviral therapy. Marked dyslipidemia in HIV-infected children on protease inhibitor-contain- ing antiretroviral therapy. Underdosing of antiretrovirals in UK and Irish children with HIV as an example of problems in prescribing medicines to children, 1997-2005: cohort study. High rate of coronary artery abnormalities in adolescents and young adults infected with human immunodeficiency virus early in life. Longitudinal changes of bone mineral density and metabolism in antiretro- viral-treated human immunodeficiency virus-infected children. The rate of serious bacterial infections among HIV-infected children with immune reconstitution who have discontinued opportunistic infection prophylaxis. Guideline for Antiretroviral Therapy of HIV-Infected Children and Adolescents. Worsening hypertriglyceridemia with oral contraceptive pills in an adoles- cent with HIV-associated lipodystrophy: a case report and review of the literature. First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, ran- domised phase 2/3 trial. PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV- 1 infection. Raltegravir: a review of its use in the management of HIV-1 infection in children and adolescents. Lipodystrophy among HIV-infected children and adolescents on highly active antiretroviral therapy in Uganda: a cross sectional study. Long-term safety and effectiveness of ritonavir, nelfinavir, and lopinavir/riton- avir in antiretroviral-experienced HIV-infected children. Long-term safety and efficacy results of once-daily emtricitabine-based highly active antiretroviral therapy regimens in human immunodeficiency virus-infected pediatric subjects. Pediatrics 2008, 121:e827-35 Steenhoff AP, WoQD SM, Rutstein RM, et al. Invasive pneumococcal disease among HIV-infected children, 1989- 2006.

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Of the high-risk patients that of Ph disease but without the presence of the BCR-ABL included in this study treated on the POG 9905 regimen purchase 60mg diltiazem with visa, those who translocation buy cheap diltiazem 180 mg on-line. The AIEOP-BFM 2000 study used PCR-based MRD measurements In infants with ALL generic 60 mg diltiazem with amex, in whom translocations involving the MLL at the end of induction (day 33) and the end of consolidation (day gene are very common, any MLL rearrangement confers a signifi- 78) in 3184 patients with precursor B-ALL to prospectively risk 15 stratify patients. In older children, the prognostic impor- tance of MLL is somewhat less clear and may be affected by age and well as those with a prednisone poor response, induction failure, or translocation partner. High-risk patients received intensi- to higher-risk therapy. Even in the context of allocation of more intensive therapy, in multivariate analysis, MRD Initial descriptions of patients with intrachromosomal amplification at the end of induction was the most important factor, although of RUNX1 (iAMP) described very poor outcomes. By MRD risk assignment alone, the EFS at 5 years abrogate this risk. With the availability of newer genomic techniques, multiple recur- rent submicroscopic genetic alterations, including gene deletions, In the UKALL 2003 trial, patients were risk stratified based on mutations, and amplifications, have been identified. One of the more common of these abnormalities is IKZF1 altera- MRD risk status, with high risk defined by the presence of 0. Of the patients with evaluable MRD, 81% of all relapses found more commonly in patients meeting NCI high-risk criteria, occurred in those who were MRD high risk. The corticosteroid, the intensive use and formulation of asparaginase,4,56 kinetics of MRD clearance in patients with T-ALL is different with and intensification of consolidation/reinduction treatment. Conversely 50% are Intensification of conventional chemotherapy has also been investi- negative by day 78 and have a 7-year cumulative incidence of gated within specific biological subsets of patients with ALL. The incidence of relapse of those who are positive Intrachromosomal amplification of chromosome 21 (iAMP) was at day 78 was significantly higher and varied by level of MRD found to be associated with a significantly inferior EFS in several positivity, with those with 10-3 having an incidence of relapse of cooperative group trials. In a study evaluating 16% over the course of 2 sequential trials. Improvement duction chemotherapy, including the COG studies evaluating the in outcome for higher-risk patients to date can largely be attributed impact of the addition of clofarabine for patients with very-high- to intensification of conventional chemotherapy. For a small risk precursor B-ALL and nelarabine for those with high-risk percentage of children with very-high-risk ALL, intensification of T-cell ALL. As opposed to improving outcomes with ongoing therapy with the use of stem cell transplantation (SCT) in first manipulation and intensification of conventional ALL therapies, remission has been applied. The use of biologically targeted therapy identification of biologically driven subsets of ALL with unique for those with less favorable disease to which a druggable target can druggable targets will likely lead to the next significant advances be identified is clearly the most appealing intervention. To date, this strategy has been shown to be success of this strategy is largely limited to the subset of patients highly effective for one subset of ALL, that of Ph ALL, which with Ph leukemia. Favorable results for treatment of children with Ph ALL with the tyrosine kinase inhibitor Therapy for ALL is generally divided into 3 components, including imatinib in addition to intensive multiagent chemotherapy, remission induction, consolidation/intensification, and maintenance leading to a 5-year disease-free survival (DFS) of 70%, has (also referred to as continuation). The most commonly used anthracyclines are like ALL, begs the question as to whether this group, that has been doxorubicin or daunorubicin. Compared in a “therapeutic window” shown to have a worse prognosis with standard high-risk therapy,70 design as part of the induction regimen, the 2 agents were found to may benefit from targeted therapy, potentially with tyrosine kinase be equally effective. With the limitation of variability on conversion ratios chemotherapy are being planned within COG (Mignon Loh, per- used between the 2 agents, data suggest that dexamethasone may be sonal communication). In the context of BFM ized trials evaluating postinduction intensification in high-risk therapy, patients with high MRD levels at the end of induction and patients over the last 2 decades have demonstrated significantly consolidation had a 5-year DFS of 45% that was not improved by improved outcomes with some intensified regimens, but others SCT. Selected randomized clinical trials evaluating intensification of postinduction therapy for patients with higher-risk ALL Patients Randomization Outcome CCG1882, 1991–199587 Age 10 y or 1–9 y with Standard vs augmented postinduction Improved EFS for augmented therapy, WBC 50 000/ L AND slow therapy; augmented therapy both in duration and intensity early responder (BM blast intensified in both duration and in 25% on d 7) and in remission intensity byd28 CCG1961, 1996–200288 Age 10–21 y or age 1 y with Intensified therapy (additional Improved outcomes for intensified WBC 50 000/ L AND rapid asparaginase/vincristine in therapy; no difference for prolonged early responder (BM blast consolidation, escalating MTX with therapy 25% on d 7) and in remission asparaginase in interim byd28 maintenance); prolonged therapy (2nd interim maintenance/delayed intensification) POG 9406, 1994–199989 Age 10–21 y without trisomies of Postinduction intensification with MTX No difference in DFS with post 4/10 OR age 1 with WBC 1 g/m2 vs 2. With the limitations of small numbers, this study did not show an TRM in high-risk ALL advantage of SCT as a component of therapy or improvement with Morbidity, both short-term and long-term, affects every patient intensified chemotherapy compared with historical controls. Despite improvements in supportive care, mortal- retrospective review combining patients from multiple clinical trials ity as a consequence of therapy persists as a cause of death. A recent showed a 32% 10-year OS for patients with initial induction meta-analysis of randomized trials of newly diagnosed pediatric failure. In both periods, those sibling donor allogeneic SCT in first remission versus chemo- classified as having high-risk leukemia had a significantly increased therapy for a group of patients defined as having very-high-risk risk of nonrelapse mortality. The lack of definition of reduced for those in the highest risk group. Hematology 2014 185 tute a unique group, with substantially higher TRM compared with non-Down’s syndrome patients (7. Studies evaluating the utility of levofloxacin prophylaxis during ALL induction and in those being treated with intensive therapy for relapsed disease are being done through the Dana-Farber Cancer Institute consortium and COG, respectively. Conclusion The goals of therapy for every child newly diagnosed with ALL include maximizing the likelihood of cure while minimizing the risks of both acute and long-term side effects. Risk stratification, intensification of therapy for higher-risk patients, and, in the case of Ph ALL, adding targeted therapy have accounted for significant improvements in outlook for children and adolescents with high- risk disease. Despite progress, stratification schemes remain imper- fect, with 1/3 of deaths in children with ALL in those who initially meet the criteria of favorable-risk disease. In addition, refining strategies for preventing TRM will allow for the tradition of remarkable progress in the care of children with ALL to continue. Disclosures Conflict-of-interest disclosure: The author declares no competing financial interests. Shown are data with Sarah Alexander, MD, The Hospital for Sick Children, 555 University long-term follow-up of patients from COG protocol AALL0031 with Ph Ave, Toronto, Ontario M5G 1X8, Canada; Phone: (416)813-7654, ext. Clinical outcome of children with newly diagnosed Philadelphia chromosome-positive acute lympho- blastic leukemia treated between 1995 and 2005. In the NOPHO ALL-92 and 2000 trials, 25% of all deaths on study 2010;28(31):4755-4761. Educational symposium on ary to infection (72%), primarily bacterial infections, with bleeding long-term results of large prospective clinical trials for childhood acute or thrombosis, organ toxicity, or complications of tumor burden lymphoblastic leukemia (1985-2000).

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