The Parathyroid Glands

Thesis (M.A.)--Boston University This item was digitized by the Internet Archive

Intravenous immunoglobulin treatment in childhood encephalitis (IgNiTE): a randomised controlled trial

Objective: To investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness. // Design: Phase 3b multicentre, double-blind, randomised placebo-controlled trial. // Setting: Twenty-one hospitals in the UK. // Participants: Children aged 6 months to 16 years with a diagnosis of acute or subacute encephalitis, with a planned sample size of 308. // Intervention: Two doses (1 g/kg/dose) of either IVIG or matching placebo given 24–36 hours apart, in addition to standard treatment. // Main outcome measure: The primary outcome was a ‘good recovery’ at 12 months after randomisation, defined as a score of≤2 on the Paediatric Glasgow Outcome Score Extended. // Secondary outcome measures: The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and IVIG safety data. // Results: 18 participants were recruited from 12 hospitals and randomised to receive either IVIG (n=10) or placebo (n=8) between 23 December 2015 and 26 September 2017. The study was terminated early following withdrawal of funding due to slower than anticipated recruitment, and therefore did not reach the predetermined sample size required to achieve the primary study objective; thus, the results are descriptive. At 12 months after randomisation, 9 of the 18 participants (IVIG n=5/10 (50%), placebo n=4/8 (50%)) made a good recovery and 5 participants (IVIG n=3/10 (30%), placebo n=2/8 (25%)) made a poor recovery. Three participants (IVIG n=1/10 (10%), placebo n=2/8 (25%)) had a new diagnosis of epilepsy during the study period. Two participants were found to have specific autoantibodies associated with autoimmune encephalitis. No serious adverse events were reported in participants receiving IVIG. // Conclusions: The IgNiTE (ImmunoglobuliN in the Treatment of Encephalitis) study findings support existing evidence of poor neurological outcomes in children with encephalitis. However, the study was halted prematurely and was therefore underpowered to evaluate the effect of early IVIG treatment compared with placebo in childhood encephalitis. // Trial registration number: Clinical Trials.gov NCT02308982; ICRCTN registry ISRCTN15791925

Intravenous immunoglobulin treatment for encephalitis in children aged 6 months to 16 years: the IgNiTE RCT

Background: There are data suggesting that intravenous immunoglobulin treatment has some benefit for certain forms of encephalitis but robust evidence from large randomised controlled trials in children with all-cause encephalitis is lacking. Objective: To evaluate whether intravenous immunoglobulin treatment improves neurological outcomes in childhood encephalitis when given early in the illness. Design: Phase 3b, investigator-initiated, randomised, double-blind, placebo-controlled trial of intravenous immunoglobulin for the treatment of encephalitis in children. Setting: Twenty-one NHS Hospitals in the UK. Participants: Children aged 6 months to 16 years with a diagnosis of acute or sub-acute encephalitis. Intervention: Two doses (1 g/kg/dose) of either intravenous immunoglobulin or matching placebo, given 24–36 hours apart, in addition to standard treatment. Main outcome measure: Participants were followed up for 12 months (+/– 4 weeks) after randomisation. The primary outcome measure was a ‘good recovery’ defined as a score of ≤ 2 on the Paediatric Glasgow Outcome Score Extended at 12 months after randomisation. Secondary outcomes: The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and intravenous immunoglobulin safety data. Results: We planned to recruit 308 children over a 42-month period. After enrolment of 18 participants (8 male; 44%) over 21 months (from December 2015 to September 2017), funding was withdrawn due to slow recruitment and the study was terminated. Ten participants were randomised to the intravenous immunoglobulin group, and eight to the placebo group, and all 18 participants were included in the analysis. At 12 months after randomisation, 9 participants [50%; intravenous immunoglobulin n = 5 (50%), placebo n = 4 (50%)] made good recovery and 5 participants [28%; intravenous immunoglobulin n = 3 (30%), placebo n = 2 (25%)] made a poor recovery. Three participants in the placebo group (43%) experienced a total of 10 serious adverse events compared with none in the intravenous immunoglobulin group but none of the adverse events were judged to be related to the study treatment. No deaths occurred during the study period. Conclusion: ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE) was halted prematurely due to slow recruitment. Given the small sample size, the study was underpowered to evaluate the effect of intravenous immunoglobulin when compared with placebo in childhood encephalitis. The study findings, albeit from a small sample size, support existing evidence that encephalitis results in poor neurological outcomes for many children. Lessons learned from the ImmunoglobuliN in the Treatment of Encephalitis trial would be valuable for the success of future trials set up to address the efficacy of early treatment with intravenous immunoglobulin in all-cause encephalitis in children. Study limitations and future work: The study was underpowered to evaluate the efficacy of intravenous immunoglobulin in the treatment of childhood encephalitis due to the small sample size achieved. Future trials should seek to address this important question. Trial registration: This trial is registered as Clinical Trials.gov (NCT02308982) and ISRCTN15791925. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/212/15) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 6. See the NIHR Funding and Awards website for further award information

Body weight, body image, and eating behaviours : relationships with ethnicity and acculturation in a community sample of young Australian women

A study was conducted to investigate associations between ethnicity and acculturation status and risk factors for eating disorders among young adult women. A community sample of 14,779 women aged 18&ndash;23 completed a comprehensive mail-out survey, which incorporated questions on country of birth, length of time spent in Australia, body weight, weight dissatisfaction, dieting, binge eating, and compensatory disordered eating behaviours. Results showed that risk factors for eating disorders were present across a range of ethnic groups. Further, a strong acculturation effect was observed, such that the longer the time spent in Australia, the more women reported weight-related values and behaviours similar to those of Australian-born women. Results challenge claims that risk factors for disordered eating are restricted to Caucasian females in Western societies. Implications for understanding ethnic and sociocultural influences on body weight, dieting, and disordered eating are considered.<br /

Breeze, The, Vol. 15, Mar. 1915

https://digitalmaine.com/milo_yearbooks/1015/thumbnail.jp

MFA13 (MFA 2013)

Catalogue of a culminating student exhibition held at the Mildred Lane Kemper Art Museum, May 3-July 29, 2013. Contents include Introduction / Buzz Spector -- The collaborative turn : new models of thinking, making, and learning / Patricia Olynyk -- [Introduction] / David Schuman -- Lyndon Barrois, Jr. / Rickey Laurentiis -- Sarah Bernhardt -- Shifting Shanghais / Hsuan Ying Chen -- Serhii Chrucky / JaNae Contag -- JaNae Contag / Emily Hanson -- Carrie DeBacker / Gabriel Feldman -- Erin M. Duhigg -- José Garza / Serhii Chrucky -- Eric Gray / Ariel Lewis -- Meghan Allynn Johnson : to or towards / Blair Allyn Johnson -- Hoa Le / Maria Xia -- Christine Eunji Lee -- Lavar Munroe : the black superhero when everyone was looking for the scapegoat / Patrick Johnson -- Jon A. Orosco : architectonics / Rickey Laurentiis -- Michael Powell / Nicholas Tamarkin -- Bridget A. Purcell : welcome home / Andy Chen -- Malahat Qureshi -- Natalie Rodgers / Katie McGinnis -- Carla Fisher Schwartz / Jennifer Padgett -- Zak Smoker -- Laurencia Strauss / Maura Pellettieri -- Lili Yang -- Vivian Zapata -- Contributors -- About the Sam Fox School.https://openscholarship.wustl.edu/books/1004/thumbnail.jp

Decision modelling using time on treatment data: evaluating the survival benefit of nilotinib versus imatinib in patients with chronic phase Ph+ CML

BACKGROUND: The ENESTnd randomised controlled trial demonstrated that nilotinib in newly diagnosed Philadelphia chromosome positive (Ph+) chronic phase chronic myeloid leukaemia (CML) has clinical superiority in terms of molecular and cytogenetic response over imatinib. However the exact relationship between improvements in major molecular response (MMR), complete cytogenetic response (CCyR) and improvements in long-term survival is as yet unknown. OBJECTIVES: (1) to evaluate the survival benefit of first-line nilotinib compared to first-line imatinib for the treatment of Ph+ chronic phase CML, and (2) to develop a decision analytic model which avoids the uncertainty of using surrogate response outcomes in economic evaluations. METHODS: A decision analytic model of first-line nilotinib compared to first-line imatinib was constructed for newly diagnosed chronic phase Ph+ CML patients. Time on treatment data from the ENESTnd trial was used to model the effectiveness of nilotinib and imatinib. This approach allows the explicit modelling of all treatment failures (patients who fail to achieve or lose response, experience intolerable adverse events or those who discontinue treatment) and provides a measure of those that continue to benefit from treatment. RESULTS: The mean undiscounted survival was estimated to be 11.80 years in the nilotinib arm compared to 10.44 years in the imatinib arm; a difference of 1.36 life-years (LYs). Using a discounting rate of 3.5%, patients will accrue an additional 0.88 LYs in the nilotinib arm compared to the imatinib arm. CONCLUSIONS: The results suggest that nilotinib produces substantially greater long-term survival than treatment with imatinib. The use of time on treatment data avoids the need for surrogate response outcomes and their associated uncertainty

Cost-effectiveness analysis of nilotinib versus imatinib for the treatment of chronic phase philadelphia chromosome positive chronic myeloid leukaemia

Background: Nilotinib is a tyrosine kinase inhibitor (TKI) for the treatment of adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML) in chronic phase. The ENESTnd phase III trial demonstrated that nilotinib has clinical superiority over current standard treatment of first-line imatinib in patients with chronic phase Ph+ CML, on the basis that fewer patients progressed to accelerated phase/blast crisis. Whilst the clinical benefits of nilotinib have been demonstrated, the cost-effectiveness of first-line nilotinib has not been explored. Aim: To evaluate the cost-effectiveness of first-line nilotinib followed by second-line dasatinib compared to first-line imatinib followed by second-line dasatinib for patients newly diagnosed with chronic phase Ph+ CML. Methods: A Markov state-transition model based on the 24 month follow-up from the ENESTnd randomised controlled trial was developed to simulate the transitions of a hypothetical cohort of patients over a lifetime. The model estimates when one treatment will fail and hence the patient is switched to an alternative treatment. Patients who discontinue first-line treatment go on to second-line dasatinib. Patients who fail on second-line dasatinib receive stem cell transplantation or HU therapy. Patients transition from chronic phase, to accelerated phase, to blast crisis, to CML-related mortality. Patients may die from other causes at any time. EQ-5D utilities were applied to patients in each health state and utility decrements were estimated for patients experiencing severe (grade 3 and 4) adverse events (AEs) on TKI therapy. Costs (2010/11 Sterling) were estimated from the perspective of the UK National Health Service (NHS) and Personal Social Services (PSS). These include the costs associated with the different drug therapies, stem cell transplantation, routine hospital appointments for administration and monitoring, and treatment for severe AEs. A patient access scheme is available for first-line nilotinib therapy and is included in the analysis. All costs and QALYs were discounted by 3.5% as recommended by NICE. Probabilistic sensitivity analysis (PSA) was conducted to explore the impact of the joint uncertainty of all model parameters on the cost-effectiveness results. Cost-effectiveness was expressed in terms of incremental cost per quality-adjusted life-years (QALYs) gained. Cost-effectiveness acceptability curves (CEACs) were also generated. Results: The mean undiscounted survival in the nilotinib arm was estimated to be 13.96 years compared to 13.32 years in the imatinib arm. Over a lifetime horizon patients are estimated to gain an additional 0.64 life-years (LYs) and 0.49 quality-adjusted life-years (QALYs) in the nilotinib arm compared to the imatinib arm. Using a discount rate of 3.5% patients are estimated to accrue an additional 0.35 LYs and 0.28 QALYs in the nilotinib arm compared to the imatinib arm. Expected lifetime (discounted) costs in the nilotinib arm were £220,416 compared to £232,941 in the imatinib arm. The nilotinib arm dominates the imatinib arm as it is more effective and less costly. Conclusions: The results suggest that nilotinib produces improvements in survival and QALYs compared to standard treatment of first-line imatinib and it is likely to offer a cost-effective use of NHS resources

Intravenous immunoglobulin treatment in childhood encephalitis (IgNiTE): a randomised controlled trial.

ObjectiveTo investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness.DesignPhase 3b multicentre, double-blind, randomised placebo-controlled trial.SettingTwenty-one hospitals in the UK.ParticipantsChildren aged 6 months to 16 years with a diagnosis of acute or subacute encephalitis, with a planned sample size of 308.InterventionTwo doses (1 g/kg/dose) of either IVIG or matching placebo given 24-36 hours apart, in addition to standard treatment.Main outcome measureThe primary outcome was a 'good recovery' at 12 months after randomisation, defined as a score of≤2 on the Paediatric Glasgow Outcome Score Extended.Secondary outcome measuresThe secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and IVIG safety data.Results18 participants were recruited from 12 hospitals and randomised to receive either IVIG (n=10) or placebo (n=8) between 23 December 2015 and 26 September 2017. The study was terminated early following withdrawal of funding due to slower than anticipated recruitment, and therefore did not reach the predetermined sample size required to achieve the primary study objective; thus, the results are descriptive. At 12 months after randomisation, 9 of the 18 participants (IVIG n=5/10 (50%), placebo n=4/8 (50%)) made a good recovery and 5 participants (IVIG n=3/10 (30%), placebo n=2/8 (25%)) made a poor recovery. Three participants (IVIG n=1/10 (10%), placebo n=2/8 (25%)) had a new diagnosis of epilepsy during the study period. Two participants were found to have specific autoantibodies associated with autoimmune encephalitis. No serious adverse events were reported in participants receiving IVIG.ConclusionsThe IgNiTE (ImmunoglobuliN in the Treatment of Encephalitis) study findings support existing evidence of poor neurological outcomes in children with encephalitis. However, the study was halted prematurely and was therefore underpowered to evaluate the effect of early IVIG treatment compared with placebo in childhood encephalitis.Trial registration numberClinical Trials.gov NCT02308982; ICRCTN registry ISRCTN15791925