Rickets in very low-birth-weight infants born at Baragwanath Hospital.

A Dissertation Submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg for the degree of Master of Medicine.Disturbed mineral and bone metabolism is frequently found in very low-birth-weight infants fed breast-milk during the first three months of life. The study was designed to assess the prevalence of this disturbed mineral homeostasis in a very low-birth-weight populatiun at Baragwanath Hospital and to determine whether the addition of a preterm infant formula to the feeds reduced the prevalence and increased the rate of weight gain. Fifty three neonates weighing less than 1200g born at Baragwanath Hospital were monitored for weight gain, growth and for biochemical and radiological evidence of metabolic bone disease. The infants were randomized to receive either breast-milk only feeds or a combination of breast-milk and a premature formula in order to assess the effect of the different feeds on the development of bone disease. Weight gain and growth were similar in both groups. Calcium and phosphorus intakes were higher in the mixed feeding group. However, serum calcium and phosphorus values were similar in the two groups throughout the study. The breast-milk group had significantly higher alkaline phosphatase levels. Radiological rickets was uncommun in both groups, although periosteal reactions and osteopenia occurred frequently and with similar prevalence in both groups. Overt rickets is not a major problem in very-low birth- weight infants born at Baragwanath Hospital, although raised serum alkaline phosphatase values occur frequently. Feeding with breast-milk and a premature infant formula in equal proportions (as opposed to breast-milk only) does not appear to have any effect on weight gain and growth in very low-birth-weight infants, but does partially prevent the pathological rise in alkaline phosphatase levels.Andrew Chakane 201

Selection and work-up for liver transplantation

The evaluation of the liver transplantation candidate is intended to confirm the indication for transplantation, determine the severity of disease, exclude contra-indications, optimise pre-transplantation care and candidate condition, and educate the patient and family on post-procedure expectations. This article is intended as a guide for the appropriate selection and work-up of patients for liver transplantation

Guidelines for the Development of Comprehensive Care Centers for Congenital Adrenal Hyperplasia: Guidance from the CARES Foundation Initiative

Patients with rare and complex diseases such as congenital adrenal hyperplasia (CAH) often receive fragmented and inadequate care unless efforts are coordinated among providers. Translating the concepts of the medical home and comprehensive health care for individuals with CAH offers many benefits for the affected individuals and their families. This manuscript represents the recommendations of a 1.5 day meeting held in September 2009 to discuss the ideal goals for comprehensive care centers for newborns, infants, children, adolescents, and adults with CAH. Participants included pediatric endocrinologists, internal medicine and reproductive endocrinologists, pediatric urologists, pediatric surgeons, psychologists, and pediatric endocrine nurse educators. One unique aspect of this meeting was the active participation of individuals personally affected by CAH as patients or parents of patients. Representatives of Health Research and Services Administration (HRSA), New York-Mid-Atlantic Consortium for Genetics and Newborn Screening Services (NYMAC), and National Newborn Screening and Genetics Resource Center (NNSGRC) also participated. Thus, this document should serve as a “roadmap” for the development phases of comprehensive care centers (CCC) for individuals and families affected by CAH

Guidelines for the Development of Comprehensive Care Centers for Congenital Adrenal Hyperplasia: Guidance from the CARES Foundation Initiative

Patients with rare and complex diseases such as congenital adrenal hyperplasia (CAH) often receive fragmented and inadequate care unless efforts are coordinated among providers. Translating the concepts of the medical home and comprehensive health care for individuals with CAH offers many benefits for the affected individuals and their families. This manuscript represents the recommendations of a 1.5 day meeting held in September 2009 to discuss the ideal goals for comprehensive care centers for newborns, infants, children, adolescents, and adults with CAH. Participants included pediatric endocrinologists, internal medicine and reproductive endocrinologists, pediatric urologists, pediatric surgeons, psychologists, and pediatric endocrine nurse educators. One unique aspect of this meeting was the active participation of individuals personally affected by CAH as patients or parents of patients. Representatives of Health Research and Services Administration (HRSA), New York-Mid-Atlantic Consortium for Genetics and Newborn Screening Services (NYMAC), and National Newborn Screening and Genetics Resource Center (NNSGRC) also participated. Thus, this document should serve as a “roadmap” for the development phases of comprehensive care centers (CCC) for individuals and families affected by CAH

Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. METHODS: We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. RESULTS: A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). CONCLUSIONS: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Guidelines for the Development of Comprehensive Care Centers for Congenital Adrenal Hyperplasia: Guidance from the CARES Foundation Initiative

Abstract Patients with rare and complex diseases such as congenital adrenal hyperplasia (CAH) often receive fragmented and inadequate care unless efforts are coordinated among providers. Translating the concepts of the medical home and comprehensive health care for individuals with CAH offers many benefits for the affected individuals and their families. This manuscript represents the recommendations of a 1.5 day meeting held in September 2009 to discuss the ideal goals for comprehensive care centers for newborns, infants, children, adolescents, and adults with CAH. Participants included pediatric endocrinologists, internal medicine and reproductive endocrinologists, pediatric urologists, pediatric surgeons, psychologists, and pediatric endocrine nurse educators. One unique aspect of this meeting was the active participation of individuals personally affected by CAH as patients or parents of patients. Representatives of Health Research and Services Administration (HRSA), New York-Mid-Atlantic Consortium for Genetics and Newborn Screening Services (NYMAC), and National Newborn Screening and Genetics Resource Center (NNSGRC) also participated. Thus, this document should serve as a "roadmap" for the development phases of comprehensive care centers (CCC) for individuals and families affected by CAH

Deception and Self-Deception

Why are people so often overconfident? We conduct an experiment to test the hypothesis that people become overconfident to more effectively persuade or deceive others. After performing a cognitively challenging task, half of our subjects are informed that they can earn money by convincing others of their superior performance. The privately elicited beliefs of informed subjects are significantly more confident than the beliefs of subjects in the control condition. By generating exogenous variation in confidence with a noisy performance signal, we are also able to show that higher confidence indeed makes subjects more persuasive in the subsequent face-to-face interactions

The Solar Neighborhood. XLIII. Discovery of New Nearby Stars with μ &lt; 0.″18 yr^-1 (TINYMO Sample)

We have conducted a novel search of most of the southern sky for nearby red dwarfs having low proper motions, with specific emphasis on those with proper motion < 0.18 arcsec yr-1, the lower cutoff of Luyten's classic proper motion catalog. We used a tightly constrained search of the SuperCOSMOS database and a suite of photometric distance relations for photographic BRI and 2MASS JHKs magnitudes to estimate distances to more than fourteen million red dwarf candidates. Here we discuss 29 stars in 26 systems estimated to be within 25 parsecs, all of which have pm < 0.18 arcsec yr-1, which we have investigated using milliarcsecond astrometry, VRI photometry, and low-resolution spectroscopy. In total, we present the first parallaxes of 20 star systems, nine of which are within 25 parsecs. We have additionally identified eight young M dwarfs, of which two are new members of the nearby young moving groups, and 72 new giants, including two new carbon stars. We also present the entire catalog of 1215 sources we have identified by this means.Comment: Submitted to the Astronomical Journa

Paediatric liver transplantation in Johannesburg revisited: 59 transplants and challenges met

Background. A paediatric liver transplant programme was started at the Wits Donald Gordon Medical Centre, Johannesburg, South Africa (SA), in November 2005. We reported on the first 29 patients in 2012. Since then we have performed a further 30 transplants in 28 patients, having met the major challenge of donor shortage by introducing a living related donor programme and increasing the use of split liver grafts.Objective. To review the Wits Donald Gordon Medical Centre paediatric liver transplant programme to date. We describe how the programme has evolved and specifically compare the outcomes of the first cohort with the most recent 28 patients.Methods. Case notes of all paediatric liver transplants performed between 14 November 2005 and 30 June 2014 were retrospectively reviewed. Data were analysed for age and weight at transplantation, indication and type of graft. Morbidity and mortality were documented, specifically biliary and vascular complications. Comparison was made between Era 1 (November 2005 - October 2012) and Era 2 (November 2012 - June 2014).Results. A total of 59 transplants were performed in 57 patients. Age at transplantation ranged from 9 months to 213 months (mean 82.39 months) and weight ranged from 5 kg to 62 kg (mean 21 kg). A total of 23 whole livers, 10 reduced-size grafts, 14 split liver grafts and 12 living donor liver transplants (LDLTs) were performed. Eight patients were referred with fulminant hepatic failure (FHF), all in Era 2. Of these, three patients were successfully transplanted. Of the 57 patients, 45 are alive and well with actuarial 1-year patient and graft survival of 85% and 84%  and 5-year patient and graft survival of 78% and 74%, respectively. Sixteen (25.42%) biliary complications occurred in 15 of our 59 transplants. Seven patients developed significant vascular complications. Comparing Era 1 with Era 2, mean age at transplant decreased from 100.86 months to 64.73 months, mean weight from 25.2 kg to 16.9 kg, and type of graft utilised changed with a trend away from the use of whole livers and reduced-sized grafts to split livers and segment 2,3 LDLT grafts.Conclusion. Initially limited by a shortage of donor organs, we aggressively explored optimal utilisation, splitting liver grafts from deceased donors as often as possible and establishing an LDLT programme. This increased access to donor livers allowed us to include patients with FHF and to perform retransplantation in recipients with early graft failure. It remains to offer liver transplantation to the entire paediatric community in SA, in conjunction with the only other established paediatric liver transplant unit, at Red Cross War Memorial Children’s Hospital in Cape Town