Bibliographic record
Abstract
Analysis: Glucocorticoids have long been a mainstay in immunosuppressive regimens in both adult and pediatric transplant recipients.Multiple complications including hypertension, diabetes, hyperlipidemia, and metabolic syndrome are attributed to their longterm use, and data in adult patients shows that steroid-free transplant recipients have a lower risk of cardiovascular events and death. 1 The consequences of steroid use have prompted multiple clinical trials in adults to eliminate steroid usage relatively quickly after transplantation.Most studies have examined whether steroids could be eliminated after transplantation typically within the fi rst 3 months and a few have evaluated even more rapid elimination protocols.A meta-analysis of the randomized clinical trials (RCTs) prior to 2000 by Kasiske and colleagues, demonstrated increased acute rejection episodes and relative risk of graft failure with early withdrawal. 2 More recent studies with treatment protocols using mycophenolate mofetil (MMF) and a calcineurin inhibitor have produced variable results, some showing increased rejection episodes and others not.3,4 Importantly, longterm patient and graft survival have been evaluated in adult transplant patients after steroid withdrawal only within observational cohorts.4,5 Thus, the question of long-term benefi ts in adults from early steroid withdrawal remains unresolved.This study by Höcker and colleagues differs from this body of literature.First, the authors examine steroid withdrawal in a pediatric population and second, steroid withdrawal is delayed to one year to reduce the risk of early acute rejection while simultaneously limiting important long-term adverse consequences of steroids in growing children.Thus, when evaluated within the context of prior clinical trial evidence on steroid sparing strategies in transplantation, the study by Höcker and colleagues should add to our clinical understanding of the potential benefi ts and limitations from one steroid withdrawal strategy.In their prospective, randomized, multicentered, controlled trial, Höcker and colleagues evaluate the effects of the late withdrawal (after >1 year of therapy) of corticosteroids in pediatric transplant recipients on measurements such as growth, hypertension, glucose and lipid metabolism, metabolic syndrome, and rejection.They demonstrated improved parameters in all areas, without increased rejection rates in a two year follow-up period.Patients enrolled in the study were considered to be at low immunological risk, as those with a high panel reactive antibody (>80%), recent acute rejections, prior steroid-resistant rejections, prior multiple rejection episodes, or biopsyproven chronic rejection were excluded from the trial.All patients were taking cyclosporine and mycofenolate mofetil along with corticosteroids.Validity and threats to validity: Patients underwent central randomization using concealed methods after block stratifi cation by pubertal status, a method to promote equity in both the control and intervention groups despite potential age-related differential responses to therapy.Enrollment and exclusion criteria were clearly defi ned and clinical data and endpoints were also rigorously measured as defi ned prior to the start of the study.The data was stringently analyzed by intentionto-treat, and only 2 patients (<5%, both from the intervention group) were lost to follow-up.The study demonstrated improved growth rates, lower blood pressure, lower cholesterol and glucose levels, lower body mass index (BMI) levels, and a reduced incidence of metabolic syndrome amongst children in the steroid withdrawal group.However, several issues that might limit study validity must be considered.Although the groups were analyzed with intention-to-treat, 30% of the intervention group and 21% of the control group Shorter Dialysis Time and Mortality
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.011 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.007 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.005 | 0.004 |
| Open science | 0.002 | 0.003 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.580 | 0.314 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".