Mariel Parman

Comparisons of Fatty Acid Taste Detection Thresholds in People Who Are Lean vs. Overweight or Obese: A Systematic Review and Meta-Analysis.

Given the increasing evidence that supports the ability of humans to taste non-esterified fatty acids (NEFA), recent studies have sought to determine if relationships exist between oral sensitivity to NEFA (measured as thresholds), food intake and obesity. Published findings suggest there is either no association or an inverse association. A systematic review and meta-analysis was conducted to determine if differences in fatty acid taste sensitivity or intensity ratings exist between individuals who are lean or obese. A total of 7 studies that reported measurement of taste sensations to non-esterified fatty acids by psychophysical methods (e.g.,studies using model systems rather than foods, detection thresholds as measured by a 3-alternative forced choice ascending methodology were included in the meta-analysis. Two other studies that measured intensity ratings to graded suprathreshold NEFA concentrations were evaluated qualitatively. No significant differences in fatty acid taste thresholds or intensity were observed. Thus, differences in fatty acid taste sensitivity do not appear to precede or result from obesity.

Late mortality after allogeneic blood or marrow transplantation in childhood for leukemia: a report from the Blood or Marrow Transplant Survivor Study-2

Allogeneic blood or marrow transplantation (BMT) is often used with curative intent to treat subgroups of childhood leukemia identified to be at a high risk of relapse [1–3]. However, there is limited information regarding overall and cause-specific late mortality experienced by children undergoing allogeneic BMT for leukemia [4–6]. We address this gap by conducting a detailed evaluation of late mortality, relapse-related mortality (RRM) and non-relapserelated mortality (NRM) among 2-year survivors after allogeneic BMT in childhood for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)/ myelodysplastic syndrome (MDS) and chronic myelogenous leukemia (CML). The Blood or Marrow Transplant Survivor Study-2 (BMTSS-2) is a collaborative effort between City of Hope (COH), University of Minnesota (UMN), and University of Alabama at Birmingham (UAB), examining long-term outcome after BMT. To be included in the present study, patients had to have received allogeneic BMT for ALL, AML, MDS or CML between 1974 and 2010 at COH or UMN, at age ≤ 21 years, and survived ≥ 2 years after transplantation. Information on type of leukemia, conditioning regimen, type of donor stem cells (related or unrelated), stem cell source, disease status at transplantation, graft vs. host disease (GvHD) prophylaxis, and demographic characteristics, was obtained from institutional transplant databases. National Death Index (NDI) Plus [7] and/or medical records provided information regarding the date and cause of death through 31 December 2015. Information from medical records and Accurint databases [8] was used to extend the vital status information through 31 December 2016. All patients were assigned a primary and, if present, a secondary cause of death. Human Subjects Committee at participating institutions approved the BMTSS-2 protocol. Informed consent was obtained in accordance with the Declaration of Helsinki. Kaplan–Meier techniques were used to describe overall survival, conditional on surviving ≥ 2 years from BMT. Standardized mortality ratio (SMR), a ratio of observed to expected number of deaths, was used to compare the mortality in this cohort to age(5-year interval), sex-, and calendar-specific mortality of the US general population [9]. Absolute excess risk (AER) was defined as the difference between the observed and expected number of deaths, per 1000 person-years of follow-up. Cumulative incidence rates * Smita Bhatia sbhatia@peds.uab.edu

Late mortality after autologous blood or marrow transplantation in childhood: a Blood or Marrow Transplant Survivor Study-2 report

Autologous blood or marrow transplantation (BMT) is a curative option for several types of childhood cancer. However, there is little information regarding the risk of late mortality. We examined all-cause mortality, relapse-related mortality (RRM), and nonrelapse-related mortality (NRM) in 2-year survivors of autologous BMT performed before age 22 between 1980 and 2010 at 1 of 2 US transplant centers. Vital status information was collected using medical records, National Death Index, and Accurint databases. Overall survival was calculated using Kaplan-Meier techniques. Cumulative incidence of mortality used competing risk methods. Standardized mortality ratio (SMR) was calculated using age-, sex-, and calendar-specific mortality rates from Centers for Disease Control and Prevention. Cox regression analysis was used to determine predictors of all-cause late mortality. Among the 345 2-year survivors, 103 deaths were observed, yielding an overall survival of 70.3% 15 years post-BMT. The leading causes of death included primary disease (50.0%), subsequent neoplasm (21.4%), and infection (18.2%). Overall, the cohort was at a 22-fold increased risk of late mortality (SMR, 21.8; 95% CI, 17.9-26.3), compared with the general population. Mortality rates remained elevated among the 10-year survivors (SMR, 20.6; 95% CI, 9.9-37.2) but approached those of the general population ≥15 years post-BMT. The 10-year cumulative incidence of RRM (14.3%) exceeded that of NRM (10.4%). The 10-year cumulative mortality rate declined over time (<1990, 35.1%; 1990-1999, 25.6%; 2000-2010, 21.8%; P = .05). In conclusion, childhood autologous BMT recipients have an increased risk of late mortality, compared with the general population. The late mortality rates have declined over the past 3 decades.

Potential Errors and Omissions Related to the Analysis and Conclusions Reported in Cuspidi C, et al., AJH 2014; 27(2):146-156.

To the Editor: We have observed what we believe to be errors and omissions in the paper “Effects of bariatric surgery on cardiac structure and function: a systematic review and meta-analysis” by Cuspidi et al.,1which may be of sufficient magnitude to meaningfully alter estimates or conclusions if corrected. We write to summarize the communications with the contact author and the journal staff to elicit corrections to the published paper. We first sent an e-mail to the contact author to request clarifications on 22 November 2014. When this went unanswered, we sent a letter directly to the journal editor on 8 September 2015. This was forwarded to the contact author (Dr Cuspidi), who replied on 8 November 2015. While some errors were acknowledged in Dr Cuspidi’s reply, other points remained unaddressed. We then received a request from the editor to submit this summary. We remain concerned that (i) the methods reported in the paper have not been reported in sufficient detail and clarity to determine exactly what was done and whether the methods were valid and, consequently, (ii) if the methods are not valid, the conclusions may be affected. The greatest issues relate to the definition and calculation of the effect sizes and associated variances. Our main concerns are as follows:

Assessment of Late Mortality Risk After Allogeneic Blood or Marrow Transplantation Performed in Childhood

Importance Allogeneic blood or marrow transplantation (BMT) is a curative option for malignant and nonmalignant diseases of childhood. However, little is known about trends in cause-specific late mortality in this population during the past 3 decades. Objectives To examine cause-specific late mortality among individuals who have lived 2 years or more after allogeneic BMT performed in childhood and whether rates of late mortality have changed over time. Design, Setting, and Participants A retrospective cohort study was conducted of individuals who lived 2 years or more after undergoing allogeneic BMT performed in childhood between January 1, 1974, and December 31, 2010. The end of follow-up was December 31, 2016. Exposure Allogeneic BMT performed in childhood. Main Outcomes and Measures All-cause mortality, relapse-related mortality, and non–relapse-related mortality. Data on vital status and causes of death were collected using medical records, the National Death Index Plus Program, and Accurint databases. Results Among 1388 individuals (559 females and 829 males) who lived 2 years or more after allogeneic BMT performed in childhood, the median age at transplantation was 14.6 years (range, 0-21 years). In this cohort, there was a total of 295 deaths, yielding an overall survival rate of 79.3% at 20 years after BMT. The leading causes of death were infection and/or chronic graft-vs-host disease (121 of 244 [49.6%]), primary disease (60 of 244 [24.6%]), and subsequent malignant neoplasms (45 of 244 [18.4%]). Overall, the cohort had a 14.4-fold increased risk for death (95% CI, 12.8-16.1) compared with the general population (292 deaths observed; 20.3 deaths expected). Relative mortality remained elevated at 25 years or more after BMT (standardized mortality ratio, 2.9; 95% CI, 2.0-4.1). The absolute excess risk for death from any cause was 12.0 per 1000 person-years (95% CI, 10.5-13.5). The cumulative incidence of non–relapse-related mortality exceeded that of relapse-related mortality throughout follow-up. The 10-year cumulative incidence of late mortality decreased over time (before 1990, 18.9%; 1990-1999, 12.8%; 2000-2010, 10.9%; P = .002); this decrease remained statistically significant after adjusting for demographic and clinical factors (referent group: <1990; 1990-1999: hazard ratio, 0.64; 95% CI, 0.47-0.89; P = .007; 2000-2010: hazard ratio, 0.49; 95% CI, 0.31-0.76; P = .002; P < .001 for trend). Conclusions and Relevance Late mortality among children undergoing allogeneic BMT has decreased during the past 3 decades. However, these patients remain at an elevated risk of late mortality even 25 years or more after transplantation when compared with the general population, necessitating lifelong follow-up.

Late Mortality after Allogeneic Blood or Marrow Transplantation for Inborn Errors of Metabolism - A Report from the Blood or Marrow Transplant Survivor Study-2 (BMTSS-2)

Allogeneic blood or marrow transplantation (BMT) is currently considered the standard of care for patients with specific inborn errors of metabolism (IEM). However, there is a paucity of studies describing long-term survival and cause-specific late mortality after BMT in these patients with individual types of IEM. We studied 273 patients who had survived ≥2 years after allogeneic BMT for IEM performed between 1974 and 2014. The most prevalent IEM in our cohort were X-linked adrenoleukodystrophy (ALD; 37.3%), Hurler syndrome (35.1%), and metachromatic leukodystrophy (MLD; 10.2%). Conditional on surviving ≥2 years after BMT, the overall survival for the entire cohort was 85.5 ± 2.4% at 10 years and 73.5 ± 3.7% at 20 years. The cohort had a 29-fold increased risk of late death compared with an age- and sex-matched cohort from the general US population (95% CI, 22- to 38-fold). The increased relative mortality was highest in the 2- to 5-year period after BMT (standardized mortality ratio [SMR], 207; 95% confidence interval [CI], 130 to 308) and declined with increasing time from BMT, but remained elevated for ≥21 years after BMT (SMR, 9; 95% CI, 4 to 18). Sequelae from the progression of primary disease were the most common causes of late mortality in this cohort (76%). The use of T cell-depleted grafts in patients with ALD and Hurler syndrome was a risk factor for late mortality. Younger age at BMT and use of busulfan and cyclosporine were protective in patients with Hurler syndrome. Our findings demonstrate relatively favorable overall survival in ≥2-year survivors of allogeneic BMT for IEM, although primary disease progression continues to be responsible for the majority of late deaths.

Randomization to randomization probability: Estimating treatment effects under actual conditions of use.

Abstract Blinded randomized controlled trials (RCT) require participants to be uncertain if they are receiving a treatment or placebo. Although uncertainty is ideal for isolating the treatment effect from all other potential effects, it is poorly suited for estimating the treatment effect under actual conditions of intended use—when individuals are certain that they are receiving a treatment. We propose an experimental design, randomization to randomization probabilities (R2R), which significantly improves estimates of treatment effects under actual conditions of use by manipulating participant expectations about receiving treatment. In the R2R design, participants are first randomized to a value, &pgr;, denoting their probability of receiving treatment (vs. placebo). Subjects are then told their value of &pgr; and randomized to either treatment or placebo with probabilities &pgr; and 1-&pgr;, respectively. Analysis of the treatment effect includes statistical controls for &pgr; (necessary for causal inference) and typically a &pgr;-by-treatment interaction. Random assignment of subjects to &pgr; and disclosure of its value to subjects manipulates subject expectations about receiving the treatment without deception. This method offers a better treatment effect estimate under actual conditions of use than does a conventional RCT. Design properties, guidelines for power analyses, and limitations of the approach are discussed. We illustrate the design by implementing an RCT of caffeine effects on mood and vigilance and show that some of the actual effects of caffeine differ by the expectation that one is receiving the active drug.