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Concept: Quartile


BACKGROUND: The clinical course of Cystic Fibrosis (CF) is usually measured using the percent predicted FEV1 and BMI Z-score referenced against a healthy population, since achieving normality is the ultimate goal of CF care. Referencing against age and sex matched CF peers may provide valuable information for patients and for comparison between CF centers or populations. Here, we used a large database of European CF patients to compute CF specific reference equations for FEV1 and BMI, derived CF-specific percentile charts and compared these European data to their nearest international equivalents. METHODS: 34859 FEV1 and 40947 BMI observations were used to compute European CF specific percentiles. Quantile regression was applied to raw measurements as a function of sex, age and height. Results were compared with the North American equivalent for FEV1 and with the WHO 2007 normative values for BMI. RESULTS: FEV1 and BMI percentiles illustrated the large variability between CF patients receiving the best current care. The European CF specific percentiles for FEV1 were significantly different from those in the USA from an earlier era, with higher lung function in Europe. The CF specific percentiles for BMI declined relative to the WHO standard in older children. Lung function and BMI were similar in the two largest contributing European Countries (France and Germany). CONCLUSION: The CF specific percentile approach applied to FEV1 and BMI allows referencing patients with respect to their peers. These data allow peer to peer and population comparisons in CF patients.

Concepts: Median, Quantile, Cystic fibrosis, Peer-to-peer, Quartile, Reference, Percentile rank, File sharing


Unconventional gas drilling (UGD) has enabled extraordinarily rapid growth in the extraction of natural gas. Despite frequently expressed public concern, human health studies have not kept pace. We investigated the association of proximity to UGD in the Marcellus Shale formation and perinatal outcomes in a retrospective cohort study of 15,451 live births in Southwest Pennsylvania from 2007-2010. Mothers were categorized into exposure quartiles based on inverse distance weighted (IDW) well count; least exposed mothers (first quartile) had an IDW well count less than 0.87 wells per mile, while the most exposed (fourth quartile) had 6.00 wells or greater per mile. Multivariate linear (birth weight) or logistical (small for gestational age (SGA) and prematurity) regression analyses, accounting for differences in maternal and child risk factors, were performed. There was no significant association of proximity and density of UGD with prematurity. Comparison of the most to least exposed, however, revealed lower birth weight (3323 ± 558 vs 3344 ± 544 g) and a higher incidence of SGA (6.5 vs 4.8%, respectively; odds ratio: 1.34; 95% confidence interval: 1.10-1.63). While the clinical significance of the differences in birth weight among the exposure groups is unclear, the present findings further emphasize the need for larger studies, in regio-specific fashion, with more precise characterization of exposure over an extended period of time to evaluate the potential public health significance of UGD.

Concepts: Cohort study, Childbirth, Epidemiology, Obstetrics, Gestational age, Quartile, Marcellus Formation, Shale


BACKGROUND:Some children feel pain during wound closures using tissue adhesives. We sought to determine whether a topically applied analgesic solution of lidocaine-epinephrine-tetracaine would decrease pain during tissue adhesive repair. METHODS:We conducted a randomized, placebo-controlled, blinded trial involving 221 children between the ages of 3 months and 17 years. Patients were enrolled between March 2011 and January 2012 when presenting to a tertiary-care pediatric emergency department with lacerations requiring closure with tissue adhesive. Patients received either lidocaine-epinephrine-tetracaine or placebo before undergoing wound closure. Our primary outcome was the pain rating of adhesive application according to the colour Visual Analogue Scale and the Faces Pain Scale - Revised. Our secondary outcomes were physician ratings of difficulty of wound closure and wound hemostasis, in addition to their prediction as to which treatment the patient had received. RESULTS:Children who received the analgesic before wound closure reported less pain (median 0.5, interquartile range [IQR] 0.25- 1.50) than those who received placebo (median 1.00, IQR 0.38-2.50) as rated using the colour Visual Analogue Scale (p = 0.01) and Faces Pain Scale - Revised (median 0.00, IQR 0.00-2.00, for analgesic v. median 2.00, IQR 0.00-4.00, for placebo, p < 0.01). Patients who received the analgesic were significantly more likely to re port having or to appear to have a pain-free procedure (relative risk [RR] of pain 0.54, 95% confidence interval [CI] 0.37-0.80). Complete hemostasis of the wound was also more common among patients who received lidocaine-epinephrine-tetracaine than among those who received placebo (78.2% v. 59.3%, p = 0.008).Conclusion:Treating minor lacerations with lidocaine-epinephrine-tetracaine before wound closure with tissue adhesive reduced ratings of pain and increased the proportion of pain-free repairs among children aged 3 months to 17 years. This low-risk intervention may benefit children with lacerations requiring tissue adhesives instead of sutures. Trial registration:, no. PR 6138378804.

Concepts: Clinical trial, Randomized controlled trial, Interquartile range, Pain, Placebo, Normal distribution, Quartile, Statistical dispersion


PURPOSE: Combretastatin A-4 disodium phosphate (CA4P) is a promising vascular disrupting agent (VDA) in clinical trials. As CA4P acts on dividing endothelial cells, we hypothesize that CA4P affects vessels of certain sizes. The aim of this study was to evaluate the effect of CA4P by the MRI-based vessel size imaging (VSI).EXPERIMENTAL DESIGN: C3H mammary carcinomas were grown to 200 mm(3) in the right rear foot of female CDF(1) mice. A control group of mice received no treatment, and a treatment group had CA4P administered intraperitoneally at a dose of 250 mg/kg. VSI was conducted on a 3 Tesla MR scanner to estimate the tumor blood volume (ζ(0)) and mean vessel radius ®. Vascularization was also estimated histologically by endothelial and Hoechst 33342 staining.RESULTS: ζ(0) and R showed different spatial heterogeneity. Tumor median and quartile values of ζ(0) were all significantly reduced by about 35% in the CA4P-treated group as compared with the control group, and the median and upper quartile of R were significantly increased. Histograms of ζ(0) and R showed a general decrease in ζ(0) following treatment, and values of R in a certain range (≈20-30 μm) were decreased in the treatment group. The drug-induced change in ζ(0) was in agreement with histology and our previous dynamic contrast enhanced MRI (DCE-MRI) data.CONCLUSIONS: Tumor blood volume and mean vessel radius showed a clear response following treatment with CA4P. VSI may prove valuable in estimation of tumor angiogenesis and prediction of response to VDAs. Clin Cancer Res; 18(23); 1-9. ©2012 AACR.

Concepts: Cancer, Angiogenesis, Blood vessel, Median, Estimation, Quartile, Combretastatin A-4, Combretastatin A-4 phosphate


Background To isolate hospital effects on risk-standardized hospital-readmission rates, we examined readmission outcomes among patients who had multiple admissions for a similar diagnosis at more than one hospital within a given year. Methods We divided the Centers for Medicare and Medicaid Services hospital-wide readmission measure cohort from July 2014 through June 2015 into two random samples. All the patients in the cohort were Medicare recipients who were at least 65 years of age. We used the first sample to calculate the risk-standardized readmission rate within 30 days for each hospital, and we classified hospitals into performance quartiles, with a lower readmission rate indicating better performance (performance-classification sample). The study sample (identified from the second sample) included patients who had two admissions for similar diagnoses at different hospitals that occurred more than 1 month and less than 1 year apart, and we compared the observed readmission rates among patients who had been admitted to hospitals in different performance quartiles. Results In the performance-classification sample, the median risk-standardized readmission rate was 15.5% (interquartile range, 15.3 to 15.8). The study sample included 37,508 patients who had two admissions for similar diagnoses at a total of 4272 different hospitals. The observed readmission rate was consistently higher among patients admitted to hospitals in a worse-performing quartile than among those admitted to hospitals in a better-performing quartile, but the only significant difference was observed when the patients were admitted to hospitals in which one was in the best-performing quartile and the other was in the worst-performing quartile (absolute difference in readmission rate, 2.0 percentage points; 95% confidence interval, 0.4 to 3.5; P=0.001). Conclusions When the same patients were admitted with similar diagnoses to hospitals in the best-performing quartile as compared with the worst-performing quartile of hospital readmission performance, there was a significant difference in rates of readmission within 30 days. The findings suggest that hospital quality contributes in part to readmission rates independent of factors involving patients. (Funded by Yale-New Haven Hospital Center for Outcomes Research and Evaluation and others.).

Concepts: Patient, Hospital, Median, Physician, Interquartile range, Centers for Medicare and Medicaid Services, Medicaid, Quartile


Objective:The potential renal acid load (PRAL) in diet may have a key role in renal stone formation through its effect on calcium and citrate metabolism. We examined the association between calcium renal stone formation and the PRAL in a population-based case-control study.Methods:A group of 123 calcium renal stone formers was compared with an equal number of age- and sex-matched controls. Dietary history was obtained by 24-h recall. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated across quartiles of dietary intakes of PRAL.Results:Compared with those in the lowest quartiles of PRAL, we found an increased risk of renal stone formation for those in the highest quartile (Q4 OR=2.51, 95% CI 1.218-5.172). Regarding individual food patterns, we found a significant protection for a high consumption of vegetables (two or more servings/day; OR=0.526, 95% CI 0.288-0.962).Conclusions:A PRAL in diet and a reduced consumption of vegetables are associated with an increased risk of calcium renal stone formation. In renal stone formers consumption of plant foods should be encouraged in order to counterbalance the acid load derived from animal-derived foods.European Journal of Clinical Nutrition advance online publication, 4 September 2013; doi:10.1038/ejcn.2013.155.

Concepts: Protein, Epidemiology, Nutrition, Fat, Diet, Kidney stone, Citrate, Quartile


Previous studies suggested that lower vitamin D might be a risk factor for autism spectrum disorders (ASDs). The aim of this study was to estimate the prevalence of ASDs in 3-year-old Chinese children and to examine the association between neonatal vitamin D status and risk of ASDs. We conducted a study of live births who had taken part in expanded newborn screening (NBS), with outpatient follow-up when the children 3-year old. The children were confirmed for ASDs in outpatient by the Autism Diagnostic Interview-Revised and Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria. Intellectual disability (ID) status was defined by the intelligence quotient (IQ < 80) for all the participants. The study design included a 1:4 case to control design. The concentration of 25-hydroxyvitamin D3 [25(OH)D3] in children with ASD and controls were assessed from neonatal dried blood samples. A total of 310 children were diagnosed as having ASDs; thus, the prevalence was 1.11% (95% CI, 0.99% to 1.23%). The concentration of 25(OH)D3 in 310 ASD and 1240 controls were assessed. The median 25(OH)D3 level was significantly lower in children with ASD as compared to controls (p < 0.0001). Compared with the fourth quartiles, the relative risk (RR) of ASDs was significantly increased for neonates in each of the three lower quartiles of the distribution of 25(OH)D3, and increased risk of ASDs by 260% (RR for lowest quartile: 3.6; 95% CI, 1.8 to 7.2; p < 0.001), 150% (RR for second quartile: 2.5; 95% CI, 1.4 to 3.5; p = 0.024), and 90% (RR for third quartile: 1.9; 95% CI, 1.1 to 3.3; p = 0.08), respectively. Furthermore, the nonlinear nature of the ID-risk relationship was more prominent when the data were assessed in deciles. This model predicted the lowest relative risk of ID in the 72rd percentile (corresponding to 48.1 nmol/L of 25(OH)D3). Neonatal vitamin D status was significantly associated with the risk of ASDs and intellectual disability. The nature of those relationships was nonlinear. © 2017 American Society for Bone and Mineral Research.

Concepts: Vitamin D, Medical statistics, Percentile, Median, Quantile, Autism, Mental retardation, Quartile


Background: Above-average dietary protein, as a single nutrient, improves musculoskeletal health. Evaluating the link between dietary protein and musculoskeletal health from a whole-diet perspective is important, as dietary guidelines focus on dietary patterns.Objective: We examined the prospective association of novel dietary protein food clusters (derived from established dietary pattern techniques) with appendicular lean mass (ALM), quadriceps strength (QS), and bone mineral density (BMD) in 2986 men and women, aged 19-72 y, from the Framingham Third Generation Study.Design: Total protein intake was estimated by food-frequency questionnaire in 2002-2005. A cluster analysis was used to classify participants into mutually exclusive groups, which were determined by using the percentage of contribution of food intake to overall protein intake. General linear modeling was used to 1) estimate the association between protein intake (grams per day) and BMD, ALM, appendicular lean mass normalized for height (ALM/ht(2)), and QS (2008-2011) and to 2) calculate adjusted least-squares mean outcomes across quartiles of protein (grams per day) and protein food clusters.Results: The mean ± SD age of subjects was 40 ± 9 y; 82% of participants met the Recommended Daily Allowance (0.8 g · kg body weight(-1) · d(-1)). The following 6 dietary protein food clusters were identified: fast food and full-fat dairy, fish, red meat, chicken, low-fat milk, and legumes. BMD was not different across quartiles of protein intake (P-trend range = 0.32-0.82); but significant positive trends were observed for ALM, ALM/ht(2) (P < 0.001), and QS (P = 0.0028). Individuals in the lowest quartile of total protein intake (quartile 1) had significantly lower ALM, ALM/ht(2), and QS than did those in the higher quartiles of intake (quartiles 2-4; (P ranges = 0.0001-0.003, 0.0007-0.003, and 0.009-0.05, respectively). However, there were no associations between protein clusters and any musculoskeletal outcome in adjusted models.Conclusions: In a protein-replete cohort of adults, dietary protein is associated with ALM and QS but not with BMD. In this study, dietary protein food patterns do not provide further insight into beneficial protein effects on muscle outcomes.

Concepts: Game theory, Protein, Nutrition, Median, Milk, Kilogram, Quartile, Myoglobin


Telomeres play a central role in cellular aging and shorter telomere length has been associated with age-related disorders including diabetes. However, a causal link between telomere shortening and diabetes risk has not been established. In a well-characterized longitudinal cohort of American Indians participating in the Strong Heart Family Study, we examined whether leukocyte telomere length (LTL) at baseline predicts incident diabetes independent of known diabetes risk factors. Among 2,328 participants free of diabetes at baseline, 292 subjects developed diabetes during an average 5.5 years of follow-up. Compared with subjects in the highest quartile (longest) of LTL, those in the lowest quartile (shortest) had an almost twofold increased risk of incident diabetes (HR 1.83, 95% CI, 1.26-2.66), whereas the risk for those in the second (HR 0.87, 95% CI, 0.59-1.29) and the third (HR 0.95, 95% CI, 0.65-1.38) quartiles was statistically nonsignificant. These findings suggest a nonlinear association between LTL and incident diabetes, and indicate that LTL could serve as a predictive marker for diabetes development in American Indians, who suffer from disproportionately high rates of diabetes.

Concepts: DNA, Epidemiology, Causality, Senescence, Risk, Actuarial science, Telomere, Quartile


BACKGROUND: There are well-documented global increases in mean body mass index (BMI) and prevalence of overweight (BMI≥25.0 kg/m(2)) and obese (BMI≥30.0 kg/m(2)). Previous analyses, however, have failed to report whether this weight gain is shared equally across the population. We examined the change in BMI across all segments of the BMI distribution in a wide range of countries, and assessed whether the BMI distribution is changing between cross-sectional surveys conducted at different time points. METHODS AND FINDINGS: We used nationally representative surveys of women between 1991-2008, in 37 low- and middle-income countries from the Demographic Health Surveys ([DHS] n = 732,784). There were a total of 96 country-survey cycles, and the number of survey cycles per country varied between two (21/37) and five (1/37). Using multilevel regression models, between countries and within countries over survey cycles, the change in mean BMI was used to predict the standard deviation of BMI, the prevalence of underweight, overweight, and obese. Changes in median BMI were used to predict the 5th and 95th percentile of the BMI distribution. Quantile-quantile plots were used to examine the change in the BMI distribution between surveys conducted at different times within countries. At the population level, increasing mean BMI is related to increasing standard deviation of BMI, with the BMI at the 95th percentile rising at approximately 2.5 times the rate of the 5th percentile. Similarly, there is an approximately 60% excess increase in prevalence of overweight and 40% excess in obese, relative to the decline in prevalence of underweight. Quantile-quantile plots demonstrate a consistent pattern of unequal weight gain across percentiles of the BMI distribution as mean BMI increases, with increased weight gain at high percentiles of the BMI distribution and little change at low percentiles. Major limitations of these results are that repeated population surveys cannot examine weight gain within an individual over time, most of the countries only had data from two surveys and the study sample only contains women in low- and middle-income countries, potentially limiting generalizability of findings. CONCLUSIONS: Mean changes in BMI, or in single parameters such as percent overweight, do not capture the divergence in the degree of weight gain occurring between BMI at low and high percentiles. Population weight gain is occurring disproportionately among groups with already high baseline BMI levels. Studies that characterize population change should examine patterns of change across the entire distribution and not just average trends or single parameters. Please see later in the article for the Editors' Summary.

Concepts: Obesity, Percentile, Median, Body mass index, Standard deviation, Body shape, Quartile