Academic Appointments

Honors & Awards

  • Howard Hughes Predoctoral Fellow in the Biological Sciences, Howard Hughes Medical Institute (1997-2002)
  • Rennie Taylor/Alton Blakeslee Fellowship for Science Writing, Council for the Advancement of Science Writing (2001-2002)
  • Teaching Award, Div of Epidemiology (HRP) (2005, 2007, 2009)

Professional Education

  • Certificate, UC-Santa Cruz, Science Writing (2002)
  • PhD, Stanford, Epidemiology (2002)
  • MS, Stanford, Statistics (1999)

Research & Scholarship

Current Research and Scholarly Interests

Science writing, science communication, biostatistics. Research areas: osteoporosis, stress fractures, sports injuries, female athlete triad.


2018-19 Courses


All Publications

  • Response. Medicine and science in sports and exercise Sainani, K. L. 2018

    View details for DOI 10.1249/MSS.0000000000001824

    View details for PubMedID 30365418

  • Breastfeeding mitigates the effects of maternal HIV on infant infectious morbidity in the Option B+ era: A multicenter prospective cohort study. AIDS (London, England) Tchakoute, C. T., Sainani, K. L., Osawe, S., Datong, P., Kiravu, A., Rosenthal, K. L., Gray, C. M., Cameron, D. W., Abimiku, A., Jaspan, H. B., INFANT study team* 2018


    OBJECTIVE: The effects of in-utero HIV-exposure on infectious morbidity and mortality in settings with universal maternal treatment and high breastfeeding rates are unclear. Further, the benefits of exclusive feeding options have not been assessed in the Option B+ era. We investigated these in two African settings with high breastfeeding uptake and good HIV treatment infrastructure during the first year of life.METHODS: Cox regression with time-changing variables in a birth cohort of 749 HIV-exposed uninfected and HIV-unexposed uninfected infants from Cape Town, South Africa and Jos, Nigeria.RESULTS: There was no difference in infectious morbidity incidence between HIV-exposed uninfected and HIV-unexposed uninfected infants (hazard ratio [HR], 1.01; 95% CI, 0.78-1.32) after adjusting for confounding variables. Formula-fed infants had significantly higher infectious morbidity incidence when compared with exclusively-breastfed infants ([HR], 1.64; 95% CI, 1.03-2.63) and mixed-breastfed infants ([HR], 1.42; 95% CI, 1.00-2.02) after adjusting for potential confounding variables. There was no significant difference in mortality among HIV-exposed infants and HIV-unexposed infants during the first year of life in this cohort (2.04% versus 0.94%, p-value = 0.38). Notably, exclusive breastfeeding for only 4 months had protective effects on morbidity up to 1 year.CONCLUSION: In settings with universal antiretroviral coverage and high breastfeeding rates, breastfeeding mitigates the effects of in-utero HIV exposure among infants during the first year of life. These findings support previous recommendations for exclusive breastfeeding among HIV-infected women and highlight the role that breastfeeding plays on the health of infants in settings where exclusive breastfeeding is not always feasible or where replacement feeding is recommended.

    View details for DOI 10.1097/QAD.0000000000001974

    View details for PubMedID 30134300

  • The Problem with "Magnitude-Based Inference". Medicine and science in sports and exercise Sainani, K. L. 2018


    PURPOSE: A statistical method called "Magnitude-Based Inference" (MBI) has gained a following in the sports science literature, despite concerns voiced by statisticians. Its proponents have claimed that MBI exhibits superior Type I and Type II error rates compared with standard null hypothesis testing for most cases. I have performed a re-analysis to evaluate this claim.METHODS: Using simulation code provided by MBI's proponents, I estimated Type I and Type II error rates for clinical and non-clinical MBI for a range of effect sizes, sample sizes, and smallest important effects. I plotted these results in a way that makes transparent the empirical behavior of MBI. I also re-ran the simulations after correcting mistakes in the definitions of Type I and Type II error provided by MBI's proponents. Finally, I confirmed the findings mathematically; and I provide general equations for calculating MBI's error rates without the need for simulation.RESULTS: Contrary to what MBI's proponents have claimed, MBI does not exhibit "superior" Type I and Type II error rates to standard null hypothesis testing. As expected, there is a tradeoff between Type I and Type II error. At precisely the small-to-moderate sample sizes that MBI's proponents deem "optimal," MBI reduces the Type II error rate at the cost of greatly inflating the Type I error rate-to two to six times that of standard hypothesis testing.CONCLUSIONS: MBI exhibits worrisome empirical behavior. In contrast to standard null hypothesis testing, which has predictable Type I error rates, the Type I error rates for MBI vary widely depending on the sample size and choice of smallest important effect, and are often unacceptably high. MBI should not be used.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

    View details for DOI 10.1249/MSS.0000000000001645

    View details for PubMedID 29683920

  • Instrumental Variables: Uses and Limitations PM&R Sainani, K. L. 2018; 10 (3): 303–8

    View details for DOI 10.1016/j.pmrj.2018.02.002

    View details for Web of Science ID 000427816500010

    View details for PubMedID 29551169

  • Lack of Diagnostic Utility of "Amino Acid Dysregulation Metabotypes". Biological psychiatry Sainani, K. L., Goodman, S. N. 2018

    View details for DOI 10.1016/j.biopsych.2018.11.012

    View details for PubMedID 30595232

  • Bone stress injuries in male distance runners: higher modified Female Athlete Triad Cumulative Risk Assessment scores predict increased rates of injury. British journal of sports medicine Kraus, E., Tenforde, A. S., Nattiv, A., Sainani, K. L., Kussman, A., Deakins-Roche, M., Singh, S., Kim, B. Y., Barrack, M. T., Fredericson, M. 2018


    OBJECTIVES: Bone stress injuries (BSI) are common in runners of both sexes. The purpose of this study was to determine if a modified Female Athlete Triad Cumulative Risk Assessment tool would predict BSI in male distance runners.METHODS: 156 male runners at two collegiate programmes were studied using mixed retrospective and prospective design for a total of 7years. Point values were assigned using risk assessment categories including low energy availability, low body mass index (BMI), low bone mineral density (BMD) and prior BSI. The outcome was subsequent development of BSI. Statistical models used a mixed effects Poisson regression model with p<0.05 as threshold for significance. Two regression analyses were performed: (1) baseline risk factors as the independent variable; and (2) annual change in risk factors (longitudinal data) as the independent variable.RESULTS: 42/156 runners (27%) sustained 61 BSIs over an average 1.9 years of follow-up. In the baseline risk factor model, each 1 point increase in prior BSI score was associated with a 57% increased risk for prospective BSI (p=0.0042) and each 1 point increase in cumulative risk score was associated with a 37% increase in prospective BSI risk (p=0.0079). In the longitudinal model, each 1 point increase in cumulative risk score was associated with a 27% increase in prospective BSI risk (p=0.05). BMI (rate ratio (RR)=1.91, p=0.11) and BMD (RR=1.58, p=0.19) risk scores were not associated with BSI.CONCLUSION: A modified cumulative risk assessment tool may help identify male runners at elevated risk for BSI. Identifying risk factors may guide treatment and prevention strategies.

    View details for DOI 10.1136/bjsports-2018-099861

    View details for PubMedID 30580252

  • The Burden of Caring for a Child or Adolescent With Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS): An Observational Longitudinal Study. The Journal of clinical psychiatry Frankovich, J., Leibold, C. M., Farmer, C., Sainani, K., Kamalani, G., Farhadian, B., Willett, T., Park, J. M., Sidell, D., Ahmed, S., Thienemann, M. 2018; 80 (1)


    OBJECTIVE: To describe the longitudinal association between disease severity, time established in clinical treatment, and caregiver burden in a community-based patient population diagnosed with pediatric acute-onset neuropsychiatric syndrome (PANS).METHODS: The study included an observational longitudinal cohort design, with Caregiver Burden Inventories (CBIs) collected between April 2013 and November 2016 at the Stanford PANS multidisciplinary clinic. Inclusion criteria for this study were as follows: pediatric patients meeting strict PANS/pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) diagnostic criteria (n = 187), having a caregiver fill out at least 1 complete CBI during a disease flare (n = 114); and having family who lives locally (n = 97). For longitudinal analyses, only patients whose caregiver had filled out 2 or more CBIs (n = 94 with 892 CBIs) were included. In the study sample, most primary caregivers were mothers (69 [71.1%] of 97), the majority of PANS patients were male (58 [59.8%] of 97), and mean age at PANS onset was 8.8 years.RESULTS: In a patient's first flare tracked by the clinic, 50% of caregivers exceeded the caregiver burden score threshold used to determine respite need in care receiver adult populations. Longitudinally, flares, compared with quiescence, predicted increases in mean CBI score (6.6 points; 95% CI, 5.1 to 8.0). Each year established in clinic predicted decreased CBI score (-3.5 points per year; 95% CI, -2.3 to -4.6). Also, shorter time between PANS onset and entry into the multidisciplinary clinic predicted greater improvement in mean CBI score over time (0.7 points per year squared; 95% CI, 0.1 to 1.3). Time between PANS onset and treatment with antibiotics or immunomodulation did not moderate the relationship between CBI score and time in clinic.CONCLUSIONS: PANS caregivers suffer high caregiver burden. Neuropsychiatric disease severity predicts increased caregiver burden. Caregiver burden tends to decrease over time in a group of patients undergoing clinical treatment at a specialty PANS clinic. This decrease could be independent of clinical treatment.

    View details for DOI 10.4088/JCP.17m12091

    View details for PubMedID 30549499

  • Response. Medicine and science in sports and exercise Sainani, K. L. 2018; 50 (12): 2611

    View details for DOI 10.1249/MSS.0000000000001737

    View details for PubMedID 30431544

  • Dealing With Binary Repeated Measures Data PM&R Tchakoute, C., Sainani, K. L. 2018; 10 (12): 1412–16

    View details for DOI 10.1016/j.pmrj.2018.11.002

    View details for Web of Science ID 000454544500016

    View details for PubMedID 30472244

  • Sport and Triad Risk Factors Influence Bone Mineral Density in Collegiate Athletes. Medicine and science in sports and exercise Tenforde, A. S., Carlson, J. L., Sainani, K. L., Chang, A. O., Kim, J. H., Golden, N. H., Fredericson, M. 2018


    PURPOSE: Athletes in weight bearing sports may benefit from higher bone mineral density (BMD). However, some athletes are at risk for impaired BMD with Female Athlete Triad (Triad). The purpose of this study is to understand the influence of sports participation and Triad on BMD. We hypothesize that athletes in high-impact and multi-directional loading sports will have highest BMD, whereas non-impact and low-impact sports will have lowest BMD. Triad risk factors are expected to reduce BMD values independent of sports participation.METHODS: 239 female athletes participating in 16 collegiate sports completed dual energy x-ray absorptiometry (DXA) scans to measure BMD Z-scores of the lumbar spine(LS) and total body(TB). Height and weight were measured to calculate body mass index (BMI). Triad risk assessment variables were obtained from preparticipation examination. Mean BMD Z-scores were compared between sports and by sport category (high-impact, multi-directional, low-impact, and non-impact). Multivariable regression analyses were performed to identify differences of BMD Z-scores accounting for Triad and body size/composition.RESULTS: Athlete populations with lowest average BMD Z-scores included synchronized swimming (LS:-0.34,TB:0.21) swimming/diving (LS:0.34,TB:-0.06), crew/rowing (LS:0.27,TB:0.62), and cross-country (LS:0.29,TB:0.91). Highest values were in gymnastics (LS:1.96,TB:1.37), volleyball (LS:1.90,TB:1.74), basketball (LS:1.73,TB:1.99), and softball (LS:1.68,TB:1.78). All Triad risk factors were associated with lower BMD Z-scores in univariable analyses; only low BMI and oligomenorrhea/amenorrhea were associated in multivariable analyses (all P<0.05). Accounting for Triad risk factors and body size/composition, high-impact sports were associated with higher LS and TB BMD Z-scores and non-impact sports with lower LS and TB BMD Z-scores compared to low-impact sport (all P<0.05).CONCLUSION: Both sport type and Triad risk factors influence BMD. Athletes in low-impact and non-impact sports and athletes with low BMI and oligomenorrhea/amenorrhea are at highest risk for reduced BMD.

    View details for DOI 10.1249/MSS.0000000000001711

    View details for PubMedID 29975299

  • Re: Sainani K. Interpreting "null" results Reply PM&R Sainani, K. L. 2018; 10 (5): 563

    View details for DOI 10.1016/j.pmrj.2017.12.013

    View details for Web of Science ID 000432673300019

    View details for PubMedID 29776490

  • Youth Multi-sport Participation Is Associated With Higher Bone Mineral Density In Female Collegiate Distance Runners Miller, E., Fredericson, M., Kussman, A., Krauss, E., Singh, S., Deakins-Roche, M., Kim, B., Tenforde, A., Sainani, K., Nattiv, A. LIPPINCOTT WILLIAMS & WILKINS. 2018: 490
  • Evaluation of Evidence of Statistical Support and Corroboration of Subgroup Claims in Randomized Clinical Trials. JAMA internal medicine Wallach, J. D., Sullivan, P. G., Trepanowski, J. F., Sainani, K. L., Steyerberg, E. W., Ioannidis, J. P. 2017


    Many published randomized clinical trials (RCTs) make claims for subgroup differences.To evaluate how often subgroup claims reported in the abstracts of RCTs are actually supported by statistical evidence (P < .05 from an interaction test) and corroborated by subsequent RCTs and meta-analyses.This meta-epidemiological survey examines data sets of trials with at least 1 subgroup claim, including Subgroup Analysis of Trials Is Rarely Easy (SATIRE) articles and Discontinuation of Randomized Trials (DISCO) articles. We used Scopus (updated July 2016) to search for English-language articles citing each of the eligible index articles with at least 1 subgroup finding in the abstract.Articles with a subgroup claim in the abstract with or without evidence of statistical heterogeneity (P < .05 from an interaction test) in the text and articles attempting to corroborate the subgroup findings.Study characteristics of trials with at least 1 subgroup claim in the abstract were recorded. Two reviewers extracted the data necessary to calculate subgroup-level effect sizes, standard errors, and the P values for interaction. For individual RCTs and meta-analyses that attempted to corroborate the subgroup findings from the index articles, trial characteristics were extracted. Cochran Q test was used to reevaluate heterogeneity with the data from all available trials.The number of subgroup claims in the abstracts of RCTs, the number of subgroup claims in the abstracts of RCTs with statistical support (subgroup findings), and the number of subgroup findings corroborated by subsequent RCTs and meta-analyses.Sixty-four eligible RCTs made a total of 117 subgroup claims in their abstracts. Of these 117 claims, only 46 (39.3%) in 33 articles had evidence of statistically significant heterogeneity from a test for interaction. In addition, out of these 46 subgroup findings, only 16 (34.8%) ensured balance between randomization groups within the subgroups (eg, through stratified randomization), 13 (28.3%) entailed a prespecified subgroup analysis, and 1 (2.2%) was adjusted for multiple testing. Only 5 (10.9%) of the 46 subgroup findings had at least 1 subsequent pure corroboration attempt by a meta-analysis or an RCT. In all 5 cases, the corroboration attempts found no evidence of a statistically significant subgroup effect. In addition, all effect sizes from meta-analyses were attenuated toward the null.A minority of subgroup claims made in the abstracts of RCTs are supported by their own data (ie, a significant interaction effect). For those that have statistical support (P < .05 from an interaction test), most fail to meet other best practices for subgroup tests, including prespecification, stratified randomization, and adjustment for multiple testing. Attempts to corroborate statistically significant subgroup differences are rare; when done, the initially observed subgroup differences are not reproduced.

    View details for DOI 10.1001/jamainternmed.2016.9125

    View details for PubMedID 28192563

  • Association of the Female Athlete Triad Risk Assessment Stratification to the Development of Bone Stress Injuries in Collegiate Athletes. American journal of sports medicine Tenforde, A. S., Carlson, J. L., Chang, A., Sainani, K. L., Shultz, R., Kim, J. H., Cutti, P., Golden, N. H., Fredericson, M. 2017; 45 (2): 302-310


    The female athlete triad (referred to as the triad) contributes to adverse health outcomes, including bone stress injuries (BSIs), in female athletes. Guidelines were published in 2014 for clinical management of athletes affected by the triad.This study aimed to (1) classify athletes from a collegiate population of 16 sports into low-, moderate-, and high-risk categories using the Female Athlete Triad Cumulative Risk Assessment score and (2) evaluate the predictive value of the risk categories for subsequent BSIs.Cohort study; Level of evidence, 3.A total of 323 athletes completed both electronic preparticipation physical examination and dual-energy x-ray absorptiometry scans. Of these, 239 athletes with known oligomenorrhea/amenorrhea status were assigned to a low-, moderate-, or high-risk category. Chart review was used to identify athletes who sustained a subsequent BSI during collegiate sports participation; the injury required a physician diagnosis and imaging confirmation.Of 239 athletes, 61 (25.5%) were classified into moderate-risk and 9 (3.8%) into high-risk categories. Sports with the highest proportion of athletes assigned to the moderate- and high-risk categories included gymnastics (56.3%), lacrosse (50%), cross-country (48.9%), swimming/diving (42.9%), sailing (33%), and volleyball (33%). Twenty-five athletes (10.5%) assigned to risk categories sustained ≥1 BSI. Cross-country runners contributed the majority of BSIs (16; 64%). After adjusting for age and participation in cross-country, we found that moderate-risk athletes were twice as likely as low-risk athletes to sustain a BSI (risk ratio [RR], 2.6; 95% confidence interval [95% CI], 1.3-5.5) and high-risk athletes were nearly 4 times as likely (RR, 3.8; 95% CI, 1.8-8.0). When examining the 6 individual components of the triad risk assessment score, both the oligomenorrhea/amenorrhea score ( P = .0069) and the prior stress fracture/reaction score ( P = .0315) were identified as independent predictors for subsequent BSIs (after adjusting for cross-country participation and age).Using published guidelines, 29% of female collegiate athletes in this study were classified into moderate- or high-risk categories using the Female Athlete Triad Cumulative Risk Assessment Score. Moderate- and high-risk athletes were more likely to subsequently sustain a BSI; most BSIs were sustained by cross-country runners.

    View details for DOI 10.1177/0363546516676262

    View details for PubMedID 28038316

  • The Value of Scatter Plots PM&R Sainani, K. L. 2016; 8 (12): 1213-1217

    View details for DOI 10.1016/j.pmrj.2016.10.018

    View details for Web of Science ID 000391085900010

    View details for PubMedID 27989418

  • Supply and Perceived Demand for Teleophthalmology in Triage and Consultations in California Emergency Departments JAMA OPHTHALMOLOGY Wedekind, L., Sainani, K., Pershing, S. 2016; 134 (5): 537-543
  • Raloxifene for women with Alzheimer disease: A randomized controlled pilot trial. Neurology Henderson, V. W., Ala, T., Sainani, K. L., Bernstein, A. L., Stephenson, B. S., Rosen, A. C., Farlow, M. R. 2015; 85 (22): 1937-1944

    View details for DOI 10.1212/WNL.0000000000002171

    View details for PubMedID 26537053

  • Obstructive Sleep Apnea Is an Independent Predictor of Postoperative Atrial Fibrillation in Cardiac Surgery JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Wong, J. K., Maxwell, B. G., Kushida, C. A., Sainani, K. L., Lobato, R. L., Woo, J., Pearl, R. G. 2015; 29 (5): 1140-1147

    View details for DOI 10.1053/j.jvca.2015.03.024

    View details for Web of Science ID 000361782900005

    View details for PubMedID 26154572

  • Identifying Sex-Specific Risk Factors for Low Bone Mineral Density in Adolescent Runners AMERICAN JOURNAL OF SPORTS MEDICINE Tenforde, A. S., Fredericson, M., Sayres, L. C., Cutti, P., Sainani, K. L. 2015; 43 (6): 1494-1504


    Adolescent runners may be at risk for low bone mineral density (BMD) associated with sports participation. Few prior investigations have evaluated bone health in young runners, particularly males.To characterize sex-specific risk factors for low BMD in adolescent runners.Cross-sectional study; Level of evidence, 3.Training characteristics, fracture history, eating behaviors and attitudes, and menstrual history were measured using online questionnaires. A food frequency questionnaire was used to identify dietary patterns and measure calcium intake. Runners (female: n = 94, male: n = 42) completed dual-energy x-ray absorptiometry (DXA) to measure lumbar spine (LS) and total body less head (TBLH) BMD and body composition values, including android-to-gynoid (A:G) fat mass ratio. The BMD was standardized to Z-scores using age, sex, and race/ethnicity reference values. Questionnaire values were combined with DXA values to determine risk factors associated with differences in BMD Z-scores in LS and TBLH and low bone mass (defined as BMD Z-score ≤-1).In multivariable analyses, risk factors for lower LS BMD Z-scores in girls included lower A:G ratio, being shorter, and the combination of (interaction between) current menstrual irregularity and a history of fracture (all P < .01). Later age of menarche, lower A:G ratio, lower lean mass, and drinking less milk were associated with lower TBLH BMD Z-scores (P < .01). In boys, lower body mass index (BMI) Z-scores and the belief that being thinner improves performance were associated with lower LS and TBLH BMD Z-scores (all P < .05); lower A:G ratio was additionally associated with lower TBLH Z-scores (P < .01). Thirteen girls (14%) and 9 boys (21%) had low bone mass. Girls with a BMI ≤17.5 kg/m(2) or both menstrual irregularity and a history of fracture were significantly more likely to have low bone mass. Boys with a BMI ≤17.5 kg/m(2) and belief that thinness improves performance were significantly more likely to have low bone mass.This study identified sex-specific risk factors for impaired bone mass in adolescent runners. These risk factors can be helpful to guide sports medicine professionals in evaluation and management of young runners at risk for impaired bone health.

    View details for DOI 10.1177/0363546515572142

    View details for Web of Science ID 000355379200027

    View details for PubMedID 25748470

  • Running habits of competitive runners during pregnancy and breastfeeding. Sports health Tenforde, A. S., Toth, K. E., Langen, E., Fredericson, M., Sainani, K. L. 2015; 7 (2): 172-176


    Running is a popular sport that may be performed safely during pregnancy. Few studies have characterized running behavior of competitive female runners during pregnancy and breastfeeding.Women modify their running behavior during pregnancy and breastfeeding.Observational, cross-sectional study.Level 2.One hundred ten female long-distance runners who ran competitively prior to pregnancy completed an online survey characterizing training attitudes and behaviors during pregnancy and postpartum.Seventy percent of runners ran some time during their pregnancy (or pregnancies), but only 31% ran during their third trimester. On average, women reduced training during pregnancy, including cutting their intensity to about half of their nonpregnant running effort. Only 3.9% reported sustaining a running injury while pregnant. Fewer than one third (29.9%) selected fetal health as a reason to continue running during pregnancy. Of the women who breastfed, 84.1% reported running during breastfeeding. Most felt that running had no effect on their ability to breastfeed. Women who ran during breastfeeding were less likely to report postpartum depression than those who did not run (6.7% vs 23.5%, P = 0.051), but we did not detect the same association of running during pregnancy (6.5% vs 15.2%, P = 0.16).Women runners reported a reduction in total training while pregnant, and few sustained running injuries during pregnancy. The effect of running on postpartum depression was not clear from our findings.We characterized running behaviors during pregnancy and breastfeeding in competitive runners. Most continue to run during pregnancy but reduce total training effort. Top reasons for running during pregnancy were fitness, health, and maintaining routine; the most common reason for not running was not feeling well. Most competitive runners run during breastfeeding with little perceived impact.

    View details for DOI 10.1177/1941738114549542

    View details for PubMedID 25984264

    View details for PubMedCentralID PMC4332642

  • Participation in Ball Sports May Represent a Prehabilitation Strategy to Prevent Future Stress Fractures and Promote Bone Health in Young Athletes PM&R Tenforde, A. S., Sainani, K. L., Sayres, L. C., Milgrom, C., Fredericson, M. 2015; 7 (2): 222-225


    Sports participation has many benefits for the young athlete, including improved bone health. However, a subset of athletes may attain suboptimal bone health and be at increased risk for stress fractures. This risk is greater for female than for male athletes. In healthy children, high-impact physical activity has been shown to improve bone health during growth and development. We offer our perspective on the importance of promoting high-impact, multidirectional loading activities, including ball sports, as a method of enhancing bone quality and fracture prevention based on collective research. Ball sports have been associated with greater bone mineral density and enhanced bone geometric properties compared with participation in repetitive, low-impact sports such as distance running or nonimpact sports such as swimming. Runners and infantry who participated in ball sports during childhood were at decreased risk of future stress fractures. Gender-specific differences, including the coexistence of female athlete triad, may negate the benefits of previous ball sports on fracture prevention. Ball sports involve multidirectional loading with high ground reaction forces that may result in stiffer and more fracture-resistant bones. Encouraging young athletes to participate in ball sports may optimize bone health in the setting of adequate nutrition and in female athletes, eumenorrhea. Future research to determine timing, frequency, and type of loading activity could result in a primary prevention program for stress fracture injuries and improved life-long bone health.

    View details for DOI 10.1016/j.pmrj.2014.09.017

    View details for Web of Science ID 000349995500019

    View details for PubMedID 25499072

  • Logistic Regression PM&R Sainani, K. L. 2014; 6 (12): 1157-1162

    View details for DOI 10.1016/j.pmrj.2014.10.006

    View details for Web of Science ID 000346402700012

    View details for PubMedID 25463689

  • Explanatory Versus Predictive Modeling PM&R Sainani, K. L. 2014; 6 (9): 841-844
  • Bonferroni, Holm, and Hochberg Corrections: Fun Names, Serious Changes to P Values PM&R McLaughlin, M. J., Sainani, K. L. 2014; 6 (6): 544-546
  • Introduction to Principal Components Analysis PM&R Sainani, K. L. 2014; 6 (3): 275-278

    View details for DOI 10.1016/j.pmrj.2014.02.001

    View details for Web of Science ID 000333548000009

    View details for PubMedID 24565515

  • Eczema and sensitization to common allergens in the United States: a multiethnic, population-based study. Pediatric dermatology Fu, T., Keiser, E., Linos, E., Rotatori, R. M., Sainani, K., Lingala, B., Lane, A. T., Schneider, L., Tang, J. Y. 2014; 31 (1): 21-26


    The relationship between food and environmental allergens in contributing to eczema risk is unclear on a multiethnic population level. Our purpose was to determine whether sensitization to specific dietary and environmental allergens as measured according to higher specific immunoglobulin E (IgE) levels is associated with eczema risk in children. National Health and Nutrition Examination Survey participants ages 1 to 17 years were asked whether they had ever received a diagnosis of eczema from a physician (n = 538). Total and specific serum IgE levels for four dietary allergens (egg, cow's milk, peanut, and shrimp) and five environmental allergens (dust mite, cat, dog, Aspergillus, and Alternaria) were measured. Logistic regression was used to examine the association between eczema and IgE levels. In the United States, 10.4 million children (15.6%) have a history of eczema. Eczema was more common in black children (p < 0.001) and in children from families with higher income and education (p = 0.01). The median total IgE levels were higher in children with a history of eczema than in those without (66.4 vs 50.6 kU/L, p = 0.004). In multivariate analysis adjusted for age, race, sex, family income, household education, and physician-diagnosed asthma, eczema was significantly associated with sensitization to cat dander (odds ratio [OR] = 1.2, 95% confidence interval [CI] 1.05, 1.4, p = 0.009) and dog dander (OR = 1.5, 95% CI, 1.2, 1.7, p < 0.001). After correction for multiple comparisons, only sensitization to dog dander remained significant. U.S. children with eczema are most likely to be sensitized to dog dander. Future prospective studies should further explore this relationship.

    View details for DOI 10.1111/pde.12237

    View details for PubMedID 24283549

  • Understanding Linear Regression PM&R Sainani, K. L. 2013; 5 (12): 1063-1068

    View details for DOI 10.1016/j.pmrj.2013.10.002

    View details for Web of Science ID 000328795700009

    View details for PubMedID 24140739

  • Higher Caloric Intake in Hospitalized Adolescents With Anorexia Nervosa Is Associated With Reduced Length of Stay and No Increased Rate of Refeeding Syndrome JOURNAL OF ADOLESCENT HEALTH Golden, N. H., Keane-Miller, C., Sainani, K. L., Kapphahn, C. J. 2013; 53 (5): 573-578


    To determine the effect of higher caloric intake on weight gain, length of stay (LOS), and incidence of hypophosphatemia, hypomagnesemia, and hypokalemia in adolescents hospitalized with anorexia nervosa.Electronic medical records of all subjects 10-21 years of age with anorexia nervosa, first admitted to a tertiary children's hospital from Jan 2007 to Dec 2011, were retrospectively reviewed. Demographic factors, anthropometric measures, incidence of hypophosphatemia (≤3.0 mg/dL), hypomagnesemia (≤1.7 mg/dL), and hypokalemia (≤3.5 mEq/L), and daily change in percent median body mass index (BMI) (%mBMI) from baseline were recorded. Subjects started on higher-calorie diets (≥1,400 kcal/d) were compared with those started on lower-calorie diets (<1,400 kcal/d).A total of 310 subjects met eligibility criteria (age, 16.1 ± 2.3 years; 88.4% female, 78.5 ± 8.3 %mBMI), including 88 in the lower-calorie group (1,163 ± 107 kcal/d; range, 720-1,320 kcal/d) and 222 in the higher-calorie group (1,557 ± 265 kcal/d; range, 1,400-2,800 kcal/d). Neither group had initial weight loss. The %mBMI increased significantly (p < .001) from baseline by day 1 in the higher-calorie group and day 2 in the lower-calorie group. Compared with the lower-calorie group, the higher-calorie group had reduced LOS (13.0 ± 7.3 days versus 16.6 ± 9.0 days; p < .0001), but the groups did not differ in rate of change in %mBMI (p = .50) or rates of hypophosphatemia (p = .49), hypomagnesemia (p = 1.0), or hypokalemia (p = .35). Hypophosphatemia was associated with %mBMI on admission (p = .004) but not caloric intake (p = .14).A higher caloric diet on admission is associated with reduced LOS, but not increased rate of weight gain or rates of hypophosphatemia, hypomagnesemia, or hypokalemia. Refeeding hypophosphatemia depends on the degree of malnutrition but not prescribed caloric intake, within the range studied.

    View details for DOI 10.1016/j.jadohealth.2013.05.014

    View details for Web of Science ID 000325751800005

    View details for PubMedID 23830088

  • Identifying sex-specific risk factors for stress fractures in adolescent runners. Medicine and science in sports and exercise Tenforde, A. S., Sayres, L. C., McCurdy, M. L., Sainani, K. L., Fredericson, M. 2013; 45 (10): 1843-1851


    PURPOSE: Adolescent females and males participating in running represent a population at high risk of stress fracture. Few investigators have evaluated risk factors for prospective stress fracture in this population. METHODS: To better characterize risk factors for and incidence of stress fractures in this population, we collected baseline risk factor data on 748 competitive high school runners (442 girls and 306 boys) using an online survey. We then followed them prospectively for the development of stress fractures for an average of 2.3±1.2 total seasons of cross-country and track and field; follow-up data were available for 428 girls and 273 boys. RESULTS: We identified prospective stress fractures in 5.4% of girls (N=23) and 4.0% of boys (N=11). Tibial stress fractures were most common in girls, and the metatarsus was most frequently fractured in boys. Multivariate regression identified four independent risk factors for stress fractures in girls: prior fracture, BMI <19, late menarche (age menarche ≥15 years), and previous participation in gymnastics or dance. For boys, prior fracture and increased number of seasons were associated with an increased rate of stress fractures, whereas prior participation in basketball was associated with a decreased risk of stress fractures. CONCLUSION: Prior fracture represents the most robust predictor of stress fractures in both sexes. Low BMI, late menarche, and prior participation in gymnastics and dance are identifiable risk factors for stress fractures in girls. Participation in basketball appears protective in boys and may represent a modifiable risk factor for stress fractures. These findings may help guide future translational research and clinical care in the management and prevention of stress fractures in young runners.

    View details for DOI 10.1249/MSS.0b013e3182963d75

    View details for PubMedID 23584402

  • Multivariate Regression: The Pitfalls of Automated Variable Selection PM&R Sainani, K. L. 2013; 5 (9): 791-794

    View details for DOI 10.1016/j.pmrj.2013.07.007

    View details for Web of Science ID 000325041600008

    View details for PubMedID 24054854

  • Interpreting "Null" Results PM&R Sainani, K. 2013; 5 (6): 520-523

    View details for DOI 10.1016/j.pmrj.2013.05.003

    View details for Web of Science ID 000321156400011

    View details for PubMedID 23790820

  • Avoiding Careless Errors: Know Your Data PM&R Sainani, K. L. 2013; 5 (3): 228-229

    View details for DOI 10.1016/j.pmrj.2013.01.012

    View details for Web of Science ID 000316433300010

    View details for PubMedID 23481330

  • Dealing With Non-normal Data PM&R Sainani, K. L. 2012; 4 (12): 1001-1005

    View details for DOI 10.1016/j.pmrj.2012.10.013

    View details for Web of Science ID 000313092100009

    View details for PubMedID 23245662

  • Propensity Scores: Uses and Limitations PM&R Sainani, K. L. 2012; 4 (9): 693-697

    View details for DOI 10.1016/j.pmrj.2012.07.002

    View details for Web of Science ID 000309436500008

    View details for PubMedID 22980422

  • Obesity and the relationship between pre-hypertension and chronic kidney disease: can we really isolate the effect of pre-hypertension? KIDNEY INTERNATIONAL Anand, S., Arce, C. M., Sainani, K. L. 2012; 82 (4): 489-489

    View details for DOI 10.1038/ki.2012.144

    View details for Web of Science ID 000307078000017

    View details for PubMedID 22846814

  • How statistics can mislead. American journal of public health Sainani, K. L. 2012; 102 (8): e3-4

    View details for DOI 10.2105/AJPH.2012.300697

    View details for PubMedID 22698033

  • Clinical Versus Statistical Significance PM&R Sainani, K. L. 2012; 4 (6): 442-445

    View details for DOI 10.1016/j.pmrj.2012.04.014

    View details for Web of Science ID 000306038700008

    View details for PubMedID 22732155

  • Communicating Risks Clearly: Absolute Risk and Number Needed to Treat PM&R Sainani, K. L. 2012; 4 (3): 220-222

    View details for DOI 10.1016/j.pmrj.2012.01.001

    View details for Web of Science ID 000305438500008

    View details for PubMedID 22443959

  • Sun protective behaviors and vitamin D levels in the US population: NHANES 2003-2006 CANCER CAUSES & CONTROL Linos, E., Keiser, E., Kanzler, M., Sainani, K. L., Lee, W., Vittinghoff, E., Chren, M., Tang, J. Y. 2012; 23 (1): 133-140


    Sun protection is recommended for skin cancer prevention, yet little is known about the role of sun protection on vitamin D levels. Our aim was to investigate the relationship between different types of sun protective behaviors and serum 25(OH)D levels in the general US population.Cross-sectional, nationally representative survey of 5,920 adults aged 18-60 years in the US National Health and Nutrition Examination Survey 2003-2006. We analyzed questionnaire responses on sun protective behaviors: staying in the shade, wearing long sleeves, wearing a hat, using sunscreen and SPF level. Analyses were adjusted for multiple confounders of 25(OH)D levels and stratified by race. Our primary outcome measures were serum 25(OH)D levels (ng/ml) measured by radioimmunoassay and vitamin D deficiency, defined as 25(OH)D levels <20 ng/ml.Staying in the shade and wearing long sleeves were significantly associated with lower 25(OH)D levels. Subjects who reported frequent use of shade on a sunny day had -3.5 ng/ml (p (trend) < 0.001) lower 25(OH)D levels compared to subjects who reported rare use. Subjects who reported frequent use of long sleeves had -2.2 ng/ml (p (trend) = 0.001) lower 25(OH)D levels. These associations were strongest for whites, and did not reach statistical significance among Hispanics or blacks. White participants who reported frequently staying in the shade or wearing long sleeves had double the odds of vitamin D deficiency compared with those who rarely did so. Neither wearing a hat nor using sunscreen was associated with low 25(OH)D levels or vitamin D deficiency.White individuals who protect themselves from the sun by seeking shade or wearing long sleeves may have lower 25(OH)D levels and be at risk for vitamin D deficiency. Frequent sunscreen use does not appear to be linked to vitamin D deficiency in this population.

    View details for DOI 10.1007/s10552-011-9862-0

    View details for Web of Science ID 000297757400013

    View details for PubMedID 22045154

  • Reliability and prevalence of digital image skin types in the United States: Results from National Health and Nutrition Examination Survey 2003-2004 JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Keiser, E., Linos, E., Kanzler, M., Lee, W., Sainani, K. L., Tang, J. Y. 2012; 66 (1): 163-165

    View details for DOI 10.1016/j.jaad.2011.02.044

    View details for Web of Science ID 000298712100031

    View details for PubMedID 22177642

  • A Closer Look at Confidence Intervals PM&R Sainani, K. L. 2011; 3 (12): 1134-1141

    View details for DOI 10.1016/j.pmrj.2011.10.005

    View details for Web of Science ID 000305872700010

    View details for PubMedID 22192323

  • The Limitations of Statistical Adjustment PM&R Sainani, K. 2011; 3 (9): 868-872

    View details for DOI 10.1016/j.pmrj.2011.06.006

    View details for Web of Science ID 000305438100011

    View details for PubMedID 21944304

  • Understanding Study Design PM&R Sainani, K. L., Popat, R. A. 2011; 3 (6): 573-577

    View details for DOI 10.1016/j.pmrj.2011.04.001

    View details for Web of Science ID 000305437700010

    View details for PubMedID 21665169

  • Understanding Odds Ratios PM&R Sainani, K. L. 2011; 3 (3): 263-267

    View details for DOI 10.1016/j.pmrj.2011.01.009

    View details for Web of Science ID 000305437400009

    View details for PubMedID 21402371

  • Comparative Profiling of Primary Colorectal Carcinomas and Liver Metastases Identifies LEF1 as a Prognostic Biomarker PLOS ONE Lin, A. Y., Chua, M., Choi, Y., Yeh, W., Kim, Y. H., Azzi, R., Adams, G. A., Sainani, K., van de Rijn, M., So, S. K., Pollack, J. R. 2011; 6 (2)


    We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC).We profiled gene expression in 31 specimens from primary CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) to identify genes differentially expressed between these two groups. To characterize the clinical relevance of two highly-ranked differentially-expressed genes, we analyzed the expression of secreted phosphoprotein 1 (SPP1 or osteopontin) and lymphoid enhancer factor-1 (LEF1) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with primary CRC.Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to primary CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP1 and LEF1 protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF1 (chi-square p = 0.042), but not SPP1 (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF1 (p<0.01), but not SPP1 (p = 0.11). Both univariate and multivariate analyses identified stage (p<0.0001) and LEF1 overexpression (p<0.05) as important prognostic markers, but not tumor grade or SPP1.Among genes differentially expressed between CLM and primary CRC, we demonstrate overexpression of LEF1 in primary CRC to be a prognostic factor for poor survival and increased risk for liver metastasis.

    View details for DOI 10.1371/journal.pone.0016636

    View details for Web of Science ID 000287761700013

    View details for PubMedID 21383983

    View details for PubMedCentralID PMC3044708

  • Overuse Injuries in High School Runners: Lifetime Prevalence and Prevention Strategies PM&R Tenforde, A. S., Sayres, L. C., McCurdy, M. L., Collado, H., Sainani, K. L., Fredericson, M. 2011; 3 (2): 125-131


    To evaluate lifetime prevalence and risk factors for overuse injuries in high school athletes currently participating in long-distance running and provide recommendations for injury prevention strategies.Retrospective study design.Twenty-eight high schools in the San Francisco Bay Area.A total of 442 female and 306 male athletes, ages 13-18 years, who are on cross-country and track and field teams.Online survey with questions that detailed previous injuries sustained and risk factors for injury.Previous overuse injuries and association of risk factors to injury (including training variables, dietary patterns, and, in girls, menstrual irregularities).Previous injuries were reported by 68% of female subjects and 59% of male subjects. More injury types were seen in girls (1.2 ± 1.1 versus 1.0 ± 1.0, P < .01). Both genders had similar participation in running (2.5 ± 2.2 versus 2.3 ± 2.1 years), and previous injury prevalence followed a similar pattern: tibial stress injury (girls, 41%; boys, 34%), ankle sprain (girls, 32%; boys, 28%), patellofemoral pain (girls, 21%; boys, 16%), Achilles tendonitis (girls, 9%; boys, 6%), iliotibial band syndrome (girls, 7%; boys, 5%), and plantar fasciitis (girls, 5%; boys, 3%). Higher weekly mileage was associated with previous injuries in boys, (17.1 ± 11.9 versus 14.1 ± 11.5, P < .05) but not in girls (14.4 ± 10.2 versus 12.6 ± 11.8, not significant). A strong association between higher mileage and faster performances was seen in both groups. No association between previous injury and current dietary patterns (including disordered eating and calcium intake) or menstrual irregularities was seen.The majority of athletes currently participating in high school cross-country and track and field have a history of sustaining an overuse injury, with girls having a higher prevalence of injury. A modest mileage reduction may represent a modifiable risk factor for injury reduction. Future research is needed to evaluate the effects of incorporating a comprehensive strength training program on the prospective development of overuse injury and performance in this population.

    View details for DOI 10.1016/j.pmrj.2010.09.009

    View details for Web of Science ID 000305437300006

    View details for PubMedID 21333951

  • Evaluating the relationship of calcium and vitamin D in the prevention of stress fracture injuries in the young athlete: a review of the literature. PM & R : the journal of injury, function, and rehabilitation Tenforde, A. S., Sayres, L. C., Sainani, K. L., Fredericson, M. 2010; 2 (10): 945-949


    Calcium and vitamin D are recognized as 2 components of nutrition needed to achieve and maintain bone health. Calcium and vitamin D have been clearly shown to improve bone density and prevent fractures at all ages. However, the literature is conflicting as to the role of these nutrients in young athletes ages 18 to 35 years, both for bone development and for the prevention of bone overuse injuries. Differences in findings may relate to study design. Although retrospective and cross-sectional studies have had mixed results, the authors of prospective studies have consistently demonstrated a relationship of increased calcium intake with an improvement in bone density and a decrease in fracture risk. A randomized trial in female military recruits demonstrated that calcium/vitamin D supplementation reduced the incidence of stress fractures. A prospective study in young female runners demonstrated reduced incidence of stress fractures and increased bone mineral density with increased dietary calcium intake. Findings from both studies suggest female athletes and military recruits who consumed greater than 1500 mg of calcium daily exhibited the largest reduction in stress fracture injuries. To date, no prospective studies have been conducted in male athletes or in adolescent athletes. In most studies, males and nonwhite participants were poorly represented. Evidence regarding the relationship of vitamin D intake with the prevention of fractures in athletes is also limited. More prospective studies are needed to evaluate the role of calcium and vitamin D intake in prevention of stress fracture injuries in both male and female adolescent athletes, particularly those participating in sports with greater incidences of stress fracture injury.

    View details for DOI 10.1016/j.pmrj.2010.05.006

    View details for PubMedID 20970764

  • Evaluating the Relationship of Calcium and Vitamin D in the Prevention of Stress Fracture Injuries in the Young Athlete: A Review of the Literature PM&R Tenforde, A. S., Sayres, L. C., Sainani, K. L., Fredericson, M. 2010; 2 (10): 945-949
  • The importance of accounting for correlated observations. PM & R : the journal of injury, function, and rehabilitation Sainani, K. 2010; 2 (9): 858-861

    View details for DOI 10.1016/j.pmrj.2010.07.482

    View details for PubMedID 20869686

  • The Importance of Accounting for Correlated Observations PM&R Sainani, K. 2010; 2 (9): 858-861
  • Nutritional factors that influence change in bone density and stress fracture risk among young female cross-country runners. PM & R : the journal of injury, function, and rehabilitation Nieves, J. W., Melsop, K., Curtis, M., Kelsey, J. L., Bachrach, L. K., Greendale, G., Sowers, M. F., Sainani, K. L. 2010; 2 (8): 740-750


    To identify nutrients, foods, and dietary patterns associated with stress fracture risk and changes in bone density among young female distance runners.Two-year, prospective cohort study. Observational data were collected in the course of a multicenter randomized trial of the effect of oral contraceptives on bone health.One hundred and twenty-five female competitive distance runners ages 18-26 years.Dietary variables were assessed with a food frequency questionnaire.Bone mineral density and content (BMD/BMC) of the spine, hip, and total body were measured annually by dual x-ray absorptiometry (DEXA). Stress fractures were recorded on monthly calendars, and had to be confirmed by radiograph, bone scan, or magnetic resonance imaging.Seventeen participants had at least one stress fracture during follow-up. Higher intakes of calcium, skim milk, and dairy products were associated with lower rates of stress fracture. Each additional cup of skim milk consumed per day was associated with a 62% reduction in stress fracture incidence (P < .05); and a dietary pattern of high dairy and low fat intake was associated with a 68% reduction (P < .05). Higher intakes of skim milk, dairy foods, calcium, animal protein, and potassium were associated with significant (P < .05) gains in whole-body BMD and BMC. Higher intakes of calcium, vitamin D, skim milk, dairy foods, potassium, and a dietary pattern of high dairy and low fat were associated with significant gains in hip BMD.In young female runners, low-fat dairy products and the major nutrients in milk (calcium, vitamin D, and protein) were associated with greater bone gains and a lower stress fracture rate. Potassium intake was also associated with greater gains in hip and whole-body BMD.

    View details for DOI 10.1016/j.pmrj.2010.04.020

    View details for PubMedID 20709302

  • Nutritional Factors That Influence Change in Bone Density and Stress Fracture Risk Among Young Female Cross-Country Runners PM&R Nieves, J. W., Melsop, K., Curtis, M., Kelsey, J. L., Bachrach, L. K., Greendale, G., Sowers, M. F., Sainani, K. L. 2010; 2 (8): 740-750
  • Misleading comparisons: the fallacy of comparing statistical significance. PM & R : the journal of injury, function, and rehabilitation Sainani, K. 2010; 2 (6): 559-562

    View details for DOI 10.1016/j.pmrj.2010.04.016

    View details for PubMedID 20630442

  • Misleading Comparisons: The Fallacy of Comparing Statistical Significance PM&R Sainani, K. 2010; 2 (6): 559-562
  • Electronic web-based surveys: an effective and emerging tool in research. PM & R : the journal of injury, function, and rehabilitation Tenforde, A. S., Sainani, K. L., Fredericson, M. 2010; 2 (4): 307-309

    View details for DOI 10.1016/j.pmrj.2010.02.004

    View details for PubMedID 20430335

  • Making sense of intention-to-treat. PM & R : the journal of injury, function, and rehabilitation Sainani, K. L. 2010; 2 (3): 209-213

    View details for DOI 10.1016/j.pmrj.2010.01.004

    View details for PubMedID 20359686

  • Making Sense of Intention-to-Treat PM&R Sainani, K. L. 2010; 2 (3): 209-213
  • The problem of multiple testing. PM & R : the journal of injury, function, and rehabilitation Sainani, K. L. 2009; 1 (12): 1098-1103

    View details for DOI 10.1016/j.pmrj.2009.10.004

    View details for PubMedID 20006317

  • The Problem of Multiple Testing PM&R Sainani, K. L. 2009; 1 (12): 1098-1103
  • Medulloblastoma Incidence has not Changed Over Time A CBTRUS Study JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Partap, S., Curran, E. K., Propp, J. M., Le, G. M., Sainani, K. L., Fisher, P. G. 2009; 31 (12): 970-971


    Earlier studies have reported changes in the incidence of medulloblastoma (MB) but have conflicted, likely because of small sample size or misclassification of MB with primitive neuroectodermal tumor (PNET). The incidence of MB and PNET from 1985 to 2002 was determined from the Central Brain Tumor Registry of the United States, a large population-based cancer registry, using strict histologic and site codes. No statistically significant change in MB incidence was observed over the last 2 decades, but there was an increase in MB and PNET combined.

    View details for Web of Science ID 000272658700019

    View details for PubMedID 19887963

  • Do children and adults differ in survival from medulloblastoma? A study from the SEER registry JOURNAL OF NEURO-ONCOLOGY Curran, E. K., Le, G. M., Sainani, K. L., Propp, J. M., Fisher, P. G. 2009; 95 (1): 81-85


    Studies investigating whether adults have diminished survival from medulloblastoma (MB) compared with children have yielded conflicting results. We sought to determine in a population-based registry whether adults and children with MB differ in survival, and to examine whether dissimilar use of chemotherapy might contribute to any disparity. 1,226 MB subjects were identified using the Surveillance Epidemiology and End Results (SEER-9) registry (1973-2002) and survival analysis performed. MB was defined strictly to exclude non-cerebellar primitive neuro-ectodermal tumors. Patients were stratified by age at diagnosis: <3 years (infants), 3-17 years (children) and >or=18 years (adults). Because the SEER-9 registry lacks treatment data, a subset of 142 patients were identified using the San Francisco-Oakland SEER registry (1988-2003) and additional analyses performed. There was no significant difference in survival between children and adults with MB in either the SEER-9 (P = 0.17) or SFO (P = 0.89) cohorts but infants fared worse compared to both children (P < 0.01) and adults (P < 0.01). In the SFO sample, children and adults who received chemotherapy plus radiation therapy (XRT) did not differ in survival. Among patients treated with XRT alone, children showed increased survival (P = 0.04) compared with adults. Children and adults with MB do not differ with respect to overall survival, yet infants fare significantly worse. For children and adults with MB treated with both XRT and chemotherapy, we could not demonstrate a survival difference. Similar outcomes between adult and childhood MB may justify inclusion of adults in pediatric cooperative trials for MB.

    View details for DOI 10.1007/s11060-009-9894-4

    View details for Web of Science ID 000269884600010

    View details for PubMedID 19396401

  • Putting P values in perspective. PM & R : the journal of injury, function, and rehabilitation Sainani, K. L. 2009; 1 (9): 873-877

    View details for DOI 10.1016/j.pmrj.2009.07.003

    View details for PubMedID 19769922

  • Putting P Values in Perspective PM&R Sainani, K. L. 2009; 1 (9): 873-877
  • A Caution on Interpreting Odds Ratios SLEEP Sainani, K. L., Schmajuk, G., Liu, V. 2009; 32 (8): 976-976

    View details for Web of Science ID 000268557600002

    View details for PubMedID 19725246

  • Incidence Patterns of Central Nervous System Germ Cell Tumors A SEER Study JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Goodwin, T. L., Sainani, K., Fisher, P. G. 2009; 31 (8): 541-544


    Incidence patterns of central nervous system (CNS) germ cell tumors (GCTs) have been reported, but the influence of underlying host risk factors has not been rigorously explored. We aimed to determine in a large, population-based cancer registry how age, sex, and race, influence the occurrence of CNS GCTs in the pediatric population.Using the Surveillance, Epidemiology, and End Results registry, we identified cases of histologically confirmed GCTs in children, adolescents, and young adults (age 0 to 29 y), diagnosed between 1973 and 2004. The cases were limited to only those with the International Classification of Childhood Cancer Xa: intracranial and intraspinal germ-cell tumors. Incidence rates (per 10,000) for each sex and race were plotted for single-age groups, and then stratified by tumor location and pathology subtype.The sample included a total of 638 cases (490 males). Males had significantly higher rates of CNS GCTs than females. Male and female rates diverged significantly starting at the age of 11 years and remained widely discrepant until the age of 30 years. There were more germinomas than nongerminomas in both sexes. Germinomas peaked in incidence during adolescence, whereas nongerminoma incidence remained relatively constant in children and young adults. Tumor location differed strikingly by sex (P<0.0001) with pineal location more common in males (61.0% vs. 15.5%). Asian race was associated with a higher rate of CNS GCTs than other races.Males have higher incidence of CNS GCTs, primarily germinomas, than females, starting in the second decade. Pineal location is strongly associated with male sex, with pineal germinomas representing over half of all CNS GCTs in males. Asian-Americans have higher rates than other races. These findings suggest a robust but poorly understood influence of sex, either genetic or hormonal, and race on the occurrence of CNS GCTs.

    View details for Web of Science ID 000268815000003

    View details for PubMedID 19636276

  • Incidence patterns for ependymoma: a Surveillance, Epidemiology, and End Results study Clinical article JOURNAL OF NEUROSURGERY McGuire, C. S., Sainani, K. L., Fisher, P. G. 2009; 110 (4): 725-729


    Previous small studies disagree about which clinical risk factors influence ependymoma incidence. The authors analyzed a large, population-based cancer registry to examine the relationship of incidence to patient age, sex, race, and tumor location, and to determine incidence trends over the past 3 decades.Data were obtained from the Surveillance, Epidemiology, and End Results (SEER-9) study, which was conducted from 1973 to 2003. Histological codes were used to define ependymomas. Age-adjusted incidence rates were compared by confidence intervals in the SEER*Stat 6.2 program. Multiplicative Poisson regression and Joinpoint analysis were used to determine annual percentage change and to look for sharp changes in incidence, respectively.From the SEER database, 1402 patients were identified. The incidence rate per 100,000 person-years was significantly higher in male than in female patients (males 0.227 +/- 0.029, females 0.166 +/- 0.03). For children, the age at diagnosis differed significantly by tumor location, with the mean age for patients with infratentorial tumors calculated as 5 +/- 0.4 years; for supratentorial tumors it was 7.77 +/- 0.6 years, and for spinal lesions it was 12.16 +/- 0.8 years. (Values are expressed as the mean +/- standard error [SE].) Adults showed no difference in the mean age of incidence by location, although most tumors in this age group were spinal. Between 1973 and 2003, the incidence increased significantly among adults but not among children, and there were no sharp changes at any single year, both before and after age adjustment.Males have a higher incidence of ependymoma than do females. A biological explanation remains elusive. Ependymoma occurs within the CNS at distinct locations at different ages, consistent with hypotheses postulating distinct populations of radial glial stem cells within the CNS. Ependymoma incidence appears to have increased over the past 3 decades, but only in adults.

    View details for DOI 10.3171/2008.9.JNS08117

    View details for Web of Science ID 000264594300017

    View details for PubMedID 19061350

  • Both Location and Age Predict Survival in Ependymoma: A SEER Study PEDIATRIC BLOOD & CANCER McGuire, C. S., Sainani, K. L., Fisher, P. G. 2009; 52 (1): 65-69


    Studies have suggested that supratentorial ependymomas have better survival than infratentorial tumors, with spinal tumors having the best prognosis, but these data have been based on small samples. Using a population-based registry of ependymomas, we analyzed how age, gender, location, race and radiotherapy influence survival in children.We queried the Surveillance Epidemiology End Results database (SEER-17) from 1973 to 2003, strictly defining ependymomas by histology. Site codes were used to distinguish between supratentorial, infratentorial, and spinal tumors when available. Outcomes were compared by location, age, gender, race and radiotherapy, using Kaplan-Meier analysis and logrank tests. Cox regression was completed, incorporating all significant covariates from univariate analysis.Six hundred thirty-five children were identified with an overall 5-year survival of 57.1 +/- standard error (SE) 2.3%. Increasing age was associated with improved survival (P < 0.0001). Five-year survival by location was 59.5 +/- SE 5.5% supratentorial, 57.1 +/- SE 4.1% infratentorial and 86.7 +/- SE 5.2% spinal. Radiotherapy of the infratentorial tumors resulted in significantly improved survival in both univariate analysis (logrank P < 0.018) and multivariate analysis restricted to this tumor location (P = 0.033). Using multivariate analysis that incorporated all tumor locations, age (P < 0.001) and location (P = 0.020) were significant predictors for survival.Age and location independently influence survival in ependymoma. Spinal tumors are associated with a significantly better prognosis than both supratentorial and infratentorial tumors, and may represent a distinct biological entity. Radiotherapy appears beneficial for survival in patients with infratentorial ependymoma.

    View details for DOI 10.1002/pbc.21806

    View details for Web of Science ID 000261300000016

    View details for PubMedID 19006249

  • Gender Affects Survival for Medulloblastoma Only in Older Children and Adults: A Study From the Surveillance Epidemiology and End Results Registry PEDIATRIC BLOOD & CANCER Curran, E. K., Sainani, K. L., Le, G. M., Propp, J. A., Fisher, P. G. 2009; 52 (1): 60-64


    Males have a higher incidence of medulloblastoma (MB) than females, but the effect of gender on survival is unclear. Studies have yielded conflicting results, possibly due to small sample sizes or differences in how researchers defined MB. We aimed to determine the effect of gender on survival in MB using a large data set and strict criteria for defining MB.A sample of 1,226 subjects (763 males and 463 females) was identified from 1973 to 2002, using the Surveillance Epidemiology and End Results (SEER-9) registry. MB was strictly defined to exclude non-cerebellar embryonal tumors (primitive neuro-ectodermal tumors). Because children <3 years of age are known to have worse survival, patients were stratified by age <3 years at diagnosis (95 males, 82 females) and >3 years (668 males, 381 females).Overall, there was no significant difference in survival between males and females (log rank P = 0.22). However, among subjects >3 years, females had significantly greater survival than males (log rank P = 0.02). In children <3 years, there was a non-significant trend toward poorer survival in females (median survival: males 27 months, females 13 months; log rank P = 0.24). This interaction between age group and gender was statistically significant (P = 0.03).Females with MB have a survival advantage only in subjects >3 years. In children <3 years, females may even have poorer outcome. The effect of gender on survival and incidence in MB warrants additional biologic investigation, and may differ in very young children with MB.

    View details for DOI 10.1002/pbc.21832

    View details for Web of Science ID 000261300000015

    View details for PubMedID 19006250

  • Effect of oral contraceptives on weight and body composition in young female runners MEDICINE AND SCIENCE IN SPORTS AND EXERCISE Procter-Gray, E., Cobb, K. L., Crawford, S. L., Bachrach, L. K., Chirra, A., Sowers, M., Greendale, G. A., Nieves, J. W., Kent, K., Kelsey, J. L. 2008; 40 (7): 1205-1212


    To examine the effect of oral contraceptives (OC) on body weight, fat mass, percent body fat, and lean mass in young female distance runners.The study population consisted of 150 female competitive distance runners aged 18-26 yr who had participated in a 2-yr randomized trial of the effect of the OC Lo/Ovral (30 microg of ethinyl estradiol and 0.3 mg of norgestrel) on bone health. Weight and body composition were measured approximately yearly by balance beam scales and dual-energy x-ray absorptiometry, respectively.Women randomized to the OC group tended to gain slightly less weight (adjusted mean difference (AMD) = -0.54 +/- 0.31 kg.yr, P = 0.09) and less fat (AMD = -0.35 +/- 0.25 kg.yr, P = 0.16) than those randomized to the control group. OC assignment was associated with a significant gain in lean mass relative to controls among eumenorrheic women (those who had 10 or more menstrual cycles in the year before baseline; AMD = 0.77 +/- 0.17 kg.yr, P < 0.0001) but not among women with fewer than 10 menstrual cycles in that year (AMD = 0.02 +/- 0.35 kg.yr, P = 0.96). Treatment-received analyses yielded similar results.This randomized trial confirms previous findings that OC use does not cause weight or fat mass gain, at least among young female runners. Our finding that this OC is associated with lean mass gain in eumenorrheic runners, but not in those with irregular menses, warrants examination in other studies.

    View details for DOI 10.1249/MSS.0b013e31816a0df6

    View details for Web of Science ID 000256981700002

    View details for PubMedID 18580398

  • Cancer risk reduction and reproductive concerns in female BRCA1/2 mutation carriers FAMILIAL CANCER Staton, A. D., Kurian, A. W., Cobb, K., Mills, M. A., Ford, J. M. 2008; 7 (2): 179-186


    Women with mutations in the BRCA1 or BRCA2 cancer susceptibility genes face unique choices regarding management of their high risk for breast and ovarian cancer that impact their reproductive options. In order to explore women's preferences for management of elevated cancer risk, we evaluated the decisions of BRCA1/2 mutation carriers about contraception, prophylactic surgery, and family planning.An internet-based questionnaire assessing high-risk women's preferences about cancer risk management and reproductive options was designed, pilot-tested and administered electronically to 284 participants of an internet-based advocacy group for women with BRCA1/2 mutations.Two hundred and thirteen eligible participants completed the majority of the survey. Mean age was 34 years; 66% were BRCA1 mutation carriers and 34% were BRCA2 mutation carriers. Most women (92%) had used oral contraceptive pills. About 88% of responders reported frequent or extreme worry about transmitting the mutation to their children. Despite their high level of worry, few responders said they would likely consider using assisted reproduction technologies such as a pregnancy surrogate (3%), cryopreservation of oocytes or embryos (8%), or pre-implantation genetic diagnosis (PGD) to select embryos without BRCA1/2 mutations (13%).Although they expressed substantial concern about transmitting BRCA1/2 mutations to their children, only a minority of the high-risk women surveyed were likely to consider currently available assisted reproductive strategies. Further research is necessary to explore the risk management preferences of patients with inherited cancer predisposition, and to incorporate these preferences into clinical care.

    View details for DOI 10.1007/s10689-007-9171-7

    View details for Web of Science ID 000256823500010

    View details for PubMedID 18026853

  • Regional bone mineral density in male athletes: a comparison of soccer players, runners and controls BRITISH JOURNAL OF SPORTS MEDICINE Fredericson, M., Chew, K., Ngo, J., Cleek, T., Kiratli, J., Cobb, K. 2007; 41 (10): 664-668


    To investigate the association of soccer playing and long-distance running with total and regional bone mineral density (BMD).Cross-sectional study.Academic medical centre.Elite male soccer players (n = 15), elite male long-distance runners (n = 15) and sedentary male controls (n = 15) aged 20-30 years.BMD (g/cm2) of the lumbar spine (L1-L4), right hip, right leg and total body were assessed by dual-energy x-ray absorptiometry, and a scan of the right calcaneus was performed with a peripheral instantaneous x-ray imaging bone densitometer.After adjustment for age, weight and percentage body fat, soccer players had significantly higher whole body, spine, right hip, right leg and calcaneal BMD than controls (p = 0.008, p = 0.041, p<0.001, p = 0.019, p<0.001, respectively) and significantly higher right hip and spine BMD than runners (p = 0.012 and p = 0.009, respectively). Runners had higher calcaneal BMD than controls (p = 0.002). Forty percent of the runners had T-scores of the lumbar spine between -1 and -2.5. Controls were similar: 34% had T-scores below -1 (including 7% with T-scores lower than -2.5).Playing soccer is associated with higher BMD of the skeleton at all sites measured. Running is associated with higher BMD at directly loaded sites (the calcaneus) but not at relatively unloaded sites (the spine). Specific loading conditions, seen in ball sports or in running, play a pivotal role in skeletal adaptation. The importance of including an appropriate control group in clinical studies is underlined.

    View details for DOI 10.1136/bjsm.2006.030783

    View details for Web of Science ID 000249621100015

    View details for PubMedID 17473003

  • The effect of oral contraceptives on bone mass and stress fractures in female runners MEDICINE AND SCIENCE IN SPORTS AND EXERCISE Cobb, K. L., Bachrach, L. K., Sowers, M., Nieves, J., Greendale, G. A., Kent, K. K., Brown, B. W., Pettit, K., Harper, D. M., Kelsey, J. L. 2007; 39 (9): 1464-1473


    To determine the effect of oral contraceptives (OC) on bone mass and stress fracture incidence in young female distance runners.One hundred fifty competitive female runners ages 18-26 yr were randomly assigned to OC (30 microg of ethinyl estradiol and 0.3 mg of norgestrel) or control (no intervention) for 2 yr. Bone mineral density (BMD) and content (BMC) were measured yearly by dual x-ray absorptiometry. Stress fractures were confirmed by x-ray, magnetic resonance imaging, or bone scan.Randomization to OC was unrelated to changes in BMD or BMC in oligo/amenorrheic (N=50) or eumenorrheic runners (N=100). However, treatment-received analyses (which considered actual OC use) showed that oligo/amenorrheic runners who used OC gained about 1% per year in spine BMD (P<0.005) and whole-body BMC (P<0.005), amounts similar to those for runners who regained periods spontaneously and significantly greater than those for runners who remained oligo/amenorrheic (P<0.05). Dietary calcium intake and weight gain independently predicted bone mass gains in oligo/amenorrheic runners. Randomization to OC was not significantly related to stress fracture incidence, but the direction of the effect was protective in both menstrual groups (hazard ratio [95% CI]: 0.57 [0.18, 1.83]), and the effect became stronger in treatment-received analyses. The trial's statistical power was reduced by higher-than-anticipated noncompliance.OC may reduce the risk for stress fractures in female runners, but our data are inconclusive. Oligo/amenorrheic athletes with low bone mass should be advised to increase dietary calcium and take steps to resume normal menses, including weight gain; they may benefit from OC, but the evidence is inconclusive.

    View details for DOI 10.1249/mss.0b013e318074e352

    View details for Web of Science ID 000249445700004

    View details for PubMedID 17805075

  • Risk factors for stress fracture among young female cross-country runners MEDICINE AND SCIENCE IN SPORTS AND EXERCISE Kelsey, J. L., Bachrach, L. K., Procter-Gray, E., Nieves, J., Greendale, G. A., Sowers, M., Brown, B. W., Matheson, K. A., Crawford, S. L., Cobb, K. L. 2007; 39 (9): 1457-1463


    To identify risk factors for stress fracture among young female distance runners.Participants were 127 competitive female distance runners, aged 18-26, who provided at least some follow-up data in a randomized trial among 150 runners of the effects of oral contraceptives on bone health. After completing a baseline questionnaire and undergoing bone densitometry, they were followed an average of 1.85 yr.Eighteen participants had at least one stress fracture during follow-up. Baseline characteristics associated (P<0.10) in multivariate analysis with stress fracture occurrence were one or more previous stress fractures (rate ratio [RR] [95% confidence interval]=6.42 (1.80-22.87), lower whole-body bone mineral content (RR=2.70 [1.26-5.88] per 1-SD [293.2 g] decrease), younger chronologic age (RR=1.42 [1.05-1.92] per 1-yr decrease), lower dietary calcium intake (RR=1.11 [0.98-1.25] per 100-mg decrease), and younger age at menarche (RR=1.92 [1.15-3.23] per 1-yr decrease). Although not statistically significant, a history of irregular menstrual periods was also associated with increased risk (RR=3.41 [0.69-16.91]). Training-related factors did not affect risk.The results of this and other studies indicate that risk factors for stress fracture among young female runners include previous stress fractures, lower bone mass, and, although not statistically significant in this study, menstrual irregularity. More study is needed of the associations between stress fracture and age, calcium intake, and age at menarche. Given the importance of stress fractures to runners, identifying preventive measures is of high priority.

    View details for DOI 10.1249/mss.0b013e318074e54b

    View details for Web of Science ID 000249445700003

    View details for PubMedID 17805074

  • Effects of ball sports on future risk of stress fracture in runners CLINICAL JOURNAL OF SPORT MEDICINE Fredericson, M., Ngo, J., Cobb, K. 2005; 15 (3): 136-141


    To evaluate whether playing ball sports during childhood and adolescence is associated with the risk of stress fractures in runners later in life.Retrospective cohort study.National track and field championships, held at Stanford University.One hundred fifty-six elite female and 118 elite male distance runners, age 18 to 44 years.A 1-page questionnaire was used to collect data regarding ages during which athletes played basketball and soccer, as well as other important covariates and outcomes.Athletes reported the ages when stress fractures occurred. Time to event was defined as the number of years from beginning competitive running to the first stress fracture or to current age, if no fracture had occurred.In both men and women, playing ball sports in youth correlated with reduced stress fracture incidence later in life by almost half, controlling for possible confounders. In men, each additional year of playing ball sports conferred a 13% decreased incidence of stress fracture (adjusted hazard ratio [HR] and 95% confidence interval, 0.87 [0.79-0.95]. Among women with regular menses, the HR for each additional year of playing ball sports was similar: 0.87 (0.75-1.00); however, there was no effect of length of time played among women with irregular menses (HR, 1.03 [0.92-1.16]). In men, younger ages of playing ball sports conferred more protection against stress fractures (HR for each 1-year-older age at first exposure, 1.29 [1.14, 1.45]).Runners who participate during childhood and adolescence in ball sports may develop bone with greater and more symmetrically distributed bone mass, and with enhanced protection from future stress fractures.

    View details for Web of Science ID 000230329000004

    View details for PubMedID 15867555

  • Disordered eating, menstrual irregularity, and bone mineral density in female runners MEDICINE AND SCIENCE IN SPORTS AND EXERCISE Cobb, K. L., Bachrach, L. K., Greendale, G., Marcus, R., Neer, R. M., Nieves, J., Sowers, M. F., Brown, B. W., Gopalakrishnan, G., Luetters, C., Tanner, H. K., Ward, B., Kelsey, J. L. 2003; 35 (5): 711-719


    To examine the relationships between disordered eating, menstrual irregularity, and low bone mineral density (BMD) in young female runners.Subjects were 91 competitive female distance runners aged 18-26 yr. Disordered eating was measured by the Eating Disorder Inventory (EDI). Menstrual irregularity was defined as oligo/amenorrhea (0-9 menses per year). BMD was measured by dual x-ray absorptiometry.An elevated score on the EDI (highest quartile) was associated with oligo/amenorrhea, after adjusting for percent body fat, age, miles run per week, age at menarche, and dietary fat, (OR [95% CI]: 4.6 [1.1-18.6]). Oligo/amenorrheic runners had lower BMD than eumenorrheic runners at the spine (-5%), hip (-6%), and whole body (-3%), even after accounting for weight, percent body fat, EDI score, and age at menarche. Eumenorrheic runners with elevated EDI scores had lower BMD than eumenorrheic runners with normal EDI scores at the spine (-11%), with trends at the hip (-5%), and whole body (-5%), after adjusting for differences in weight and percent body fat. Runners with both an elevated EDI score and oligo/amenorrhea had no further reduction in BMD than runners with only one of these risk factors.In young competitive female distance runners, (i) disordered eating is strongly related to menstrual irregularity, (ii) menstrual irregularity is associated with low BMD, and (iii) disordered eating is associated with low BMD in the absence of menstrual irregularity.

    View details for DOI 10.1249/01.MSS.0000064935.68277.E7

    View details for Web of Science ID 000182714200001

    View details for PubMedID 12750578

  • Oral contraceptives and bone mineral density in white and black women in CARDIA OSTEOPOROSIS INTERNATIONAL Cobb, K. L., Kelsey, J. L., Sidney, S., Ettinger, B., Lewis, C. E. 2002; 13 (11): 893-900


    To examine whether exposure to oral contraceptives (OCs) is associated with bone mineral density (BMD) in young women, we studied, cross-sectionally and longitudinally, 216 white and 260 black women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Spine, hip and whole body BMDs were measured by dual-energy X-ray absorptiometry (DXA) when the women were aged 25-37 years, and whole body BMD was remeasured in 369 of the women 3 years later. A comprehensive history of OC use, including dose of ethinyl estradiol (estrogen) and duration of use, was determined from an interviewer-administered questionnaire. After adjustment for other relevant variables, we found that cumulative estrogen from OCs (mg) explained 4.0% of the variation in spine BMD ( p = 0.024) among white women, but did not explain any of the variance in BMD in black women. Cumulative OC estrogen was associated with a decreased risk for low bone density (lowest quartile) at the spine, hip and whole body in white women. The odds ratios (95% CIs) comparing women in the highest quartile of cumulative OC estrogen with those in the lowest quartile were, at the spine: 0.08 (0.02, 0.46); at the hip: 0.23 (0.06, 0.87); and at the whole body: 0.37 (0.11, 1.26). OC exposure was not related to low bone density in black women. OCs did not predict longitudinal changes in whole body BMD in either race. These results suggest that exposure to the estrogen from OCs during the premenopausal years may have a small beneficial effect on the skeleton in white women. Benefit is proportional to the cumulative estrogen exposure, suggesting that previous cross-sectional studies that considered OC use as a dichotomous variable may have lacked the power to detect an association.

    View details for Web of Science ID 000179554500007

    View details for PubMedID 12415437