Normal Curves: Sexy Science, Serious Statistics

Coffee and the Heart: Is caffeine a trigger for AFib?

Does coffee trigger atrial fibrillation — or have doctors been warning people away from caffeine without strong evidence? We dig into two recent randomized clinical trials testing whether caffeinated coffee causes dangerous heart rhythm problems. Along the way, we talk about AFib, survival analysis, intention-to-treat versus as-treated analyses, and one surprisingly elaborate effort to catch clinical trial cheaters with receipts and geolocation tracking. We also explore how a pope may have fueled a European coffee resurgence, why plants make caffeine, and how a game show competition explains hazard ratios. Statistical topics * adherence and compliance * as-treated analysis * confidence intervals * Cox proportional hazards regression * hazard ratios * intention-to-treat analysis * micro-randomization * multiple testing * PICOT * pre-registration * primary vs secondary outcomes * randomized clinical trials * sensitivity analyses * SMART framework * survival analysis Methodological morals * “Never trust conventional wisdom until you see the randomized controlled trial.” * “Trust your participants, but design the study so that they can be honest about their dishonesty.” References * Harrington D, D'Agostino RB Sr, Gatsonis C, et al. New Guidelines for Statistical Reporting in the Journal [https://pubmed.ncbi.nlm.nih.gov/31314974/]. N Engl J Med. 2019;381(3):285-286. doi:10.1056/NEJMe1906559 * Marcus GM, Rosenthal DG, Nah G, et al. Acute Effects of Coffee Consumption on Health among Ambulatory Adults. [https://pubmed.ncbi.nlm.nih.gov/36947466/] N Engl J Med. 2023;388(12):1092-1100. doi:10.1056/NEJMoa2204737 * Wong CX, Cheung CC, Montenegro G, et al. Caffeinated Coffee Consumption or Abstinence to Reduce Atrial Fibrillation: The DECAF Randomized Clinical Trial. [https://pubmed.ncbi.nlm.nih.gov/41206802/]JAMA. 2026;335(4):317-325. doi:10.1001/jama.2025.21056 * @MarcKatzMD’s short video The Pitt- atrial fibrillation cardioversion scene  [https://youtube.com/shorts/MfkO5lpxPf8?si=iZIUvB-M0jSCoZMX] Kristin and Regina’s online courses: Demystifying Data: A Modern Approach to Statistical Understanding [https://online.stanford.edu/courses/som-xche0033-demystifying-data-modern-approach-statistical-understanding]   Clinical Trials: Design, Strategy, and Analysis [https://online.stanford.edu/courses/som-xche0030-clinical-trials-design-strategy-and-analysis]  Medical Statistics Certificate Program [https://online.stanford.edu/programs/medical-statistics-program]   Writing in the Sciences [https://www.coursera.org/learn/sciwrite]  Epidemiology and Clinical Research Graduate Certificate Program [https://online.stanford.edu/programs/epidemiology-and-clinical-research-graduate-certificate]  Programs that we teach in: Epidemiology and Clinical Research Graduate Certificate Program [https://online.stanford.edu/programs/epidemiology-and-clinical-research-graduate-certificate]  Find us on: Kristin -  LinkedIn [https://www.linkedin.com/in/kristin-sainani-642b5914/] & Twitter/X [https://x.com/KristinSainani] Regina - LinkedIn [https://www.linkedin.com/in/reginanuzzo/] & https://www.reginanuzzo.com/ReginaNuzzo.com [http://reginanuzzo.com] * (00:00) - - Introduction * (02:15) - - What is AFib? * (04:36) - - Frisky Goats and Satan's Bitter Invention * (10:44) - - How Caffeine Works * (14:43) - - The CRAVE Trial * (15:53) - - PICOT: Evaluating the Study Design * (24:21) - - CRAVE Results * (31:04) - - Catching the Coffee Cheaters * (37:58) - - The DECAF Trial * (42:49) - - Time-to-Event Outcomes * (44:40) - - Hazard Ratios: Balance Beams Over Shark Tanks * (48:25) - - DECAF Results: Team Coffee Wins * (51:57) - - Why Would Coffee Be Protective? * (55:16) - - Rating the Claim

Sleep and Exercise: Does working out on too little sleep speed up aging?

Can exercise actually be bad for you if you don’t get enough sleep? A widely shared claim says yes—that working out while sleep deprived may speed up aging. In this episode, we put that claim under the microscope. We examine the study behind it, unpack how sleep and aging were measured, and explore key statistical ideas like interaction effects and flexible models that can “dance” to the data. With the help of a $400,000 handbag and a man with seven boats, we also break down what it really takes to show that one variable changes the effect of another. What we find: some clear study bloopers, inconsistent modeling results, and interpretations that are flat-out wrong.  Statistical topics * Measurement error  * Model specification * Piecewise linear regression * Regression models * Residual confounding * Splines * Statistical interactions * Survey design Methodological morals * “Before you believe something shocking, ask what had to go wrong to make it true.” * “If slight modeling changes flip the story, there wasn't much story to begin with.” * “Unethical Life Pro Tip: If you do not want your analysis critiqued, then just make it impossible to understand.” Kristin’s Biological Age Calculator [https://www.normalcurves.com/biological-aging-calculator/] References * Original Viral Tweet: Ng D. "People who slept under 6 hours and exercised actually aged faster." [https://x.com/DrDominicNg/status/2030916265859338399] X. March 9, 2026. * Holmer B. Does exercise “age you faster” if you don’t sleep enough? [https://bradyholmer.medium.com/does-exercise-age-you-faster-if-you-dont-sleep-enough-8bb0806ea6c4] Medium. March 16, 2026. * You Y. Chen Y. Liu R., et al. Inverted U-shaped relationship between sleep duration and phenotypic age in US adults: a population-based study [https://www.nature.com/articles/s41598-024-56316-7]. Sci Rep. 2024;14:6247.  * Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan [https://pmc.ncbi.nlm.nih.gov/articles/PMC5940111/]. Aging. 2018;10:573-591.  Kristin and Regina’s online courses:  Demystifying Data: A Modern Approach to Statistical Understanding [https://online.stanford.edu/courses/som-xche0033-demystifying-data-modern-approach-statistical-understanding]   Clinical Trials: Design, Strategy, and Analysis [https://online.stanford.edu/courses/som-xche0030-clinical-trials-design-strategy-and-analysis]  Medical Statistics Certificate Program [https://online.stanford.edu/programs/medical-statistics-program]   Writing in the Sciences [https://www.coursera.org/learn/sciwrite]  Epidemiology and Clinical Research Graduate Certificate Program [https://online.stanford.edu/programs/epidemiology-and-clinical-research-graduate-certificate]  Programs that we teach in: Epidemiology and Clinical Research Graduate Certificate Program [https://online.stanford.edu/programs/epidemiology-and-clinical-research-graduate-certificate]  Find us on: Kristin -  LinkedIn [https://www.linkedin.com/in/kristin-sainani-642b5914/] & Twitter/X [https://x.com/KristinSainani] Regina - LinkedIn [https://www.linkedin.com/in/reginanuzzo/] & https://www.reginanuzzo.com/ReginaNuzzo.com [http://reginanuzzo.com] * (00:00) - Introduction * (04:05) - What is NHANES? * (06:38) - The Sleep Duration Results * (12:50) - The 2015 Sleep Mystery * (17:10) - Measuring Biological Aging * (22:32) - The Penalized Cox Regression * (29:13) - Sleep and Aging Results * (31:00) - Cubic Splines and Dancing * (38:08) - Adding Exercise to the Mix * (42:16) - Boats, Handbags, and Interaction Effects * (49:39) - The Cubic Spline Exercise Analysis * (52:40) - The Opposite Result * (57:13) - Academic Writing Gone Wrong * (59:46) - The Writing Makeover * (01:02:31) - Rating the Claim with Gatorinis

Sex Recession: Are young people really having less sex?

Are young people really having less sex? Headlines about a “sex recession” suggest a dramatic decline—but what do the data actually show? In this episode, we trace that claim back to the research behind it—and find a story that’s far more nuanced than the headlines suggest. We examine large national surveys, including the General Social Survey and the National Survey of Sexual Health and Behavior, and uncover how small analytical choices can completely change the story. Along the way, we tackle ordinal versus quantitative data, why averages can mislead, how logistic regression reframes the question, and what happens when researchers try to time-travel with statistics. Plus: the surprising role of extreme values, why “eight fewer sexual encounters per year” may not mean what you think, and whether young men and women are really following the same trends. Statistical topics * Average vs distribution * Binary variables * Effect size vs statistical significance * Logistic regression * Measurement / operationalization * Ordinal variables * Outliers / extreme values * Self-reported datagoog * Social desirability bias * Variable coding / transformation Methodological morals * “You shouldn't use data from people in their 80s to guess what they were doing in their 20s unless your data come with a time machine.” * “When extreme values drive the average, the average stops describing most people.” References * Julian K. Why are young people having so little sex? The Atlantic. December 2018. Accessed April 19, 2026. https://www.theatlantic.com/magazine/archive/2018/12/the-sex-recession/573949/ [https://www.theatlantic.com/magazine/archive/2018/12/the-sex-recession/573949/] * Skwarecki B. Nearly half of Gen Z adults have never had sex: report. Newsweek. January 7, 2025. Accessed April 19, 2026. https://www.newsweek.com/nearly-half-of-gen-z-adults-have-never-had-sexreport-11052178 [https://www.newsweek.com/nearly-half-of-gen-z-adults-have-never-had-sexreport-11052178] * Virginity survey. DatingAdvice.com. Accessed April 19, 2026. https://www.datingadvice.com/studies/virginity-survey [https://www.datingadvice.com/studies/virginity-survey] * Twenge JM, Sherman RA, Wells BE. Declines in sexual frequency among American adults, 1989-2014 [https://pubmed.ncbi.nlm.nih.gov/28265779/]. Arch Sex Behav. 2017;46(8):2389-2401. * Ueda P, Mercer CH, Ghaznavi C, Herbenick D. Trends in frequency of sexual activity and number of sexual partners among adults aged 18 to 44 years in the US, 2000-2018 [https://pubmed.ncbi.nlm.nih.gov/32530470/]. JAMA Netw Open. 2020;3(6):e203833. * Herbenick D, Rosenberg M, Golzarri-Arroyo L, et al. Changes in penile-vaginal intercourse frequency and sexual repertoire from 2009 to 2018: findings from the National Survey of Sexual Health and Behavior [https://pubmed.ncbi.nlm.nih.gov/34799832/]. Arch Sex Behav. 2022;51(3):1419-1433. * Wellings K, Palmer MJ, Machiyama K, Slaymaker E. Changes in, and factors associated with, frequency of sex in Britain: evidence from three National Surveys of Sexual Attitudes and Lifestyles (Natsal) [https://pubmed.ncbi.nlm.nih.gov/31064762/]. BMJ. 2019;365:l1525. Published 2019 May 7. doi:10.1136/bmj.l1525 * Burghardt J, Beutel ME, Hasenburg A, Schmutzer G, Brähler E. Declining Sexual Activity and Desire in Women: Findings from Representative German Surveys 2005 and 2016 [https://pubmed.ncbi.nlm.nih.gov/31802290/]. Arch Sex Behav. 2020 Apr;49(3):919-925. doi: 10.1007/s10508-019-01525-9. Epub 2019 Dec 4. Erratum in: Arch Sex Behav. 2020 Apr;49(3):927. doi: 10.1007/s10508-019-01622-9. PMID: 31802290. * Twenge JM. Possible Reasons US Adults Are Not Having Sex as Much as They Used To [https://pubmed.ncbi.nlm.nih.gov/32530467/]. JAMA Netw Open. 2020;3(6):e203889. Published 2020 Jun 1. doi:10.1001/jamanetworkopen.2020.3889 Kristin and Regina’s online courses:  Demystifying Data: A Modern Approach to Statistical Understanding [https://online.stanford.edu/courses/som-xche0033-demystifying-data-modern-approach-statistical-understanding]   Clinical Trials: Design, Strategy, and Analysis [https://online.stanford.edu/courses/som-xche0030-clinical-trials-design-strategy-and-analysis]  Medical Statistics Certificate Program [https://online.stanford.edu/programs/medical-statistics-program]   Writing in the Sciences [https://www.coursera.org/learn/sciwrite]  Epidemiology and Clinical Research Graduate Certificate Program [https://online.stanford.edu/programs/epidemiology-and-clinical-research-graduate-certificate]  Programs that we teach in: Epidemiology and Clinical Research Graduate Certificate Program [https://online.stanford.edu/programs/epidemiology-and-clinical-research-graduate-certificate]  Find us on: Kristin -  LinkedIn [https://www.linkedin.com/in/kristin-sainani-642b5914/] & Twitter/X [https://x.com/KristinSainani] Regina - LinkedIn [https://www.linkedin.com/in/reginanuzzo/] & https://www.reginanuzzo.com/ReginaNuzzo.com [http://reginanuzzo.com] * (00:00) - Introduction * (04:04) - Fact-Checking the Headlines * (07:37) - The Twenge Study and the GSS * (16:02) - The Hill-Shaped Trend * (19:23) - The Ordinal Variable Problem * (24:59) - The Married vs. Never-Married Paradox * (28:39) - Time-Traveling to the 1920s * (32:35) - The Ueda Study: A Better Approach * (36:22) - The Two Classrooms * (43:39) - What Counts as Sex? * (50:49) - Historical Sex Terms * (54:32) - The Sexual Repertoire Results * (57:50) - Why Is This Happening? * (01:04:09) - Rating the Claim

Diagnostic Testing: Do the stats tell you what you need to know?

Diagnostic testing: what do those statistics actually tell you? Sensitivity, specificity, positive predictive value . . . you’ve probably seen these terms before. Maybe you memorized them for a test. But do you actually know what they mean? In this episode, we take a closer look at how diagnostic tests are evaluated—and how they’re often misinterpreted. From a genetic test for cellulite to a blood test for autism, we explore how “statistically significant” findings can turn into tests that don’t actually help anyone. Along the way we meet the freckle gene, the wanderlust gene, and infidelity gene. Statistical topics * Base Rate * Bayes Rule * Case-Control Study * Matching * Conditional Probability * Sensitivity * Specificity * Positive Predictive Value * Prevalence * Negative Predictive Value * False Positives and Negatives * True Positives and Negatives Methodological morals * “A biomarker paper is not the same thing as a biomarker test.” * “If your sample doesn't match the real world, then for all of your positive predictive value needs, call on Bayes' theorem.” Detailed Show Notes [https://www.normalcurves.com/diagnostic-testing/] with calculations References * Emanuele E, Bertona M, Geroldi D. A multilocus candidate approach identifies ACE and HIF1A as susceptibility genes for cellulite. [https://onlinelibrary.wiley.com/doi/10.1111/j.1468-3083.2009.03556.x] Journal of the European Academy of Dermatology and Venereology; 2010. 24: 930-35.  * https://genomelink.io/traits/cellulite [https://genomelink.io/traits/cellulite] * https://www.genexdiagnostics.com/ [https://www.genexdiagnostics.com/]  * Ebstein RP, Novick O, Umansky R, et al. Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking [https://www.nature.com/articles/ng0196-78]. Nat Genet. 1996;12:78-80.  * Kluger AN, Siegfried Z, Ebstein RP. A meta-analysis of the association between DRD4 polymorphism and novelty seeking [https://www.nature.com/articles/4001082]. Mol Psychiatry. 2002;7:712-7. * He Y, Martin N, Zhu G, Liu Y. Candidate genes for novelty-seeking: a meta-analysis of association studies of DRD4 exon III and COMT Val158Met [https://journals.lww.com/psychgenetics/abstract/2018/12000/candidate_genes_for_novelty_seeking__a.1.aspx]. Psychiatr Genet. 2018 Dec;28(6):97-109.  * Smith AM, King JJ, West PR, et al. Amino Acid Dysregulation Metabotypes: Potential Biomarkers for Diagnosis and Individualized Treatment for Subtypes of Autism Spectrum Disorder. [https://pmc.ncbi.nlm.nih.gov/articles/PMC6837735/] Biol Psychiatry. 2019;85:345-54. * Sainani K, Goodman S. Lack of Diagnostic Utility of “Amino Acid Dysregulation Metabotypes.” [https://www.biologicalpsychiatryjournal.com/article/S0006-3223(18)32024-9/abstract]Biol Psychiatry. 2018; 85: e41-e42. Kristin and Regina’s online courses * Demystifying Data: A Modern Approach to Statistical Understanding [https://online.stanford.edu/courses/som-xche0033-demystifying-data-modern-approach-statistical-understanding]   * Clinical Trials: Design, Strategy, and Analysis [https://online.stanford.edu/courses/som-xche0030-clinical-trials-design-strategy-and-analysis]  * Medical Statistics Certificate Program [https://online.stanford.edu/programs/medical-statistics-program]   * Writing in the Sciences [https://www.coursera.org/learn/sciwrite]  * Epidemiology and Clinical Research Graduate Certificate Program [https://online.stanford.edu/programs/epidemiology-and-clinical-research-graduate-certificate]  * Programs that we teach in: * Epidemiology and Clinical Research Graduate Certificate Program [https://online.stanford.edu/programs/epidemiology-and-clinical-research-graduate-certificate]  Find us on: Kristin -  LinkedIn [https://www.linkedin.com/in/kristin-sainani-642b5914/] & Twitter/X [https://x.com/KristinSainani] Regina - LinkedIn [https://www.linkedin.com/in/reginanuzzo/] & https://www.reginanuzzo.com/ReginaNuzzo.com [http://reginanuzzo.com] * (00:00) - Introduction * (02:24) - The Cellulite Test * (06:41) - Understanding Sensitivity and Specificity * (12:50) - Enter Positive Predictive Value * (18:40) - Why Base Rates Matter * (24:06) - More Ridiculous Tests * (33:30) - The Wanderlust Gene Deep Dive * (41:27) - The NeuroPoint Autism Test * (53:34) - Trying to Set the Record Straight * (01:02:39) - Personal Stories * (01:05:54) - Wrap-up

Epidurals: Are labor epidurals really linked to autism?

Epidurals are widely used and widely trusted for pain relief during labor. So when a 2020 study reported that they might be linked to autism, it raised a troubling question: could a routine medical decision have long-term consequences? We follow that claim from headline to evidence—and watch what happens when other scientists take a closer look. We dig into the original study, a wave of replication studies from around the world, and a meta-analysis that tries to make sense of it all. Along the way, we unpack hazard ratios, Cox regression, inverse probability weighting, and sibling analyses—and why even sophisticated statistical adjustment can’t eliminate confounding. Plus: why bigger datasets don’t solve everything, what happens when results shrink after adjustment, and how a controversial study turned into a case study in science working as it should. Bonus: our first guest journalist interview! Statistical topics * Confounding * Cox regression * Hazard ratios * Inverse probability weighting (IPTW) * Multivariable adjustment * Observational studies * Residual confounding * Retrospective cohort studies * Sibling analysis * Statistical adjustment * Statistical significance vs practical significance * Survival analysis Methodological morals * “Every time you adjust the model and the effect gets smaller, that's the universe whispering, maybe don't build a causal story out of this.” * “Consistency across studies is gold.” * “There's more to the story than the statistics.” References * Dattaro, Laura. A questionable study linked autism to epidurals. Then what? [https://www.thetransmitter.org/spectrum/a-questionable-study-linked-epidurals-to-autism-then-what/] Spectrum. April 18, 2023.  * Dattaro, Laura. How to find baby sharks. [https://nautil.us/how-to-find-baby-sharks-852820] Nautilus. September 9. 2024. * Laura Dattaro’s home page [https://www.lauradattaro.com/]. * Phil Kearney’s blog post [https://www.linkedin.com/feed/update/urn:li:activity:7424924334152024064/] about the SMART framework. * Qiu C, Lin JC, Shi JM, et al. Association Between Epidural Analgesia During Labor and Risk of Autism Spectrum Disorders in Offspring [https://pmc.ncbi.nlm.nih.gov/articles/PMC7551212/]. JAMA Pediatr. 2020;174:1168-1175.  * Joint Statement. Labor Epidurals Do Not Cause Autism; Safe for Mothers and Infants, say Anesthesiology, Obstetrics, and Pediatric Medical Societies [https://www.asahq.org/about-asa/newsroom/news-releases/2020/10/labor-epidurals-and-autism-joint-statement]. American Society of Anesthesiologists. October 12, 2020. * Wall-Wieler E, Bateman BT, Hanlon-Dearman A, Roos LL, Butwick AJ. Association of Epidural Labor Analgesia With Offspring Risk of Autism Spectrum Disorders [https://pmc.ncbi.nlm.nih.gov/articles/PMC8056314/]. JAMA Pediatr. 2021;175:698-705.  * Christakis DA. More on epidurals and autism. [https://jamanetwork.com/journals/jamapediatrics/article-abstract/2778780] JAMA Pediatrics. 2021; 175: 705. * Mikkelsen AP, Greiber IK, Scheller NM, Lidegaard Ø. Association of Labor Epidural Analgesia With Autism Spectrum Disorder in Children [https://jamanetwork.com/journals/jama/fullarticle/2784508]. JAMA. 2021;326:1170–1177.  * Hanley GE, Bickford C, Ip A, et al. Association of Epidural Analgesia During Labor and Delivery With Autism Spectrum Disorder in Offspring [https://pubmed.ncbi.nlm.nih.gov/34581736/]. JAMA. 2021;326:1178-1185.  * Hegvik TA, Klungsøyr K, Kuja-Halkola R, et al. Labor epidural analgesia and subsequent risk of offspring autism spectrum disorder and attention-deficit/hyperactivity disorder: a cross-national cohort study of 4.5 million individuals and their siblings [https://pubmed.ncbi.nlm.nih.gov/35973476/]. Am J Obstet Gynecol. 2023;228:233.e1-233.e12. Epub 2022 Aug 13. Hu X, Wang B, Chen J, Han D, Wu J.  * Association Between Epidural Labor Analgesia and Autism Spectrum Disorder in Offspring: A Systematic Review and Meta-Analysis [https://pmc.ncbi.nlm.nih.gov/articles/PMC10790590/]. J Pain Res;17:227-240.  Kristin and Regina’s online courses:  Demystifying Data: A Modern Approach to Statistical Understanding [https://online.stanford.edu/courses/som-xche0033-demystifying-data-modern-approach-statistical-understanding]   Clinical Trials: Design, Strategy, and Analysis [https://online.stanford.edu/courses/som-xche0030-clinical-trials-design-strategy-and-analysis]  Medical Statistics Certificate Program [https://online.stanford.edu/programs/medical-statistics-program]   Writing in the Sciences [https://www.coursera.org/learn/sciwrite]  Epidemiology and Clinical Research Graduate Certificate Program [https://online.stanford.edu/programs/epidemiology-and-clinical-research-graduate-certificate]  Programs that we teach in: Epidemiology and Clinical Research Graduate Certificate Program [https://online.stanford.edu/programs/epidemiology-and-clinical-research-graduate-certificate]  Find us on: Kristin -  LinkedIn [https://www.linkedin.com/in/kristin-sainani-642b5914/] & Twitter/X [https://x.com/KristinSainani] Regina - LinkedIn [https://www.linkedin.com/in/reginanuzzo/] & https://www.reginanuzzo.com/ReginaNuzzo.com [http://reginanuzzo.com] * (00:00) - Intro * (01:40) - Why autism is hard to study * (05:18) - The original 2020 study * (11:38) - Results & hazard ratios * (15:24) - Confounding & adjustment * (27:29) - Criticism & plausibility * (35:08) - Replications begin * (45:57) - Converging evidence & meta-analysis * (52:07) - What does it mean? * (54:57) - Guest & wrap-up