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14. Daniel Burka: How to Design Successful and User-friendly Healthcare Applications

In this episode, Mitch Belkin and Daniel Belkin speak with Daniel Burka about his work at Resolve to Save Lives and the project Simple.org, a hypertension reduction application. They discuss the importance of iterative building processes that trial various ideas and then quantifiably measure success. Daniel Burka stresses the importance of understanding the goals of all users–physicians, patients, public healthcare experts–when designing successful healthcare applications.

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Who is Daniel Burka?

Daniel Burka is the director of product and design at Resolve To Save Lives, where he works on the web-based, open-source hypertension reduction application Simple.org. Previously, he was a Design Partner at Google Ventures, the Creative Director for Digg.com, and the Director of Design for Tiny Speck which later became Slack. Among many notable projects, he designed the Firefox logo and Mozilla’s website.

What is Resolve to Save Lives?

Resolve to Save Lives is an initiative to prevent 100 million cardiovascular deaths over the next 30 years. The initiative is funded by Bloomberg Philanthropies, the Bill & Melinda Gates Foundation, Gates Philanthropy Partners, and the Chan Zuckerberg Foundation. Methods to reduce deaths include hypertension reduction, trans fat elimination, and sodium reduction initiatives. In addition, Resolve to Save Lives aims to increase epidemic preparedness.

What is Simple.org?

Simple.org is a project of Resolve to Save Lives. It is an ultralight weight electronic health record system designed to manage patients with hypertension and diabetes. As of January 2022, 1.4 million patients in India, Bangladesh, and Ethiopia use the application.

What is DHIS2?

District Health Information Software 2 (DHIS2) is a free, open-source health management data platform. It was initially developed for three health districts in Cape Town, South Africa in 1998-99, but has since spread to more than 40 countries in Africa, Asia and Latin-America, as well as the EU. DHIS2 is used to aggregate statistical data collection, analysis, management, and visual presentation. It is completely web-based and has the ability to create analysis from live data in seconds. In addition, DHIS2 can be used to monitor patient health outcomes, improve disease surveillance, map disease outbreaks, and speed up health data access for health facilities and government organizations. 

References:

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13. Stephan Guyenet, PhD: GLP-1, Semaglutide, and the Big Future of Weight Loss Therapies

In this interview, Mitch Belkin and Daniel Belkin speak with Stephan Guyenet, PhD, about Glucagon-like peptide-1 (GLP-1) and Semaglutide. They discuss GLP-1’s mechanisms of action, Anthony Sclafoni’s experiments on food reinforcement and nutrient receptors in the small intestines. Finally, they touch on some exciting new weight loss drugs that may replace semaglutide and potentially even bariatric surgery.

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Who is Stephan Guyenet?

Dr. Stephan Guyenet received his PhD in Neurobiology and Behavior from the University of Washington. Afterward, he completed a postdoctoral fellowship in the neuroscience of obesity. He is the author of the book The Hungry Brain. Dr. Guyenet is the founder & director of Red Pen Reviews, which publishes expert reviews of popular nutrition books with structured semi-quantitative evaluations. In addition, he is a senior researcher at GiveWell where he conducts cost effectiveness analyses on water quality interventions and malnutrition treatments in low income countries.

What is GLP-1 ?

Glucagon-like peptide-1 is a hormone produced by the intestines. It is an incretin, meaning it signals the pancreas to increase insulin secretion in a glucose-dependent manner. Initially, GLP-1 agonists were developed for the treatment of diabetes. In both animal and human models, it was discovered that GLP-1 agonists suppress food intake, which led to weight loss. This discovery spurred its use in obesity trials, including STEP 1

What is Semaglutide?

Semaglutide is a GLP-1 agonist that was used in the STEP trials.

What is STEP 1?

Semaglutide Treatment in People (STEP) 1 is a randomized double blind, placebo controlled trial that enrolled 1961 non-diabetic adults with a BMI over 30 (or a BMI of > 27 if the participants had other weight-related co-morbidities like hypertension, dyslipidemia, obstructive sleep apnea, etc). Participants were randomly assigned in a 2:1 ratio to 68 weeks of treatment with once weekly subcutaneous Semaglutide or placebo, plus lifestyle intervention. In the trial, the Semaglutide group lost an average of 14.9% of their body weight as compared to the placebo group which lost an average of 2.4%. Additionally, participants who received Semaglutide had greater improvement with respect to cardiometabolic risk factors (such as a decrease in waist circumference, lower blood pressure, and reduced glycated hemoglobin levels and lipid levels). 

What are the common side effects of Semaglutide?

Nausea and diarrhea are the most commonly reported adverse events with Semaglutide. During the trial, these side effects were typically transient and mild-to-moderate in severity. Of note, more participants in the Semaglutide group than in the placebo group discontinued treatment due to gastrointestinal events (4.5% vs. 0.8%).

What are the strengths and weaknesses of the STEP 1 Trial?

Strengths of this trial include the relatively large sample size and the high rates of adherence to the treatment regimen. Limitations include that it was predominantly white (~75%) and had a relatively large percentage of women (~75%) so it may not be generalizable to other populations. Additional limitations were that it was a relatively short trial (only 68 weeks) and it excluded people with type 2 diabetes, who represent a large percentage of individuals who are obese. Furthermore, the participants who were enrolled may represent a subgroup in the population with a greater commitment to weight-loss efforts than the general population. 

Are there any health benefits to Semaglutide besides weight loss and reductions in diabetes?

Taking Semaglutide lowers cardiovascular risk on par with statins – a 25% reduction in cardiovascular risk.

What are other theoretical concerns for Semaglutide?

1. Pancreatic and Thyroid Cancer. Animal models and case reports from other GLP-1 agonists demonstrate higher incidences of these types of cancer. However, these have not been borne out in human trials on Semaglutide thus far in the tens of thousands of patients who have used the medication for weight loss. Of course, it is possible these trials were insufficiently powered or too short to demonstrate potential rare effects.

2. Depression, suicidal ideation. A different weight loss medication — Rimonabant, which is a cannabinoid receptor antagonist — was taken off the market due to increases in suicidal ideation and a trend toward increases in suicide. Although Semaglutide has not been associated with increases in depression and suicidal ideation, individuals taking the medication do report decreased pleasure-seeking behaviors (e.g., alcohol consumption, recreational drug use, sex). This is similar to the effects of other centrally-acting weight loss drugs because of their effects on the dopaminergic pathways. While this could be considered a positive effect of the drug, theoretically decreases in the dopaminergic pathway could cause depressive type symptoms.

Citations for Stephan Guyenet:

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12. Emily Oster, PhD: Breastfeeding Recommendations, Rising C-section Rates, and Other Controversies

In this interview, Mitch Belkin and Daniel Belkin speak with Brown Economics Professor Emily Oster about the studies behind breastfeeding recommendations, the dramatic increase in the U.S. C-section delivery rate over the last half century, and how she approaches analyzing studies. 

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Who is Emily Oster?

Emily Oster is the Royce Family Professor of Teaching Excellence and Professor of Economics at Brown University where she studies health, behavioral, and development economics. She received her PhD from Harvard University and taught at the University of Chicago Booth School of Business. She is the author of three popular books on pregnancy and parenting: Expecting Better, Cribsheet, and The Family Firm

What topics do we cover in this episode?

This interview focuses on two major topics: breastfeeding and the C-section rate, which are best covered in Cribsheet and Expecting Better, respectively.

Breastfeeding

What are the official recommendations on breastfeeding?

The CDC and the American Academy of Pediatrics recommend exclusive breastfeeding for 6 months and then continued breastfeeding while introducing food until 12 months of age or older. The benefits of breastfeeding are said to include: decreased risk of asthma; decreased ear, respiratory, and gastrointestinal infections; lower rates of obesity and type 1 diabetes. Some also claim that breastfeeding can lead to increased infant IQ and higher wages in adulthood, among many other purported benefits. For mothers, the benefits of breastfeeding are said to include decreased risk of ovarian cancer, breast cancer, type 2 diabetes, and hypertension.

What does Professor Emily Oster think about breastfeeding?

Professor Oster argues that at least some of these claims are overblown or based on relatively weak evidence. In large part, this is because most of the claims come from observational and case-control studies, which do not allow one to draw causal conclusions. As Professor Oster reiterates in this podcast, women in the developed world who choose to breastfeed differ from women who choose not to breastfeed in significant ways. For example, they tend to be wealthier and more educated. These demographic factors are already correlated with better infant outcomes independent of whether women choose to breastfeed or not.

Do any large breastfeeding RCTs exist?

Yes, the PROBIT study (AKA the Promotion of Breastfeeding Intervention Trial) is a Randomized Controlled Trial in Belarus conducted in the 1990s that took 17,046 healthy mother-infant pairs of full-term singleton infants and randomly assigned them to either an intervention arm that encouraged breastfeeding or a control group that had the usual infant feeding recommendations.

What were the results of the PROBIT study?

At 12 months, infants from the intervention group were about twice as likely to be breastfed compared to the control group (19.7% vs 11.4%). This demonstrates that the encouragement intervention was effective in promoting breastfeeding. At 3 months, the intervention group was six times more likely to be exclusively breastfed (43.3% vs 6.4%; P<.001). The intervention group also had a significant reduction in the risk of 1 or more gastrointestinal tract infections (9.1% vs 13.2%) and of atopic eczema (3.3% vs 6.3%). However, there was no significant reduction in respiratory tract infection.

Cesarean sections

Where does the name Cesarean section come from?

There are numerous explanations of where the word came from. One apocryphal story is that Julius Caesar was actually born by C-section, which is almost certainly untrue given that his mother survived long after childbirth. There are also many other etymological explanations for the name, including the root of the word coming from a similar root as the Latin word for “to cut” (caedere).

Why are C-sections performed?

C-sections are a surgical procedure used to deliver a baby through an incision in the abdomen and uterus. They are usually performed when a vaginal delivery presents increased risks for baby and/or mom. Medical reasons for the surgery include prolonged or abnormal labor, twin pregnancy, pre-eclampsia, breech birth, fetal distress, and problems with the placenta or umbilical cord.

The rise in C-sections:

In 1970, 5% of U.S. births were by Caesarean section. In 2019, the CDC’s official C-section rate was 31.7%.  This 6-fold increase could be due to a number of factors, which we discuss in this episode. Though we do not discuss it in great detail, the WHO has a so-called “ideal C-section rate” which is between 10-15%. This ideal rate stems from the following argument: as caesarean sections rise towards 10% in a given population, the number of maternal and newborn deaths decreases. However, when the rate is greater than 10%, there is no evidence of improvements in mortality. Some possible explanations for the increase in the U.S. C-section rate include:

  1. An increase in the number of high risk pregnancies due to increases in obesity, diabetes, pre-eclampsia, hypertension, and maternal age.
  2. Increased litigation (or fear of litigation). For example, malpractice premiums are positively correlated with higher rates of C-sections.
  3. The advent and increasing use of continuous fetal heart rate monitors, which have been demonstrated to increase the rate of c-sections
  4. Increased patient preference for c-sections.
  5. Attending preference. Studies show an increased number of C-sections just prior to the end of shifts and before lunch time.
  6. Insufficient training with breech births leading physicians to opt for c-sections in circumstances that previously would have been delivered vaginally.
  7. Higher physician and/or hospital compensation for c-sections as compared to vaginal births may lead hospitals to incentivize performing more c-sections.

Please note this is not a complete list of the possible reasons for the increased C-section rate.

Miscellaneous:

In our podcast, we reference the following papers, ideas, and talks:

Errata:

  1. In the introduction, we accidentally say Academy of Pediatrics at one point when we meant to say American Academy of Pediatrics.
  2. In the introduction, we state that one reason for C-section delivery is “protracted vaginal delivery”. We meant to say “protracted labor” defined as the arrest of cervical dilation prior to vaginal delivery.
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11. Katherine Flegal, PhD: The Obesity Wars and the Politicization of Science

In this interview, Mitch Belkin and Daniel Belkin speak with Katherine Flegal about the relationship between BMI and excess mortality. Dr. Flegal’s publication of two papers in the Journal of the American Medical Association led to substantial controversy among obesity researchers. They discuss the data regarding the U-shaped mortality curve, the history of BMI, as well as the politicization of science.

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Who is Katherine Flegal?

Katherine Flegal is an epidemiologist and former senior scientist at the Centers for Disease Control and Prevention’s National Center for Health Statistics. She is one of the most cited scientists in the field of obesity epidemiology. After receiving a bachelor’s from UC Berkley, a PhD from Cornell, and an MPH from Pittsburgh, she worked in the biostatistics department of University of Michigan prior to working at the CDC in the National Center for Health Statistics.

Dr. Flegal worked on the National Health and Nutrition Examination Survey (NHANES), which is a comprehensive data set of nationally representative cross-sectional data from the US that combines interviews, physical exams, and laboratory tests along with demographic, socioeconomic, and dietary data. Her 2005 analysis of the NHANES data set and her 2013 meta-analysis demonstrated that people who are “overweight” (defined as a BMI between 25 and 30) have significantly lower all cause mortality compared to people who are “normal weight” (BMI 18.5 – 24.9). In addition, her publications showed no significant difference in mortality between people who have a BMI of 30-35 and people who are normal weight.

References

The Obesity Wars and the Education of a Researcher: A Personal Account (Progress in Cardiovascular Diseases, 2021)

Excess deaths associated with underweight, overweight, and obesity (JAMA, 2005)

Association of All-Cause Mortality With Overweight and Obesity Using Standard Body Mass Index CategoriesA Systematic Review and Meta-analysis (JAMA, 2013)

 

 

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10. Karl Friston on Understanding Schizophrenia using the Free Energy Principle

In this interview, Mitch Belkin and Daniel Belkin speak with Dr. Karl Friston about his proposed free energy principle. They discuss how it applies to various psychiatric and neurological disorders including schizophrenia, depression, autism, and Parkinson’s. They also touch on the disconnection hypothesis of schizophrenia, how theories of schizophrenia have evolved over the last two centuries, and the relationship between schizophrenia and autism.

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Who is Karl Friston?

Dr. Friston is a professor of neuroscience at University College London and an authority on brain imaging. He is the 20th most-cited living scientist with over 260,000 citations for his works. After studying natural sciences at Cambridge, he completed his medical studies at King’s College Hospital in London and worked for 2 years in an inpatient psychiatric facility on the outskirts of Oxford, where treated patients suffering from schizophrenia.

Dr. Friston has developed a number of statistical tools for analyzing data from the brain, including statistical parametric mapping (SPM), voxel-based morphometry (VBM) or dynamic causal modeling (DCM). His mathematical contributions include variational Laplacian procedures and generalized filtering for hierarchical Bayesian model inversion.

References

Scott Alexander – On attempting to Understand Friston’s Free Energy Principle

The Disconnection Hypothesis – Karl Friston

The Free Energy Principle – Karl Friston