Vitals #8

Last Time the Market Was This Expensive, Investors Waited 14 Years to Break Even

In 1999, the S&P 500 peaked. Then it took 14 years to gradually recover by 2013.

Today? Goldman Sachs sounds crazy forecasting 3% returns for 2024 to 2034.

But we’re currently seeing the highest price for the S&P 500 compared to earnings since the dot-com boom.

So, maybe that’s why they’re not alone; Vanguard projects about 5%.

In fact, now just about everything seems priced near all time highs. Equities, gold, crypto, etc.

But billionaires have long diversified a slice of their portfolios with one asset class that is poised to rebound.

It’s post war and contemporary art.

Sounds crazy, but over 70,000 investors have followed suit since 2019—with Masterworks.

You can invest in shares of artworks featuring Banksy, Basquiat, Picasso, and more.

24 exits later, results speak for themselves: net annualized returns like 14.6%, 17.6%, and 17.8%.*

My subscribers can skip the waitlist.

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_{*Investing involves risk. Past performance is not indicative of future returns. Important Reg A disclosures: masterworks.com/cd.}

Welcome to the 2 new subscribers who have joined Future Human since our last edition! Join 335 other leaders learning about the future of human health by subscribing here:

Hi friend,

Welcome back to Future Human! We hope you all had a wonderful holiday season. We are rapidly approaching the end of the year. We here at Future Human are unbelievably grateful for the year we have had. Since launching in February, we have released 31 deep dives (Workups), added a second newsletter series with Vitals, interviewed a dozen founders/CEOs, got invited out to HLTH Las Vegas, met hundreds of healthtech stakeholders, and built an amazing audience of 330+ here on Beehiiv and 650+ on LinkedIn. You all come from unique backgrounds.

Survey says:

• For current position/role:

  • 33% Students (MD, PhD, MS, BS, etc.)

  • 10% Founders

  • 10% Investors

  • 10% Physicians

  • 10% Other Healthcare Professionals

  • 5% Executives (CEO, CMO, etc.)

  • 20% Other (engineer, academic, product manager)

• For current company:

  • Pharma/med tech: GSK, Merck, GE Healthcare, Edwards, Intuitive

  • Investing: Flagship Pioneering, Blackstone, ARTIS, Vergil

  • Academia: Cornell, Stanford, Johns Hopkins, Yale, Harvard

  • Health Systems: MGH, Mount Sinai, NYU Langone, Weill Cornell

We are only just beginning. None of the above would be possible without all of you and your support, so thank you! Here’s to another amazing year of discovery and innovation for the benefit of patients around the world. We will see you in 2026.

To more lives saved,

Andrew, Nicholas, and Isabelle

1. Stimulant ADHD Medications Found to Work Differently Than Thought

Andrew’s Take

If you have been a student in the last 30 years, you have undeniably witnessed the explosion of prescription stimulant use in schools. Names like Ritalin and Adderall ring out in hallways across the country in order to help countless students focus on their assignments. You have also, whether in the medical field or not, probably heard that they work by acting on regions of the brain that control attention. That was the accepted theory until last week.

Neurology researchers at Washington University School of Medicine in St. Louis just showed for the first time that these drugs seem to actually work on the brain’s reward and wakefulness centers, rather than on attention regions. The attention is a secondary effect brought on by making individuals more alert and generally interested in the traditionally boring task ahead.

The work, published in Cell, examined MRI data from 5,795 children ages 8 to 11 from the Adolescent Brain Cognitive Development (ABCD) Study, which is tracking child neurodevelopment across America. Children who had taken stimulants on the day of the scan showed increased activity in the brain regions linked to arousal/wakefulness and reward. The regions associated with attention did not show significantly increased activity. These finding were then validated with five healthy adults without ADHD who do not take stimulant medication.

Although this approach may not materially change the pharmaceutical industry—the underlying drug efficacy is unchanged—it has the potential to redefine how digital therapeutics drive behavior change. Designing interventions that tie tasks to a sense of reward, rather than obligation, may become the dominant model going forward.

2. HHS Issues HTI-5 Rule to Deregulate Health IT

Andrew’s Take

The administration’s broader deregulatory agenda has made its way into Health IT. Although Future Human usually centers on patient-facing breakthroughs, changes this consequential have the potential to rewire how the healthcare system functions at a foundational level. Even if invisible to patients, the downstream impact could be significant enough to warrant coverage.

The Department of Health and Human Services (HHS) just released a proposed rule—HTI-5—aimed at significantly rolling back federal health IT regulatory requirements to reduce burdens on developers and accelerate interoperable, AI-enabled data exchange. The proposal does not hold back. We are talking about eliminating 34 of 60 existing certification criteria and revising several more, with HHS arguing many current rules no longer meaningfully advance interoperability. The proposal would also formalize regulatory flexibilities by making enforcement discretion permanent, allowing regulators to continue refraining from penalties when certain requirements are low value. It would reduce mandatory reporting, cutting back on audits and compliance tasks that many vendors argue slow innovation. Oversight would shift away from technical mandates toward voluntary, industry-led standards. At the same time, the rule strengthens information-blocking protections, preventing companies from using algorithms to restrict data flow.

Health IT incumbents have historically siloed data not because of technical limits, but because data lock-in is a powerful competitive moat. In our view, lighter rules may simply invite more sophisticated, harder-to-detect ways of doing the same thing. Even with tighter information-blocking language around AI, companies with legal resources are likely to find gray areas that preserve advantage while technically staying compliant. The success of this rule will depend less on what’s removed and more on whether regulators can actually enforce against anti-competitive behavior in a system that has long optimized for it.

3. MultiCare uses Predictive Analytics to Add 3,200 Surgeries in One Year

Andrew’s Take

Here in medical school, I recently had a number of meetings to plan out upcoming research all about surgical pitfalls and inefficiencies. For that reason, the timing of this headline was quite awesome and I will certainly be taking away some key lessons. 

A Washington not-for-profit health system, Multicare, recently announced a successful data-driven initiative to improve surgical efficiency across its 13 hospitals, 2,400 beds, and 100 ORs. Faced with 13 different leadership structures and surgical KPIs, they dedicated this last year to developing a single system to improve surgical efficiency and outcomes. Newsflash, it worked.

After meeting with physicians and frontline staff across all facilities, they collected what was working, what was not, and how each team wanted to get involved in the improvement process. They then agreed on the LeanTaaS iQueue system for OR data management. The platform helped forecast demand and manage staffed rooms as well as place new cases in the right location at the right time. The team highlights the one source of truth across the health system as the key to this initiative's success. From there, with their tools selected, they standardized how cases would be scheduled using a machine learning model to optimize for access.

Over the last year, they added 3,200 additional surgeries without building new rooms or hiring more staff (Multicare performs almost 100,000 surgeries per year on average). They improved room utilization by 25% and prime time utilization by 14%. It seems physician-led governance alongside streamlined processes and clean data allowed for system-wide change. Now let’s see what we can do at NY Presbyterian.

4. FDA Approves Edwards Lifesciences' SAPIEN M3 Mitral Valve Replacement System

Andrew’s Take

Can’t beat another innovation in minimally invasive cardiac care. Edwards has joined the list of recipients in this end of year FDA approval spree. The FDA has given the nod to their SAPIEN M3 mitral valve replacement system. It is the first transcatheter mitral valve replacement delivered via a transseptal approach approved for patients with moderate-to-severe mitral regurgitation who are not candidates for surgery or edge-to-edge repair (TEER), as well as select patients with mitral stenosis or heavy calcification.

The approval was informed by the year-long ENCIRCLE trial, which achieved all primary and secondary endpoints for safety and effectiveness (299 patients unsuitable for other treatment options), achieving significant MR elimination and meaningful improvements in symptoms.

The M3 is delivered using a fully percutaneous approach, meaning there is no open-heart surgery. The procedure begins with access through the femoral vein in the groin. From there, a catheter is advanced up to the right atrium, where the operator performs a transseptal puncture to cross the interatrial septum and enter the left atrium. From there, it is a two-step delivery. First, a dedicated docking system is positioned and secured within the native mitral valve anatomy. This dock provides a stable anchor and helps align the replacement valve. Once the dock is in place, the transcatheter valve is delivered through it and expanded, replacing the function of the native mitral valve. As for how this compares to other options, the transseptal puncture method is already used by edge-to-edge repair devices (ie. MitraClip), but these merely repair the native valve instead of replacing it. This is the first approved transseptal transcatheter mitral valve replacement.

5. FDA Approves Agios’ AQVESME™ for the Treatment of Anemia in Adults with Alpha- or Beta-Thalassemia

Andrew’s Take

For the final story of the final edition of Vitals for the year, we have an exciting new drug approval for anemia brought on by either type of thalassemia. For those who are less versed, alpha- and beta-thalassemia are inherited blood disorders causing anemia due to reduced hemoglobin. Alpha-thalassemia involves missing/reduced alpha-globin chains (from 1-4 gene deletions), while beta-thalassemia involves faulty/missing beta-globin (from gene mutations). Both lead to excess of the other chain type, causing more severe red blood cell damage.

Agios just became the first to get the approval to offer an oral medication for either type. AQVESME (mitapivat) is a pyruvate kinase (PK) activator. It binds to and activates the enzyme pyruvate kinase in red blood cells (RBCs). Pyruvate kinase plays a critical role in glycolysis, the process that generates energy (ATP) in RBCs. By activating PK, AQVESME improves RBC energy metabolism, which helps RBCs function better and survive longer.

The decision was based on results from the ENERGIZE and ENERGIZE-T Phase 3 trials in adults with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia. A total of 452 patients were enrolled in the trials. The trials showed that the therapeutic improves hemolytic anemia and a key quality-of-life measure compared to placebo, including significant reductions in transfusion burden and significant improvements in hemoglobin and fatigue.

We hope you enjoyed this edition of Vitals!

We always appreciate feedback, questions, and conversation, so feel free to reach out on LinkedIn or by replying to this email.

To more lives saved,,

Andrew, Nicholas, and Isabelle