
We designed shade out of our cities. We can design it back in
As temperatures continue to reach record highs—and climate change increases the likelihood of heat waves—the sun has become foe, and shade has become king. Shade can lower the ambient temperature of the air by as much as 15 to 20 degrees Fahrenheit. It can cool surfaces by as much as 45 degrees.
But where is it?
Ten thousand years ago, more than half of the land on Earth was shaded by tree canopies. Today, after millennia of deforestation, agriculture, and urbanization, that number has dropped to just 30%. The problem is particularly dire in cities: A recent map by UCLA and the nonprofit American Forests revealed staggering 'shade deserts' in almost every major urban region in the U.S. According to journalist and author Sam Bloch, this dearth of shade is by design.
In his new book, simply titled Shade, Bloch argues that the absence of shade from our lives is not an accident. 'Shade has been deliberately designed out of our environments,' he tells me on a recent phone call. 'Those decisions may have made sense in the past, but we are rapidly moving into a new world where sun protection is going to be as important as sun access.'
Shade as old as time
Humans have sought shade for as long as we have lived under the sun. 'Forget palm trees and ponds,' Bloch writes. 'In ancient Mesopotamia, cities were the real oases.' Four thousand years ago, in places where temperatures could soar up to 130 degrees, Sumerians used city walls for shade. They built deep, narrow streets and packed houses close together. Unlike modern cities, which are laid out along the cardinal directions, Sumerians also oriented their cities diagonally, which offered equal amounts of sun and shade on both sides of the street.
In his book, Bloch mentions the work of Mary Shepperson, a U.K. archaeologist who specializes in urban archaeology of the Middle East. After modeling the sun's daily and seasonal paths over Mesopotamian cities, Shepperson found that the orientation of streets, their narrowness, and small protrusions like vertical rooftop parapets and horizontal eaves likely made for pleasant, shaded cities.
The 'wisdom of shade,' as Bloch calls it, was known to the Syrians, Phoenicians, and Persians. Later, it was embraced by the Greeks and Romans, and eventually exported by the Islamic caliphate to modern-day Spain and Portugal. But that is the extent it traveled. Europeans had their own beliefs about what makes a healthy city, and they exported those beliefs to the New World. 'In temperate climates, the sun was their friend, not their enemy,' Bloch writes. 'They had little use for shade.'
How we designed shade out of our cities
If shade is as old as time, so are our preconceptions against it. Over 2,000 years ago, the Greek philosopher Onesicritus taught that shade stunted growth. As Bloch points out, our prejudice against shade even shines through in the language we use: When something is dubious, it's shady. When we feel offended, we take umbrage.
Americans, perhaps more so than others, take particular umbrage at shade. 'We think shade is yucky. It's for damp corners and fetid ponds,' Bloch writes. This goes back to the early colonizing days. When Europeans arrived in modern-day America, they brought with them a 'deep and abiding fear of forests,' which were considered pagan and unholy. In 1771, an English patrician proclaimed 'a garden in a street is not less absurd than a street in a garden.' Or as the author puts it: 'A city dweller who planted trees in their front yard was just another country bumpkin.'
Many factors further contributed to the downfall of shade, but perhaps the most significant of them is our ancestors' fear of tuberculosis. Early research from the 1900s showed that bacteria could be killed with sunlight. This understanding birthed a fixation for sunlight that translated to some of the most famous modernist buildings of the time, including Alvar and Aino Aalto's Paimio Sanatorium in Finland.
In the U.S., urban planners introduced zoning that called for 'setbacks.' They wrote 'solar codes' into urban plans. They widened roads (which also helped cars thrive) and carved out paths for sunlight to reach deep into the streets. 'This fear of tuberculosis has driven so much of our urban design,' Bloch tells me.
The approach trickled down to buildings, as architects clad office buildings and homes with large expanses of glass. Le Corbusier declared glass the foundational material of modernism. Ludwig Mies van der Rohe famously said, 'It's up to the engineers to find some way to stop the heat from coming in or going out,' about his Farnsworth House.
Glass, we know now, is notorious for trapping heat. But it has survived as a material of choice, thanks to another notorious invention: AC. Modern air-conditioning was invented in 1902 by American engineer Willis Carrier, who designed a system to control humidity at a printing plant in Brooklyn, New York. Suddenly, external shading systems like brise-soleils, awnings, sun sails—systems that have been used in European cities for centuries—were dismissed as costly add-ons that could never match the level of comfort provided by cool air being fanned through your house. Case in point: After the Truman administration renovated the White House in the 1950s—installing mechanical cooling in the process—it foolishly took down the stripy summer awnings that once kept it cool.
Air-conditioning revolutionized cooling around the world, but as Bloch writes, 'it came at a cost.' It distanced us from nature and trapped us inside climate-controlled boxes. It lowered our comfort level and our defenses. Even worse: It exacerbated the heat problem it's supposed to solve by sucking the hot air from our houses and expelling it in our cities. According to computer simulations from Paris and Phoenix, the waste heat from AC units makes the surrounding air about 2 to 3 degrees warmer. 'All this happened when we turned our backs on shade,' Bloch writes.
How we can design shade back into our cities
So, how do we learn to love shade again? The good news is that there's no need to reinvent the wheel. In his book, Bloch highlights examples from cities all over the world. In Bologna and Singapore alike, people can walk under miles of covered sidewalks that are carved out of the ground floors of buildings. Italians call them portici (porticoes). In Singapore, they're known as 'five-foot ways.'
In Seville—where seats at the bullring cost two to three times more when they're in the shade—practically all windows are shaded by roller blinds, or persianas de esparto, which are threaded grass curtains that Sevillanos drape over their balconies. Every spring, the Spanish city also installs toldos over streets and plazas. These 'sun sails' have been used for so long (over 500 years) that they have become a proud tool in the city's shade vernacular.
Naturally, every city's 'shade tool kit' will vary based on its climate policy, geographic and socioeconomic conditions, and affinity for design-led solutions. Barcelona has set up 'climate shelters,' while Dallas has been planting thousands of trees. And Los Angeles has been coating its streets and roofs with solar reflective paint.
Since the early 2000s, architects have been pushing for more passive houses. But as Bloch writes, the incentives largely benefit the future occupants, whose energy bills are lowered, not the developers, whose bottom lines remain the same whether or not a building is climate-resilient. This 'split incentive' problem has notably hampered construction and can only be solved if cities implement stronger building codes and grant developers stronger financial incentives. (Building a passive house typically costs around 10% more.)
Perhaps it would help shift our perception of shade if cities classified heat as an environmental hazard, like water or air pollution. The Clean Water Act limited what industries and farms could dump into waterways. The Clean Air Act required power plants and factories to monitor, control, and report their emissions. A similar requirement for heat might help us take more actionable steps toward heat mitigation.
'If we ever agree that heat is a threat to our freedom and happiness, then we might also decide that shade, our defense against it, is an inalienable right,' Bloch writes. (Even if studies have shown the cooling benefits of shade, Bloch says there is no single, widely accepted index to measure shade's thermal impact.)
For Bloch, the problem with shade access isn't necessarily technological but psychological. Some of the experts he interviewed for the book are even calling for a life 'after comfort'—where architecture is made more porous, and where we can learn to live with heat. Studies have found that people who are forced to deal with heat can tolerate it more than those who can escape it.
In the U.S., the ideal indoor temperature ranges between 73 and 78 degrees. In Ouagadougou, Burkina Faso—where AC is virtually nonexistent—studies say that the Burkinabe people's ideal temperature is closer to 86. Similar studies have shown that people in Marrakech, Morocco, are more likely to feel comfortable than people in Phoenix, Arizona, despite a similar climate.
Bloch knows that the cooling effect provided by shade is never going to replace the icy blast of AC. 'Even on a thermodynamic level, it's not doing the same thing,' he tells me. 'But if we can adjust our expectations as to what comfort really is, we might be able to be more tolerant of shade as a viable solution.'
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Medscape
30 minutes ago
- Medscape
Jul 25 2025 This Week in Cardiology
Please note that the text below is not a full transcript and has not been copyedited. For more insight and commentary on these stories, subscribe to the This Week in Cardiology podcast , download the Medscape app or subscribe on Apple Podcasts, Spotify, or your preferred podcast provider. This podcast is intended for healthcare professionals only. In This Week's Podcast For the week ending July 25, 2025, John Mandrola, MD, comments on the following topics: The group at the University of Leeds in the UK have published an interesting paper on endurance athletes, cardiac fibrosis, and ventricular arrhythmia. They cheekily named it Ventoux to correspond to a recent Tour de France stage finishing on Mount Ventoux. I've climbed Ventoux. It took me 1 hour 42 minutes. Tadej and Jonas did it this week in 54 minutes—a record by a minute. Imagine liking, no, loving, the notion of climbing a 10% gradient for well more than hour and you will understand the mindset of older endurance athletes. Thinking this is fun is a sort of disease. People who do this day in and day out for decades have an affliction. I know because I do. We are like rodents who, given a wheel in our cage, will run on it, for no purpose other than to run on it. Before I say anything else, I want to start with the fact that exercise is one of the pillars of health. It's in every expert consensus document and oodles of observational studies correlate exercise with longevity. But 60-year-old people who cycle or run more than 10 hours per week for decades are not normal exercisers. For instance, if you do an hour ride 5 days per week, to get to that level of exercise, you have to do a 5-hour ride on the weekend or two 3-hour rides on Saturday and Sunday. That's a lot. I co-wrote a book called The Haywire Heart in which my chapters were basically narrative reviews of the cardiac effects of all this exercise. The one, single observation that got me interested in this topic is that endurance athletes have a heightened relative risk of getting atrial fibrillation (AF) and, electrically and structurally, their atria remodeling resembles that of a person of obesity and hypertension. Isn't that wild? But AF is not the topic of this paper. Endurance athletes can also develop both myocardial fibrosis (scar) and ventricular arrhythmias (VA). The VA story is less fleshed out than the AF story, perhaps because it is less common. But again, you have the paradox: endurance exercise correlates with scar seen in healed myocarditis and other cardiomyopathies. Something amazing for health — regular exercise — perhaps can be detrimental in huge doses. And we all know that myocardial scar can predispose to ventricular arrhythmias—which, can in rare cases, lead to sudden cardiac death. Now to the Ventoux study: The Leeds group recruited about 100 endurance athletes and 27 controls with the purpose of studying MRI, CMR, and monitoring for VA with implantable loop recorders (ILRs) over 2 years. All participants had to agree to an ILR implant, which is likely an important factor in the study's interpretation. This study is a great effort. I congratulate the authors. The average age was about 60. All were men. None could have any symptoms or heart disease. The athletes were pretty strong. The functional threshold power, what can be held for an hour, was around 244 watts. That's not close to elite but it's not Mickey Mouse either. Another factor was that the Leeds group is a well-known and experienced in imaging. So, the MRI imaging can be trusted, and an expert in imaging told me these are likely real findings. And here are the topline results: Nearly half (47%) had myocardial fibrosis on MRI, the vast majority had inferior lateral location of scar. The main way the authors display the results is with two groups—those with scar and those without scar. About 1in 5 athletes overall had some ventricular arrythmia on the ILR during 2 years of follow-up Those with fibrosis had a 4.7% higher relative risk of VA. (But crucially, the 95% CI were wide from 80% higher risk to 13x higher). Athletes with fibrosis were slightly older than athletes without fibrosis (62 years versus 57 years) Athletes with fibrosis exhibited a greater prevalence of premature ventricular contractions (PVC) during exercise testing than athletes without fibrosis (71% vs 42%; P =.003) All three of the athletes with VT longer than 30 seconds, which we call sustained VT, had fibrosis on cardiac MRI. And all 3 who experienced sustained VT were symptomatic and developed an episode of nonsustained VT before the onset of VT. One athlete received an ICD due to presyncope, one was scheduled for an EP study (the results of which were not known), and the third was advised to cease competing due to recurrent VT during exercise but declined further investigation Of those who experienced a ventricular arrhythmia, 78% of the athletes had myocardial fibrosis on CMR compared with 22% athletes who did not ( P < .001). Two other predictors of having VT were left ventricular (LV) dilation and exercise-induced PVCs. Late gadolinium enhancement (LGE) at the right ventricular (RV) insertion point was super common. This is also well known in athletes but it had no statistically significant correlation with VA. But confidence intervals (CI) were wide again. Both groups had normal left ventricular ejection fraction (LVEF). Both had similar and normal RV function. There were no significant differences in T2 times between athletes with and without ventricular arrhythmia. No athlete had T2 values indicative of acute myocardial edema, and no athlete fulfilled Lake Louise Criteria for acute myocarditis. The authors concluded that fibrosis incidence was high and associated with VA, and RV insertion point LGE was not associated with VA and…sit down for this conclusion: 'Further studies are needed to establish whether myocardial fibrosis itself is arrhythmogenic or in the case of athlete's indicative of a myopathic process.' I like this conclusion, and it's different from many of the posts I have seen on social media—which go too far in scaring people about exercise. There is much to say about these observations, but, sadly, most are questions rather than answers. First: Why was the fibrosis presence so high? Almost half of people. I think the issue here is a systemic bias in this study: it's a selection bias. Or more specifically , self-selection . A researcher who does a lot of normal volunteer studies told me that, after the fact, many asymptomatic volunteers admit to symptoms they wanted checked. Now…Recall this study was done in the UK, where getting checked out may not be so easy. So you enroll 100 people who have to agree to get ILRs. To me this is a special population, who are probably more than just curious; they are probably concerned. Endurance athletes tend to be obsessive and read a lot about the heart issues in athletes. I would almost consider getting an ILR a collider bias. You are not looking at a general population of endurance exercisers but rather those endurance exercisers interested in monitoring for some reason. Second issue: There is the issue of ILR monitoring . These things are always on. They, like pacemakers, pick up everything . They are far more sensitive than a 2-week ECG or even an Apple Watch. So you have a population enhanced by concern wearing a monitor that misses nothing. In my device clinic, I probably get three nonsustained VT alerts per day — 99% of which I say, just follow. I've become increasingly convinced that short episodes of atrial and ventricular tachycardia are probably normal in older adults. Indeed, in VENTOUX, only 3 of the 100 individuals had symptoms that required clinical action—an ICD, an EP study, results unknown, and an exercise restriction. All three were symptomatic, so clinically, I agree 100% with the authors, that there is nothing in this data that would suggest screening with MRIs and ILRs. Let me repeat: VENTOUX does not support screening athletes with MRI. You can and should wait for symptoms. The third matter is the degree of LGE. The scar burden was only 2%. These are tiny scars, and most serious VT we take care of in EP comes from much larger scars. But while it is true that any scar is abnormal, we don't know if it is from exercise or healed myocarditis. And we don't know the benefit/harm ratio of lifelong exercise. Lifelong exercise is protective against diabetes, hypertension, coronary artery disease (CAD), but it may cause small LGEs in a very small proportions of patients. Notice that all these are comments are questions. This study is interesting. Intensely interesting. It's a great effort, but to offer more actionable results, beyond, don't ignore symptoms , which is an easy thing to tell people, we would need larger samples that were crucially more random in sampling. Though they tried, VENTOUX is not all a random sampling of heavy exercisers. Imagine a study wherein you went to an endurance race, and you signed up one out of every five 30-year-olds and followed them serially, as they did in Framingham, with CMR every 5 years for two or three decades. Then we might know more. But such a study is vast and super expensive. For now, I recommend regular exercise as if it was a heart pill or AF pill. You take it daily. Todos los dias. The vast majority of people I see don't exercise enough. What bike racers like to do is not at all for health . It is for fun, or for sanity; whether it is a net harm remains to be seen. But even if it were, I am not sure most of us would stop doing it. Because rodents must run on the wheel. An Australian group of researchers have published a massive systematic review and meta-analysis of daily steps in and health. Lancet Public Health published the study, which was covered in 176 news outlets as of this morning. Most of the news stories say something like the 10,000-step myth has been busted and 7000 is sufficient. The news' stories are wrong. And I will briefly cover this study because it bookends the extreme exercise study quite well. The research team had 57 studies from 35 cohorts included in the systematic review and 31 studies from 24 cohorts included in meta-analyses. They looked at dose response (in steps) and many outcomes including all-cause mortality, cardiovascular disease incidence, dementia, falls, and type 2 diabetes. The comparator or control group was 2000 steps. Compared to that those who reported or documented with counter 7000 steps per day had a: 47% reduction in all-cause death (HR 0.53 [95% CI, 0.46–0.60]; I 2 =36.3; 14 studies) 25% reduction in CV disease incidence (HR 0·75 [0·67–0·85]; I 2 =38·3%; 6 studies) 47% reduction in CV mortality (HR 0·53 [0·37–0·77]; I 2 =78·2%; 3 studies) 37% reduction in cancer mortality (HR 0·63 [0·55–0·72]; I 2 =64·5%; 3 studies) 14% reduction type 2 diabetes (HR 0·86 [0·74–0·99]; I 2 =48·5%; 4 studies) 38% reduction in dementia (HR 0·62 [0·53–0·73]; I 2 =0%; 2 studies) 28% reduction in falls (HR 0·72 [0·65–0·81]; I 2=47·5%; four studies) My issue with this study is that when you go to the main figure, the plots with hazard ratio (HR) on the y-axis and step counts on the x-axis, you see a clear dose response of steps and specific outcomes. 2000 steps is where the HR is 0. If it's less than 2000 steps, the outcomes are actually higher, but as the step count increases the HR drops. The authors pick 7000, I assume because that is where the slope of benefit seems to plateau, but when you look at the curves, the HR keeps dropping with more steps. The authors quantify the added benefit of > 7000 steps per day in Table 8 of the supplement. For all-cause death, there is an added 10% lower HR with 10,000 vs 7000. Same for cancer mortality and depressive symptoms—an added 10% lower relative risk. So I don't think any myths were busted. 7000 is fine. 7000 steps per day is associated with lower bad health outcomes. But for many, including all-cause death, 10,000 is better. The added benefits reached statistical significance. So if a patient asks, the number is still 10,000. Though 7000 is also good. And 5000 is better than 4000, which is better than 3000. After reviewing this study, the thought about European vs American life popped into my head. We have probably 2000 people working at my hospital. Less than 5 of them walk to work; less than 10 of them ride their bike. When I visited the team at Basel, Switzerland last fall, it looked like more than 75% walked or cycled to work. Very few American cities are set up for walking. That's sad. So Americans have to make an effort to be active. I think it's worth it. And I recommend it in the clinic. For my height, 7000 steps is about 3 miles. 10,000 steps is nearly 5 miles. The optimal dose is the longer one. But some is better than none. Everyone Deserves a Shot at the American Dream: Sinus Rhythm Let me say a few words here about rate vs rhythm control, because this may actually be the number one issue in all of electrophysiology. The stimulus for writing such a review piece I think comes from the PRAGUE 25 trial of lifestyle modification vs AF ablation. I have opined on that in my July 11 podcast. In sum, AF ablation led to less AF than risk factor (RF) modification alone, though 35% (or 1 in 3 patients) in the risk factor modification group had sinus rhythm (SR) without ablation. And RF modification led to more weight loss, better glycemic control, and better fitness as measured by VO 2 max. PRAGUE 25 also found no statistical differences in AF burden nor quality of life measures. The sits in the literature as a 'positive' ablation trial, but I actually think, healthwise, it is a 'positive' trial for RF modification. The Medscape article cites a 'hybrid' approach wherein all patients who pursue rhythm control also get risk factor modification, which I totally agree with, and I have to say, is underused, at least in my zip code. The absolute wrong thing to do is ablate the AF and not help the patient lose weight and improve cardiometabolic health. Because if you do this, you have merely reduced a surrogate marker — AF episodes. Health is not improved if obesity, hypertension, diabetes, and poor exercise tolerance remain. You succeed as a proceduralist but fail as a doctor in this scenario. The Medscape article goes on to celebrate the benefits of SR over AF. The next logical step is to laud rhythm control over rate control. And here I have a problem. And I somewhat disagree with friend and colleague Eric Prystowsky, MD. Eric is well known for his criticism of AFFIRM and how that trial set EP back years. But I had the pleasure of speaking in Calgary and met the late Dr. George Wyse, the principal investigator of AFFIRM. AFFIRM is one of those landmark trials that deserves your attention. Published in 2002, a total of 4060 patients with AF were randomized to rate or rhythm control. Mortality was the primary endpoint. Patients in AFFIRM were like those we see every day. 70 years old. Most with hypertension, a third with CAD. At 5 years, 23.8% in the rhythm control arm died vs 21.3% in the rate control arm. The HR was 1.15, or 15% worse for rhythm control. CIs were 0.99-1.34 so the P value for arm was just outside 0.05 but the upper bound or worse case was a 34% higher rate of death in the rhythm control arm. More patients in the rhythm-control group than in the rate-control group were hospitalized, and there were more adverse drug effects in the rhythm-control group as well. AFFIRM was largely interpreted as showing no differences in the two strategies. But, really, there was a strong trend for worse outcomes in the rhythm-control arm. One of the major changes in knowledge that came from AFFIRM is the importance of maintaining oral anticoagulation (AC). In AFFIRM, patients in the rhythm control arm who were maintaining SR could stop their oral AC. This led to a difference in AC use 85% vs 70% rate vs rhythm control. In fact, AFFIRM largely changed the view that patients with AF with either strategy should remain on oral AC. The Sherman et al substudy in JAMA Internal Medicine found that patients who remained on warfarin were 68% less likely to have stroke. A large proportion of ischemic strokes (113 of 157) occurred in patients in whom anticoagulation had been stopped (on the basis of re-established normal sinus rhythm) and who had a subtherapeutic international normalized ratio. Eric's point about AFFIRM is it led to too many patients with AF being told that there was no reason to try to get into SR, and if you don't try, and you leave patients in AF, it becomes impossible to restore SR after a year or so. The other problems (or criticisms) of AFFIRM were that patients had to be able to tolerate rate-control. So highly symptomatic patients were excluded. AFFIRM should never have been applied to these patients. Many of these symptomatic patients were younger, and it is a serious error to just leave a symptomatic younger person with AF forever in AF. Another criticism of AFFIRM was that it only included antiarrhythmic drugs (AAD), and amiodarone was the most common one used. AAD were all that was available at the time. We now know that AF ablation is far more effective at rhythm control than drugs. So there is a like a bridge to SR early on, and many patients can be put into SR with rhythm control. Proponents of aggressive rhythm control also cite the EAST-AF trial, a rhythm vs rate control trial, which strongly favored rhythm control. But EAST-AF suffered from serious performance bias issues wherein the rhythm control arm got oodles more interactions with the health system. Here is my take of the decision: AFFIRM still applies. If you have an older person with minimal to no symptoms from AF, rate control is not only fine but maybe preferred. But if there are a) symptoms, and b) clues that rhythm control is possible (e.g., the LA size is not ginormous, or the patient can cooperate, and maybe the AF is not more than 2 years persistent), I try rhythm control. But I tell patients that while there is benefit from SR (in terms of quality of life) rhythm control is hard. It costs a lot, not only in money, but investment in their time and effort. Patients have to know that RF modification is crucial, they will also have to spend a few days in the hospital (for cardioversions, maybe drug initiation or ablation). Remember, when you are getting cardioversions and AAD and ablations you are not at work or on a bike. You are being a patient. It's fine. It's an investment but patients need to know that rhythm control is unlike a gallbladder operation or an appendectomy. Rhythm control is a process that requires a friendship with a cardiologist. It's not one and done. There are also risks to rhythm control. Drug side effects and ablation complications do occur. My friends, be careful flying close to the sun with rhythm control. One of the biggest mistakes I see in general cardiology is leaping to cardioversion without a plan. CV of AF is fine, but you have to have a plan for what will happen in a week or month when the patient is back in AF. CV doesn't modify the problem of AF. It just resets the heart. In the end: EP is here to help. Get us involved. Especially when there are symptoms. And doubly especially, when there is heart failure. But don't dismiss AFFIRM. It is important trial that shows that rate control is not a terrible strategy in selected patients. GLP-1 RAs Protective Against Stroke, Neurodegeneration? A GLP-1 study purports to show benefit in cerebrovascular health. It actually shows how observational studies can mislead you. The title of the study is, 'Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity.' It was published in JAMA Network Open . The goal of the Taiwan group was to evaluate the association of semaglutide and tirzepatide with the incidence of dementia, Parkinson disease, ischemic stroke, intracerebral hemorrhage, and all-cause mortality compared with other antidiabetic drugs in adults with type 2 diabetes and obesity. It's an important question. The best way would be to randomize, but that would be hard and costly. So this was a retrospective cohort study using electronic health records from the TriNetX US network, 2017-2024. The two groups in this study were those on GLP-1, either semaglutide or tirzepatide, vs those on any other diabetic medicines, such as metformin, sulfonylureas, DPP4, SGLT2 inhibitors, and others. This was a large study. About 30,000 in each of the two groups. The groups are not randomized. A doctor chose which of the two groups of drugs to use. So, since it's not randomized the authors did propensity matching. Age 57. Half female. BMI on average 40, and 70 % with hypertension. Here were the main results: During a 7-year follow-up, GLP-1 RA users had a lower risk of dementia (HR, 0.63; 95% CI, 0.50-0.81) lower risk of stroke (HR, 0.81; 95% CI, 0.70-0.93) lower all-cause mortality (HR, 0.70; 95% CI, 0.63-0.78) and had no significant differences in the risk of Parkinson disease or intracerebral hemorrhage. The authors concluded: 'These findings suggest potential neuroprotective and cerebrovascular benefits of GLP-1 receptor agonists beyond glycemic control, warranting further trials to confirm these outcomes.' Maybe these drugs are beneficial for cerebrovascular health, especially in young people (age 57 and diabetes and BMI of 40) But this is a hopelessly confounded study where healthier patients got the more pricey and newer drug. How do I know that? There are two clues. First, is that the Kaplan-Meier curve diverges immediately and continues in parallel. That's what you expect when healthier patients get one treatment. Immediately better outcomes. If the GLP-1 was better than other drugs, you'd see gradually increasing benefit. Second reason: the mortality benefit is huge. A 30% reduction in death. In the SELECT trial of semaglutide vs placebo in patients with heart disease and obesity, semaglutide only reduced CV mortality by 15%. In the SUSTAIN-6 trial of semaglutide vs placebo, semaglutide had no sig reduction in death or CV death and required a composite endpoint to drive positive results. My overall take, therefore, is that GLP-1 drugs induce weight loss. They do modify disease in patients with obesity and diabetes and patients with obesity and atherosclerotic disease. But whether they reduce important cerebrovascular outcomes like dementia cannot be answered by these confounded observational studies. I am not sure it's worth doing these studies because the only value is to show readers the signs of bias in non-random, retrospective comparison studies.

Wall Street Journal
3 hours ago
- Wall Street Journal
‘Going Nuclear' and ‘Atomic Dreams': Fission's Big Comeback
Seventy years ago, at the dawn of the nuclear age, atomic energy was viewed as the next great hope of modern civilization. Lewis Strauss, then the chairman of the Atomic Energy Commission, infamously said it could be the key to making energy 'too cheap to meter' and a catalyst for an age of enduring peace. Today, a similar optimism animates the pursuit of nuclear energy. This time, however, the framing is that the peaceful atom is too important to ignore because of its potential to free us of fossil fuels. In 'Going Nuclear: How Atomic Energy Will Save the World,' Tim Gregory sees nuclear energy as the 'only hope' for 'mitigating' climate change because it eliminates 'emissions released as a by-product of burning fossil fuels.' Similarly, in 'Atomic Dreams: The New Nuclear Evangelists and the Fight for the Future of Energy,' Rebecca Tuhus-Dubrow believes 'nuclear advocacy and climate alarm . . . go hand in hand.' These books join dozens of other pro-nuke books published in the past few years.


Medscape
4 hours ago
- Medscape
EMA Launches Review of Tecovirimat Effectiveness for Mpox
The European Medicines Agency (EMA) has initiated a review of Tecovirimat SIGA, also called TPOXX, a medicine used to treat mpox. This follows emerging clinical trial data suggesting a lack of effectiveness. The mpox virus is an orthopoxvirus, a class that includes the smallpox virus. Tecovirimat SIGA was originally approved in the US to treat smallpox. The EMA and the Medicines and Healthcare products Regulatory Agency in the UK authorized its use in January 2022, at the start of an mpox outbreak in Europe, for the treatment of smallpox, mpox, cowpox, and vaccinia complications following smallpox vaccination, in adults and children weighing at least 13 kg. The drug is an oral medicine that interferes with a protein called VP37 found on the surface of orthopoxviruses, preventing them from reproducing normally and thus slowing the spread of infection. No other treatments are authorized for mpox or cowpox infections, which may in rare cases be fatal. European Cases Linked With Risky Sexual Behaviors Mpox is a zoonotic infection occurring mainly in West and Central Africa, with most cases in Europe before 2022 either imported from countries where mpox is endemic or from contacts with documented epidemiological links to imported cases. The outbreak in the EU and UK has been transmitted between humans mainly through sexual contact. It primarily affects gay, bisexual, or other men who have sex with men and who have multiple sexual partners, participate in group sex, or attend sex-on-premises venues. Transmission occurs primarily within interconnected sexual networks. Symptoms of mpox typically appear 1-3 weeks after infection and include fever, headache, chills, physical weakness, lymph node swelling, back pain, and muscle aches, along with a distinct, fast-spreading papular rash on the skin and mucosal sores in the mouth, nose, throat, or digestive tract that then turn into fluid-filled vesicles. Mild-to-moderate symptoms usually last 2-4 weeks and are followed by full recovery, though some people develop permanent scars. During outbreaks, the case fatality of mpox ranges from 0% to 11%. People who are immunocompromised, including those with HIV infection or AIDS, are at a higher risk for severe disease. Exceptional Circumstances Approval During Outbreak Approval for Tecovirimat SIGA was granted under 'exceptional circumstances' provisions, based only on pharmacodynamic and pharmacokinetic studies, because the disease is rare and sporadic, so human studies were not available. A condition of such authorization is that the company marketing Tecovirimat SIGA is required to provide an annual update on benefits and risks. The EMA's review is a postauthorization procedure that involves a scientific assessment by the agency on behalf of the EU aimed at resolving issues such as concerns over the safety or benefit-risk balance of a medicine or a class of medicines. In the case of Tecovirimat SIGA (tecovirimat), the review was initiated at the request of the European Commission. The review follows publication of preliminary results from two clinical trials. In the randomized, placebo-controlled PALM007 trial involving 597 children and adults with laboratory-confirmed clade I mpox in the Democratic Republic of the Congo (DRC), results reported in April in The New England Journal of Medicine showed that the drug did not reduce the duration of mpox lesions (median time to resolution, 7 vs 8 days). The overall mortality among enrollees, regardless of whether or not they received the drug, was 1.6% — much lower than that generally reported in the DRC, but this was attributed to hospitalization and high-quality supportive care within the trial. The other trial, STOMP, involved people from multiple countries with mild-to-moderate laboratory-confirmed or presumptive clade II mpox. Again, the active drug did not demonstrate efficacy in time to skin and mucosal lesion resolution compared with placebo. The EMA said that similar results had recently been obtained from another study, UNITY, which also did not indicate faster skin lesion resolution on tecovirimat compared with placebo. Further analyses from ongoing or recently completed studies are still awaited and will also inform the EMA's final assessment.