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older man lifting weights


The TRAVERSE Study, a randomized controlled trial comparing TRT to placebo in hypogonadal men, found that TRT did not increase the risk of cardiovascular events over 33 months, albeit average treatment length was only 22 months and testosterone levels in the TRT group were below typical targets (median of 371 ng/dl). The large size of the trial (N=5246) made it a desirable setting to evaluate other TRT outcomes, spurring a number of recently published substudies. Findings from those analyses are summarized below.
  • Erectile function and libido - TRT did not improve ED, while daily libido events (e.g., sexual activity, sexual thoughts, flirting, sexual daydreams, spontaneous erections), which had a baseline average of 1.8 per day in both groups, improved to 2.8 in the TRT group and 2.3 in the placebo group, yielding a difference of 0.47 that was statistically significant (p=0.011)
  • Bone health - small studies have found that TRT increases BMD, so it was surprising that TRT-treated subjects had a significantly higher fracture risk over a median of 3.19 years (3.5% vs 2.46%, HR 1.43, 95%CI [1.04 to 1.97])
  • Diabetes and insulin resistance - TRT did not reduce progression to diabetes among prediabetics, nor did it improve glucose control in diabetics
  • Cognition, sleep, mood, energy - TRT had a modest but significant effect on mood and energy but no effect on cognition or sleep
  • Prostate events - TRT did not increase the risk of prostate events (e.g., prostate cancer, acute urinary retention, prostate biopsy)

TRT proponents often tout it as a fountain of youth, and defining its true effects has been difficult, as past studies have been mostly small and heterogeneous. TRAVERSE helps close the knowledge gap and dispel some myths, but its short treatment duration and modest testosterone levels in the TRT group are significant weaknesses.

Combination inhaler with albuterol and budesonide available
asthma inhaler
Inhaled corticosteroids (ICS), short-acting beta agonists (SABA), and long-acting beta agonists (LABA) are the most commonly prescribed asthma treatments. Recent studies have found that as-needed ICS/LABA therapy is equal or superior to a daily ICS and as-needed SABA, contradicting traditional views that an ICS must be used daily to be effective. Recent GINA guidelines also recommend as-needed ICS/LABA therapy for most asthmatics. Keeping with the trend, Airsupra, the first inhaler to combine a SABA with an ICS, has been approved. It contains albuterol and budesonide and comes in a canister with 120 inhalations. Dosing is two puffs as needed with a max of 12 in 24 hours. It was superior to albuterol as a rescue inhaler in a double-blind study (N=3132) where participants were receiving maintenance ICS therapy.

infant lying in hospital bed with oxygen


Two prior studies found that nirsevimab, a monoclonal antibody against RSV virus, reduced symptomatic RSV infections by 6.9% in preterm infants (29 to <35 weeks gestation) and 3.8% in infants born ≥35 weeks. RSV hospitalizations, a secondary outcome, were reduced by 3.3% (p<0.001) and 1% (p=0.07), respectively. A third study using RSV hospitalization as the primary outcome was recently published. The HARMONIE trial randomized 8058 healthy infants born at ≥ 29 weeks gestational age (85% were born at ≥37 weeks) to nirsevimab or usual care before or during RSV season. At the end of the trial, RSV hospitalization occurred in 0.3% of nirsevimab-treated patients and 1.5% of the usual care group (p<0.001). Two infants in the nirsevimab group were admitted to the ICU compared to five in the usual care group. One patient in the usual care group was intubated, and no deaths occurred.

A major weakness of this study is its open-label design, as RSV hospitalization criteria were not standardized, and knowing the patient's nirsevimab status potentially swayed the admitting physician's decision. The authors were aware of this critique and tried to argue it away in a discussion that raised more questions than answers. Hard outcomes like ICU admission (7 patients) and mechanical ventilation (1 patient) were rare, as this was primarily a study in healthy term infants.

Collectively, these three studies show that nirsevimab reduces the severity of RSV infection, with infants born before 35 weeks receiving the greatest benefit. Its effect in healthy term infants is small and of questionable value. The CDC recommends all infants receive the shot, but these studies support prioritizing preterm infants, as 99% of term infants are fine without it. There was a shortage of nirsevimab during the height of last fall's RSV season, which means many preterm infants went without, thus showing the potential hazard of blanket recommendations that are common with the CDC.
Studies evaluate antithrombotics for atrial fibrillation precursors
heart with atrial fibrillation tracing
Traditionally, atrial fibrillation (AF) has been diagnosed with ECGs, telemetry, or holter monitors that provide days of tracings. In the past 20 years, new implantable devices (e.g., loop recorders, implantable defibrillators, pacemakers) have been introduced that give continuous readings over months to years. Longer tracings are able to detect asymptomatic episodes of atrial tachyarrhythmias that have undetermined clinical significance. Two events that have been loosely defined are atrial high-rate episodes (AHRE) and subclinical AF. While criteria aren't standardized across professional organizations, the following definitions are often seen:
  • AHRE - atrial tachyarrhythmia episodes with a rate > 170 beats/min detected by cardiac implantable electronic devices
  • Subclinical AF - an asymptomatic AHRE lasting greater than 6 minutes and less than 24 hours

Observational studies have found these events, which often precede the development of clinical AF, are associated with a higher-than-normal but less-than-AF stroke risk, spurring two recent studies that evaluated the effects of antithrombotics in affected patients. The first study (N=2536) compared edoxaban to placebo in patients with AHREs. It was stopped early due to futility, as CV events were not significantly lower with edoxaban, and major bleeding was worse. The other study (N=4012) randomized patients with subclinical AF to apixaban or aspirin. After 3.5 years of follow-up, apixaban reduced stroke risk (0.78%/patient-year vs 1.21%/patient-year) but increased major bleeding (1.53%/patient-year vs 1.12%/patient-year).

These studies do not support anticoagulation in AHRE or subclinical AF, while recent AHA guidelines state that it is "reasonable" in certain high-risk patients. Over the course of both trials, a significant number of subjects developed clinical AF (18% and 24%, respectively), underpinning the importance of continued close monitoring.

doctor measureing obese abdomen


Wegovy and Zepbound are all the rage as Americans struggle to contain their waistlines. At their highest doses, weight loss over a year averages 16% with Wegovy and 21% with Zepbound, which rivals the effects of sleeve gastrectomy. Two studies have now looked at what happens when people stop these medications. In the first one, 902 overweight adults (average BMI 38) were treated with Wegovy for 20 weeks and lost 10.6% of their body weight. They were then randomized to continue Wegovy or switch to placebo for an additional 48 weeks. At the end of the randomization phase, Wegovy-continuers lost an additional 7.9%, while the placebo group gained back 6.9%. In a similar study, 670 patients (average BMI 38) received Zepbound for 36 weeks, achieving an average weight loss of 20.9%. They were then randomized to continue Zepbound or switch to placebo for 52 weeks. At the end of the study, Zepbound-continuers lost an additional 5.5%, while the placebo group gained back 14%.

The results of these studies aren't surprising, given that once the medications wear off, appetite is no longer suppressed, and patients who struggled with overeating before return to their previous habits. Many patients don't want to take these medications for life, which brings them back to where all weight-loss journeys seem to begin and end - diet and exercise. As for those who complain about the drug prices, calorie counting and jogging around the block are free.
Percutaneous coronary intervention (PCI) improves stable angina in repeat study
doctors performing pci
If at first you don't succeed, change your study design and try again. That's what researchers did in two studies evaluating the effects of PCI on stable angina. Both studies randomized patients with primarily single-vessel disease to PCI or a sham procedure, but the use of angina medications was changed after the original trial found no benefit. In the first study (ORBITA 2018), patients (N=230) received optimal angina medication therapy during the post-procedure 6-week follow-up period. The study found no significant effect of PCI on the primary outcome of difference in exercise time. In the second trial (ORBITA-2 2023), patients (N=301) discontinued angina medications before the procedure and used them as needed during the 12-week post-procedure follow-up. PCI was found to be superior to the sham procedure for the primary outcome of angina symptom score (angina episodes, need for angina meds, and clinical events).

These studies essentially showed that optimal medical therapy is as effective as PCI in patients with stable angina. In both studies, 60% of PCI-treated patients reported angina symptoms during the follow-up period even though stress echocardiography showed near-normalization of ischemia. This suggests other factors may affect a patient's perception of angina. A longer study evaluating hard outcomes like mortality and MI is needed but would require larger sample sizes and more funding. Interestingly, the negative trial (ORBITA) was published in the Lancet, while the positive one (ORBITA-2) made it into the more prestigious New England Journal of Medicine. This suggests publication bias, which is a tendency for positive studies to receive more attention.


"Wellbutrin DM" hits the market

bottle of tablets
A new antidepressant called Auvelity combines bupropion, a widely prescribed dopamine-norepinephrine reuptake inhibitor, with dextromethorphan, a cough suppressant that inhibits NMDA receptors. One caveat of the combination is that bupropion inhibits dextromethorphan's metabolism, increasing its exposure. Auvelity comes in one strength (dextromethorphan 45 mg/bupropion 105 mg), and maintenance dosing is one tablet twice daily. A very small 6-week study (N=87) found that it was superior to bupropion monotherapy for treating depression in adults. For those who are interested, GoodRx shows Auvelity costs more than $1000 for 60 tablets, while a one-month bupropion prescription and a bottle of dextromethorphan will set you back about $30.

Janus kinase inhibitor slows progression of type one diabetes

diabetic injecting insulin
A new strategy for treating type one diabetes is early immunosuppression to prevent beta-cell destruction. Building on that approach, a recent study evaluated the effects of baricitinib (Olumiant), a janus kinase inhibitor, on beta-cell function in newly diagnosed type one diabetics. Ninety-one patients were randomized to baricitinib (4mg/day) or placebo, and after 48 weeks, baricitinib-treated patients had significantly higher meal-stimulated C-peptide levels. Baricitinib is currently approved to treat rheumatoid arthritis, alopecia areata, and COVID-19.

Pneumococcal vaccine recommendations - there's an app for that

doctor using smartphone
For years, there were two pneumococcal vaccines, now there are four. Figuring out which vaccine to give, how many, and what to do with the previously vaccinated can be perplexing. To help with the confusion, the CDC has created an online and mobile app that tells which vaccine to administer based on the patient's age, medical conditions, and prior vaccination history.

New topical ED treatment Eroxon® available over the counter

Eroxon box
Eroxon, an FDA-approved topical gel used to treat ED, is now widely available over the counter. A small amount is applied to the head of the penis, where it purportedly "stimulates nerve endings" as it evaporates, causing an erection within 10 minutes. It contains no active ingredient and is considered a medical device. Eight single-dose tubes cost $100 on Amazon, where, so far, the reviews are lousy.



  • Meniscal surgery - It's one of the most common orthopedic procedures performed, but does it do anything?
  • CPAP for sleep apnea - Sleep doctors are on every corner it seems, but what are the benefits of diagnosing and treating sleep apnea?
  • Knee injections - these treatments are popular among orthopedists and primary care doctors, but are they effective?
  • Pneumonia vaccines in adults - vaccine manufacturers, the CDC, and Medicare want everyone to get a pneumonia vaccine, so they must be highly effective, right?

Primary care providers, meet your newest competitors
computer with telemedicine
Two new telehealth businesses aim to siphon popular services from office-based primary care practices. LetsGetChecked, which bills itself as a "healthcare solutions" company, just received FDA approval for an at-home gonorrhea and chlamydia test that uses a urine sample collected by the patient and mailed to a lab. The test is $99, and for $50 more, patients can add trichomoniasis, along with HIV and syphilis performed on blood collected from a finger prick. After patients mail their specimens in, results are delivered in 2 - 5 days, and appropriate infections can be treated over telehealth for $39. At-home hepatitis B and C, herpes, vaginitis (using a vaginal swab), male and female hormones, and thyroid testing are also available.

The other new competitor is drug manufacturer Eli Lilly, which is now offering LillyDirect, a service where they connect consumers with telehealth doctors who can prescribe Eli Lilly medications for diabetes, migraines, and weight loss, including the popular Zepbound. Eli Lilly then ships the drug directly to the patient. LillyDirect also accepts prescriptions from other providers, essentially serving as a mail-order pharmacy for Eli Lilly products.

Primary care providers know that STD screening requests are common - and often obsessive - so there is little doubt LetsGetChecked will be a popular service. Eli Lilly wading into direct-to-consumer care will be interesting to watch, particularly in the obesity drug category.

Study finds very-low sodium diet lowers blood pressure
salt shaker
A study (N=213) in the JAMA evaluated the effects of a very low-sodium diet (500 mg/day) on blood pressure in adults 50 to 75 years old. Subjects crossed over in 1-week intervals between a low-sodium diet (500 mg/day) and a high-sodium diet (> 5 grams/day), with 24-hour ambulatory blood pressure performed at the end of each week. Compared to the high-sodium week, average systolic and diastolic blood pressures were 8 and 3 mmHg lower, respectively, during the low-sodium week. Reductions from baseline during the low-sodium week were 5 and 2 mmHg, respectively.

In this small study, extreme sodium restriction had a modest effect on blood pressure. The average American consumes 3600 - 4800 mg/day, making this degree of reduction unrealistic for most. Professional organizations recommend an intake of less than 2300 mg/day, but this is not supported by several large studies that found consuming less than 3000 mg/day is associated with worse outcomes. Patients should also be aware that salt substitutes (e.g., NoSalt) contain 16.4 mEq of potassium per 1/4 tsp and can increase the risk of hyperkalemia when consumed with common medications (e.g., ACE, ARB, mineralocorticoid antagonists).


A 45-year-old female comes to see you for her annual physical. She reports having gastric bypass surgery three years ago and says she followed up with her surgeon once and never went back. She asks you to order her routine lab work.

Given her history of gastric bypass, what lab work is recommended? Are any other studies indicated? Find out at the link below.