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Here are the studies from this week’s edition of the One-Minute Telegram. Subscribe now to access the most important findings broken down into one minute of reading.
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🧭 10-second takeaway: Fewer than 5% of patients whose medical record is flagged with a penicillin allergy label have a true penicillin allergy. This study demonstrated that a direct oral challenge in patients with a low-risk penicillin allergy was safe and noninferior to skin testing followed by an oral challenge in verifying an actual penicillin allergy. Direct oral penicillin testing could reduce the burden of proactive penicillin allergy delabeling and improve antibiotic stewardship.

Study breakdown

👥 Study population: 377 adults with a reported penicillin allergy in their medical record and a PEN-FAST score of < 3

Methods: multicenter open-label, randomized clinical trial
- PEN-FAST score (range 0–5) calculated based on:
• Penicillin allergy reported
• ≤ 5 years since reaction (2 points)
• Angioedema or anaphylaxis OR severe cutaneous adverse reactions (2 points)
• Treatment required (1 point)
- Randomized 1:1 to direct oral penicillin challenge (intervention) or standard skin testing followed by oral challenge if the skin test was negative (control)
- Primary outcome: immune-mediated reaction within one hour of oral challenge
- Secondary outcomes: safety, delabeling possible

Main results
- The oral penicillin challenge was positive in 0.5% of participants in both groups (RR 1.02; 90% CI, 0.10–10.34).
- Adverse events within 5 days were similar between groups.
- The penicillin allergy label was removed from 99.5% of participants records in the intervention group and from 97.9% in the control group.

Limitations include:
- The majority of patients had a PEN-FAST score of < 2, limiting generalizability to patients with higher scores.
- Patients with any history of drug-induced anaphylaxis were excluded, limiting generalizability regarding safety and noninferiority in that population.

Study funding: Austin Medical Research Foundation

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🧭 10-second takeaway
Antibiotics are often overprescribed for children with upper respiratory tract symptoms and suspected acute sinusitis. This study demonstrated that antibiotics were more effective than placebo in reducing symptoms of acute sinusitis, but mainly when nasopharyngeal pathogens (NPP) were present. The effectiveness of antibiotics in reducing symptoms was similar in patients with clear or colored nasal discharge. Point-of-care testing for bacterial colonization may help reduce unnecessary antibiotic use.

Study breakdown

👥 Study population: 515 children aged 2–11 (54% male, 52% White, 89% non-Hispanic) meeting established criteria for acute sinusitis

Methods: randomized clinical trial

- Subgroups stratifed by presence or absence of green or yellow nasal discharge
- NPP bacterial cultures obtained at beginning and end of study
- Randomized 1:1 to a combination of amoxicillin 90 mg/kg/day and clavulanate 6.4 mg/kg/day PO or placebo
- Primary outcome: daily symptom burden based on the Pediatric Rhinosinusitis Symptoms Scale (PRSS)

Main results

- Mean PRSS scores were significantly lower in the antibiotic group than in the placebo group.
- Median time to symptom resolution was lower in the antibiotic group (7 days) than in the placebo group (9 days).
- Subgroup analysis
• Mean PRSS score difference was greatest in the subgroup with culture-proven NPP.
• Mean PRSS score difference was similar across groups regardless of nasal discharge color.
- Higher incidence of diarrhea in antibiotic group than in placebo group: 11.4% vs. 4.7% (RR 2.40; 95% CI, 1.26–4.59)

Limitations include:
- Limited generalizability to children with mild or severe sinusitis
• Study participants had higher PRSS scores than those who declined to participate.
• Patients with severe sinusitis were excluded.

Study funding: National Institute of Allergy and Infectious Diseases

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🧭 10-second takeaway
Testosterone replacement therapy (TRT) is frequently used to treat symptoms of hypogonadism in men, but previous studies have provided conflicting information about its cardiovascular safety. In this large-scale study, TRT in men with preexisting or a high risk of cardiovascular disease (CVD) was noninferior to placebo for the incidence of major adverse cardiac events (MACE), but was associated with a higher incidence of atrial fibrillation, acute kidney injury, and pulmonary embolism. Because testosterone deficiency is not life-threatening, clinicians should continue to individualize the decision to begin TRT.

Study breakdown

👥 Study population: 5204 men aged 45–80 years with preexisting or a high risk of CVD, symptoms of hypogonadism, and two morning testosterone levels < 300 ng/dL

Methods: noninferiority, multicenter, randomized, double-blind, placebo-controlled trial
- Randomized 1:1 to daily transdermal 1.62% testosterone gel (TRT group) or placebo gel
- The testosterone dose in the TRT group was adjusted to maintain a testosterone level between 350 and 750 ng/dL.
- Primary endpoint: first MACE, i.e., death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke
- Mean duration of treatment: 22 ± 14 months; mean follow-up: 33 ± 12 months

Main results
- TRT was noninferior to placebo for incidence of MACE: 7.0% in the TRT group vs. 7.3% in the placebo group (HR, 0.96; 95% CI, 0.78–1.17)
- The incidence of several adverse effects was higher in the TRT group than the placebo group.
• Atrial fibrillation: 3.5% vs. 2.3%
• Acute kidney injury: 2.3% vs. 1.5%
• Pulmonary embolism: 0.9% vs. 0.5%

Limitations include: Adherence and retention rates were low.

Study funding: AbbVie, Acerus Pharmaceuticals, Endo Pharmaceuticals, Upsher-Smith Laboratories

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🧭 10-second takeaway:
Major depressive disorder (MDD) and anxiety disorders are common conditions with a potential to profoundly impact the well-being of affected individuals. USPSTF has reaffirmed its previous recommendation to screen all adults for MDD and added a new recommendation to screen adults under 64 years of age for anxiety disorder. There was insufficient evidence to support a recommendation to screen for risk of su***de. Medical providers should use their clinical judgment to determine screening intervals.

Recommendation breakdown

Recommendations
⊙ The USPSTF concluded with moderate certainty that there is a benefit to screen for MDD in all adults and for anxiety disorders in adults < 64 years.
⊙ There was insufficient evidence to recommend screening for:
- Anxiety disorders in adults ≥ 65 years
- Risk of su***de in adults

Applicable population: asymptomatic adults ≥ 19 years, including pregnant and postpartum individuals

Additional information
⊙ Commonly used screening tests for depression included the Patient Health Questionnaire (PHQ) and Geriatric Depression Scale (GDS).
⊙ Commonly used screening tools for anxiety included versions of the Generalized Anxiety Disorder (GAD) Scale.
⊙ Potential harms of screening
- Treatment of newly diagnosed anxiety disorders may result in addiction and/or misuse of benzodiazepines.
- Some interventions for elevated risk of su***de may increase the risk for self-harm.

Limitations include:
⊙ There is limited data for recommendations on screening intervals for anxiety disorders and MDD.
⊙ The recommendations do not apply to depressive disorders other than MDD.
⊙ Further research is needed on:
- Screening tools for anxiety disorders in specific populations
- Benefits of screening for risk of su***de

Study funding: The Agency for Healthcare Research and Quality (AHRQ)

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🧭 10-second takeaway:
Current guidelines recommend the use of low molecular weight heparin (LMWH) to prevent recurrent venous thromboembolism (VTE) in patients with cancer. This trial demonstrated that direct oral anticoagulants (DOACs) were noninferior to LMWH in the prevention of recurrent VTE in patients with cancer. DOACs are likely a safe and convenient alternative to LMWH for patients with cancer-associated VTE.
Study breakdown

👥 Study population: 671 adults with cancer (solid tumors, lymphoma, chronic lymphocytic leukemia, or multiple myeloma) and a recently diagnosed VTE with platelets ≥ 50,000/mcL, eGFR ≥ 15 mL/min/1.75 m2, and life expectancy ≥ 3 months

Methods: multicenter, randomized, nonblinded pragmatic effectiveness study
- Randomized 1:1 to a DOAC (n = 335) or LMWH (n = 336) for 6 months
- Specific agents were chosen based on individual patient factors and availability.
- Primary outcome: cumulative recurrence of nonfatal VTE at 6 months
- Other outcomes: bleeding, death, health-related quality of life, patients’ perceptions of anticoagulation therapy, serious and severe adverse events, adherence

Main results
- No significant difference in recurrent VTE rate in DOAC group (6.1%) vs. LMWH group (8.8%): difference less than the predefined 3% noninferiority margin
- Agents received
⊙ DOAC group: 58% apixaban, 37% rivaroxaban, 3% dabigatran, 2% edoxaban
⊙ LMWH group: 90% enoxaparin, 7% fondaparinux, 3% dalteparin
- No significant difference in major bleeding, death, or patient-reported outcomes
- Higher adherence in the DOAC group at 6 months (71% vs. 59%)

Limitations include:
- Participants and their treating physicians were nonblinded.
- Some participants received different anticoagulation before randomization.
- Potential bias toward DOAC efficacy due to lower adherence to LMWH

Study funding: Patient-Centered Outcomes Research Institute

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