Annals of Internal Medicine (original) (raw)
June 2026: 179(6):874-884
Human health and natural systems are intrinsically linked—stable natural systems enable healthy human life. Health systems aim to promote, restore, and maintain health. Health systems may promote human health while having detrimental effects on natural systems, contributing to the transgression of planetary boundaries, such as biosphere integrity, climate change, and the introduction of new entities like microplastics. To date, the health guideline field lacks methods to assess the impacts of health interventions on planetary boundaries. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group established the Planetary Health Project Group in 2023 to develop formal GRADE guidance for integrating planetary health into guideline recommendations to address this gap.
Guided by the concepts of planetary health and planetary boundaries and following established methods for GRADE guidance development, the project group conducted iterative case study analyses, expert workshops, and a 2-round global Delphi consensus process. Four case studies were selected for application of this guidance before recommendations were finalized. The GRADE Working Group approved the official guidance.
The Planetary Health Project Group presents 7 domains of guidance for incorporating planetary health aspects into the guideline development process, including highly desirable items and optional items. Highly desirable items include formally addressing planetary health in public health and health system guidelines and explicitly justifying its exclusion where it is not addressed. Judgments within the evidence-to-decision (EtD) framework should systematically integrate included evidence across the prioritized planetary boundaries and equity. This guidance aims to support guideline developers and policymakers in making evidence-based, trustworthy recommendations to protect individual and planetary health, while maintaining thoroughness and feasibility for guideline developers within the GRADE approach.
June 2026: 179(6):868-873
In July 1955, a devastating polio epidemic struck Massachusetts only 3 months after the licensing of the Salk vaccine. One of the last major polio epidemics in the United States, it overwhelmed the local health care system. At Massachusetts General Hospital, 2 assistant residents—the equivalent of today's postgraduate year 2 trainees—were assigned to oversee a hastily organized polio ward and a rising second-year medical student was charged with setting up and running an adjoining laboratory. There, they and other residents conducted original patient-oriented research while providing round-the-clock care for patients, most in iron lungs, under crisis conditions. Their work was facilitated by a strong preexisting culture of bedside research at the hospital. Extremely long work hours ensured constant, close patient observation. A lack of role boundaries between the physician as researcher and as clinician and an absence of formal requirements for patient consent to research in that era also facilitated the studies, which were of similar methodological sophistication and ethical consideration to contemporaneous studies of other diseases. There is evidence that this experience influenced their subsequent careers. The autonomy granted these trainees contrasts sharply with the restricted roles permitted to medical students and residents during the initial surge of the recent COVID-19 pandemic.
June 2026: 179(6):857-867
Iron deficiency anemia (IDA) is the most common cause of anemia worldwide and a major cause of disability, manifesting with symptoms including fatigue, weakness, exercise intolerance, worsening heart failure, impaired concentration, irritability, and depression. Women of reproductive age are disproportionately affected due to menstrual blood loss and gynecologic disorders. Iron deficiency anemia is diagnosed in patients who have both iron deficiency (ID), noted by low ferritin level and/or transferrin saturation, and anemia. Notably, iron deficiency (ID) can also occur in the absence of anemia, and overreliance on hemoglobin thresholds may risk missing the diagnosis in menstruating women due to flawed sex-specific reference ranges. Work-up for ID and IDA should focus on identifying the underlying cause of anemia, and may include a gynecologic work-up, bidirectional endoscopy, testing for Helicobacter pylori infection and celiac disease, as well as administering a trial of iron. Iron deficiency can be treated with either oral or intravenous iron. Although several guidelines address the diagnosis or management of ID and IDA, they differ in their recommendations based on the population studied, the clinical context, and the quality of the underlying evidence. Here, 2 hematologists and coauthors of the 2025 Iron Consortium Guideline published in Lancet Haematology discuss areas of guideline uncertainty relating to the diagnosis, evaluation, and treatment of patients with IDA and for Ms. B, a young woman diagnosed with ID.
June 2026: 179(6):842-856
Description:
The purpose of this updated guidance statement is to guide internal medicine physicians and other clinicians on screening for breast cancer in asymptomatic, average-risk adult females.
Methods:
The American College of Physicians updated its guidance statement on screening for breast cancer using high-quality clinical guidelines from national guideline developers around the world.
Guidance Statement 1:
In asymptomatic, average-risk females aged 40 to 49 years, clinicians should discuss the female's risk of breast cancer, values and preferences, and uncertainty around benefits and harms of screening for breast cancer. Following shared decision making, if a female in this population prefers to get screened for breast cancer, clinicians should then initiate screening mammography every 2 years (biennial).
Guidance Statement 2:
In asymptomatic, average-risk females aged 50 to 74 years, clinicians should use biennial mammography for screening for breast cancer.
Guidance Statement 3:
In asymptomatic, average-risk females aged 75 years or older or asymptomatic, average-risk females with a limited life expectancy, clinicians should discuss discontinuation of breast cancer screening based on shared decision making that includes the female's risk of breast cancer, values and preferences, and uncertainty around benefits and harms of screening for breast cancer.
Guidance Statement 4:
In asymptomatic, average-risk adult females with breast density of Breast Imaging Reporting and Data System (BI-RADS) category C or D, clinicians should consider using supplemental digital breast tomosynthesis based on benefits, harms, additional radiation exposure, availability, values and preferences, and cost.
Guidance Statement 5:
In asymptomatic, average-risk adult females with breast density of BI-RADS category C or D, clinicians should not use supplemental magnetic resonance imaging or ultrasound.
June 2026: 179(6):839-841
The United States pays some of the highest prices for prescription drugs in the world, with drug prices and overall spending increasing year-over-year. Ballooning prescription drug costs can result in low rates of medication adherence, negatively affecting public health and straining national health care systems and resources. The 340B Drug Pricing Program (340B Program), which allows health care safety-net settings to purchase prescription drugs at deep discounts, has long sought to function as a bulwark against increasing drug prices for institutions serving those most vulnerable in society. Savings from the program have facilitated expanded access to health care services for low-income and uninsured patients. However, shortcomings in the program's design, implementation, and oversight obscure to what degree low-income and uninsured patients are realizing program benefits and create incentives for institutions to undertake profit-seeking behaviors at the expense of patients. To strengthen the 340B Program and ensure it is best serving its intended audience, reforms are needed within the program to promote transparency in how drug savings are reinvested into patient care and mandate demonstrated benefit to low-income and uninsured populations. Access to contract pharmacies—that is, the specialty or community-based pharmacies that 340B Program “covered entities” have an agreement with to distribute medications to patients—should be preserved, with appropriate guardrails to prevent unauthorized diversion. Federal regulators should be empowered with the resources and clear statutory authority necessary to engage in meaningful oversight of all program participants.
Annals of Internal Medicine. July 2026: 178(7):948-956
Background:
Confirmatory testing to verify the diagnosis of primary aldosteronism (PA) in patients who have an abnormal screening result is of uncertain benefit.
Objective:
To perform a blinded assessment of the seated saline suppression test (SSST).
Design:
Diagnostic test accuracy study. (ClinicalTrials.gov: NCT04422756)
Setting:
The regional Endocrine Hypertension Clinic in Calgary, Alberta, Canada.
Participants:
156 adults with a positive screening result for PA.
Intervention:
The SSST was done by administering 2 L of 0.9% sodium chloride intravenously over 4 hours with the patient seated.
Measurements:
Treatment response was considered the reference standard for determining disease status and was based on blood pressure lowering, reduction of antihypertensive drug dose, and normalization of biochemistry. Measures of diagnostic test accuracy, including sensitivity, specificity, positive predictive value, and negative predictive value, were estimated.
Results:
Post-SSST aldosterone concentrations measured using immunoassay overlapped between treatment responders (median, 329 pmol/L [IQR, 227 to 525 pmol/L]) and nonresponders (median, 255 pmol/L [IQR, 162 to 346 pmol/L]). The SSST could not discriminate between response statuses (area under the curve, 62.1% [95% CI, 45.1% to 79.1%]). The positive and negative likelihood ratios were equivocal for aldosterone cutoffs ranging from 140 to 300 pmol/L. These findings remained consistent after differences in treatment, occurrence of hypokalemia, and laboratory assay used were accounted for.
Limitation:
The study population had many patients with high-risk features of PA and few nonresponders.
Conclusion:
The SSST is associated with a high false-negative rate, and reliance on it may lead to missed opportunities for intervention.
Primary Funding Source:
The Canadian Institutes of Health Research, Hypertension Canada, and the Heart and Stroke Foundation of Canada.
Managing a patient with suspected hyperaldosteronism includes a blood test to measure the aldosterone-renin ratio, confirmatory testing in those who test positive (most often with a seated saline suppression test [SSST]), adrenal vein sampling in those confirmed to have the diagnosis, and surgery for lateralizing disease or a mineralocorticoid receptor antagonist for nonlateralizing disease. This study examines whether the SSST is a necessary part of this management.
Annals of Internal Medicine. June 2026: 179(6):765-772
Background:
Ambient artificial intelligence (AI) scribes can reduce the burden of administrative documentation. Prior evaluations have been vendor specific and not focused on measures of documentation quality.
Objective:
To compare the quality of AI-generated clinical notes with that of human-produced notes.
Design:
Cross-sectional evaluation of notes generated from standardized primary care clinical cases.
Setting:
Veterans Health Administration (VHA).
Participants:
11 AI scribe tools, 18 human note takers, and 30 human raters.
Intervention:
Five standardized primary care cases were audio recorded using standardized patients (for example, new patient, back pain, chest pain, pharmacy, and nurse care manager). Vendors and human clinicians generated encounter notes from the audio files.
Measurements:
Blinded raters assessed all notes using the modified Physician Documentation Quality Instrument (PDQI-9), which measures 10 domains of note quality on a 5-point Likert scale (maximum score 50).
Results:
Across all 5 clinical cases, human-generated notes received higher overall modified PDQI-9 scores than AI-generated notes. The largest difference was seen in the acute low back pain case (human: 43.8 [95% CI, 37.4 to 50.3] vs. AI: 20.3 [CI, 15.4 to 25.2]; difference −23.5 [CI, −29.2 to −17.9]). Pooled domain analysis showed lower AI scores across all 10 domains, with the largest deficits in domains related to being thorough (−1.23 [CI, −1.82 to −0.65]), organized (−1.06 [CI, −1.65 to −0.47]), and useful (−1.03 [CI, −1.61 to −0.44]).
Limitation:
Cases were simulated; human-generated notes were not generated under real-world constraints.
Conclusion:
Notes generated by AI had lower-quality scores than human-generated notes across 5 standardized care cases. Although ambient AI scribes hold promise for reducing clinician burden, independent, vendor-neutral evaluations of note quality are essential before large-scale clinical deployment.
Primary Funding Source:
VHA.
Visual Abstract.
Annals of Internal Medicine. June 2026: 179(6):773-784
Background:
Many treatments are recommended for chronic low back pain (cLBP), but comparative effectiveness and adaptive interventions have not been adequately studied.
Objective:
To compare the effectiveness of physical therapy (PT) and cognitive behavioral therapy (CBT) as first-stage treatment and switching treatments versus mindfulness as second-stage treatment.
Design:
Multisite sequential, multiple-assignment, randomized trial with 52-week follow-up. (ClinicalTrials.gov: NCT03859713)
Setting:
Three health care systems.
Participants:
Adults with cLBP.
Intervention:
Eight weeks of PT or CBT in stage I. Nonresponders were randomly assigned again to 8 weeks of stage II treatment.
Measurements:
Co-primary outcomes were function measured with the Oswestry Disability Index (ODI; range, 0 to 100) and pain intensity (range, 0 to 10) at 10 (stage I), 26, and 52 (stage II) weeks.
Results:
The sample comprised 749 participants. After 10 weeks, there was greater improvement in function in the PT group (adjusted mean ODI difference, 2.8 [96% CI, 0.38 to 5.1]) and no difference in pain intensity (adjusted mean difference, 0.32 [99% CI, −0.07 to 0.71]). The mean difference in ODI was below the minimum important difference of 6. After 52 weeks, there were no differences in stage II treatments for nonresponders for either function (adjusted mean ODI difference, 0.43 [96% CI, −0.29 to 2.4]) or pain intensity (adjusted mean difference, −0.05 [96% CI, −0.58 to 0.48]).
Limitations:
Treatment initiation was lower than expected, particularly for CBT and for nonresponders. Participants were not blinded. Sample size was reduced due to the COVID-19 pandemic.
Conclusion:
Patients with cLBP may benefit from PT as first-line treatment. Among nonresponders, there were no differences in second-stage treatment with mindfulness or switching.
Primary Funding Source:
Patient-Centered Outcomes Research Institute (PCORI).