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Evidence-based decision making in health often requires comparison of multiple options for a given condition. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) evidence-to-decision (EtD) framework provides a structured approach for moving from evidence to decisions but was originally designed for pairwise comparisons. Hence, there is a need to accommodate decision making based on multiple comparisons, especially with the increasing use of systematic reviews and network meta-analyses in guideline development. Furthermore, since the original EtD framework was developed, further relevant GRADE guidance has been developed. The aim of this work was to develop a new EtD framework to accommodate multiple comparisons and reflect current GRADE guidance. The new EtD framework was revised and developed through iterative discussion, feedback, and refinement by the GRADE EtD Project Group and the GRADE Working Group. Experiences and examples from guideline developers, methodological experts, and other stakeholders informed improvements in its structure and usability for multiple comparisons and were subsequently approved by the GRADE Working Group. This article describes the new EtD framework, which now includes 2 corresponding parts for reviews of pairwise and multiple comparisons. The authors describe application to a review with multiple comparisons for the different parts of the EtD framework: the question definition, which now includes the presentation of values of health outcomes and decision thresholds; the assessment section, where the new “net effect” criterion has been included; and the conclusion section, which includes an adaptation for multiple comparisons. The article provides examples and suggestions for presentation of findings. The framework does have limitations, in that its usability has not been tested across a broad spectrum of guideline development contexts.

Artificial Intelligence Scribes: Enhancing Workflow Efficiency at What Expense?

Confronting America’s Firearm Injury Epidemic: Using Your Voice to Protect Your Patients

2025 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline for the Primary Care Management of Chronic Kidney Disease

Description: Management of chronic kidney disease (CKD) has been rapidly evolving, now involving many interventions that can be managed in the primary care setting. In April 2025, leadership within the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline (CPG) for the primary care management of CKD. This synopsis reviews the 2025 recommendations related to diagnosis, assessment, and management of CKD. Methods: The VA/DoD Evidence-Based Practice Work Group assembled a team to update the 2019 VA/DoD CPG for the management of CKD. Guideline development conformed to the National Academy of Medicine’s tenets for trustworthy CPGs. The work group developed 12 key questions to guide a systematic evidence review and distilled 23 recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The work group also created algorithms and appendices to help guide clinical decision making. Funding for the development of the guideline was provided by the VA. Recommendations: This synopsis reviews updated recommendations for the diagnosis, assessment, and monitoring of CKD; general management strategies including team management and education; shared decision making and indications for referral to nephrology for consideration of kidney replacement therapy or conservative management; management of hypertension; pharmacotherapy to reduce the risk for major adverse cardiovascular events, progression of kidney disease, and mortality; and prevention of contrast-associated acute kidney injury. New and updated recommendations about pharmacotherapy, such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, nonsteroidal mineralocorticoid receptor antagonists, and statins, are highlighted in this synopsis.

A Synopsis of the 2025 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline for the Primary Care Management of Asthma

Description: The U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DOD) updated the 2019 joint clinical practice guideline (CPG) for the primary care management of asthma. This synopsis provides primary care providers with a summary of the updated 2025 recommendations regarding evaluation and management of veterans and military members with asthma. Methods: In 2024, the VA/DOD convened a guideline work group (WG), including clinical stakeholders, to update the joint VA/DOD guideline and conformed to the National Academy of Medicine's tenets for trustworthy CPGs. The WG drafted 12 key questions, reviewed systematically identified literature (20 July 2018 through 15 May 2024), evaluated the evidence, created algorithms, and advanced 21 evidence-based recommendations in accordance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Recommendations: The WG strongly recommended inhaled corticosteroids (ICS) and streamlined management of asthma by suggesting a combination of ICS and rapid-onset long-acting β-agonist as both reliever and controller agents and step-up therapy by increasing ICS and/or adding long-acting anticholinergic agents. The WG also supported the management of symptomatic gastroesophageal reflux disease and obesity for better control of asthma. The WG suggested against the use of indoor air filtration devices. Finally, the WG outlined decision points for referral to a subspecialist.

Timing of Pegfilgrastim Administration and Pegfilgrastim-Induced Bone Pain: A Prospective, Randomized, Phase 3 Trial: Annals of Internal Medicine: Vol 179, No 5

Background: Pegfilgrastim-induced bone pain (PIBP) is common and lacks effective treatment. Objective: To determine whether there is an association between the timing of pegfilgrastim administration and PIBP. Design: Three-arm randomized controlled trial. (ClinicalTrials.gov: NCT05841186) Setting: A tertiary A-level hospital. Patients: Patients with I to III stage breast cancer who were naive to chemotherapy. Intervention: Patients were randomly allocated in a 1:1:1 ratio to the 24-hour, 48-hour, or 72-hour group based on the timing of pegfilgrastim administration postchemotherapy. Measurements: The primary end point was the area under the curve (AUC) of the daily worst bone pain score (assessed using the “worst pain” question from the Brief Pain Inventory, a 0 to 10 numerical rating scale [NRS]) for 5 consecutive days in the first chemotherapy cycle. Secondary end points included the incidence of severe bone pain (>5 on the NRS), neutropenia, and febrile neutropenia (FN). Results: The intention-to-treat analyses included 159 patients, with 53 in each group. For the first cycle, in the 72-hour group, the mean AUC exhibited a statistically significant reduction from 12.74 in the 24-hour group and 14.20 in the 48-hour group to 6.05 (all P < 0.001). Furthermore, the incidence of severe bone pain also declined significantly from 58.5% in the 24-hour group and 66.0% in the 48-hour group to 22.6% in the 72-hour group (all P < 0.001). There was no substantial difference in the incidence of neutropenia among groups, and no patients developed FN. Limitation: Open label, single center, and relatively small sample size. Conclusion: Administration of pegfilgrastim 72 hours postchemotherapy reduced PIBP compared with 24- and 48-hour administration and did not seem to be associated with higher rates of neutropenia or FN. Primary Funding Source: National Natural Science Foundation of China.

Complications Associated With Transvenous Cardiac Implantable Electronic Devices: Recognition and Management: A Narrative Review: Annals of Internal Medicine: Vol 178, No 11

Cardiac implantable electronic devices (CIEDs) have increased the quality and duration of life for millions of patients. As their utilization continues to grow exponentially, clinicians need to diagnose and manage several device-associated complications that may arise during the CIED life cycle. This primer is tailored for the general internal medicine physician or hospitalist, who will inevitably take care of patients with CIEDs, to provide a contemporary update on the incidence and clinical manifestations of the 4 most common CIED complications, with the latest evidence to guide clinical management and expected outcomes. Specifically, this review focuses on: 1) generator/lead failure, which has decreased to less than 1% per year due to continuous advances in manufacturing and programming and is mostly managed conservatively with close monitoring; 2) CIED infections, which, while also rare at approximately 1% per year, carry a short-term mortality of 10% to 20%, thus requiring immediate diagnosis and often urgent treatment with lead extraction because antibiotic treatment is rarely effective; and 3) lead-related venous obstruction, which has highly variable incidence (5% to 30%) and manifestations, ranging from arm swelling to superior vena cava syndrome. Management options range from anticoagulation to balloon venoplasty, often with unsatisfying results. This review will also focus on 4) lead-related tricuspid regurgitation, which affects 20% to 30% of CIEDs and has become an area of intense interest with the development of percutaneous tricuspid treatments—where evidence is urgently needed to inform the need for lead extraction versus jailing during tricuspid interventions. The progressive adoption of leadless devices may significantly reduce many of these complications. Nonetheless, optimal management requires input from a multidisciplinary team of electrophysiologists and imaging, heart failure, and structural interventional specialists—who should be able to recognize and treat each complication promptly based on a rapidly evolving evidence base.

Palliative Care Educational App for Family Caregivers of Homebound Patients With Incurable Cancer: A Single-Center Randomized Trial: Annals of Internal Medicine: Vol 178, No 12

Background: Home-based palliative care relies on empowered family caregivers to overcome the limited availability of palliative care professional resources in managing incurable cancer. Objective: To explore whether adding a palliative care educational app to clinical palliative care could enhance health-related quality of life (HRQoL) in homebound patients with incurable cancer. Design: Single-center, open-label, individual randomized trial. (Chinese Clinical Trial Registry: ChiCTR2300077346) Setting: Single site in Shanghai, China. Participants: Patients with incurable cancer (aged ≥18 years; Karnofsky Performance Status ≤70) receiving palliative care along with consistent family caregivers (aged ≥18 years) enrolled between 28 July and 3 November 2023. Intervention: Patient–caregiver pairs were randomly assigned in a 1:1 ratio to either the intervention group (the app plus palliative care as usual [app]) or the control group (palliative care as usual). The app provided multimedia education on symptom and adverse effect management and nursing information for family caregivers. Measurements: The primary outcome was the mean between-group difference at month 2 in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) score, with the summary score ranging from 0 to 100 and higher scores indicating better outcomes. The primary analysis used the intention-to-treat approach. Results: Of 154 randomly assigned pairs, 147 completed baseline assessments (intervention: n = 74; control: n = 73). The mean age of patients was 59.9 years, and 42.9% were female. At month 2, EORTC QLQ-C30 summary scores were 51.9 (95% CI, 45.4 to 58.5) in the intervention group and 35.7 (CI, 28.6 to 42.9) in the control group, with a mean difference of 16.2 (CI, 9.3 to 23.1). Limitations: Single-center design in China, Chinese-only WeChat app platform, unknown education levels of caregivers and patients, open-label design, and short 2-month follow-up with self-reported outcomes. Conclusion: The palliative care educational app through WeChat improved HRQoL among patients with incurable cancer at 2 months. This finding has implications for future study and development. Primary Funding Source: Shanghai Xingchuan Health Technology Co., Ltd.

Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, with a prevalence of 4% to 10%. It is a chronic condition characterized by abdominal pain in conjunction with altered bowel habits, abdominal distention, or bloating. IBS can present with 3 different defecation patterns: IBS with constipation, IBS with diarrhea, or mixed IBS. Recent advances in IBS include a positive diagnosis based on symptom-based criteria and a treatment plan based on IBS subtype and bothersome symptoms. In addition to diet and lifestyle modifications, this article discusses the role of new pharmacologic and nonpharmacologic treatment options for the management of IBS.

Heat-Related Illnesses

Climate change is anticipated to continue to adversely affect public health, with heat stress the predominant threat. Accordingly, heat-related illness is predicted to increase as extremely hot days become more frequent. Heat stroke, the most serious heat-related illness, is a medical emergency that may be fatal if it is not promptly recognized, addressed with early and rapid cooling, and accompanied by multidisciplinary supportive care as clinically indicated. Heat stroke is a preventable illness that occurs in 2 distinct forms—classic and exertional—that have distinct demographic profiles and clinical courses but similar management paradigms.

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