Annals of Internal Medicine最新文献

Background: The Centers for Medicare & Medicaid Services (CMS) Severe Sepsis and Septic Shock Management Bundle (SEP-1) is now included in the Hospital Value-Based Purchasing (VBP) Program.

Purpose: To assess the evidence supporting SEP-1 compliance or SEP-1 implementation in improving sepsis mortality.

Data sources: PubMed, Web of Science, EMBASE, CINAHL Complete, and Cochrane Library from inception to 26 November 2024.

Study selection: Studies of adults with sepsis that included 3- or 6-hour sepsis bundles defined by SEP-1 specifications.

Data extraction: Article screening, full-text review, data extraction, and risk-of-bias assessment were independently performed by 2 authors. Level of evidence was determined using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria and National Quality Forum criteria.

Data synthesis: A total of 4403 unique references were screened, and 17 studies were included. Twelve studies assessed the relationship between SEP-1 compliance and mortality; 5 showed statistically significant benefit, whereas 7 did not. Among studies showing benefit, 1 did not adjust for confounders, 1 found benefit only among patients with severe sepsis, 1 included only patients with septic shock, and 1 included only Medicare beneficiaries. Five studies assessed the relationship between SEP-1 implementation and sepsis mortality; only 1 showed significant benefit, but it did not adjust for mortality trends before SEP-1 implementation. All 17 studies were observational, and none had low risk of bias.

Limitations: The conclusions are limited by the underlying quality of the available studies, as all were observational. Because there was considerable methodologic heterogeneity among the included studies, a meta-analysis was not performed as the results could have been misleading.

Conclusion: This review found no moderate- or high-level evidence to support that compliance with or implementation of SEP-1 was associated with sepsis mortality. CMS should reconsider the addition of SEP-1 to the Hospital VBP Program.

Primary funding source: None. (PROSPERO: CRD42023482787).

Background: In several settings, therapeutic-dose non-vitamin K oral anticoagulants (NOACs) are superior to aspirin for the prevention of arterial and venous thromboembolism.

Purpose: To estimate differences in bleeding risks between NOACs and single antiplatelet therapy.

Data sources: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to June 2024 without language restrictions.

Study selection: Randomized controlled trials (RCTs) comparing therapeutic-dose NOACs versus single antiplatelet therapy, with a minimum treatment duration of 3 months.

Data extraction: Data extraction was done independently and in duplicate.

Data synthesis: Nine RCTs with 26 224 participants were included. All studies used aspirin as antiplatelet therapy. Compared with aspirin, apixaban had similar rates of major bleeding (risk difference [RD], 0.0 percentage point [95% CI, -1.3 to 2.6 percentage points]; 5 trials) and intracranial hemorrhage (RD, -0.2 percentage point [CI, -0.6 to 1.4 percentage points]; 5 trials). Compared with aspirin, dabigatran had similar rates of major bleeding (RD, 0.5 percentage point [CI, -2.1 to 19.6 percentage points]; 2 trials) and intracranial hemorrhage (RD, 0.0 percentage point [CI, -1.1 to 24.5 percentage points]; 2 trials). Compared with aspirin, rivaroxaban had higher rates of major bleeding (RD, 0.9 percentage point [CI, -0.1 to 3.7 percentage points]; 2 trials) and intracranial hemorrhage (RD, 0.3 percentage point [CI, -0.1 to 79.7 percentage points]; 2 trials). The evidence certainty ranged from low to moderate.

Limitation: Confidence intervals were wide and included the possibility of a null effect.

Conclusion: In this systematic review of RCTs, rates of major bleeding for therapeutic-dose apixaban and dabigatran were similar to those for low-dose aspirin, whereas rates were higher for rivaroxaban.

Primary funding source: None. (PROSPERO: CRD42024553683).

Background: Future U.S. congressional funding for the President's Emergency Plan for AIDS Relief (PEPFAR) program is uncertain.

Objective: To evaluate the clinical and economic impacts of abruptly scaling back PEPFAR funding ($460 million) from South Africa's total HIV budget ($2.56 billion) in 2024.

Design: Model-based analysis of 100%, 50%, and 0% PEPFAR funding with proportional decreases in HIV diagnosis rates (26.0, 24.3, 22.6 per 100 person-years [PY]), 1-year treatment engagement (people with HIV [PWH] receiving/initiating antiretroviral therapy: 92.2%/80.4%, 87.1%/76.0%, 82.0%/71.5%), and primary prevention (4.0%, 2.2%, 0.5% reduction in incidence with no programming [1.24 per 100 PY]).

Data sources: Published HIV care continuum; PEPFAR funding estimates.

Target population: South African adults (HIV prevalence, 16.2%; incidence, 0.32 per 100 PY).

Time horizon: Lifetime.

Perspective: Health care sector.

Intervention: PEPFAR funded 100% (PEPFAR_100%), 50% (PEPFAR_50%), or 0% (PEPFAR_0%).

Outcome measures: HIV infections, life expectancy, and lifetime costs (2023 U.S. dollars).

Results of base-case analysis: With current HIV programming (PEPFAR_100%), 1 190 000 new infections are projected over 10 years; life expectancy would be 61.42 years for PWH, with lifetime costs of $11 180 per PWH. Reduced PEPFAR funding (PEPFAR_50% and PEPFAR_0%) would add 286 000 and 565 000 new infections, respectively. PWH would lose 2.02 and 3.71 life-years with nominal lifetime cost reductions of $620 per PWH and $1140 per PWH that would be offset at the population level by more PWH requiring treatment for infection.

Results of sensitivity analysis: Countries with similar HIV prevalence and greater reliance on PEPFAR funding could experience disproportionately higher incremental infections and survival losses.

Limitation: Budget fungibility and exact programmatic implications of reducing PEPFAR funding are unknown.

Conclusion: Abrupt PEPFAR cutbacks would have immediate and long-term detrimental effects on epidemiologic and clinical HIV outcomes in South Africa.

Primary funding source: National Institutes of Health.

Background: In the United States, older adults have elevated prevalence of latent tuberculosis infection (LTBI) and incidence of tuberculosis (TB).

Objective: To estimate the health benefits and cost-effectiveness of LTBI testing and treatment among the Medicare-eligible population.

Design: Model-based cost-effectiveness analysis.

Data sources: Nationally representative surveys and published evidence.

Target population: Medicare-eligible persons aged 65 years or older with at least 1 of 15 factors associated with elevated TB risk, as identified by guidelines from the U.S. Preventive Services Task Force (USPSTF) and other organizations.

Time horizon: Lifetime.

Perspective: Societal.

Intervention: One-time offer of LTBI testing and treatment versus no intervention.

Outcome measures: Lifetime TB cases and deaths averted, quality-adjusted life-years (QALYs) gained, costs, and incremental cost-effectiveness ratios (ICERs).

Results of base-case analysis: In 2022, there were an estimated 29.9 million Medicare-eligible persons (95% uncertainty interval [UI], 28.4 to 31.6 million persons) aged 65 years or older with elevated TB risks, including 14.7 million (95% UI, 13.4 to 16.0 million) with USPSTF-recommended factors. In the target population, 4.9 million persons (95% UI, 4.0 to 5.8 million persons) (16.4% [95% UI, 13.9% to 19.1%]) were estimated to have LTBI. Testing and treatment of LTBI was estimated to prevent 10 946 TB cases (95% UI, 4684 to 20 579 cases) and 2579 TB deaths (95% UI, 1106 to 4882 deaths), with 13 234 lifetime QALYs (95% UI, 5343 to 25 519 lifetime QALYs) gained. For the overall target population and for persons with USPSTF-recommended factors, ICERs were $192 000 (95% UI, $92 000 to $503 000) and $155 000 (95% UI, $77 000 to $393 000) per QALY gained, respectively.

Results of sensitivity analysis: The ICER was $109 000 (95% UI, $49 000 to $285 000) per QALY gained for 65-year-olds newly eligible for Medicare.

Limitation: Health benefits from averted post-TB sequelae were not estimated.

Conclusion: Medicare-eligible persons represent approximately one third of all U.S. persons with LTBI. Testing and treatment of LTBI in this population could lead to substantial reductions in TB and TB-related mortality, particularly among 65-year-olds newly eligible for Medicare.

Primary funding source: Centers for Disease Control and Prevention.

Background: Decision making regarding pharmacologic treatments for the prevention of episodic migraine may depend on the importance that patients place on outcomes and specific treatment preferences.

Purpose: To assess patients' values and preferences regarding pharmacologic treatments for the prevention of episodic migraine.

Data sources: MEDLINE and CINAHL from inception to April 2024.

Study selection: Quantitative studies reporting on values and preferences regarding pharmacologic treatments for the prevention of migraine in adults were eligible.

Data extraction: We extracted data on study design, participants, and findings and assessed risk of bias using a tool developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) working group.

Data synthesis: We included 6 studies (5 discrete choice experiments and 1 survey) comprising a total of 2307 participants and assessing the importance of a total of 32 attributes. Risk of bias was moderate in 3 and low in 3 studies; all but 1 were industry spon sored. Migraine severity, frequency, and duration were found to be the most important among several outcomes including acute medication need and side effects (low certainty). Other outcomes of importance were migraine attack on day 1 postdosing (moderate certainty) and duration of daily activity limitations (high certainty). Patients preferred oral tablets to injections and infusions (moderate certainty).

Limitations: Importance of attributes relative to each other could not be assessed due to the scarcity of direct comparisons. Participant sampling was unclearly reported in most studies.

Conclusion: Patients may have the strongest preference for oral treatments that reduce the severity, frequency, and duration of their migraine attacks, which reduce the duration of daily activity limitations and reduce risk of migraine on day 1. Side effects may be less important.

Primary funding source: American College of Physicians. (PROSPERO: CRD42023414305).