Daily Archives: January 3, 2025
AGA Clinical Practice Update on Managing Portal Vein Thrombosis in Cirrhotic Patients: Expert Review
3 Jan, 2025 | 10:00h | UTCIntroduction: This summary highlights key recommendations from an AGA expert review on portal vein thrombosis (PVT) in cirrhotic patients. PVT is common in cirrhosis, with an estimated five-year incidence of around 11%, and may worsen portal hypertension and elevate mortality. Management is challenging because of limited evidence, the potential complications of both PVT and anticoagulation, and significant heterogeneity regarding clot characteristics, host factors, and cirrhosis severity. This review presents the latest guidance on identifying clinically relevant PVT, selecting anticoagulation, and considering endovascular interventions, including TIPS (transjugular intrahepatic portosystemic shunt).
Key Recommendations:
- No Routine Screening: Asymptomatic patients with compensated cirrhosis do not require regular screening for PVT in the absence of suggestive clinical changes.
- Imaging Confirmation: When Doppler ultrasound reveals suspected PVT, contrast-enhanced CT or MRI is recommended to confirm the diagnosis, exclude malignancy, and characterize clot extent and occlusion.
- Hypercoagulability Testing: Extensive thrombophilia workup is not indicated unless there is family or personal history of thrombotic events, or associated laboratory abnormalities.
- Intestinal Ischemia Management: Patients who develop PVT with evidence of intestinal ischemia should receive prompt anticoagulation and, ideally, multidisciplinary team care involving gastroenterology, hepatology, interventional radiology, hematology, and surgery.
- Observation of Minor or Recent Thrombi: In cirrhotic patients without ischemia, with recent (<6 months) thrombi that are <50% occlusive, close imaging follow-up every three months is a reasonable option to track potential spontaneous clot regression.
- Anticoagulation for Significant PVT: Consider anticoagulation for more extensive or obstructive (>50%) recent PVT, especially if the main portal vein or mesenteric vessels are involved. Candidates for liver transplantation and those with inherited thrombophilia may derive additional benefit.
- Chronic Cavernous PVT: Anticoagulation is generally not advised in patients with long-standing (>6 months) complete occlusion and well-formed collateral channels.
- Variceal Screening: Perform endoscopic screening or ensure prophylaxis for varices. Avoid delays in initiating anticoagulation, as timeliness is essential for better recanalization outcomes.
- Choice of Anticoagulant: Vitamin K antagonists, low-molecular-weight heparin, and direct oral anticoagulants (DOACs) are all viable options in cirrhosis. DOACs may be appropriate in well-compensated (Child-Turcotte-Pugh class A or certain class B) cirrhosis but should be avoided in class C. Treatment selection should consider patient preferences, monitoring feasibility, and risk of bleeding.
- Duration of Therapy: Reassess clot status with cross-sectional imaging every three months. Continue anticoagulation for transplant-eligible individuals who show partial or complete recanalization, and consider discontinuation in nonresponders after six months if futility is evident.
- TIPS Revascularization: Portal vein revascularization using TIPS may be pursued in patients who have other TIPS indications (like refractory ascites or variceal bleeding) or to improve transplant feasibility by recanalizing portal flow.
Conclusion: PVT in cirrhosis remains a complex clinical issue requiring careful evaluation of clot extent, timing, and the potential need for transplantation. The recommendations presented here underscore prompt imaging, timely anticoagulation for high-risk thrombi, and individualized therapy based on Child-Turcotte-Pugh classification and bleeding risk. When necessary, multidisciplinary collaboration is key to achieving optimal patient outcomes. Prospective randomized trials and standardized classifications of PVT will be instrumental in refining future guidelines.
Reference:
Davis JPE, Lim JK, Francis FF, Ahn J. AGA Clinical Practice Update on Management of Portal Vein Thrombosis in Patients With Cirrhosis: Expert Review. Gastroenterology. 2024. DOI: http://doi.org/10.1053/j.gastro.2024.10.038
Cohort study: Higher Telehealth Use Linked to Lower Rates of Select Low-Value Services in Medicare
3 Jan, 2025 | 09:30h | UTCBackground: Telehealth has rapidly expanded in recent years, potentially transforming how primary care is delivered. However, questions remain regarding its impact on low-value services—tests or procedures that confer minimal benefit and might be wasteful. Previous research raised concerns that virtual encounters could either reduce or increase unnecessary care, but rigorous data on this matter have been limited.
Objective: To assess whether a primary care practice’s adoption of telehealth is associated with changes in the rate of eight established low-value services, comprising office-based procedures, laboratory tests, imaging studies, and mixed-modality interventions.
Methods: This retrospective cohort study used Medicare fee-for-service claims from 2019 through 2022 for 577,928 beneficiaries attributed to 2,552 primary care practices in Michigan. Practices were grouped into low, medium, or high tertiles of telehealth volume in 2022. A difference-in-differences approach was performed, comparing annualized low-value service rate changes between the prepandemic (2019) and postpandemic (2022) periods.
Results: Overall, high-telehealth practices demonstrated reduced rates of certain office-based low-value services, specifically cervical cancer screening (−2.9 services per 1000 beneficiaries, 95% CI −5.3 to −0.4) among older women. Additionally, high-telehealth practices showed lower rates of select low-value thyroid tests (−40 per 1000 beneficiaries, 95% CI −70 to −9). For five other measures—including imaging for low back pain, imaging for uncomplicated headache, and PSA tests in older men—no significant association was observed between greater telehealth use and low-value service rates. Notably, telehealth volume increased markedly from 2019 to 2022, while in-person visits generally decreased.
Conclusions: These findings suggest that widespread telehealth adoption in Michigan primary care was not associated with elevated low-value service use. In fact, certain office-based low-value tests appeared to decline, possibly owing to fewer face-to-face opportunities to perform unnecessary interventions. Nonetheless, caution is warranted in generalizing these findings, as telehealth’s effects may vary across different clinical contexts.
Implications for Practice: Health care systems should consider structured telehealth protocols that encourage judicious testing and minimize overuse. While telehealth can broaden access, clinicians must remain vigilant to avoid missing necessary care. Clear guidelines, effective triage, and patient education might help balance convenience with quality.
Study Strengths and Limitations: Strengths include a large Medicare population and established low-value service metrics, enhancing the study’s validity. Limitations include a single-state focus (Michigan) and reliance on claims data without detailed clinical information, restricting the scope of outcomes assessed.
Future Research: Further investigation is needed to verify whether these trends extend to other states, different insurance models, and additional low-value services (including medications). Evaluations of telehealth’s role in both low-value and high-value care could offer deeper insights into its broader effects on cost and quality.
Reference: Liu T, Zhu Z, Thompson MP, et al. Primary Care Practice Telehealth Use and Low-Value Care Services. JAMA Network Open. 2024;7(11):e2445436. DOI: http://doi.org/10.1001/jamanetworkopen.2024.45436
RCT: Chlorthalidone Shows No Renal Advantage Over Hydrochlorothiazide Under Equivalent Dosing in Older Adults With Hypertension
3 Jan, 2025 | 09:00h | UTCBackground: Hypertension is a critical factor in chronic kidney disease (CKD) progression and cardiovascular risk. Thiazide-type diuretics, such as chlorthalidone and hydrochlorothiazide, are first-line antihypertensive treatments. However, whether one agent confers stronger renal protection remains contested, especially at doses considered pharmacologically comparable. Prior observational studies suggested potential discrepancies in kidney outcomes and hypokalemia incidence. This secondary analysis of the Diuretic Comparison Project (DCP) further clarifies the comparative effectiveness of chlorthalidone versus hydrochlorothiazide on renal endpoints.
Objective: To evaluate whether chlorthalidone (12.5–25 mg/day) prevents CKD progression more effectively than hydrochlorothiazide (25–50 mg/day) in adults ≥65 years with hypertension and no pre-specified exclusion by renal function.
Methods: The DCP is a pragmatic, open-label randomized clinical trial embedded in Veterans Affairs (VA) facilities across the United States. Between June 1, 2016, and December 31, 2023, patients already receiving hydrochlorothiazide (25 or 50 mg/day) for hypertension were randomized either to continue that medication or switch to chlorthalidone (12.5–25 mg/day), reflecting equivalent potency.
The prespecified primary kidney outcome was a composite of doubling of serum creatinine, a terminal estimated glomerular filtration rate (eGFR) <15 mL/min, or dialysis initiation. Secondary measures included ≥40% eGFR decline, incident CKD (new eGFR <60 mL/min), eGFR slope, and relevant adverse events. Laboratory data were obtained through usual clinical care rather than protocol-driven testing.
Results: Among 13,523 randomized participants, 12,265 had analyzable renal data (mean [SD] age, 71 [4] years; 96.8% male). The mean (SD) follow-up was 3.9 (1.3) years. Chlorthalidone did not demonstrate superiority over hydrochlorothiazide for the composite kidney endpoint (6.0% vs 6.4%; hazard ratio, 0.94; 95% CI, 0.81–1.08; P=.37). Additional analyses showed no differences in CKD incidence, ≥40% eGFR decline, or eGFR slope. Hypokalemia occurred more frequently in chlorthalidone users (overall ~2% higher rate of low potassium measurements), and hospitalizations for hypokalemia also trended higher.
Conclusions: Under dosing regimens designed to achieve equivalent antihypertensive potency, chlorthalidone provided no measurable renal benefit over hydrochlorothiazide but posed a modestly elevated risk of hypokalemia. These findings reinforce the clinical interchangeability of both agents for long-term blood pressure management in older adults, provided serum potassium is monitored.
Implications for Practice: Clinicians can confidently employ either chlorthalidone or hydrochlorothiazide in older patients with hypertension, including those with mild or moderate CKD, since renal deterioration rates did not differ significantly. Importantly, the trial used half the milligram amount of chlorthalidone (12.5–25 mg/day) to match the usual doses of hydrochlorothiazide (25–50 mg/day). Recognizing this equivalence helps guide therapy transitions and dosing decisions. Vigilant monitoring of electrolytes remains essential, particularly when prescribing chlorthalidone, given the slightly higher incidence of hypokalemia.
Study Strengths and Limitations: Strengths include the randomized design, broad participant inclusion, and pragmatic structure that mirrors real-world prescribing. Limitations involve potential underestimation or overestimation of renal events due to reliance on routine (rather than scheduled) lab tests. Also, nearly all participants had prior hydrochlorothiazide exposure, which may have influenced tolerance and adherence patterns.
Future Research: Further clinical trials focusing on more advanced CKD stages, distinct comorbidities, or combination regimens (e.g., with potassium-sparing agents) would expand our understanding of how thiazide-type diuretics influence long-term kidney outcomes. Extended follow-up or additional subgroup analyses could also shed light on the interplay of dose-response effects in highly vulnerable populations.
Reference: Ishani A, Hau C, Raju S, et al. “Chlorthalidone vs Hydrochlorothiazide and Kidney Outcomes in Patients With Hypertension: A Secondary Analysis of a Randomized Clinical Trial.” JAMA Netw Open. 2024;7(12):e2449576. DOI: http://doi.org/10.1001/jamanetworkopen.2024.49576
Cohort Study: One in Four Patients Demonstrates Covert Cognition Despite Behavioral Unresponsiveness
3 Jan, 2025 | 08:30h | UTCBackground: Cognitive motor dissociation (CMD) refers to the presence of specific neuroimaging or electrophysiological responses to commands in patients otherwise incapable of voluntary behavioral output. Detecting CMD is clinically relevant because its underdiagnosis may lead to premature decisions regarding goals of care, life-sustaining treatment, and rehabilitation efforts. Although several single-center studies have suggested that CMD may exist in 10–20% of patients with disorders of consciousness, larger multinational data were lacking, particularly using both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG).
Objective: To determine how often CMD occurs in a large, multinational cohort of adults with impaired consciousness and to evaluate the clinical variables potentially associated with this phenomenon.
Methods: This prospective cohort study included 353 adults with disorders of consciousness recruited from six international centers between 2006 and 2023. Enrolled participants had at least one behavioral assessment using the Coma Recovery Scale–Revised (CRS-R) and underwent task-based fMRI, EEG, or both. Sites utilized validated analytic pipelines and automated data processing to minimize false positives. Participants were divided into two groups: those without observable responses to verbal commands (coma, vegetative state, or minimally conscious state–minus) and those with observable responses (minimally conscious state–plus or emerged). CMD was defined as the absence of any observable behavioral response to commands, combined with a positive command-following signal on fMRI or EEG.
Results: Among 241 participants with no overt command-following, 25% showed CMD through either fMRI alone, EEG alone, or both. CMD was more common in younger patients, those assessed later after injury, and those with traumatic brain injury. Interestingly, in 112 participants who did exhibit command-following on bedside exams, only 38% demonstrated confirmatory responses on fMRI or EEG. These findings support the notion that the tasks used for neuroimaging and electrophysiological assessments may require more sustained cognitive engagement than typical bedside evaluations.
Conclusions: CMD was identified in about one in four patients who lacked behavioral command-following. Combining fMRI with EEG likely increases detection rates compared to either modality alone. The results highlight the need for increased awareness of covert cognitive activity in this population, given potential ramifications for prognosis, family counseling, and clinical care.
Implications for Practice: Clinicians should consider the possibility of CMD in patients who appear unresponsive at the bedside. When feasible, employing both fMRI and EEG might reveal hidden cognitive capacities that can guide patient-centered decisions, encourage targeted therapies, and allow healthcare teams to respect potential consciousness and autonomy. However, such technologies remain limited to specialized centers.
Study Strengths and Limitations: Strengths include a diverse sample from multiple international sites and the integration of two complementary neurodiagnostic techniques. Limitations involve heterogeneous recruitment practices, variations in local data acquisition methods, and potential selection biases toward patients who survived until advanced testing was available. Additionally, the absence of standardized paradigms across sites reduced consistency of results.
Future Research: Further large-scale investigations should standardize fMRI and EEG protocols and determine whether earlier and more consistent identification of CMD affects functional outcomes. Efforts to refine and validate automated analytic pipelines could facilitate widespread adoption of these techniques in routine clinical settings.
Reference: Bodien YG, Allanson J, Cardone P, et al. Cognitive Motor Dissociation in Disorders of Consciousness. New England Journal of Medicine. 2024;391:598-608. DOI: http://doi.org/10.1056/NEJMoa2400645
RCT: Discontinuing First-Line DMT in Long-Term Stable Relapsing MS Leads to Recurrence of Disease Activity
3 Jan, 2025 | 08:00h | UTCBackground: Increasing numbers of patients with relapsing-onset multiple sclerosis (MS) are receiving first-line disease-modifying therapies (DMTs) to control inflammatory lesions and reduce disability progression. Yet, extended therapy raises questions regarding overtreatment, adverse effects, and costs, especially in older or clinically stable individuals.
Objective: This randomized, multicenter, rater-blinded clinical trial (DOT-MS) assessed whether discontinuing first-line DMT in adults with MS who had at least five years of clinical and radiological stability is safe in terms of recurrence of significant inflammatory disease activity.
Methods: Eighty-nine participants (median age 54 years, 67% female) were randomly assigned 1:1 to either continue or discontinue their first-line DMT. Inclusion required relapse-onset MS without new, sizeable brain MRI lesions (≤1 new T2 lesion in the previous five years or ≤3 new T2 lesions in the past ten years). Follow-up included clinical evaluations, gadolinium-enhanced brain MRI at baseline and months 3, 6, 12, 18, and 24, and optional unscheduled visits. The primary endpoint was significant inflammatory disease activity, defined as clinical relapse and/or ≥3 new T2 lesions or ≥2 contrast-enhancing lesions. The trial was prematurely terminated by the data safety monitoring board due to higher-than-expected disease activity in the discontinue arm.
Results: After a median follow-up of 15.3 months, none of the 44 participants in the continue group had significant disease activity, versus 8 of 45 (17.8%) in the discontinue group (95% CI for difference, 0.09–0.32). Nearly all events were MRI-detected new or enhancing lesions, though two participants experienced clinical relapses. Most individuals with reactivation were able to regain stability upon DMT reintroduction. Serum neurofilament light levels rose during episodes of inflammatory activity, but neither NfL nor GFAP levels reliably predicted disease recurrence at baseline. No difference in serious adverse events emerged between groups.
Conclusions: In this trial, discontinuation of first-line DMT in long-term stable MS was associated with a significant risk (about 20%) of inflammatory reactivation, particularly noted in participants under 55 years old. As a result, close clinical and MRI monitoring should be mandatory if discontinuation is attempted, with early DMT reinitiation if necessary.
Implications for Practice: Clinicians may consider stopping first-line DMT in select patients who exhibit prolonged stability, especially in older adults, but must remain vigilant. Rapid detection of any radiological or clinical sign of reactivation is crucial, as reintroducing therapy may reestablish disease control.
Study Strengths and Limitations: Strengths include its randomized design, systematic imaging schedule, and thorough biomarker sampling. Limitations involve early trial termination, restricting subgroup analyses and definitive noninferiority testing. Routine spinal cord imaging was not performed, potentially underestimating subclinical disease activity.
Future Research: Longer-term observational follow-up is ongoing to clarify how these participants fare over time and to identify biomarkers that may better predict risk of rebound activity. Evaluating cost-effectiveness and long-term clinical outcomes will guide future decisions about DMT discontinuation.
Reference: Coerver EME, et al. Discontinuation of First-Line Disease-Modifying Therapy in Patients With Stable Multiple Sclerosis: The DOT-MS Randomized Clinical Trial. JAMA Neurology. 2024. DOI: http://doi.org/10.1001/jamaneurol.2024.4164