1. For older adults with atrial fibrillation (AF), warfarin, dabigatran, and rivaroxaban are associated with higher risk of ischemic stroke and major bleeding events compared to apixaban, and this risk is higher for patients with dementia.
Evidence Rating Level: 2 (Good)
Guidelines for adults living with atrial fibrillation (AF) recommend anticoagulation therapy due to the increased risk of embolic stroke. While the effectiveness and safety profile of oral anticoagulants (OACs) have been studied across many demographics, patients with dementia have often been excluded from trials, likely due to the complexity of informed consent. Therefore, this comparative effectiveness study examined the ischemic stroke risk and risk of major bleeding events on various OACs for AF patients 65 years and older, stratified by dementia status. The study made use of claims data in the United States and identified patients filling a new prescription for an OAC, with no other indication for anticoagulation apart from AF, enrolled in coverage for at least 1 year. 3 cohorts were made, comparing warfarin, dabigatran, and rivaroxaban respectively to apixaban, the OAC generally preferred amongst older adults. The composite end point outcome was ischemic stroke or major bleeding events over 6 months follow-up. In total, there were 1,160,462 patients in the study, 7.9% of whom had dementia. The results showed that compared to apixaban, warfarin patients had higher rates of the composite outcome (adjusted hazard ratio 1.5, 95% CI 1.3-1.7), and the same was true for dabigatran (aHR 1.5, 95% CI 1.2-2.0) and rivaroxaban (aHR 1.3, 95% CI 1.1-1.5). When examining the rate differences (RDs) of the composite outcome per 1000 person-years across all 3 cohorts, the RD estimates were consistently higher for patients with dementia compared to those without. For the warfarin vs apixaban cohort, the RD estimate was 29.8 (95% CI 18.4-41.1) events compared to 16.0 (95% CI 13.6-18.4) events in patients with and without dementia respectively; for dabigatran vs apixaban, it was 29.6 (95% CI 11.6-47.6) events compared to 5.8 (95% CI 1.1-10.4) events; and for the rivaroxaban vs apixaban cohort, it was 20.5 (95% CI 9.99-31.1) compared to 15.9 (95% CI 11.4-20.3) events. Overall, this study demonstrated that apixaban has lower risk of ischemic stroke and major bleeding events compared to other OACs, and that this benefit is particularly more pronounced in patients with dementia.
1. Adding disulfiram and copper to standard alkylating chemotherapy for glioblastoma (GB) was not associated with improved survival or quality of life, and was associated with increased adverse events.
Evidence Rating Level: 1 (Excellent)
New systemic treatments for glioblastoma (GB) have not been well-established since the arrival of temozolomide. However, disulfiram with or without copper has shown some benefit in preclinical studies for GB in vitro and in vivo. Therefore, this randomized controlled trial compared the effects of disulfiram and copper with standard alkylating chemotherapy to alkylating chemotherapy alone. This RCT spanned 7 centres in Norway and Sweden, including patients with first recurrence of histologically verified GB. Patients were randomized 1:1 to the control group, receiving the standard of care (SOC) alkylating chemotherapy treatment, or to the intervention group, receiving SOC plus disulfiram and copper. In total, there were 88 patients, with 45 randomized to SOC and 43 in SOC plus disulfiram and copper. The results demonstrated no difference in the primary outcome of 6-month survival post-randomization, with 62% survival in the control and 44% in the intervention (p = 0.10). There were also no significant differences at 9, 12, and 24 months respectively. Additionally, there was no difference in median progression-free survival (PFS), which was 2.6 (95% CI 2.4-4.6) months in the control and 2.3 (95% CI 1.7-2.6) months in the intervention. There was also no difference in the quality of life metric (EuroQol-5D-3L score) at 3 and 6 months, and no difference in mean daily growth from volumetric analysis from MRI. However, there were significantly greater adverse events in the intervention compared to control (41% vs 16%, p = 0.02) including events with CTCAE grade 3 or greater (34% vs 11%, p = 0.02). Overall, this study demonstrated no benefit to adding disulfiram and copper to standard alkylating chemotherapy treatment for GB, but demonstrated significantly more adverse events.
1. Higher cardiovascular health scores on the American Heart Association’s Life’s Essential 8 are associated with reduced risk of both all-cause and cardiovascular disease mortality, with a linear dose-response relationship.
Evidence Rating Level: 2 (Good)
In 2022, the American Heart Association (AHA) made an update to their cardiovascular health (CVH) recommendations. Known as the Life’s Essential 8 goals, the AHA added the goal of sleep health and refined the Life’s Simple 7 established in 2010. There has yet to be a study done to validate this metric. Therefore, this prospective cohort study investigated the association between scores on Life’s Essential 8 with cardiovascular disease (CVD) mortality and all-cause mortality in American adults. This study utilized self-reported and objective data from the ongoing, cross-sectional National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018, as well as mortality data from the National Death Index. A total of 19,951 adults between 30 and 79 years old were included. Metrics corresponding to the Life’s Essential 8 included diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipid levels, blood pressure, and blood glucose. The total CVH score was divided into low, intermediate, and high categories with 0-49, 50-74, and 75-100 points respectively. Over a median (IQR) follow-up of 7.6 (4.3-10.9) years, the results demonstrated significant risk reductions in all-cause mortality, in both intermediate (hazard ratio 0.60, 95% CI 0.51-0.71) and high (HR 0.42, 95% CI 0.32-0.56) CVH score categories, compared to patients with low CVH scores. BMI and blood lipid scores were not individually associated with all-cause mortality, whereas physical activity, nicotine exposure, and diet being the most significant contributors individually. Furthermore, there were significant risk reductions in CVD mortality in both intermediate (HR 0.62, 95% CI 0.46-0.83) and high (HR 0.36, 95% CI 0.21-0.59) CVH scores, compared to low CVH scores. The CVH metrics of physical activity, sleep health, BMI, and blood pressure were not significantly associated with risk reductions in CVD mortality individually, but demonstrated a similar trend of higher CVH scores generally correlating with lower mortality, with physical activity, blood pressure, and blood glucose being the most significant contributors. As well, the study demonstrated a roughly linear dose-response association between total CVH scores with all-cause and CVD mortality. Overall, this study showed an association between higher CVH scores on the AHA’s Life’s Essential 8 goals and both all-cause and CVD mortality.
1. In vascular access intervention therapy (VAIVT) for hemodialysis patients, patient factors for vessel rupture include lower BMI, fewer prior VAIVT procedures, and shorter access vintage.
2. Hemodynamic risk factors for vessel rupture found on ultrasound imaging include lower blood flow quantity, higher resistance index, and lower brachial artery flow volume.
Evidence Rating Level: 2 (Good)
Vascular access for hemodialysis patients, including arteriovenous fistulas (AVFs) and arteriovenous grafts (AVGs), can have high failure rates due to thrombosis or stenosis, with 1-year patency rates of 86% and 51% for AVF and AVG respectively. Therefore, vascular access intervention therapy (VAIVT), also known as percutaneous transluminal angioplasty, is used to maintain vascular access. There can be risks associated with VAIVT though, particularly vessel rupture. This retrospective cohort study examined the risk factors associated with vessel rupture in VAIVT, including hemodynamic factors based on ultrasound imaging. This was a single-centre study based in Japan from 2019-2021, which included patients receiving VAIVT with ultrasound imaging. Indications for VAIVT included low blood flow, high resistance index, and venous stenosis more than 50%. In total, the study evaluated 628 VAIVT procedures, consisting of 83% male patients, and a median age of 73. There were 20 vessel ruptures (3.18%). On risk factors analysis, patients with ruptures had lower BMI (p = 0.043), underwent fewer VAIVT procedures (p = 0.006), and had shorter access vintage (p = 0.017). Hemodynamic risk factors on ultrasound included lower blood flow quantity (p = 0.005), higher resistance index (p = 0.011), and lower brachial artery flow volume (p = 0.018). Overall, this study demonstrated several patient and hemodynamic risk factors associated with risk of vessel rupture in VAIVT procedures.
Targeting earlier diagnosis: What symptoms come first in Degenerative Cervical Myelopathy?
1. The most commonly self-reported symptoms of degenerative cervical myelopathy (DCM) include poor balance, clumsiness, neck stiffness, impaired grip strength, and hand numbness.
2. The most commonly self-reported initial symptoms of DCM include neck pain, shoulder pain, hand parasthesias, arm pain, and Lhermitte’s phenomenon.
Evidence Rating Level: 3 (Average)
Degenerative cervical myelopathy (DCM) is a progressively debilitating condition involving degeneration in structures compressing the cervical spinal cord. While surgical decompression can halt progression and offer recovery, the prognosis depends on the extent of damage, where treatment within 6 months is associated with better outcomes. DCM is associated with long time to diagnosis, 2-5 years on average, likely due to poor awareness of the disease. Therefore, this survey study aimed to identify commonly patient-reported symptoms of DCM that may be applied to improve early diagnosis of DCM. This survey listed 56 DCM symptoms identified through semi-structured interviews of patients and caregivers, and was disseminated through an international charity website for DCM patients, myelopathy.org. Respondents were asked to identify current symptoms and the first symptom they recall experiencing with the disease. In total, there were 78 respondents to the survey. The most common symptoms included imbalance (84.2%), clumsiness (80.7%), neck stiffness (78.4%), poor grip strength (76.6%), and numbness in the hands (75.4%). The most common initial symptoms were neck pain (13.5%), shoulder pain (8.8%), hand parasthesias (7.0%), arm pain (5.3%), and Lhermitte’s phenomenon (5.3%) – a transient electric shock down the spine and extremities occurring with neck flexion. No one symptom was individually associated with early or late diagnosis. Overall, this study elucidated the most common patient-reported symptoms of DCM, including the commonly presenting initial symptoms.
Image: PD
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