Association Between History of Adverse Pregnancy Outcomes and Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography
Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk.
KEY FINDINGS: Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk. Further research is needed to understand the clinical importance of these associations.
BACKGROUND: Purpose of this study is to assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening.
DETAILS: Cross-sectional study of a population-based cohort of women in Sweden (n = 10,528) with 1 or more deliveries in 1973 or later, ascertained via the Swedish National Medical Birth Register, who subsequently participated in the Swedish Cardiopulmonary Bioimage Study at age 50 to 65 (median, 57.3) years in 2013-2018. Delivery data were prospectively collected. A median 29.6 (IQR, 25.0-34.9) years after first registered delivery, 18.9% of women had a history of adverse pregnancy outcomes, with specific pregnancy histories ranging from 1.4% (gestational diabetes) to 9.5% (preterm delivery). The prevalence of any coronary atherosclerosis in women with a history of any adverse pregnancy outcome was 32.1% (95% CI, 30.0%-34.2%), which was significantly higher (prevalence difference, 3.8% [95% CI, 1.6%-6.1%]; prevalence ratio, 1.14 [95% CI, 1.06-1.22]) compared with reference women. History of gestational hypertension and preeclampsia were both significantly associated with higher and similar prevalence of all outcome indexes. For preeclampsia, the highest prevalence difference was observed for any coronary atherosclerosis (prevalence difference, 8.0% [95% CI, 3.7%-12.3%]; prevalence ratio, 1.28 [95% CI, 1.14-1.45]), and the highest prevalence ratio was observed for significant stenosis (prevalence difference, 3.1% [95% CI, 1.1%-5.1%]; prevalence ratio, 2.46 [95% CI, 1.65-3.67]). In adjusted models, odds ratios for preeclampsia ranged from 1.31 (95% CI, 1.07-1.61) for any coronary atherosclerosis to 2.21 (95% CI, 1.42-3.44) for significant stenosis. Similar associations were observed for history of preeclampsia or gestational hypertension among women with low predicted cardiovascular risk.
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Source: Lawesson, S. S., Swahn, E., Pihlsgard, M., et al. (2023). Association Between History of Adverse Pregnancy Outcomes and Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography. JAMA. 2023; 329(5): 393-404. Published: February 7, 2023. DOI: 10.1001/jama.2022.24093.
Immunogenicity, Safety, and Efficacy of the Vaccine H56:IC31
Vaccination with H56:IC31 at treatment completion for pulmonary tuberculosis did not reduce the risk of recurrent disease. H56:IC31 was well tolerated and immunogenic but might have increased the risk of relapses by endogenous strains.
Summary
Immunogenicity, Safety, and Efficacy of the Vaccine H56:IC31 In Reducing the Rate of Tuberculosis Disease Recurrence In HIV-negative Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis: A Double-Blind, Randomised, Placebo-Controlled, Phase 2b Trial
[Posted 2/Jul/2025]
AUDIENCE: Infectious Disease, Family Medicine
KEY FINDINGS: Vaccination with H56:IC31 at treatment completion for pulmonary tuberculosis did not reduce the risk of recurrent disease. H56:IC31 was well tolerated and immunogenic but might have increased the risk of relapses by endogenous strains.
BACKGROUND: People with tuberculosis who complete treatment remain at risk of recurrent disease. The vaccine H56:IC31 has been shown to be safe and immunogenic in phase 1 and 2 studies, but whether it can reduce the risk of tuberculosis recurrence is unknown.
DETAILS: In a double-blind, randomised, placebo-controlled, phase 2b trial in South Africa (five clinical trial sites) and Tanzania (one clinical trial site), we enrolled participants aged 18-60 years, without HIV, who had completed more than 5 months (22 weeks) of treatment for drug-susceptible pulmonary tuberculosis. During trial screening (<=7 days after starting treatment), two sputum samples were obtained and frozen for later comparison to recurrent isolates by whole-genome sequencing (WGS). Eligible participants were randomly assigned (1:1; block size of four) to receive two intramuscular doses in the deltoid, 56 days apart, of H56:IC31 or placebo. After the first dose of H56:IC31 or placebo, participants were followed up until study day 421 (1 year after the second dose) and checked at each visit for tuberculosis signs and symptoms. If tuberculosis was suspected, two sputum samples were obtained: one sample was tested by automated molecular test (Xpert MTB/RIF Ultra) and sent for liquid culture; and the other sample was stored frozen for later analysis by whole-genome sequencing (WGS). At the last visit (day 421), two sputum samples were obtained from all sputum-productive participants, regardless of symptoms, to detect cases of asymptomatic tuberculosis. The primary endpoint was culture-confirmed recurrent pulmonary tuberculosis (due to relapse with the same strain, reinfection by a different strain, or indeterminate) occuring during the period starting at day 70 (14 days after the second dose) and ending on day 421 (1 year after the second dose). Vaccine efficacy against recurrent tuberculosis was derived from Cox proportional hazards models. Secondary endpoints included vaccine efficacy to prevent tuberculosis relapse or reinfection independently, as differentiated by WGS, and safety and immunogenicity outcomes (H56-specific CD4 T-cell responses and humoral anti-H56 IgG responses). Primary analysis of vaccine efficacy was based on modified intention-to-treat (mITT), in all randomly assigned participants except those with tuberculosis disease recurrence or who withdrew before day 70 (or 14 days after the second dose for those who received both doses). Safety was assessed in all randomly assigned participants who received at least one dose of vaccine or placebo. The trial was registered with ClinicalTrials.gov, NCT03512249, and is complete. 831 participants (mean age 34.7 years [SD 11.1]; 229 [28%] female and 602 [72%] male; 549 [66%] Black) were enrolled from Jan 31, 2019, to Jan 20, 2022; 415 participants were randomly assigned to receive H56:IC31 and 416 to receive placebo. Follow-up was completed by March 20, 2023 (mean follow-up duration 410.1 days [SD 82.8]). In the primary mITT analysis, recurrent tuberculosis occurred in 23 of 400 participants in the H56:IC31 group (12 relapses, eight reinfections, and three indeterminate); and in 14 of 406 in the placebo group (six relapses, seven reinfections, and one indeterminate). Vaccine efficacy for prevention of recurrence was -73.8% (95% CI -246.9 to 9.8; p=0.10). Vaccine efficacy for prevention of relapse was -116.1% (-522.2 to 16.3; p=0.11) and for prevention of reinfection was -21.1% (-245.3 to 56.5; p=0.71). 2 weeks after the planned second dose, H56:IC31 had significantly increased the frequencies of H56-specific CD4 T cells expressing interferon-γ, tumour necrosis factor, interleukin (IL)-2, or IL-17 in vaccinees (median percentage of CD4 T cells, 0.35% [IQR 0.19 to 0.57]) compared with placebo (0.11% [0.09 to 0.23]; p < 0.0001). H56-specific IgG responses were significantly higher in H56:IC31 recipients (median arbitrary units per mL, 6.84 [IQR 1.64 to 32.8]) than in placebo recipients (1.94 [1.05 to 3.86]; p < 0.0001). A greater proportion of H56:IC31 recipients had mild-to-moderate injection site reactions than placebo recipients (165 [40%] of 415 vs 78 [19%] of 416). No treatment-related serious adverse events were reported. Two participants who received H56:IC31 and six who received placebo died.
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Source: Borges, A. H., Russell, M., Tait, D., et al. Immunogenicity, Safety, and Efficacy of the Vaccine H56:IC31 In Reducing the Rate of Tuberculosis Disease Recurrence In HIV-negative Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis: A Double-Blind, Randomised, Placebo-Controlled, Phase 2b Trial. The Lancet Infectious Diseases. 2025; 25(7): 751-763. Published: July, 2025. DOI: 10.1016/S1473-3099(24)00814-4.
Association of Nonmodifiable Risk Factors With Alzheimer Disease Blood Biomarkers in Community-Dwelling Adults in the ESTHER Study
This population-based study on dementia biomarkers found that P-tau181 was dependent on age and APOEe4; NfL on age and sex; and GFAP on age, sex, APOEe4, and menopause status. GFAP levels and rate of increase were higher in women, especially in premenopausal participants.
KEY FINDINGS: This population-based study on dementia biomarkers found that P-tau181 was dependent on age and APOEe4; NfL on age and sex; and GFAP on age, sex, APOEe4, and menopause status. GFAP levels and rate of increase were higher in women, especially in premenopausal participants. Future research should confirm these findings and further explore the role of menopause in dementia pathogenesis among women.
BACKGROUND: Dementia-related blood biomarkers are the future of large-scale dementia risk stratification; however, the extent to which phosphorylated tau (P-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are associated with nonmodifiable risk factors has yet to be confirmed in the community, and the role of menopause has yet to be investigated. Therefore, the aim of this study was to examine the association of age, sex, APOEe4 status, and menopause, with dementia-related blood biomarker levels (P-tau181, NfL, and GFAP) and rate of change over 11 years in longitudinal biomarker measurements in community-dwelling adults.
DETAILS: Within this German population-based Epidemiologische Studie zu Chancen der Verhütung, Früherkennung und optimierten Therapie chronischer Erkrankungen in der älteren Bevölkerung cohort study (n = 9,940), a nested case-control study of 1,026 participants (1:1, without dementia during follow-up: incident dementia during follow-up) aged 50-75 years at baseline followed over 17 years was conducted. Blood biomarker measurements (P-tau181, NfL, and GFAP) were completed in blood from baseline, 8-year, and 11-year follow-ups, and cross-sectional and longitudinal regression analyses were used to assess the association with age, sex, APOEe4, and menopause. The mean age of participants was 64 years, and women accounted for slightly over half (54%) of the sample. Age was cross-sectionally and longitudinally significantly associated with all dementia-related biomarkers (p < 0.001). NfL and GFAP levels more strongly correlated (Spearman R = 0.55 and 0.49) with age at baseline than P-tau181 levels (Spearman R = 0.21). Women experienced significantly higher levels and rates of increase in GFAP (p < 0.001) while men experienced higher levels of NfL after adjusting for age and APOEe4 (p < 0.01). APOEe4 status was significantly associated with baseline and longitudinal levels of P-tau181 (baseline β = 0.30, p < 0.05) and GFAP (baseline β = 15.84, p < 0.001). Of interest, premenopausal status was significantly associated with higher GFAP levels after adjusting for age, sex, and APOEe4 (β = 19.09, p < 0.05).
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Source: Stocker, H., Beyer, L., Trares, K., et al. Association of Nonmodifiable Risk Factors With Alzheimer Disease Blood Biomarkers in Community-Dwelling Adults in the ESTHER Study. American Academy of Neurology. 2025; 104(9): 213500. Published: May 27, 2025. DOI: 10.1212/WNL.000000000021350.
Time to Start Minimal Enteral Nutrition in Low Birth Weight Infants and Its Predictors
As early of initiation of minimal enteral nutrition has a significant role to shorten the time to reach full enteral feeding and reducing malnutrition in the NICU health care staffs treating LBW neonates should consider nutrition as part of the management and special concerns should be given for those who are very preterm and very LBW. Experts in the area and hospitals should prepare feeding initiation protocol to be used across all hospitals and health care staffs to avoid a variation in time to MEN among different neonatal units.
KEY FINDINGS: As early of initiation of minimal enteral nutrition has a significant role to shorten the time to reach full enteral feeding and reducing malnutrition in the NICU health care staffs treating LBW neonates should consider nutrition as part of the management and special concerns should be given for those who are very preterm and very LBW. Experts in the area and hospitals should prepare feeding initiation protocol to be used across all hospitals and health care staffs to avoid a variation in time to MEN among different neonatal units.
BACKGROUND: In Ethiopia the proportion of low birth weight infants is thought to be 17.3%. The purpose of this study was to determine the time to minimal enteral nutrition (MEN) and its predictors in LBW neonates admitted to neonatal intensive care unit in selected hospitals of Addis Ababa, Ethiopia.
DETAILS: An institutional based prospective follow up study was conducted. Both primary and secondary data was used by interviewing mothers and prospective medical chart review of neonates. The Cox regression model was used and variables having a p-value less than 0.05 with 95% CIs in a multivariable analysis were declared as statistically significant association with time to minimal enteral nutrition. 79.4% of them were initiated with MEN. The median time to MEN was 37 h. BW, GA, weight for gestational age, hospital acquired infection, respiratory support and NICU location (hospital) were found to have a statistically significant association with time to initiate minimal enteral nutrition.
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Source: Terefe, A., Tachbele, E., Mislu, E., et al. Time to Start Minimal Enteral Nutrition in Low Birth Weight Infants and Its Predictors: A Prospective Follow Up Study. Journal of Neonatal Nursing. 2025; 31(3): 101648. Published: June, 2025. j.jnn.2025.101648.
Relationship Between Time-Varying Achieved HbA1c and Risk of Coronary Artery Disease Events Among Common Haptoglobin Phenotype Groups with Type 2 Diabetes
The present ADVANCE analysis suggests that not having HbA1c equal to or above 8.0%, rather than achieving HbA1c less than 7.0%, was found to be particularly important for CAD prevention among people with type 2 diabetes and the common Hp2-2 phenotype. While the subgroup analyses were likely underpowered, their inclusion is hypothesis generating and can be used in future meta-analyses to improve power and generalizability.
KEY FINDINGS: The present ADVANCE analysis suggests that not having HbA1c >=8.0%, rather than achieving HbA1c <7.0%, was found to be particularly important for CAD prevention among people with type 2 diabetes and the common Hp2-2 phenotype. While the subgroup analyses were likely underpowered, their inclusion is hypothesis generating and can be used in future meta-analyses to improve power and generalizability.
BACKGROUND: This study sought to determine whether the association between attaining specific glycated hemoglobin (HbA1c) targets (<7.0% (<53 mmol/mol) and >=8.0% (>=64 mmol/mol) compared with 7.0%-7.9%) over time and risk of incident coronary artery disease (CAD) was dependent on haptoglobin (Hp) phenotype in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study.
DETAILS: Prospectively collected HbA1c data from the ADVANCE biomarker case-cohort study, updated at 6 months and every 12 months thereafter over a median of 5.0 (IQR 4.5-5.3) years, were analyzed in relation to incident CAD in the Hp2-2 (n=1323) and non-Hp2-2 (n=2069) phenotypes separately using weighted multivariable-adjusted Cox regression models. Additional a priori stratifications by sex, race, previous cardiovascular disease (CVD), and type 2 diabetes duration were performed. Mean HbA1c was similar in each phenotype group throughout the study. Compared with HbA1c of 7.0%-7.9%, HbA1c <7.0% was not associated with CAD risk for any phenotype group or subgroup. HbA1c >=8.0% compared with 7.0%-7.9% over time was associated with higher CAD risk for the Hp2-2 phenotype only (HR 1.53, 95% CI 1.01 to 2.32; no significant association in the non-Hp2-2 type: 1.26, 0.89 to 1.77, p-interaction=0.71); this was pronounced when those with previous CVD at baseline were excluded (Hp2-2: 2.80, 1.41 to 5.53, p-interaction=0.03). Compared with HbA1c of <8.0%, having HbA1c >=8.0% was associated with a 59% higher CAD risk among participants with the Hp2-2 phenotype (1.59, 1.12 to 2.26) and a 39% higher CAD risk among participants without the Hp2-2 phenotype (1.39, 1.03 to 1.88, p-interaction=0.97).
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Source: Cahill, L. E., Warren, R. A., Lavallée, S. K., et al. Relationship Between Time-Varying Achieved HbA1c and Risk of Coronary Artery Disease Events Among Common Haptoglobin Phenotype Groups With Type 2 Diabetes: The ADVANCE Study. BMJ Open Diabetes Research & Care. 2025; 13(3): e004713. Published: May 6, 2025. DOI: 10.1136/bmjdrc-2024-004713.
Medication Prescriptions for Chronic Diseases in Terminal Cancer Patients in Korea
These findings underscore the need to reevaluate prescription practices for terminal cancer patients. Optimizing medication use can decrease polypharmacy, reduce adverse drug reactions, and increase the quality of life (QOL) for these individuals.
KEY FINDINGS: These findings underscore the need to reevaluate prescription practices for terminal cancer patients. Optimizing medication use can decrease polypharmacy, reduce adverse drug reactions, and increase the quality of life (QOL) for these individuals.
BACKGROUND: This study aimed to investigate the prescribing patterns of medications for chronic diseases in patients with terminal cancer in South Korea as their life expectancy declined.
DETAILS: This study analyzed data on cancer patients from the National Health Insurance Service (NHIS) database in South Korea. It included a total of 89,606 patients who died of cancer in 2021. We evaluated prescriptions for dyslipidemia, hypertension, diabetes, and osteoporosis at 52, 12, 4, and 1 week prior to death. A significant proportion of patients nearing death continued to receive prescriptions for chronic disease medications, despite guidelines suggesting that these medications can be discontinued when life expectancy is limited. For instance, 2.6% of patients were prescribed medications for dyslipidemia just 1 week before death, highlighting a discrepancy between clinical practice and recommended guidelines.
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Source: Kim, M., Kim, Y., Park, J., et al. Medication Prescriptions for Chronic Diseases in Terminal Cancer Patients in Korea: A Real-World Study. Journal of Hospice & Palliative Nursing. 2025; 28(1): 18-24. Published: April, 2025. DOI: 10.14475/jhpc.2025.28.1.18.
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