bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Laboratory-Confirmed Creutzfeldt-Jakob Disease From 3 Ontario Tertiary Care Centers Between 2012 and 2022: A Retrospective Cohort Study
Authors: Gaete Kayla , Dalai Soma , Cabrera Ana , Li Xena , Sheth Prameet M , Kozak Robert A , Biondi Mia J 
Published: September 2024

Abstract

Background
Globally, Creutzfeldt-Jakob disease (CJD) affects one in one million people annually, but there is a paucity of recent Canadian data. This study summarizes epidemiology trends and diagnostic timelines of laboratory-confirmed CJD cases in three tertiary Ontario hospitals.

Method
Using laboratory information systems, we identified 30 patients with a laboratory-confirmed CJD diagnosis between 2012 and 2022 at three major tertiary hospitals in Ontario. Retrospective chart reviews were then completed.

Results
Patients had a mean of 2.2 hospital visits (SD, 1.2) prior to being admitted for testing. The most common symptom presentations included loss of coordination (63.3%), behavioral changes (60%), progressive mobility loss (53.4%), memory loss (50.0%), and involuntary movements (50.0%). Magnetic resonance imaging findings showed potential CJD in 76.7% of cases, and 56.7% exhibited periodic sharp wave complexes characteristic of CJD on electroencephalogram. The mean duration from symptom onset to microbiologic testing was 91 days (SD, 90.7). End-point quaking-induced conversion (EP-QuIC) testing of cerebrospinal fluid was positive in 90.0% of patients, while 83.3% tested positive for 14-3-3 on enzyme-linked immunosorbent assay. Elevated cerebrospinal fluid 14-3-3 levels significantly correlated with shorter duration from symptom onset to death (R2 = 0.71, F = 19.55, P = .0022). Post-diagnosis, 46.7% of patients were discharged home, 16.6% were transferred to external palliative care or hospice facilities, and 36.7% died during admission. The mean time from symptom onset to death was 121 days (SD, 120.7), and from diagnosis to death 35 days (SD, 83.9).

Conclusions
This study highlights the importance of early CJD consideration and laboratory testing when appropriate neurologic symptoms are present.
Non-adherence to urate lowering therapy in gout after 5 years is related to poor outcomes: results from the NOR-Gout study
Authors: Uhlig Till , Karoliussen Lars F , Sexton Joe , Provan Sella A , Haavardsholm Espen A , Dalbeth Nicola , Hammer Hilde Berner 
Published: September 2024

Abstract

Objectives
Patients with gout need to adhere to medication over time to achieve good outcomes. We assessed self-reported adherence to medication with urate lowering therapy (ULT) 5 years after a treat-to-target intervention and studied how non-adherence was related to baseline demographic and disease variables.

Methods
Patients in the NOR-Gout observational study were included after a recent gout flare and serum urate &gt;360 µmol/l. Patients [mean age 56.2 (S.D. 13.6), 94.5% males, 17.2% with tophi] attended tight-control visits over one year with escalating urate lowering therapy using a treat-to-target strategy. Five-year follow-up included the Medication Adherence Report Scale (MARS-5) questionnaire (range 5–25) for adherence. Flares and SUA target achievement were compared for 5-year adherence to medication.

Results
At 5 years most of the 163 patients used ULT (95.1%). MARS-5 adherence scores after 5 years were high (median 24, interquartile range 22–25). Patients in the lowest MARS-5 quartile had, compared with the highest quartile, more often a flare during the last year of follow-up (33.3% vs 9.5%, P = 0.004) and reached the 5-yr serum urate treatment target less frequently (45.2% vs 87.5%, P &lt; 0.001). Baseline lower age (OR 0.56, 95%CI 0.39–0.79), non-European origin (OR 0.22, 95%CI 0.06–0.80), lower SF-36 mental health scores (OR 0.94, 95%CI 0.91–0.98) and less joint pain during last flare (OR 0.73, 95%CI 0.58–0.92) were independent risk factors for non-adherence to medication.

Conclusions
Patients reported high adherence to medication after 5 years. Non-adherence was related to more flares and less urate target achievement. Younger age and non-European origin were associated with non-adherence.
Immune checkpoint blockade lowers the threshold of naïve T-cell priming to drug-associated antigens in a dose-dependent fashion
Authors: Grice Sophie , Saide Katy , Farrell Liam , Wells Georgia , Betts Catherine , Hammond Sean , Naisbitt Dean J 
Published: September 2024

Abstract
A growing body of clinical and experimental evidence indicates that immune checkpoint blockade enhances patient susceptibility to hypersensitivity reactions to co-administered medications. In this study, we utilized an in vitro T-cell priming assay to demonstrate one of the mechanistic hypotheses on how this occurs; through lowering of the threshold in patients to elicit aberrant T-cell responses. We outline the dependency of de novo T-cell priming responses to drug-associated antigens on dose at initial exposure. Findings support the aforementioned hypothesis and offer an experimental representation of fundamental parameters at play in hypersensitivity reactions to low molecular weight compounds.
O22 MATERNAL AND FETAL OUTCOMES OF VARIOUS ANTIHYPERTENSIVE TREATMENT REGIMENS DURING PREGNANCY: INSIGHTS FROM THE CZECH NATIONAL REGISTRY 2012-2022
Authors: Vaclavik Jan , Ramik Zdenek , Jarkovsky Jiri , Pohlova Radka , Jirova Jitka , Zouharova Anna 
Published: September 2024

Introduction:
Arterial hypertension affects about 5-10% of pregnancies and has detrimental effects on pregnancy outcomes in both the mother and fetus. This study aimed to analyze the outcomes of pregnancy in women treated with different antihypertensive drugs.

Methodology:
Nationwide data on all births and abortions in the period 2012-2022 in the Czech Republic were obtained from the National Registry of Reproductive Health (NRRZ) and the National Registry of Reimbursable Health Services (NRHZS). Women who had the diagnosis I10 within one year before pregnancy and were prescribed any antihypertensive drug from selected ATC groups (C02, C03, C07, C08, C09) were classified as pre-existing hypertension. Women diagnosed with O13 or I10 during pregnancy were classified as pregnancy-induced hypertension. Hypoxia in the newborn was defined as pH <7.1 or Apgar score <8 present after delivery. For all factors, univariate logistic regression was used to calculate the odds ratios (OR) of adverse outcomes.

Results:
There were a total of 1,154,648 deliveries in the 11-year period. 95,215 women (8.2%) had hypertension in pregnancy, out of these 21,094 (22.2%) were treated with antihypertensive drugs. Odds ratios for caesarean section, pre-term delivery, low birth weight, newborn hypoxia, and pre-eclampsia in women using different antihypertensive classes and drugs are shown in the Figure. The risk of maternal and fetal complications was higher with calcium channel blockers (mainly amlodipine) compared to methyldopa and beta-blockers. Among beta-blockers, bisoprolol had the most favorable safety profile. Although used in limited numbers, diuretics, verapamil, ACE-inhibitors and angiotensin receptor blockers (ARBs) appeared to be comparably safe to methyldopa. A combination of multiple antihypertensive drugs was associated with a higher risk of adverse outcomes.

Conclusion:
Bisoprolol, verapamil, and diuretics seem to have a risk of adverse maternal and fetal outcomes comparable to methyldopa. Amlodipine and multiple antihypertensive drug combinations are associated with increased risk.
O25 ARE COMMUNITY HEALTH WORKERS EFFECTIVE IN MANAGING HYPERTENSION AND DIABETES SIMULTANEOUSLY? A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Thapa Rajshree , Zaman Sojib Bin , Thrift Amanda , Mishra Shiva Raj , Zengim Ayse 
Published: September 2024

Background and objective:
To evaluate and summarise the effectiveness of community health worker (CHW)-led interventions to manage risk factors for NCDs. We further assessed whether CHWs could simultaneously manage hypertension and diabetes.

Methods:
We searched six different databases for randomised controlled trials and cluster randomised trials. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. We used random effects models to assess the sample average mean difference between intervention and control groups. The primary outcomes for this review were net mean differences in systolic blood pressure (SBP), diastolic blood pressure (DBP), blood glucose (HbA1c and fasting blood glucose), blood lipids (low-density lipoprotein (LDL) and triglycerides) and obesity (body mass index (BMI) ≥ 25 kg/m2).

Results:
Among 10,508 potential articles identified, 68 were included in the systematic review, and 43 for meta-analysis (11223 participants) after excluding studies not meeting the inclusion criteria. Interventions undertaken by CHWs were effective in reducing SBP [-2.94 mmHg (95% CI, -4.28 to -1.59); I2=73%], DBP [-1.63 mmHg (95% CI, -2.60 to -0.66); I2=81%], HbA1c% [-0.30 (95% CI, -0.45 to -0.16), I2=54%], and triglycerides [-8.32 mg/dl (95%. CI, -13.54 to -3.10)]. Greater reductions in SBP were observed in low- and middle-income countries (LMICs) than in high-income countries (HICs). No detectable difference was observed in the change in HbA1c% in LMICs (only three studies). Interventions targeting diabetes as the primary outcome not only reduced HbA1c% but were also effective in reducing SBP by -2.03 mmHg (95% CI, -3.85 to -0.21). There was no evidence that these interventions improved body mass index or LDL

Conclusions:
We demonstrate that CHW-led interventions are effective in reducing SBP, DBP, HbA1c% and triglycerides, thus reinforcing the importance of engaging CHWs in the management of NCDs. This study represents an important step towards expanding the role of CHWs in addressing multiple risk factors in LMICs and marginalised groups in HICs.

Figure 1: Effect of CHW-delivered intervention on primary and secondary outcomes of systolic blood pressure
O28 EVALUATE THE IMPACT OF STRUCTURED TRAINING COURSE ON HEALTHCARE PROVIDERS KNOWLEDGE AND AWARENESS OF LIFESTYLE MODIFICATIONS FOR HYPERTENSION MANAGEMENT
Authors: Patil Mansi , Patil Vishal 
Published: September 2024

Background:
This study explores how structured training program enhances healthcare professionals’ awareness of lifestyle modifications for hypertension. Assessing its impact on both knowledge and patient guidance, with an aim to improve healthcare delivery by equipping professionals with informed strategies for lifestyle modification.

Design and Methods:
A quasi-experimental design was employed with sample size of 750 HCPs. The Hypertension Knowledge-Level Scale (HK-LS), a modified questionnaire based on guidelines from the World Health Organization (WHO), was utilized to assess participants’ understanding of hypertension, knowledge of lifestyle modification, and clinical practice. A 12-week online course comprising seven modules was delivered to the HCPs, followed by pre- and post-tests to measure changes in knowledge regarding lifestyle modifications.

Results:
The analysis revealed a substantial increase in HCPs knowledge levels post-intervention compared to pre-intervention regarding hypertension (t = 4.90, p = 0.001), lifestyle modification (t = 3.62, p = 0.001), and their proficiency in offering lifestyle advice to patients (t = 3.56, p = 0.001). In addition to these positive outcomes among HCPs, the intervention also highlighted significant gender disparities in attendance and outcomes among participants. Females exhibited a higher attendance rate of 75% compared to males, with consequent improvements in practice, while males showed a more substantial enhancement in knowledge levels post-intervention. These findings underscore the importance of addressing gender-specific barriers to improvement, such as socio-cultural factors for females and preconceived notions for males, to optimize the effectiveness of future interventions in promoting healthier behaviors and outcomes.

Conclusions:
Structured training programs are imperative for enhancing HCPs’ knowledge of lifestyle modification, particularly in the context of hypertension, as a crucial component of primary prevention strategies. This signifies the effectiveness of the structured training program in enhancing HCPs’ comprehension of hypertension management and their ability to guide patients toward adopting healthier lifestyles.
O63 SARS-CoV-2 S PROTEIN REDUCES CYTOPROTECTIVE DEFENSES AND PROMOTES HUMAN ENDOTHELIAL CELL DYSFUNCTION AND SENESCENCE: PROTECTION BY KLOTHO AND ANGIOTENSIN-(1-7)
Authors: Villacampa Alicia , Shamoon Licia , Valencia Inés , Morales Cristina , Figueiras Sofía , de la Cuesta Fernando , Sánchez-Niño Dolores , Díaz-Araya Guillermo , Lorenzo Óscar , Sánchez-Pérez Isabel , Sánchez-Ferrer Carlos F. , Peiró Concepción 
Published: September 2024

Background and objective:
Premature vascular aging and endothelial cell senescence are major risk factors for cardiovascular diseases, including hypertension and atherothrombotic disturbances, which are main complications of both acute and long COVID-19. SARS-CoV-2 S protein, which forms the crown of the coronavirus, can induce endothelial cells inflammation and has been found as an isolated element in both the circulation and human tissues reservoirs months after infection. The aim of this study was to investigate whether S protein is able to directly induce endothelial cell senescence and endothelial dysfunction and to decipher some of the mechanisms involved in such deleterious effect.

Methods:
Using primary cultures of human umbilical vein endothelial cells (HUVEC), cellular senescence was assessed by senescence-associated-β galactosidase (SA-β-gal) staining and the quantification of DNA damage response markers (γH2AX) and growth-arrest effectors (p53, p21, p16) by Western blot. Cytoprotective proteins were equally determined by Western blot. In isolated murine mesenteric microvessel, myography was used to assess defective vascular relaxation, as a key marker of endothelial dysfunction.

Results:
In primary cultures of human umbilical vein endothelial cells (HUVEC), SARS-CoV-2 S protein enhanced in a concentration-dependent manner from a threshold of 35 nmol/L the cellular content of senescence and DNA damage response markers, as well as growth-arrest effectors. In parallel, the S protein reduced the availability of cytoprotective proteins, such as the anti-aging protein klotho, Nrf2 or heme oxygenase-1, and caused functional harm by impairing ex vivo endothelial-dependent vasorelaxation in murine microvessels. These effects were prevented by the pharmacological inhibition of the NLRP3 inflammasome with MCC950. Furthermore, the supplementation with either recombinant klotho or angiotensin-(1-7), equally protected against the pro-senescence, pro-inflammatory and pro-oxidant action of the S protein.

Conclusions:
Globally, this study proposes novel mechanisms of disease in the context of COVID-19 and its vascular sequelae and provides pharmacological clues in order to prevent such complications.
O46 PSYCHOSOCIAL STRESSORS AT WORK ARE ASSOCIATED WITH INCREASED BLOOD PRESSURE VARIABILITY
Authors: Bergeron Nicolas , Lavigne-Robichaud Mathilde , Trudel Xavier , Milot Alain 
Published: September 2024

Background and Objectives:
Elevated blood pressure variability (BPV) is associated with an increased risk of cardiovascular morbidity and mortality, independently of blood pressure values. Psychosocial stressors at work are modifiable risk factors from the work environment, shown to increase the risk of hypertension and cardiovascular diseases. The present study aims to determine whether psychosocial stressors at work have a detrimental effect on BPV.

Methods:
The present study relied on a prospective cohort of 3 645 white-collar workers in Quebec City evaluated at three visits: at recruitment, 3 years, and 5 years. At each visit, participants wore an ambulatory blood pressure monitor during working hours and answered a questionnaire on psychosocial work stressors, as measured using validated instruments according to the demand-control (DC) and effort-reward imbalance (ERI) models. Working hours BPV was calculated using average real variability.

Results:
A total of 7 078 observations (n = 4 246 in women and n = 2 832 in men) were available. Using the DC model, systolic and diastolic BPV were higher in active (high psychological demands, high job control) when compared to non-exposed participants (low demands, high control). Using the ERI model, systolic and diastolic BPV were higher among participants exposed to an imbalance between efforts at work and rewards when compared to unexposed participants. These associations were robust to adjustment for socio-demographics, lifestyle-related risk factors and clinical risk factors.

Conclusions:
Participants exposed to psychosocial stressors at work showed higher BPV than non-exposed participants. Since these risk factors are amenable to appropriate preventive intervention in workplaces, they should be considered for the primordial prevention of hypertension and cardiovascular diseases.

Adjusted for age, education, body mass index, alcohol intake, smoking status, sedentary behaviors, family history of CVD and medication for hypertension (as well as for sex in analyses conducted in the total sample).
O54 THE EFFECT OF SACUBITRIL/VALSARTAN TREATMENT ON HYPERTENSIVE PATIENTS
Authors: Nozato Yoichi , Takami Yoichi , Takahashi Toshimasa , Fujimoto Taku , Yoshida Shino , Hongyo Kazuhiro , Koriyama Hiroshi , Akasaka Hiroshi , Rakugi Hiromi , Yamamoto Koichi 
Published: September 2024

Background and Objective:
Sacubitril/Valsartan was approved in Japan in 2020 for the treatment of heart failure and subsequently for the treatment of hypertension. It is a drug with a novel mechanism of action that inhibits both angiotensin receptors and neprilysin. Besides its cardioprotective and antihypertensive effects, a subanalysis of previous clinical trials in heart failure patients has shown that it tends to slow the rate of decline in renal function, and is expected to have therapeutic effects against CKD. However, its effect on renal function in hypertensive patients is unknown. In this study, we examined renal prognosis in patients with essential hypertension.

Methods:
166 consecutive patients who received an initial dose of ARNI(Sacubitril/Valsartan) (N=104) or ARB (Azilsartan) (N=42) and had blood tests performed before and within 3 months after the first dose at Osaka University Hospital from June 2020 to April 2023 were analyzed retrospectively.

Results:
ARNI tended to be administered to elderly patients and patients with impaired renal function in both male and female patients. eGFR did not decrease in the ARNI group at either 3 or 12 months post-dose. eGFR decreased over time in the ARB group at 3 and 12 months post-dose. 5 patients on ARNI had drug discontinuations that were thought to be due to adverse drug events (hypotension in 2, numbness in 1, dizziness in 1, syncope in 1 patient).

Conclusions:
In this study, ARNI tended to be administered in more elderly hypertensive patients. Although there were a few treatment interruptions due to adverse drug events, the adverse effects on renal function were rather minor compared to ARBs, and under careful management, ARNI may be a useful antihypertensive treatment modality even in elderly patients and patients with impaired renal function.
O55 ETHNIC DISPARITY IN HYPERTENSION AMONG LIVING KIDNEY DONORS
Authors: Tantisattamo Ekamol , Rochanaroon Voramol , Phoonakh Thutpharritchn , Sinkajarern Varissara , Noree Wanprapit , Sodsri Tulaton , Mongkolporn Ariya , Prasitsumrit Vitchapong , Kanthajan Tatchaya , Ngaohirunpat Sorawis , Chuenchaem Urairat , Sripusanapan Adivitch , Siramongkholkarn Smuch , Rodsom Kamonluk , Kookanok Chutawat 
Published: September 2024

Background and Objective:
Whether the disparity among different ethnicities in living kidney donors (LKD) exists is unknown. We aim to examine the association between ethnicity and the risk of developing hypertension in LKD.

Methods:
A retrospective cohort study using OPTN/SRTR included adult LKD, who underwent donation between 6/1972 and 9/2022. Systolic and diastolic hypertension (SHTN and DHTN) were defined by SBP ≥130 and DBP ≥80 mmHg, respectively. The association of different ethnicities with the time-to-event of developing SHTN and DHTN was examined by multiple Cox regression.

Results:
Of 174,311 adult LKD, the mean±SD age was 41±12 years and 60% were female. Hispanic patients account for 13%. Mean pre-donation BP of Hispanics and non-Hispanics were 120±13/73±9 and 122±13/74±9, respectively (mean(SBP difference) -2.1 mmHg, 95%CI -2.3, -1.9, P <0.001; mean(DBP difference) -1.4 mmHg, 95%CI -1.6, -1.3, P <0.001; Figure 1). The median follow-up times for developing SHTN and DHTN were 13.2 (IQR 6.8, 24.4) and 12.2 (IQR 6.3, 24.1) months, respectively and the corresponding incidence rates were 0.020 and 0.003 person-months. After adjusting for age, gender, race, U.S. citizenship, education level, history of pre-donation hypertension, diabetes, pre-donation BMI, SBP, DBP, eGFR, and urine protein:creatinine ratio, Hispanics had 28% significantly greater risk for SHTN (HR 1.28, 95%CI 1.00, 1.63, P 0.046). There were no statistically significant differences in DHTN between Hispanics and non-Hispanics (1.15, 95%CI 0.95, 1.39, P 0.150). Gender was an effect measured modifier with an increased risk of developing SHTN in male, but not female LKD (HR(male) 1.501128, 95%CI 1.082693, 2.081278, P 0.015; HR(female) 1.05, 95%CI 0.72, 1.51, P 0.81)

Conclusions:
Hispanic LKD, particularly male Hispanics, are at increased risk for developing SHTN compared to non-Hispanics. As the fastest-growing ethnic minority in the United States, strategies to mitigate the risk of developing post-donation HTN in Hispanics should be implemented to avoid long-term medical complications in this at-risk population.