bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroprotective efficacy of combined antihypertensive treatment with the inclusion of nitrendipine in patients with arterial hypertension
Authors: Yusupova K H F , Abdullaeva G J , Khamidullaeva G A , Ibrohimov N N
Published: November 2023

Aim

To evaluate the efficacy of 12-months combined antihypertensive treatment with the inclusion of nitrendipine on cognitive functions in patients with arterial hypertension (AH).

Material and methods

Surveyed 59 patients with I – III AH degree (ESH / ESC, 2018) of both sexes. The average age of patients was 58,8 ± 11.6 years, the average duration of AH 11.1 ± 7.04 years. An average daily dose 13.18±7.4 mg of nitrendipine was prescribed to patients with AH in combination with other antihypertensive drugs. Furthermore, office systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in all patients before and after 12 months treatment. Cognitive functions were evaluated using neuro-psychological tests: the Mini-Cog test (drawing a clock, reproduction of words), Montreal Cognitive Assessment (MoCA), a self-assessment questionnaire of memory, attention, thinking, ability to cope with their affairs, ability to make decisions. The results are presented as M ± SD.

Results

Analysis of office BP indicators showed a good 12-month antihypertensive efficacy with the inclusion of Nitrendipine in patients with AH. In particular, the SBP before treatment was 157,8 ± 16,18 mm Hg, after – 125,5 ± 10,7 (p = 0,000); the DBP 96,35 ± 8,55 mm Hg versus 79,7 ± 5,9 mm Hg, respectively (p = 0,000); MBP (mean blood pressure) 116,8 ± 9,95 mm Hg versus 94,97 ± 7,09 mm Hg, respectively (p = 0,000). The analysis of influence of AHT with the inclusion of Nitrendipine on cognitive functions in patients with AH showed an increase in the total score on the Mini-Cog test: 3,83 ± 1,11 versus 4,49 ± 0,81 points (p = 0,000), mainly due to a significant improvement in the reproduction of words: 2,16 ± 0,87 versus 2,69 ± 0,62 points (p = 0,000). According to the MOCA scale, abstract thinking significantly improved: initially amounting to 1,37±0,66 points versus 1,81±0,5 points in dynamics (p=0,000), as well as delayed reproduction of words: 2,49±1,23 points initially versus 3,2±1,4 points in dynamics (p=0,004). Significant memory improvement was observed against the background of 12-month antihypertensive therapy based on nitrendipine, initially was 7,04±2.34 points against 8,22±1.24 in dynamics (p=0,000) and decision-making function was 7,8±2,2 points initially against 9,02±1,3 in dynamics (p=0,000).

Conclusion

Thus, high antihypertensive efficacy and improvement of cognitive functions were shown against the background of antihypertensive combination therapy with the inclusion of nitrendipine in patients with AH.
Therapeutic inertia in the management of hypertension by moroccan general practitioners
Authors: Aloutmani B , Ismaili N , El Ouafi N
Published: November 2023

Background

Hypertension is an important and remediable risk factor for cardiovascular disease. Therapeutic inertia has been identified as one of the main factors associated with poor blood pressure control.

Purpose

This study aims to evaluate predictive factors of therapeutic inertia in the management of hypertension among moroccan general practitioners.

Methods

We conducted a descriptive and analytical cross-sectional study, from October 2021 to January 2022, involving moroccan general practitioners using a standardized, anonymous questionnaire, covering numerous areas; their socio-demographic characteristics, assessment of hypertension knowledge, reasons not to intensify therapy and clinical scenarios. A univariate analysis was performed using the Chi-square test for the comparison of percentages. A multivariable logistic regression analysis was also applied to study variables possibly associated with therapeutic inertia.

Results

A total of 130 physicians participated in our study. The majority of the practitioners were female (62.3%). The average age was 38.61 years (±13,95). The percentage of physicians who had practiced for 5 years or less was 51.5% vs. 48,5% having practiced for more than 5 years. The median number of patients seen per day was estimated at 30 patients with an interquartile range of [15, 50]. The average medical visit time was estimated at 11,88 ± 7,03 minutes. The overall frequency of therapeutic inertia among general practitioners was estimated at 78,5% CI 95% [70,4-85,2]. Furthermore, the two main reasons for therapeutic abstention reported by physicians were: the importance of improving patient compliance, lifestyle and dietary measures before intensifying treatment (81,5%), in addition to the fact that the office blood pressure does not reflect the patient's "true" BP and didn’t need any further ambulatory monitoring (43,8%). Multivariable regression showed that when the patient is diabetic, the general practitioners tend to be 4 times more ‘therapeutically inert’ [OR 4.42 (95% CI 1.2–7.23)]. A patient’s history of ischemic stroke was also positively associated with TI [OR 1.53 (95% CI 1.23–4.23)].

Conclusion

This study revealed a significant frequency of therapeutic inertia in primary care. A good understanding of the determinants of this phenomenon will lead to better management of hypertension and therefore better blood pressure control. According to our study, a history of diabetes or stroke was positively associated with inertia, even though this would normally require exhaustive BP control. Thus, the development of operational and consensual definitions based on empirical data and the exploration of the intimate mechanisms underlying this inertia is of crucial importance.Table 1
The safety and efficacy of quadruple ultra-low-dose combination (quadpill) for hypertension treatment: a meta-analysis of randomized controlled trials
Authors: Abuelazm M , Siddiq A , Saleh O , Badr A , Altobaishat O , Albarakat M M , Aboutaleb A M , Ibrahim M , Abdelazeem B
Published: November 2023

Background

Hypertension is a significant healthcare burden, with an average global prevalence of 1.28 billion adults aged between 30 -79 years old. Using antihypertensive drug combinations is considered more effective in controlling elevated blood pressure than monotherapy; however, psychological factors of the patients and the physicians’ caution from the drugs' adverse effects are still barriers against antihypertensive drug combinations. Quadpill, a single pill containing a quadruple combination of quarter doses of four antihypertensive agents, has been investigated for hypertension treatment.

Purpose

We aim to evaluate the efficacy and safety of the quadruple ultra-low-dose combination of antihypertensive drugs (quadpill) in patients with hypertension.

Methods

We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs) evaluating quadpill versus monotherapy or placebo in patients with hypertension, which were retrieved by systematically searching: PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through February 17th, 2023. Continuous and dichotomous outcomes were pooled using mean difference (MD) and risk ratio (RR) along with confidence interval (CI), using Revman V. 5.4 software.

Results

Four RCTs with a total of 781 patients (372 in the quadpill group and 425 in the control group) were included in our analysis. Quadpill was effective in controlling automated systolic blood pressure on the short-term (4-6 weeks) (RR: -13.00 with 95% CI [-17.22, -8.78], P= 0.00001) and on the long-term (12 weeks) (RR: -6.18 with 95% CI [-9.35, -3.01], P= 0.0001). Quadpill was also effective in controlling automated diastolic blood pressure on the short-term (4-6 weeks) (MD: -8.15 with 95% CI [-9.42, -6.89], P= 0.00001) and on the long-term (12 weeks) (MD: -6.35 with 95% CI [-10.37, -2.33], P= 0.002). Moreover, patients in the quadpill group significantly achieved target blood pressure < 140/90 (RR: 1.77 with 95% CI [1.26, 2.51], P= 0.001), compared to the control group. Finally, there was no difference between the quadpill and the control groups regarding the safety outcomes, including the incidence of any adverse events (RR: 1.36 with 95% CI [0.86, 2.15], P= 0.19), any serious adverse events (RR: 1.13 with 95% CI [0.56, 2.25], P= 0.74), and any adverse events leading to drug discontinuation (RR: 0.89 with 95% CI [0.19, 4.11], P= 0.88).

Conclusion

Quadruple ultra-low-dose combination of antihypertensive drugs (quadpill) was effective and safe for hypertension treatment. However, further large-scale multicenter RCTs are still warranted before endorsement in the clinical practice as current evidence is based on a small number of RCTs and quadpill holds a promising strategy for hypertension treatment.Figure 1Figure 2
Ultra-processed food consumption and cardiovascular events risk
Authors: Qu Y , Hu W , Xing C , Yuan L , Huang J
Published: November 2023

Background

The consumption of ultra-processed food (UPF) has been suggested to be associated with cardiovascular events risk, but their dose-response relationship have not reached a consensus.

Methods

We searched PubMed, EMBASE, Cochrane Library, and Web of Science databases for manuscripts published from inception to November 17, 2021, which reported the relationship between UPF consumption and cardiovascular events risk. A total of ten studies were included with 325,403 participants and 38,720 cardiovascular events cases. Using the fixed/random-effects models, hazard ratios of pooled outcomes were estimated.

Results

A non-linear relationship of UPF consumption with cardiovascular events risk was identified (P for heterogeneity = 0.013, P for dose-response < 0.001, P for non-linearity = 0.013). Compared with the lowest UPF consumption category, the third highest pooled HR for cardiovascular events risk was 1.02 (95% CI, 0.98 to 1.05), the second highest was 1.08 (95% CI, 1.04 to 1.12) and the highest was 1.24 (95% CI, 1.16 to 1.32). A linear association between UPF consumption and coronary heart disease (CHD) risk was identified (P for heterogeneity = 0.110, P for dose-response < 0.001, P for non-linearity = 0.202). A 10% increase in UPF consumption in daily calorie intake was associated with a 6% increase in CHD risk. UPF consumption was non-linearly associated with cerebrovascular disease (CeVD) risk (P for heterogeneity = 0.001, P for dose-response < 0.001, P for non-linearity = 0.026).

Conclusions

There was a nonlinear relationship between UPF consumption and cardiovascular events. Moderate intake of UPF was associated with a lower risk of cardiovascular events, with the lowest risk at <15%/day of UPF consumption out of total calorie intake. Heavy UPF consumption was significantly and positively associated with increased risk of cardiovascular events.
Acute electrophysiological effects of energy drink, energy gum and coffee: a double-blind randomized placebo-controlled crossover study
Authors: Alviar C , Lapierre S , Soonhuae C , Leong M C , Yan X , Ruzieh M , Handberg E , Christou D
Published: November 2023

Background

Energy drink consumption is highly prevalent in young adults, especially in males, and has been associated with adverse cardiovascular events, including QT prolongation and atherothrombosis. A proposed mechanism underlying these adverse cardiovascular effects is caffeine, but this has not been systematically evaluated. Therefore, the purpose of this study was to compare the acute electrophysiological effects of energy drink consumption with other forms of caffeine consumption in young males.

Methods

We performed a randomized, double-blind, placebo-controlled, crossover study in 16 young healthy males. Each participant underwent electrocardiography assessment at pre- and post-treatment (1-hour and 2-hours) in response to 4 beverage and gum combinations: 1) energy drink + placebo gum (ED); 2) coffee + placebo gum (C); 3) placebo beverage + caffeinated energy gum (EG); and 4) placebo beverage + placebo gum (P). Caffeine content was the same in all treatment combinations and a washout period of at least 1-week was allowed among treatments.

Results

At 1-hour post-treatment, heart rate increased in response to ED while it decreased in response to EG (p<0.05 for ED vs. EG; Figure 1A). At 2-hours post-treatment, the increase in heart rate after ED and Coffee was significantly greater compared to the change in heart rate in response to the other treatments (p<0.05). The increase in QRS duration 1-hour post-treatment was significantly greater after ED compared to EG and Placebo (p <0.05). Corrected QT (QTc) duration was significantly reduced at 1-hour post-treatment in response to EG vs. ED (p<0.05), but was not different compared to the other treatments. At 2-hours post-treatment, QTc duration was significantly reduced in response to EG and was increased in response to Coffee (p < 0.05 for EG vs. ED and C, Figure 1C). The most prominent increase from baseline in the percentage of participants experiencing ventricular ectopy was in response to ED (Figure 1D).

Conclusions

The acute electrophysiological effects of energy drink, energy gum and coffee do not appear to be mediated by caffeine content. Further investigations are warranted to better understand the cardiovascular effects of these caffeinated products.
Comparing electrophysiological biomarkers and circulating cardiac biomarkers in predicting cardiovascular mortality and all-cause mortality in the akershus sleep apnea (ASAP) epidemiological cohort
Authors: Nahoui H , Feng X , Oeverby T C , Sigurdardottir F D , Hrubos-Stroem H , Omland T , Einvik G , Nikkonen S , Leppaenen T , Arnardottir E S , Toeyraes J , Myllymaa S
Published: November 2023

Background

Major cardiovascular events (MACE) and mortality in obstructive sleep apnea (OSA) patients have been frequently reported. However, there is an ongoing debate regarding biomarkers predicting MACE and mortality in OSA. The Apnoea Hypopnea Index (AHI) has been used to assess the severity of Obstructive Sleep Apnea (OSA) despite poor association with adverse outcomes in OSA patients. Novel electrophysiological biomarkers (EPBs) such as desaturation parameters have been suggested as an alternative, and have been reported to be stronger predictors of cardiovascular mortality and heart failure. However, circulating cardiac biomarkers (CCBs) remain strong predictors of mortality and cardiovascular disease in the general population.

Purpose

To detect the incidence of MACE and all-cause mortality after a median of 13.8 years follow-up in individuals with OSA, and to assess the ability of CCBs and EPBs to predict MACE and all-cause mortality.

Methods

Polysomnography and CCB analyses (cardiac troponin I (cTnI) and T (cTnT)) were conducted in 459 participants in the Akershus Sleep APnea study (ASAP) between 2006-2008. EPBs evaluated were the AHI, oxygen desaturation index (ODI), desaturation duration (DesDur) and desaturation severity (DesSev). Cox regression and cumulative incidence Kaplan-Meier curves were used for survival analysis. Comparison of EPBs and CCBs in predicting MACE and all-cause mortality was assessed by the area under the curve (AUC).

Results

77 and 35 participants reached the endpoint of MACE and all-cause mortality, respectively. In the adjusted cox regression model, cTnI and cTnT were significantly associated with MACE with a hazard ratios of 1.84 [95% Confidence interval [CI], 1.43, 2.37] and 1.52 [1.05, 2.20], respectively. Association of these CCBs with all-cause mortality was with a hazard ratios of 2.02 [1.38, 2.96] and 1.75 [1.05, 2.92], respectively. Moreover, cTnI had the highest AUC of 0.77 and 0.75 in predicting MACE and all-cause mortality. Notably, high AHI, ODI, DesDur and DesSev (upper quartile) increased the cumulative incidence of MACE and all-cause mortality in the subgroup of patients with high CCBs (upper quartile) compared to the subgroup of patients with high CCBs and low EPBs (lower quartile).

Conclusion

CCBs were more associated with all-cause mortality and MACE than EPBs in ASAP epidemiological cohort. However, the tested EPBs are important biomarkers that increase CCBs prediction of both MACE and all-cause mortality.
Lower 6-minutes walk test result and presence of cardiovascular risk factors linked to healthcare facility visits of pilgrims: the importance of fitness in hajj pilgrimage
Authors: Harsoyo P M , Ardiana M , Sufiyah I M , Hermawan H O , Rahma S
Published: November 2023

Background

Hajj pilgrimage, a mandatory religious practice for the Muslims, is a physical rite attributed heavily on the fitness of the participants due to increased workload in performing its activities. The 6-minutes walk test is a simple assessment to predict candidates’ fitness level.

Objective

We sought to determine the association between pilgrim candidate fitness level, determined by 6-minutes walk test result during predeparture preparation, as well as pre-existing potential risk factors of hajj pilgrim participants.

Method

In this retrospective cohort, we obtained the data of 2022 pilgrimage participants from Indonesian Ministry of Religious Affairs, consisting of demographic characteristics, anthropometric indexes, medical history, physical examination, and functional exercise capacity predicted by 6-minute walk test conducted during pre-departure preparation. Baseline demographic, bivariate tests for each variable, and multivariate test were analyzed by IBM SPSS 26.

Result

There was significant correlation between age of ≥60 (p < 0.001), hypertension (p < 0.001), diabetes mellitus (p < 0.001), 6-minutes walk test (p < 0.001), smoker status (p = 0.008), high LDL-C (p = 0.026), obesity (p =0.033), female sex (p = 0.043) and healthcare visit episode of pilgrims. The risk ratio value for low result group of 6-minutes walk test (< 500 meters) against outpatient incidence during hajj period was 1.08 (95% CI; 1.04 -1.12). It indicated that the inability of reaching >500 meters in 6-minutes walk test is related to outpatient incidence by 1.08 times.

Conclusion

There is a slight increase in healthcare visit incidence in pilgrims with low result of 6-minutes walk test. The 6-minutes walk test, a simple and reproducible assessment of fitness level, may provide useful information to improve preparation of pilgrimage.
Coronary artery calcification score and 19 biomarkers on cardiovascular events; a 10-year follow-up DanRisk substudy
Authors: Schaeffer M , Rasmussen J H , Fredgart M H , Hasific S , Steffensen F H , Lambrechtsen J , Sand N P R , Rasmussen L M , Diederichsen A C P
Published: November 2023

Background

SCORE2 is recommended for the estimation of the 10-year risk of cardiovascular disease (CVD), and guideance of medical therapy. However, the prediction is deficient. Coronary artery calcification (CAC) score has been proven to improve the risk assessment in primary prevention of CVD, however, it is also resource-intensive. Biomarkers may be an advantageous alternative.

Purpose

This study aims to determine and compare the additive value of CAC-score and 19 biomarkers in risk prediction.

Methods

Classic cardiovascular (CV) risk factors, CAC-score, and a wide range of blood samples (including lipids, calcium-phosphate metabolism, troponin, inflammation, and kidney function), were collected from 1,211 randomly selected middle-aged men and women in this multicentre prospective cohort in 2009-2010. 10-year follow-up data on CV-events (death from CVD, stroke, myocardial infarction, heart failure or coronary artery revascularization) were obtained from the Danish Health Registries. The association between SCORE2, CAC-score, biomarkers, and CV-events was displayed in Kaplan Meier diagrams, assessed using cox proportional hazard rates (HR) and compared using area under the curve (AUC) calculation of receiver operating characteristic (ROC) curves. The net reclassification improvement (NRI) for CAC-score compared to SCORE2 was also calculated.

Results

92 participants had CV-events. Events were seen in 29.3% of 41 participants with a very high risk (SCORE2 ≥10%) and 24.2% of 66 participants with CAC-score ≥400. Adjusted for risk factors, CAC-score was significantly associated with events adjusted HR 1.91 (95%CI: 1.10;3.31), 3.61 (95%CI: 1.93;6.76), and 5.2 (95%CI: 2.63;10.29) for CAC-score 1-99, CAC-score 100-399 and CAC-score ≥400, respectively. HR for the highest quartile of C-reactive protein (CRP) was 2.34 (95%CI: 1.15;4.47), while none of the remaining biomarkers improved HR.

CAC-score improved AUC of the SCORE2 model (AUC_CAC+SCORE2: 0.72, AUC_SCORE2: 0.67, p<0.01) as seen in Figure 1. A combination of selected biomarkers (total cholesterol, low-density lipoprotein, phosphate, troponin I, CRP, and creatinine) borderline improved AUC (AUC_Biomarkers+SCORE2: 0.71, AUC_SCORE2: 0.67, p=0.06).

Inclusion of CAC-score in the SCORE2 model improved the risk prediction. For participants with a CV-event, 73.9% had increased probabilities and 26.1% had decreased probabilities, compared to 42.4% increased and 57.6% decreased probabilities for participants without an event. NRI was 63% (p<0.0001)

Conclusion

CAC-score remained to improve the prediction of CV-events, while the selected biomarkers did not.ROC of SCORE2 versus CAC-score+SCORE2
Comparison of SCORE and SCORE2 in determination rates with very high cardiovascular risks
Authors: Demirci D , Ersan Demirci D , Gerald C , Guven A Z , Elhan A H , Gibson C M
Published: November 2023

Background

Appropriate risk stratification is fundamental for cardiovascular disease (CVD) prevention. The European Society of Cardiology recently updated the Systematic Coronary Risk Estimation (SCORE) algorithm to SCORE2 for estimating the 10-year risk of first-onset CVD among Europeans. However, the performance of SCORE2 has not been examined in the non-European population.

Purpose

This study aimed to compare the results of CVD risk assessments between the SCORE and SCORE2 algorithms.

Methods

A total of 1089 non-diabetic patients who experienced their first episode of acute coronary syndrome (ACS) were included in the study. CVD risks were evaluated according to the SCORE charts based on age, sex, smoking status, blood pressure, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and non-HDL levels.

Results

The SCORE2 algorithm identified 58.8% (n=640) of patients as very high risk, whereas the SCORE algorithm identified only 22.5% (n=245) of patients as such, demonstrating a statistically significant difference (p < 0.001). Furthermore, there was a noticeable sex disparity in very high-risk classification between the two algorithms. Specifically, the SCORE algorithm identified a considerably higher proportion of males (25.7%; n=233) as very high risk compared to females (4.9%; n=12) (p < 0.001). In contrast, the SCORE2 algorithm demonstrated a relatively smaller difference in the very high-risk category between males (59.7%; n=540) and females (54.3%; n=100) (p=0.181). A lower proportion of patients were classified as low to intermediate risk by the SCORE2 algorithm compared to the SCORE algorithm (3.9 % vs. 49.7%; p < 0.001). On the other hand seven patients (0.6 %) aged between 70 to 73 years were reclassified from the very high-risk category by SCORE to the very high-risk category by SCORE2.

Conclusion

The study suggests that the SCORE2 algorithm is superior to the SCORE algorithm in classifying patients who developed first-onset ACS as very high risk. In the very high-risk category, the sex gap was less prominent using the SCORE2 algorithm than the SCORE algorithm. However, the SCORE2 algorithm may underestimate CVD risk levels among patients aged between 70 to 73 years.General characteristics of the patientsThe Comparison of CV risk levels
The association of lipoprotein(a) with patient characteristics and mortality in a primary prevention cohort: data from our clinic database
Authors: Cho L , Brennan D , Costa-Scharplatz M , Itani T , Nissen S
Published: November 2023

Background

Lipoprotein(a) [Lp(a)] has emerged as a causal risk factor for development of cardiovascular (CVD) and valvular heart disease. However, not much is known about the gender differences and Lp(a). The aim of our study was to investigate gender differences in clinical and laboratory characteristics of primary prevention patients with elevated Lp(a) and to study the associations between Lp(a) and all-cause mortality by gender.

Method

We analyzed data obtained from the Preventive Cardiology Information System (PreCis), a database of clinical and laboratory information on 8,136 consecutive primary prevention patients seen at our clinic preventive cardiology clinic from 1999-2018. Primary prevention was defined as having no history of coronary artery disease (CAD), coronary and peripheral arterial revascularization, nor atherosclerosis. Data regarding mortality were gathered from a combination of sources including the Social Security Death Index (SSDI), the Ohio State Department of Health Vital Statistics, and electronic medical record. All-cause mortality was assessed using time to event analyses, and adjusted Cox proportional hazards models. All statistical analyses were conducted using SAS version 9.4.

Result

In the overall cohort (n=8,136), 57% were female at a median age of 54 years and 43% were male at a median age of 52 years. Median Lp(a) was 24 (IQR 8-63) mg/dL in females and 18.6 (IQR 7-51) mg/dL in males. The proportion of females increased with increasing Lp(a) values from 54% with Lp(a) <30 mg/dL to 69% with Lp(a) ≥90mg/dL. Female patients with Lp(a) ≥50 mg/dL were significantly more likely to have dyslipidemia (40.5% vs 34.1%; p>0.001) and hypertension (27.3% vs 23.3%; p>0.001) compared to <50 mg/dL. There was a trend toward increased all-cause mortality in elevated Lp(a) group among female patients (<50 mg/dL vs ≥50 mg/dL; (HR (95%CI): 1.22 (0.98-1.52); p=0.083).

Conclusion

In this primary prevention population, a higher proportion of females had elevated Lp(a) than males. Females with elevated Lp(a) presented with more comorbidities and a trend towards increased all-cause mortality. These findings suggest a gender difference in the distribution of Lp(a) and all-cause mortality in the primary prevention setting, which warrants further investigation.
Lipoprotein(a) is not a causal factor for the development of diabetes - a two-sample Mendelian randomization study
Authors: Lejawa M , Golawski M , Osadnik T , Jozwiak J , Gierlotka M , Lisik M , Pawlas N , Banach M
Published: November 2023

Introduction

The association between lipoprotein(a) [Lp(a)] and coronary artery disease is well known. Nevertheless, because physiological function of Lp(a) is not well understood, it is not clear what sort of adverse effects therapies aimed at Lp(a) reducing might have. One of the associations that was observed for the reduced Lp(a) levels was the increased incidence of diabetes. As genetic factors have a clear impact on Lp(a) levels, we applied Mendelian Randomization [MR] approach as a tool to determine the impact of Lp(a) on the risk of diabetes onset.

Purpose

To assess the impact of Lp(a) levels on the incidence of diabetes.

Methods

We conducted a two-sample MR study. Publicly available datasets were used as sources for summary statistics of genetic correlations. UK Biobank was the source of correlations for Lp(a) levels and FinnGen was used as the source of genetic correlations for type 2 diabetes. Only variants in the LPA gene region were utilized. Inverse-variance-weighted mean method was used for primary analysis. Secondary analyses were conducted by weighted median, mode, and MR-Egger methods. Sensitivity analyses were performed by leaving out random 30% of the variants as well as by using LPA gene variants that were previously published as significantly affecting Lp(a) levels.

Results

Data regarding genetic determinants of Lp(a) levels were available for 318922 participants, while summary statistics for type 2 diabetes were available for 49114 cases and 283207 controls. Primary analysis indicated that Lp(a) levels are not correlated with diabetes [p=0.362]. Genetic associations of included variants with Lp(a) levels (horizontal axis) and with type 2 diabetes mellitus (vertical axis) are presented in Figure. Secondary analyses were consistent with this finding [median p=0.100; mode p=0.156; MR-Egger p=0.243]. Selected variants did not show appreciable pleiotropy as indicated by MR-Egger intercept test [p=0.450]. Sensitivity analyses did not result in statistically significant findings [leave-30%-out analysis IVM p-values: 0.153-0.960].

Conclusions

Lp(a) levels determined by genetic background are not correlated with type 2 diabetes risks. This indicates that Lp(a) levels has likely no causal role in type 2 diabetes onset. This suggests that treatments aimed at reducing Lp(a) levels will not likely increase the risk of developing type 2 diabetes.
Hyperlipoproteinemia(a) in coronary artery disease patients: who are patients with very high levels and how do they respond to the PCSK9 antibody therapy?
Authors: Novakovic M , Trsan J , Krevel B , Cevc M , Fras Z , Jug B
Published: November 2023

Introduction

Lipoprotein(a) [Lp(a)] is a considerable risk factor for coronary artery disease [CAD] and a possible target for novel risk management therapy. On the one hand, increased Lp(a) levels may help select at-risk CAD patients who are better candidates for PCSK9 antibody therapy; on the other hand, PCSK9 antibody therapy has been shown to reduce Lp(a) levels.

Purpose

The aim of our study was two-fold: i) to appraise the prevalence and characteristics of CAD patients with elevated Lp(a), and ii) to identify possible predictors of Lp(a) levels reduction in CAD patients on PCK9 antibody therapy.

Methods

Consecutive patients with established CAD referred for cardiac rehabilitation from 2020 to 2022 were included and had Lp(a) serum levels measured using the Lp(a) assay on the RX Daytona+ automated biochemistry analyzer. Clinical and demographic predictors of Lp(a) >50 mg/dL and >100 mg/dL were assessed (namely age, sex and traditional risk factors). Furthermore, in patients with CAD and increased Lp(a) levels (>100 mg/dL, which makes them eligible for full reimbursement of alirocumab or evolocumab as per national insurance policy), clinical and demographic predictors of Lp(a) levels reduction after 12 weeks of PCSK9 antibody therapy were assessed.

Results

We included 518 patients (average age 58 years, 21% females): 84 (16.2%) had Lp(a) levels >100 mg/dL and 137 (26.4%) had Lp(a) levels >50 mg/dL. Only the female sex was independently associated with increased Lp(a) levels >100 mg/dL and >50 mg/dL (32.1%, p=0.008 and 27.7%, p=0.030, respectively). In 57 patients on PCSK9 antibody therapy based on Lp(a) >100 mg/dL, cigarette smoking and body mass index (BMI) were independent baseline-adjusted predictors of Lp(a) reduction after 3 months of PCSK9 antibody therapy; non-smokers had 27.5 mg/dL greater decrease in Lp(a) as compared to smokers (p=0.004), and BMI was associated with a decrease of 2.6 mg/dL per unit of BMI (p=0.020), respectively.

Conclusion

In patients with established CAD, the female sex is the only independent clinical predictor of increased Lp(a) levels, suggesting Lp(a) may be an important driver of CAD, especially in women. Conversely, Lp(a) reduction with PCSK9 antibody therapy was associated only with lifestyle risk factors (namely smoking and BMI), suggesting the possibility that lifestyle modification could improve response to treatment to PCSK9 inhibitors and should be researched further in prospective studies.
Impact of dilution on stochastically driven methanogenic microbial communities of hypersaline anoxic sediments
Authors: Font-Verdera Francisca , Liébana Raquel , Rossello-Mora Ramon , Viver Tomeu
Published: November 2023

Sediments underlying the solar salterns of S’Avall are anoxic hypersaline ecosystems dominated by anaerobic prokaryotes, and with the especial relevance of putative methanogenic archaea. Slurries from salt-saturated sediments, diluted in a gradient of salinity and incubated for > 4 years revealed that salt concentration was the major selection force that deterministically structured microbial communities. The dominant archaea in the original communities showed a decrease in alpha diversity with dilution accompanied by the increase of bacterial alpha diversity, being highest at 5% salts. Correspondingly, methanogens decreased and in turn sulfate reducers increased with decreasing salt concentrations. Methanogens especially dominated at 25%. Different concentrations of litter of Posidonia oceanica seagrass added as a carbon substrate, did not promote any clear relevant effect. However, the addition of ampicillin as selection pressure exerted important effects on the assemblage probably due to the removal of competitors or enhancers. The amended antibiotic enhanced methanogenesis in the concentrations ≤ 15% of salts, whereas it was depleted at salinities ≥ 20% revealing key roles of ampicillin-sensitive bacteria.
3-D induction log modelling with integral equation method and domain decomposition pre-conditioning
Authors: Saputera D H , Jakobsen M , van Dongen K W A , Jahani N , Eikrem K S , Alyaev S
Published: November 2023

The deployment of electromagnetic (EM) induction tools while drilling is one of the standard routines for assisting the geosteering decision-making process. The conductivity distribution obtained through the inversion of the EM induction log can provide important information about the geological structure around the borehole. To image the 3-D geological structure in the subsurface, 3-D inversion of the EM induction log is required. Because the inversion process is mainly dependent on forward modelling, the use of a fast and accurate forward modelling tool is essential. In this paper, we present an improved version of the integral equation (IE) based modelling technique for general anisotropic media with domain decomposition pre-conditioning. The discretized IE after domain decomposition equals a fixed-point equation that is solved iteratively with either the block Gauss–Seidel or Jacobi pre-conditioning. Within each iteration, the inverse of the block matrix is computed using a Krylov subspace method instead of a direct solver. An additional reduction in computational time is obtained by using an adaptive relative residual stopping criterion in the iterative solver. Using this domain decomposition scheme, numerical experiments show computation time reductions by factors of 1.97–2.84 compared to solving the full-domain IE with a GMRES solver and a contraction IE pre-conditioner. Additionally, the reduction of memory requirement for covering a large area of the induction tool sensitivity enables acceleration with limited GPU memory. Hence, we conclude that the domain decomposition method is improving the efficiency of the IE method by reducing the computation time and memory requirement.
The redistributive effect of the public health system: the case of Sierra Leone
Authors: Gabani Jacopo , Mazumdar Sumit , Hadji Sylvester Bob , Amara Michael Matthew
Published: November 2023

Universal health coverage (UHC), health equity and reduction of income inequalities are key objectives for the Sierra Leone government. While investing in health systems may drive economic growth, it is less clear whether investing in health systems reduces income inequality. Therefore, a crucial issue is to what extent the Sierra Leone public healthcare system reduces income inequality, and finances and provides healthcare services equitably. We use data from the Sierra Leone Integrated Household Survey 2018 to complete a financing and benefit incidence analysis of the Sierra Leone public healthcare system. We extend these analyses by assessing the redistributive effect of the public healthcare system (i.e. fiscal incidence analysis). We compute the redistributive effect as the change in Gini index induced by the payments for, and provision of, public healthcare services. The financing incidence of the Sierra Leone public healthcare system is marginally progressive (i.e. Kakwani index: 0.011*, P-value <0.1). With regard to public healthcare benefits, while primary healthcare (PHC) benefits are pro-poor, secondary/tertiary benefits are pro-rich. The result is that overall public healthcare benefits are equally distributed (concentration index (CI): 0.008, not statistically different from zero). However, needs are concentrated among the poor, so benefits are pro-rich when needs are considered. We find that the public healthcare system redistributes resources from better-off quintiles to worse-off quintiles (Gini coefficient reduction induced by public healthcare system = 0.5%). PHC receives less financing than secondary/tertiary care but delivers a larger reduction in income inequality. The Sierra Leone public healthcare system redistributes resources and reduces income inequality. However, the redistributive effect occurs largely thanks to PHC services being markedly pro-poor, and the Sierra Leone health system could be more equitable. Policy-makers interested in improving Sierra Leone public health system equity and reducing income inequalities should prioritize PHC investments.
Quality of antenatal care in primary health care in Brazil: a latent class analysis
Authors: Ortelan Naiá , Flores-Quispe Maria Del Pilar , Luz Leandro A. da , Martufi Valentina , Anjos Eduarda F. dos , Lima Acácia M. P. de , Almeida Josemir R. de , Passos Michelle P. V. dos , Santos Ythalo H. S , Amorim Leila D.A.F , Aquino Rosana , Vieira-Meyer Anya P. G. F , Ichihara Maria Yury T , Barreto Mauricio L , Pinto-Junior Elzo P
Published: November 2023

Background

Adequate antenatal care (ANC) is fundamental in preventing maternal and neonatal mortality. Developing indicators for assessing the ANC quality in Primary Health Care (PHC) is essential.

Objective

To characterize subgroups of quality of care with respect to ANC at the PHC level in Brazil.

Methods

We conducted a cross-sectional study with data from the first Brazil’s National Program for Improving Primary Care Access and Quality (PMAQ-AB) Cycle (2011–2012). A total of 16 566 PHC teams participated in the first cycle of the PMAQ-AB, corresponding to 49.6% of the teams active across Brazil, distributed across 69.3% of Brazilian municipalities. To assess the quality of ANC, six indicators were defined: ‘Group of medicines,’ ‘Protocols and patient flows,’ ‘Record-keeping practices,’ ‘ANC routine tests,’ ‘Protocols for early detection of pregnant women and ANC provision,’ and ‘Identification and ANC of low/high-risk pregnancies.’ Latent Class Analysis (LCA) was carried out to characterize the quality of care provided by PHC teams according to these six indicators.

Results

‘Identification and ANC of low/high-risk pregnancies’ indicator had the highest percentage of teams providing adequate care (39.5%), while ‘ANC routine tests’ had the lowest percentage (16.8%). The LCA identified three classes, and 20.5% of PHC teams had the probability of belonging to the class denominated ‘High adequacy.’

Conclusion

Using a national PHC-level dataset, we evaluated PHC teams’ ANC adequacy through six indicators. Brazilian PHC teams consistently show weaknesses across these indicators, particularly in essential care. This approach can guide global initiatives to evaluate the quality of ANC.
Unveiling the influence of adaptation time on xylanase and arabinoxylan-oligosaccharide efficacy: a study on nutrient digestibility, viscosity, and scanning electron microscopy in the small and large intestine of growing pigs fed insoluble fiber
Authors: Petry Amy L , Huntley Nichole F , Bedford Michael R , Patience John F
Published: November 2023

The experiment objective was to evaluate the impact of xylanase over time on viscosity and digestibility in growing pigs fed corn-based fiber. Twenty gilts with an initial body weight of 30.6 ± 0.2 kg (n = 5 per dietary treatment) were fitted with t-cannulae in the medial jejunum and terminal ileum, housed individually, and randomly assigned to one of four dietary treatments: low-fiber control (LF) with 10.4% total dietary fiber (TDF), 30% corn bran high-fiber control (HF; 26.4% TDF), HF + 100 mg xylanase/kg (XY; Econase XT 25P; AB Vista, Marlborough, UK), and HF + 50 mg arabinoxylan-oligosaccharide/kg (AX). Gilts were limit fed for three 17 d periods (P1, P2, P3); each included 5 d adaptation, 2 d fecal collection, 3 d ileal collection, 3 d jejunal collection, and 4 d related rate of passage study. Data were analyzed as repeated measures using a linear mixed model with surgery date as a random effect, and dietary treatment, period, and their interaction as fixed effects. Jejunal and ileal digesta viscosity did not differ among dietary treatments or periods (P > 0.10). There was a dietary treatment × period interaction for the apparent jejunal digestibility (AJD) of dry matter (DM), gross energy (GE), insoluble dietary fiber (IDF), neutral detergent fiber (NDF), total arabinoxylan (T-AX), total non-starch polysaccharide (T-NSP), and TDF (P≤ 0.05). In P1, LF had the greatest AJD of DM (15.5%), and relative to HF and AX, XY decreased it (9.3%, 10.1 %, and 6.3%, respectively). In P2, the AJD of DM in XY was greater than HF (11.7% vs. 9.1%) but did not differ from AX (10.5%). Relative to HF, in P3, XY increased AJD of DM (11.7 vs 15.3%), and AX decreased it (7.2%). For the AJD of NDF, AX performed intermediately in P1; in P2, relative to HF, XY, and AX increased the AJD of NDF (8.4%, 13.1%, and 11.7%, respectively), and in P3, XY, and LF did not differ (13.6 vs. 14.4%). A similar response was observed for the AJD of IDF and TDF, except for XY having the greatest AJD of IDF, T-AX, T-NSP, and TDF in P3 (P < 0.05). Compared to LF, irrespective of period, HF decreased the apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of IDF, TDF, and NDF (P < 0.05). Relative to HF, XY partially mitigated this effect, improving the AID and ATTD of TDF, IDF, and NDF (P < 0.05). Increased corn-based fiber decreased nutrient digestibility, but XY partially mitigated that effect in the small intestine through enhanced fiber digestibility when given sufficient adaptation time.
Double Marginalization, Market Foreclosure, and Vertical Integration
Authors: Choné Philippe , Linnemer Laurent , Vergé Thibaud
Published: November 2023

Double marginalization is a robust phenomenon in procurement under asymmetric information when sophisticated contracts can be implemented. In this context, vertical integration causes merger-specific elimination of double marginalization but biases the make-or-buy decision against independent suppliers. If the buyer has full bargaining power over prices and quantities, a vertical merger benefits final consumers even when it results in the exclusion of efficient suppliers. If on the contrary the buyer’s bargaining power is reduced after she has committed to deal exclusively with a limited set of suppliers, exclusion of efficient suppliers may harm final consumers.
High levels of short-chain fatty acids secreted by Candida albicans hyphae induce neutrophil chemotaxis via free fatty acid receptor 2
Authors: Khamzeh Arsham , Dahlstrand Rudin Agnes , Venkatakrishnan Vignesh , Stylianou Marios , Sanchez Klose Felix P , Urban Constantin F , Björnsdottir Halla , Bylund Johan , Christenson Karin
Published: November 2023

Candida albicans belongs to our commensal mucosal flora and in immune-competent individuals in the absence of epithelial damage, this fungus is well tolerated and controlled by our immune defense. However, C. albicans is an opportunistic microorganism that can cause different forms of infections, ranging from superficial to life-threatening systemic infections. C. albicans is polymorphic and switches between different phenotypes (e.g. from yeast form to hyphal form). C. albicans hyphae are invasive and can grow into tissues to eventually reach circulation. During fungal infections, neutrophils in particular play a critical role for the defense, but how neutrophils are directed toward the invasive forms of fungi is less well understood. We set out to investigate possible neutrophil chemoattractants released by C. albicans into culture supernatants. We found that cell-free culture supernatants from the hyphal form of C. albicans induced both neutrophil chemotaxis and concomitant intracellular calcium transients. Size separation and hydrophobic sorting of supernatants indicated small hydrophilic factors as responsible for the activity. Further analysis showed that the culture supernatants contained high levels of short-chain fatty acids with higher levels from hyphae as compared to yeast. Short-chain fatty acids are known neutrophil chemoattractants acting via the neutrophil free fatty acid receptor 2. In line with this, the calcium signaling in neutrophils induced by hyphae culture supernatants was blocked by a free fatty acid receptor 2 antagonist and potently increased in the presence of a positive allosteric modulator. Our data imply that short-chain fatty acids may act as a recruitment signal whereby neutrophils can detect C. albicans hyphae.
Incarceration and screen-detectable cancer diagnosis among adults in Connecticut
Authors: Richman Ilana B , Soulos Pamela R , Lin Hsiu-ju , Aminawung Jenerius A , Oladeru Oluwadamiloa T , Puglisi Lisa B , Wang Emily A , Gross Cary P
Published: November 2023

Although incarcerated adults are at elevated risk of dying from cancer, little is known about cancer screening in carceral settings. This study compared stage-specific incidence of screen-detectable cancers among incarcerated and recently released people with the general population, as a reflection of screening practices. We calculated the age- and sex-standardized incidence ratios (SIR) for early- and late-stage cancers for incarcerated and recently released adults compared to the general Connecticut population between 2005 and 2016. Our sample included 143 cancer cases among those incarcerated, 406 among those recently released, and 201 360 in the general population. The SIR for early-stage screen-detectable cancers was lower among incarcerated (SIR = 0.28, 95% CI = 0.17 to 0.43) and recently released (SIR = 0.69, 95% CI = 0.51 to 0.88) individuals than the general population. Incidence of late-stage screen-detectable cancer was lower during incarceration (SIR = 0.51, 95% CI = 0.27 to 0.88) but not after release (SIR = 1.32, 95% CI = 0.93 to 1.82). Findings suggest that underscreening and underdetection of cancer may occur in carceral settings.
Moslosooflavone protects against brain injury induced by hypobaric hypoxic via suppressing oxidative stress, neuroinflammation, energy metabolism disorder, and apoptosis
Authors: Zhang Jie , Zhao Tong , Zhang Pengpeng , Shi Zhiqun , Da Qingyue , Ma Huiping , Jing Linlin
Published: November 2023

Objectives

To investigate the protect effect of moslosooflavone against brain injury induced by hypobaric hypoxia (HH) in mice.

Methods

Protective effects of moslosooflavone in oxidative stress, neuroinflammation, energy metabolism disorder, and apoptosis were studied in HH-induced brain damage mice. The pathological morphology in the cortex of mice was determined by hematoxylin and eosin staining. The related protein expressions were detected by western blot.

Key findings

Moslosooflavone improved HH-induced brain histopathological changes, reduced the contents of ROS and MDA, and elevated the levels of antioxidant enzymes and GSH in HH-exposed brains of mice. Moslosooflavone also markedly enhanced the ATPase activities and PK, ATP contents, while reducing LDH activity and the LD, TNF-α, IL-1β, and IL-6 contents HH-exposed brains of mice. In addition, moslosooflavone notably decreased the expression of HIF-1α, VEGF, Bax, and cleaved caspase-3 dramatically increasing the expression of Bcl-2, Nrf2, and HO‑1 in HH-exposed brains of mice.

Conclusions

Our current studies indicate that moslosooflavone protects HH-induced brain injury possibly through alleviating oxidative stress and neuroinflammation, maintaining the balance of energy metabolism, and inhibiting cell apoptosis.