Parkinson’s disease (PD) is often clinically associated with posture instability and more easily falling. The Berg balance scale is a clinical indicator commonly used to subjectively evaluate a patient’s balance ability. Meanwhile, computerized force platforms have been used in research on postural control. The various parameters obtained from posturography are interpreted to assess balance ability. The present study aims to explore the correlations between posturographic variables and the BBS, and furthermore to efficiently evaluate postural instability and fall risk of early and moderate PD patients.A total of 46 PD patients were involved in the experiment. Patients were asked to perform BBS tests and force platform tests under eye open (EO) and eye closed (EC) conditions. The recorded COP signal was analyzed with the time domain statistical method, the frequency domain method of Power Spectral Density (PSD), and structural methods of Stabilogram Diffusion Analysis (SDA), Sway Density Plot (SDP) to retrieve different posturographic variables. The correlation between posturographic variables under EO and EC conditions with BBS was compared statistically. The significantly correlated posturographic parameters were then applied to analyze posturographic differences between different groups: faller vs. non-faller .Among the different posturographic parameters, the prediction ellipse area, the slope of the regression line at a high-frequency band of PSD in the medial-lateral (ML) direction, the crossover point of the regression lines of SDA in the anterior-posterior (AP) direction, and the distance between successive peaks of SDP had significant correlations with BBS. These selected BBS-related parameters also showed significant differences between faller and non-faller. The selected posturographic parameters can be used as effective indicators to evaluate the balance ability of Parkinson’s disease patients.The online version contains supplementary material available at 10.1186/s12883-023-03386-1. Parkinson’s disease (PD), is a neurodegenerative disease clinically characterized by symptoms such as static tremoring, mobility delays, reduced voluntary movement, posture and balance disorders, and freeze of gait . PostureAt present, clinical rating scales, such as Berg Balance Scale (BBS) are commonly adopted as clinical methods to evaluate patients’ balance ability , 7. BBS Postural instability can be quantitatively assessed under open and closed eyes conditions using force platforms, which provide a more objective and sensitive measurement than clinical scales, despite the different intra-subject variability of the computed posturographic parameters –15. The Time domain parameters have been used to evaluate postural stability in PD patients in many studies. The change in body sway can be described by many variables, such as area, velocity, path, root mean square and standard deviation of COP . PD patiComparatively, frequency domain global parameters and structural parameters are hypothesized to reveal the control mechanism of human body balance , 30, 31.Since the characteristic variables obtained from COP data reveal the postural control ability, we hypothesize that these variables may correlate with BBS in PD. The current study aims to characterize the PD patients’ posturography in quiet standing through a comprehensive analysis of COP data with global and structural variables, and to correlate these variables with the BBS total score. By correlation, optimal posturographic variables can be retrieved to evaluate the balance ability of PD patients, and the underlying balance control mechanisms in PD patients can be explored.A total of 46 patients, including 24 males and 22 females, with an average age of 68.2 ± 7.1 years, participated in the experiment. The PD patients had baseline characteristics with a disease duration of 3.96 ± 1.84  was noted as the x direction, and the coordinate origin was the central point of the platform. Before the experiment, participants were informed of the test procedure. As shown in Fig. In this study, the force platform  was used to retrieve patients’ COP time series. The sampling frequency of the force measuring system was 500 Hz. According to the position of patients standing, anterior-posterior (AP) was noted as the Before each measurement, the range of the distance between heels was reconfirmed within 20 ± 3 cm, and the range of angles of the foot with respect to AP axis was also reconfirmed within 20 ± 2 degrees. Their eyes were focused on a black dot on the wall 3 m in front. The participants were tested under two states: open-eye state (EO), as shown in Fig. x and y directions were removed before calculation. The difference in the average value of the COP displacements between patients was in the range of 2 to 40 mm. In this study, global and structural parameters were calculated as shown in Table The time series COP data were collected at 500 Hz sampling rate and were processed offline using the Matlab® software with a 10 Hz, fourth-order, low-pass Butterworth filter. After that, the posturographic parameters  represents the strength variation of the signal as a function of frequency. The PSD was calculated by the fast Fourier transform (FFT) method . The PSDSDA_SSlope, SDA_LSlope, SDA_CP) were calculated and are indicated in the Fig. The stabilogram diffusion analysis (SDA) method is a quantitative statistical measure of the apparent random variations in COP trajectories. The COP velocity signal is decomposed into different time scale parts . One parSDP_MP, SDP_MD, SDP_MT) were depicted in the Fig. SDP_MP) was the mean value of the peaks (number of samples) in SDP. The mean value of distances (SDP_MD) was the mean displacement between successive peaks, and the mean value of time interval (SDP_MT) was the mean time interval between successive peaks.The sway density plot (SDP) is based on a concept proposed by Baratto et al. . The SDPIBM SPSS statistics 25.0 was used for statistical analysis. Baseline characteristics and postural parameters were summarized using either means and standard deviations (SD), or frequencies and percentages as appropriate. Shapiro-Wilk test was performed to evaluate the normality of demographics and posturographic parameters in each group. The non-parametric Spearman correlation was used to calculate the correlation between each variable with BBS values. The paired sample t test or Mann-Whitney test was used to compare posturographic differences between faller with non-faller. A P value < 0.05 was considered statistically significant. To determine the sample size, a power analysis was performed based on the previously published studies . A samplCOP_PEA) had the highest correlation with BBS at EO state . Among the frequency domain variables, the slope of the regression line at a high-frequency band of PSD in the medial-lateral (ML) direction (PSD_HSlopex) was most correlated with BBS at EO state . With regard to the structural variables, the highest statistically significant correlation was the crossover point of the short-term and long-term regional regression lines in AP direction (SDA_CPy)  at EO state. The second most relevant structural parameter was the population mean value of the distance between successive peaks (SDP_MD) .Correlations between posturographic parameters with BBS were listed in Table COP_PEA, PSD_HSlopex, SDA_CPy and SDP_MD were the most relevant to BBS posturographic variables. The correlations of these four parameters with BBS under both EO and EC states were shown in Table COP_PEA , PSD_HSlopex , SDP_MD . However, the variable SDA_CPy did not show correlation with BBS at EC .As mentioned above, COP_PEA with P value = 0.015; PSD_HSlopex with P value = 0.011; SDA_CPy, with P value = 0.05; SDP_MD with P value = 0.015).The four correlated variables with BBS in the EC state were then applied to analyze the difference between two groups of PD patients: faller vs. non-faller . The four parameters were all significantly different between the faller and non-faller groups, as depicted in the Fig. This study explored the characterization of posturographic parameters and their correlation with the functional balance ability in PD patients. Functional balance was evaluated by the clinical method of the Berg Balance Scale, while their postural stability was measured and analyzed with their COP data collected from a precise force platform.COP_PEA, PSD_HSlopex, SDA_CPy,SDP_MD were the most correlated variables with BBS. In the state of EC, the variables COP_PEA, PSD_HSlopex, SDP_MD also showed significant correlation with BBS. However, in the EC state, there was no obvious correlation between SDA_CPy and BBS. Visual input has predominantly influenced corrective responses for the control of AP sway in all bandwidths [SDA_CPy was reduced without visual feedback, and its correlation with BBS was reduced. These four variables were compared between the faller and the non-faller groups, and all reached the extent of significant difference. The result was also consistent with the fact that BBS predicts the risk of falling [Among the global and structural posturographic variables, several variables showed significant correlation with BBS in the state of EO, and ndwidths . When thndwidths . Consequ falling .COP_PEA obtained from posturography are used to assess human postural stability. For example, relatively larger sizes of area are considered signs of postural instability [COP_PEA was the highest correlated variable with BBS and can be used as an effective indicator to assess the standing balance of PD patients.Global COP parameters like tability . In our PSD_Hslopex) was positively correlated with BBS in the ML direction. There was strong evidence that most of the COP power was exhibited between 0.01 and 1.2 Hz [Analysis with PSD transfers the time series of the COP position signal into frequency domains. Examining the power spectra of the COP time series provides more information about the structure of the COP signal. As shown in the results, the slope of the regional regression line of 0.5–1.2 Hz  can be used to represent the characteristics of the short-term persistent and long-term anti-persistent signals. The postural control system adopts an open-loop control scheme associated with persistence, while a closed-loop control scheme is associated with anti-persistent signals [SDA_CP result indicates that PD patients with higher BBS scores would more actively adjust their postural stability. This is consistent with the results given by Perera et al. that the frequency of PD patients’ intermittent adjustment was positively correlated with balance ability [The results of SDA showed that the crossover point (CP) in the AP direction had a negative correlation with BBS under EO. In the diffusion diagram obtained by SDA, there were two straight fitting lines Fig.  with slo signals . Recentl signals . The COP signals . The siz signals . The sma ability .SDP supposedly decomposes the motion control into a series of motion commands, and its variables reflected the ability of the ankle joint to receive feedforward control commands in human body control [SDP_MD was negatively correlated with BBS in the EO state, meaning that the spacing between SDP peaks increased as BBS decreased and indicating a decreasing frequency of patients receiving feed-forward signals. As previously mentioned in the intermittent control theory, preprogrammed command is very important in postural control, and a decreasing frequency of receiving feed forward indicates reduced postural control activity, which is often resulted from impairment of the Central Nervous System (CNS). Jacono et al. studied the relationship between SDP and the underlying postural stabilization process, and found that SDP is associated with the critical ankle torque component for overall stability of the human’s standing posture [The  control . The exp posture .COP_PEA, (r=-0.55)which was only mid-strong if only the correlation coefficient was considered. This study pursued to correlate the posturographic variables with the total BBS score as commonly applied in clinical diagnosis. The BBS has 14 items and their roles in the balance assessment are different. BBS items related to single leg standing (from 13 to 14) are the most distinctive evaluation items for assessing PD patients, whereas items related to double legs (from 1 to 12) are low distinguishable [The strongest correlation presented was the variable uishable . The patCOP_PEA was statistically correlated with BBS in PD patients and can potentially be applied as quantitative indicators of balance ability in PD patients. In addition, frequency analysis and structural analysis by PSD, SDA, and SDP revealed that many variables obtained from the analyses were also statistically correlated with BBS. Since the frequency analysis and structural analysis reflect corresponding postural control mechanisms, the increase or decrease in these variables may imply enhancement or impairment of postural control in PD patients. Moreover, different stages of PD result in different balance ability. In the future research, the comparison of the balance ability between different stages of PD shall be studied. Although the subjective posturographic measurements cannot replace the observation scaling method in clinic applications, it still has merits as a supplemental diagnostic measure. The findings demonstrated that some parameters which have most correlated with BBS may be given particular attention during clinical practice. There exist certain limitations in the current study, for example, intra-subject variability of posturographic parameters (such as COP_PEA) was not performed, which may affect the accuracy of the statistical results. Also, the place of foot may cause variation of the standing position and affect obtained COP signal for each subject.The current study revealed that the global posturographic variable This study confirmed that the Berg Balance Scale is associated with some posturographic parameters of PD patients during quiet standing. The findings demonstrate that some posturographic parameters could be applied as indices for the assessment of PD patients balance ability and fall risk. The moderate correlation between some of the structural variables and BBS can be explained by the postural control mechanisms involved in the structural analyses. These indices would be helpful for the clinical diagnosis of balance ability in PD patients.Below is the link to the electronic supplementary material.Supplementary Material 1


Endothelial dysfunction is the primary step for the development of CKD-related cardiovascular disease. Early prediction and management can influence patient survival. Serum testing of FGF 23 hormone and urinary phosphate excretion were studied as predictors of all-cause cardiovascular morbidity in CKD patients; however, their relation to endothelial dysfunction is controversial. A combination of both in one index is hypothesized to increase their sensitivity in detecting endothelial dysfunction, especially in the early stages of CKD before the dominance of hyperphosphatemia, the original risk.A cross-sectional comparative analysis between thirty CKD stage 3 patients and sixty stage 4–5 CKD patients was conducted. All patients were tested for markers of mineral bone disorders including serum FGF 23 and 24-h urinary phosphate excretion. A combination of both in one index (nephron index) is calculated and hypothesized to correlate with nephron number. Endothelial dysfunction was assessed by measuring the post-occlusion brachial flow-mediated dilatation (FMD).r = 0.74, P 0.01). This was not applied to stage 4–5 CKD patients where serum phosphorus , intact PTH , uric acid , and measured GFR  were the highest correlates to FMD; the Nephron index had the weakest correlation  and is not predictive of endothelial dysfunction.In univariate and multivariate regression analyses, the nephron index was the only predictor of endothelial dysfunction in individuals with stage 3 CKD (Nephron index calculation showed better correlation with endothelial dysfunction than using any of its determinants alone in early stages of CKD when FGF 23 levels are just beginning to rise. In advanced CKD patients, hyperphosphatemia, hyperparathyroidism, hyperuricemia, and measured GFR are more reliable than nephron index. The vascular endothelium regulates multiple vital processes, including vascular tone and permeability, inflammatory responses, thrombosis, and angiogenesis. Endothelial dysfunction (ED) is a major pathogenetic inducer of atherosclerosis and cardiovascular disease. Chronic kidney disease (CKD) is characterized by reduced nitric oxide bioavailability, which is almost present in all patients approaching end-stage renal disease (ESRD). Numerous factors can affect the expression of endothelial NO synthase and contribute to the low NO bioavailability in CKD . Among tThis cross-sectional study was conducted on 90 CKD adult patients, who were recruited from Mansoura University Hospital  and attended Nephrology Clinic, Mansoura University, over a period of 2 years from 2019 to 2021.2 or markers of kidney damage. The study population was grouped according to measured creatinine clearance to Stage 3 CKD (30 patients) with creatinine clearance between 30 and 60 ml/min/1.73 m2, and stage 4–5 CKD (60 patients) with creatinine clearance below 30 ml/min/1.73 m2. We included CKD patients aged ≥ 18 and The patients were selected based on their measured creatinine clearance by 24-h urine collection. CKD diagnosis was established according to KDIGO 2012 guidelines  which deCalculation relied upon a previous cross-sectional report by Recio-Mayoral A et al. . Using tThe current study sample size guaranteed a 99% confidence estimate of mean FMD with a 0.6% margin of error.All patients were subjected to history taking, physical examination, and laboratory evaluation including Serum calcium, serum phosphorus, intact parathyroid hormone (iPTH), and total urine collected for 24 h was sent to the laboratory for estimating creatinine clearance and daily phosphate excretion. Serum human fibroblast growth factor-23 (FGF23) was assayed by enzyme-linked immunosorbent assay (ELISA) supplied by SinoGeneClon Biotech Co. The nephron index represents nephron number and is suggested to be correlated positively with the ratio of urinary phosphate excretion (mg/day) to serum FGF23 .Evaluation of endothelial dysfunction through brachial artery flow-mediated dilatation (FMD) was performed according to the American College of Cardiology guidelines . The brat test was used to compare parametric data of independent variables of the 2 groups, and Mann–Whitney U test was used to compare non-parametric data of independent variables of the 2 groups. Spearman’s rank-order correlation is used to determine the strength and direction of a linear relationship between two non-normally distributed continuous variables and /or ordinal variables. Multivariable linear regression analysis was done to determine the predictors of endothelial dysfunction in CKD patients. A P value less than 0.05 was considered statistically significant.Data were fed to the computer and analyzed using IBM SPSS Corp. Released in 2013. IBM SPSS Statistics for Windows, Version 22.0. Qualitative data were described using numbers and percentages. Quantitative data were described using median (minimum and maximum) for non-parametric data and mean ± standard deviation for parametric data after testing normality using the Kolmogorov–Smirnov test. For qualitative data Chi-Square test was done for comparing 2 groups, the Student 2. Stage 3 CKD patients had significantly higher hemoglobin, serum calcium, and nephron index values. They also have significantly lower phosphate, serum FGF 23, PTH, and uric acid levels. Median value of FMD percentage was much lower in CKD patients with creatinine clearance below 30  prevalence which is much higher in CKD patients with creatinine clearance below 30 ml/min/1.73 mr = 0.47, P = 0.006). However, in CKD patients with creatinine clearance below 30 ml/min/1.73 m2, FMD change was positively albeit weakly correlated to nephron index  and measured GFR. In the same group, FMD change was negatively correlated to duration of HTN, serum phosphorus, PTH, serum bicarbonate, and serum FGF 23 levels . Of them, the nephron index was the only statistically significant predictor in the supposed regression model. In the patients with measured GFR below 30 ml/min/1.73 m2, associations of FGF23 with mortality and cardiovascular events are stronger in persons with lower urinary phosphorus excretion independent of PTH and kidney function. In such individuals, the renal tubular response to FGF23 may be suboptimal [There is day-by-day growing evidence that CKD per se is one of the most important risk factors for cardiovascular morbidity and mortality . Endotheboptimal . In 142 boptimal . In anotboptimal . To our The Nephron index can be a more accessible tool for the prediction of ED in early CKD patients than the known complex biomarkers of ED which are not freely available. This index is a good estimate for the resistance of phosphaturic action of FGF 23 which is the primary step in the CKD-related cardiovascular effect.


APP) mutations are implicated in hypertension development. Nonetheless, studies on the association of APP gene polymorphism and promoter methylation with hypertension are limited. Therefore, this case–control aims to evaluate the genetic association of APP gene polymorphism and promoter methylation with EH in Guizhou populations.Single-nucleotide polymorphisms (SNPs) and DNA methylation are crucial regulators of essential hypertension (EH). Amyloid precursor protein  in the Guizhou province of China to analyze 11 single-nucleotide polymorphisms  in the χ2 = 6.343, P = 0.039). The CC genotype reduced the risk of hypertension compared to the TT or TC genotype . For rs2040273 in the Miao population, AG or GG genotype reduced the hypertension risk compared with the AA genotype . Haplotype TCC (rs364051–rs438031–rs463946) increased the risk of EH in Guizhou . Each 1% increase in CpG_19 (− 613 bp) methylation level was associated with a 4.1% increase in hypertension risk . Each 1% increase in CpG_1 (− 296 bp) methylation level was associated with an 8% decrease in hypertension risk in women . CpG_19 significantly correlated with systolic blood pressure . The methylation levels of CpG_19 in hypertensive patients with rs466433, rs364048, and rs364051 minor alleles were lower than that with wild-type alleles (P < 0.05). Moreover, rs467021 and rs364051 showed strong synergistic interaction with EH . CpG_11, CpG_19, and rs364051 showed weak synergistic interaction with EH .In the Han population, the rs2211772 genotype distribution was significantly different between disease and control groups (APP gene may be linked to EH in Guizhou populations. Our findings will provide novel insights for genetic research of hypertension and Alzheimer's disease.In summary, rs2211772 polymorphism and promoter methylation level of The online version contains supplementary material available at 10.1186/s40246-023-00462-y. In a national survey of hypertension in 2018, the prevalence of hypertension among Chinese adults was 24.7% (approximately 274 million). Hypertension is a serious health problem in China . DNA metAPP) is a gene located in the 21q21.3 region of human chromosomes and encodes the production of the amyloid precursor protein. β-Amyloid (Aβ) is a polypeptide produced via hydrolysis of amyloid precursor proteins mediated by β- and γ-secretases; it circulates in the blood, cerebrospinal fluid, and interstitial fluid  Lun Shen No. 45. All subjects voluntarily participated in the study and signed informed consent.The inclusion criteria for the hypertension group were as follows: (1) meet the criteria of the 2010 Chinese Guidelines for the Prevention and Treatment of Hypertension: (2) age ≥ 18 years; blood pressure measured three times on different days, resting systolic blood pressure ≥ 140 mmHg (1 mm Hg = 0.133 kPa) and/or diastolic blood pressure ≥ 90 mmHg; (3) patients diagnosed with EH and currently taking antihypertensive drugs with normotensive blood pressure. All study subjects were Han, Miao, and Buyi people living in Guizhou, with no history of interracial marriage within three generations. Patients with secondary hypertension, congenital heart disease, cardiomyopathy, valvular disease, liver and kidney failure, pregnant women, substance abuse, or a history of mental illness were excluded.The inclusion criteria for the control group are as follows. (1) systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg; (2) no history of hypertension; (3) no antihypertensive drugs; all study subjects were Han, Miao, and Buyi people living in Guizhou, with no history of interracial marriage within three generations. Exclusion criteria were similar to that of the hypertension group.2) divided the study subjects into low BMI (BMI < 18.5 kg/m2), normal BMI (18.5 kg/m2 ≤ BMI < 24.0 kg/m2), and overweight BMI (24.0 kg/m2 ≤ BMI < 28.0 kg/m2), BMI obesity (BMI ≥ 28.0 kg/m2).All research subjects recorded basic information including nation, gender, age, blood pressure, height, and weight, and were calculated based on the “Guidelines for the Prevention and Control of Overweight and Obesity in Chinese Adults”; the body mass index (BMI) formula  was used to extract DNA from EDTA anticoagulated venous blood of the research subjects, and the concentration and purity were determined by NanoDrop2000 (Thermo Fisher Scientific Inc.). SNP detection requirements included: DNA concentration > 20 ng/μl, AIn the dbSNP database , the SNPAPP gene, and the target sequence is located at chr21:26,171,035–26,171,512 (GRCh38/hg38), covering 478 bp, including 12 detectable CpG sites . PCR primer sequences of the corresponding fragments were synthesized using the PAGE primer purification method  or transcriptase cleavage reaction (for methylation detection), resin purification, chip spotting, and mass spectrometry detection were sequentially performed using the MassARRAY detection platform. The TYPER 4.0  was used to collect the original data, genotyping map, and other test results. The sequences of CpG sites between two bases A were digested to obtain small fragments with similar molecular weight, then these CpG sites were combined and detected, and the result was the average methylation degree of these CpG sites. Therefore, CpG_3, CpG_4, and CpG_5; CpG_6 and CpG_16; CpG_8 and CpG_9 were detected as a unit.P < 0.05 indicated a statistically significant difference.Statistical analyses were performed using the SPSS 26.0 software . Normal measurement data were expressed as mean ± standard deviation (mean ± sd), and comparison between groups was performed by the Student's t test; skewed measurement data were represented by , and comparison between groups was performed by Mann–Whitney test. The count data were expressed as frequency (constituent ratio), and the comparison between groups was performed using the Chi-square test or Fisher's exact test. Binary logistic regression was used to analyze the relationship between SNPs and EH. Allele and genotype frequencies and the Hardy–Weinberg equilibrium test were calculated using the SNPStats online software . LinkageAdditional file 1: Table S1.APP allele and genotype distribution.


Hypertension is a critical component of cardiovascular disease progression in patients with chronic kidney disease, and specifically diabetic kidney disease (DKD). Causation versus correlation remains up for debate, but what has been confirmed is the delay of DKD progression when hypertension is controlled or moved to guideline drive ranges. Many medications have been studied and used in real world experience for best outcomes, and we discuss below the proven winners thus far making up the renin angiotensin aldosterone system. As well, we discuss guideline changing medications including sodium-glucose cotransporter 2 inhibitors and newer generation mineralocorticoid receptor antagonists. With the growing prevalence of diabetes and DKD in the population, newer agents are emerging in multiple drug class and will be highlighted below. Clinicians continue to search for the optimal care plans for this challenging patient population. When considering the treatment of hypertension in diabetic patients with chronic kidney disease, two main questions arise: What should our target blood pressure be, and what pharmacologic interventions should we use to achieve these targets? The answer to the first question has been the topic of much debate over the past decades, with a shift from a less intensive 130/80 goal historically to a trend toward tighter control post-SPRINT reflected in 2021 KDIGO Guidelines [Pharmacological blockade of the renin–angiotensin–aldosterone system (RAAS) using angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) has become the cornerstone for patients with type 2 diabetes (T2D) and kidney involvement. Several clinical trials have demonstrated that the use of RAAS inhibitors (RAASi) slows chronic kidney disease (CKD) progression and reduces proteinuria in patients with proteinuric CKD, including diabetic kidney disease (DKD) ,7,8,9,10p = 0.88), but overall, the trial has been a cornerstone for establishing RAASi as a major difference makers.There are two seminal randomized clinical trials showing kidney benefits from RAASi independent of their blood pressure-controlling effects: the IDNT  and the On the other hand, for patients with CKD, hypertension, diabetes, and no albuminuria, current evidence does not support clear clinical benefits of RAASi for CKD progression, and other antihypertensive drugs are appropriate for BP management; however, the Kidney Disease Improving Global Outcomes guidelines (KDIGO) stated that these patients may be preferably treated with RAASi (ACEi or ARB), given the cardiovascular (CV) protection benefits, especially in patients with a higher glomerular filtration rate (GFR)1. There has been some criticism about the superiority of RAS inhibitors compared to other hypertensive agents in albuminuric patients , but genIt is also important to consider that beyond the need for renoprotection, patients with kidney insufficiency have a substantially increased risk of cardiovascular death . The HOPOverall, there was no difference between ACEi and ARB for the outcomes of MI, stroke, and kidney function in CKD patients with diabetes, with or without albuminuria . HoweverRAASi agents should be utilized using the highest approved tolerated dose because the proven benefits were achieved in trials using these doses. Changes in BP, serum creatinine , and serGiven the potent morbidity and mortality benefits described in patients with DKD, every effort should be made to continue therapy with RAS blockade. In fact, discontinuation of RAS blockade for hyperkalemia was associated with increased mortality and CV events . RAASi s2, discontinuation of RAASi did not significantly improve kidney function compared to the RAASi continuation group and did not prevent any patients from starting dialysis during the study period [Traditionally, many clinicians discontinued RASi in very advanced CKD to try to preserve eGFR. The STOP-ACE trial showed that in advanced CKD, eGFR < 30 mL/min/my period  This supy period .Though the combined use of ACEi and ARBs is not recommended, there is certainly a role for additive blockade of the RAS system with the addition of mineralocorticoid receptor antagonists. This class of medication has been studied extensively in patients with heart failure, in whom ACEi and ARBs are the standard care.Non-specific MRAs, such as spironolactone, eplerenone, and drospirenone are steroidal in nature. These drugs bind directly and block the mineralocorticoid receptor, preventing its activation by aldosterone or 11-deoxycorticosterone. They also inhibit the receptors stimulated by testosterone and dihydrotestosterone, leading to common side effects such as gynecomastia, breast tenderness, and feminization. Specific MRAs are non-steroidal and were designed to minimize those adverse effects, including finerenone and esaxerenone. p = 0.008), lower risk of sudden cardiac death , and improvement in systolic and diastolic blood pressure compared with placebo. Notably, these benefits came with a small additional risk of hyperkalemia (5% versus 3.9% in placebo) despite the exclusion of patients with hyperkalemia at initiation [p < 0.001) as well as an overall reduction in systolic blood pressure of 2.5 ± 17.2 mmHg in comparison to placebo (p = 0.001).As previously discussed, patients with DKD are at high risk of cardiovascular events. Though not specific for patients with diabetic kidney disease, the EPHESUS trial assessed the efficacy of eplerenone in patients with heart failure and myocardial infarction, demonstrating a benefit in decreasing mortality , with the benefit driven primarily by a lower incidence of hospitalization for heart failure. Not all individual secondary endpoints were significant, but the trial was positive overall for the composite endpoint.The later FIGARO trial confirmed these cardiac benefits in a diabetic population when comparing finerenone to placebo in diabetic CKD patients already on ACEi/ARB; the mean difference in change from baseline in systolic blood pressure was −3.5 mmHg at month 4 and −2.6 mmHg at month 24 . The priThe benefits of MRA addition are not limited to decreased cardiac mortality. However, the addition of MRA to ACEi/ARB in proteinuric diabetic patients has long been a treatment strategy to improve albuminuria and, theoretically, slow the progression of kidney disease. Though no large clinical trials had investigated the addition of a mineralocorticoid receptor antagonist to standard RAS blockade (ACEi/ARB) in diabetic patients for renoprotection with eGFR endpoints, meta-analyses showed a significant and dramatic (near 30%) reduction in albuminuria with this combination .Then, in the FIDELIO-DKD trial, patients with CKD and type 2 diabetes mellitus were randomized to finerenone or placebo . In thisOne of the risks of using MRAs is the associated risk of hyperkalemia, which is theoretically increased when blocking steps of the RAAS in sequence. Indeed, a meta-analysis of small trials adding steroidal and non-steroidal MRAs to ACE/ARB found that the risk of hyperkalemia was higher with the combination of medications than with ACE/ARB alone. This was not seen in the EMPHASIS trial of heart failure patients, in which 93% of patients were on ACE/ARB concurrently with eplerenone and which notably excluded patients with a serum potassium of >5 mmol/L from randomization. Similarly, the FIDELIO-DKD trial did not randomize any patients with a starting potassium of >4.8 mmol/L and noted fairly low risk of mild (21.4%) and moderate (4.5%) hyperkalemia over 2.6 years of follow-up. At initiation, 2.5% of patients were on potassium-lowering medications at baseline, and by the end of the study, approximately 10% of patients needed such medications ,29.The design of the more recent studies of finerenone can be considered when making therapeutic decisions for our patients. Patients in whom serum potassium is near or above 5 mmol/L on ACE/ARB alone should be considered to be outside the safety parameters included within these studies, and the decision to start MRA should be made carefully. In all patients, routine potassium monitoring, occasional temporary treatment interruption, and dose reduction are advised in the event of hyperkalemia. Combination with oral potassium binders can also be considered for hyperkalemic patients on RAS inhibition therapy. This strategy was tested in the OPAL-HK Trial and found to be effective in patients with CKD . It is wAlthough thought of as a glucose-lowering medication with proven cardiovascular benefits, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown positive effects on blood pressure. Early evidence in the EMPA-REG OUTCOME and CANVAS trials demonstrated reduced blood pressure in treatment groups, the cause of which has been the subject of debate and research ,31.The mechanism of this observed blood pressure-lowering effect is thought to be secondary to natriuresis and osmotic diuresis via local inhibition of RAAS. The increased sodium delivery to the juxtaglomerular apparatus is thought to cause an increase in sodium excretion by 15–20% . These hp < 0.001) [p = 0.0002). SGLT2i had a synergistic effect with calcium channel blockers and beta-blockers but not with thiazide diuretics [p = 0.0025) at 24 weeks [In 2015, investigators evaluated the blood pressure effect of empagliflozin in patients with type 2 diabetes and hypertension, observing a systolic BP reduction of 3.4 mmHg with 10 mg of empagliflozin and 4.1 mmHg with 25 mg of empagliflozin, respectively  . In a triuretics . Ferdina24 weeks . A post 24 weeks . In all 24 weeks . Although these BP improvements are significant, they are small in magnitude, and additional studies are needed to determine their role as primary antihypertensive agents. There are concerns about orthostatic hypotension with the use of any diuretic. However, a meta-analysis of 16 randomized controlled trials (RCT) demonstrated that SGLT2i were not significantly associated with orthostatic hypotension. This meta-analysis noted that if baseline BP ≥ 130/80 mmHg, there was an increasing risk of orthostatic hypotension and a trend toward increased risk in patients with longer duration of T2DM .SGLT2i might have a role in cases of resistant hypertension  ,44,45. ILastly, diverse representation in clinical trials is very important, as clinicians must ensure the treatment is effective for other racial/ethnic populations. Black individuals’ participation in these trials is low. Although underrepresentation continues in clinical trials, several efforts have been made to decrease the gap, as these medications can reduce and theoretically eliminate disparities if they are widely prescribed ,48.In general, SGLT2i are well-tolerated, and data about their safety has been replicated multiple times. The risk of hypoglycemia appears to be non-significant; however, it is advised to adjust insulin or sulfonylureas if needed and continue blood glucose monitoring . Five laEuglycemic diabetic ketoacidosis (DKA) has a low incidence and has been shown to be statistically non-significant. Although it is recommended to be cautious about starting SGLT2is in diabetic patients with peripheral vascular disease, only one trial demonstrated a higher risk of lower limb amputation with canagliflozin . HoweverThe ROTATE 3 study, a randomized crossover clinical trial of dapagliflozin and eplerenone taken together, demonstrated a presumed physiologic principal that glycosuria may increase potassium excretion, as the combination in the study decreased the risk of hyperkalemia  . In a ra2. The non-steroidal MRA finerenone is recommended in patients with CKD and albuminuria if eGFR is at least 25 mL/min/1.73 m2 as a class I recommendation with an “A” level of evidence [In the most recent guidelines for hypertension, SGLT2i, and non-steroidal MRAs are mentioned as having mild to moderate BP effects in comparison to classical anti-hypertensives but with the added benefit of improving cardiovascular and kidney outcomes. The 2023 European Society of Hypertension, in addition to the standard recommendation of starting with ACEi/ARBs, suggests adding SGLT2i for patients with diabetic and non-diabetic CKD if eGFR is at least 20 mL/min/1.73 mevidence . The AHAevidence .In the ADA-KDIGO joint statement for the management of diabetes in patients with CKD, SGLT2i is recommended as a first-line add-on therapy, and non-steroidal MRAs are recommended as additional risk-based therapy in patients with persistent albuminuria despite maximum dose of RAAS blockade . Not allIt is an exciting time for those who care for patients with diabetic kidney disease. Several agents are being tested for efficacy in this population for additional benefit beyond hypertension control. SGLT2i have been increasingly studied on the secondary downstream effects. Some evidence has suggested that chronic hypoxia may be the primary pathophysiological pathway driving diabetic kidney disease and CKD, among other causes. Diabetes mellitus is thought to compromise the oxygen balance by impairing oxygen delivery owing to hyperglycemia-associated microvascular damage and exacerbating oxygen demand owing to increased sodium reabsorption as a result of SGLT upregulation and glomerular hyperfiltration. Adding an SGLT2i may decrease hypoxia-inducible factor-1alpha  in the kidney, revealing less tissue hypoxia . More rePentoxifylline is a nonspecific phosphodiesterase inhibitor that has anti-inflammatory properties. In vitro, it showed promise as it reduced proliferation and differentiation of renal fibroblasts . SubsequMeanwhile, while GLP-1 agonists have gained popularity for their role in weight loss and glucose control, their independent renoprotective effects have also come into the limelight. The GLP-1 receptor is expressed in the renal blood vessels, cortex, and tubules, and its inhibition has been shown in vivo and in animal models to decrease pro-fibrotic signaling. For example, in the rat model of obesity-related glomerulonephropathy, TNF-alpha signaling was decreased in response to liraglutide treatment, and morphological changes to podocytes were improved . To thatOther novel therapies are upcoming in the kidney space for CKD that may offer unknown insights and clinical improvements. Tirzepatide (LY3298176), a novel insulinotropic polypeptide and GLP-1 combination injection is being studied in combination with ACEi/ARB in the TREASURE-CKD trial . This study will look at patients with diabetes and outcomes of kidney oxygenation, UACR change, and body weight. Improvements in these parameters may have a positive impact on measured blood pressure concomitantly. The ZENITH-CKD trial  is ongoing, which combines SGLT2i dapagliflozin with ETA receptor antagonist zibotentan in patients with CKD . PrimaryWhen considering the treatment of hypertension in diabetic patients with chronic kidney disease, a focus should be made to maximize therapy, which demonstrates additional benefits in proteinuria reduction, prevention of eGFR decrease, or cardiovascular benefit. Though hyperkalemia and cost can be dose- or class-limiting, these medications should be maximized when possible. Novel therapies such as pentoxifylline and GLP-1 agonists may provide some blood pressure-neutral interventions for diabetic kidney disease and could be used simultaneously with existing therapies. Chronic hypertension is a major public health problem, and existing drugs like SGLT2i and non-steroidal MRAs have shown cardiovascular and kidney benefits in major clinical trials. The addition of SGLT2 inhibitors and finerenone should be considered in the treatment of hypertension as well as resistant hypertension.


Hyperandrogenism and supraphysiologic glucocorticoid replacement may lead to subclinical atherosclerosis in people with congenital adrenal hyperplasia (CAH) and predispose the development of cardiovascular diseases from an early age.To determine if cardiometabolic risk factors and subclinical atherosclerosis are more frequent in patients with CAH due to 21-hydroxylase deficiency (21OHD) and if there is an association with clinical, hormonal and treatment of 21OHD.A descriptive prospective cross-sectional study exploring clinical variables, biochemical, hormonal variables, endothelial dysfunction (flow-mediated dilation < 5%) and carotid intima media thickness (≥ 95 percentile in adolescents and ≥ 75 percentile in adults) and epicardial fat. Adolescents and young patients with 21OHD were compared with controls matched by age, sex, body mass index and Tanner stage.p < 0.01). Epicardial fat was similar between groups and in patients with CAH it was related to cholesterol levels , time since CAH diagnosis  and glucocorticoid dose . Carotid intima media thickness (CIMT) had a tendency to be increased in patients (p = 0.07) and was directly related to 17-hydroxyprogesterone , diastolic blood pressure  and the homeostatic model assessment (HOMA) index . Endothelial dysfunction was not different between groups.Forty four subjects (22 with CAH), 36 (82%) females, with a mean age of 17.1 ± 5.5 years (range 10–30 years) were included. Family history revealed diabetes, hypertension, and hypercholesterolemia with high frequencies in both groups. The blood pressure was similar in both groups. Blood glucose levels were lower and triglycerides higher in patient (both Some cardiometabolic risk factors were increased in patients with CAH and were associated with clinical, hormonal and treatment parameters of CAH. Cardiometabolic risk should be evaluated regularly in patients with CAH. Congenital adrenal hyperplasia (CAH) refers to a group of inherited enzyme defects in cortisol biosynthesis. It is the most common adrenal disorder in childhood with equal involvement of both sexes and with a very wide spectrum of clinical manifestations , 2. The Achieving normal growth and development remains a primary goal of treatment for CAH. Glucocorticoids and, when necessary, mineralocorticoids, are the mainstay of treatment in these patients, both for substitution of deficient steroids and for the purpose of suppressing excessive adrenal androgen production , 4.Patients with CAH are considered to be at higher cardiometabolic risk compared to general population, due to more risk factors such as obesity, insulin resistance hypertension and dyslipidemia. The constellation of these factors, which begins in childhood, could result in endothelial dysfunction and predispose to atherosclerosis, metabolic syndrome and cardiovascular diseases at an early age –12.The exact reasons that explain the increased cardiovascular risk in patients with CAH and the pathophysiology of the metabolic alterations detected are still unknown. The combination of supraphysiological glucocorticoid replacement, hyperandrogenism, and hypofunction of the adrenal medulla due to CAH, an element that has been added in recent years , 13, 14,Atherosclerosis is the most common underlying cause of cardiovascular diseases and is considered the main cause of morbidity and mortality internationally. In addition, it is the main cause responsible for disability and impaired quality of life in all developed countries and in those where infections are not the primarily cause of mortality , 10–12.Subclinical atherosclerosis is defined as the asymptomatic or preclinical phase of atherosclerosis. Markers of subclinical atherosclerosis are a set of anatomical, functional or serological findings that allow diagnosing atherosclerotic disease in the preclinical stage and thus classifying patients into the appropriate risk category .The measurement of the flow-mediated dilation (FMD) of the brachial artery that reflects the endothelial function, as well as the measurement of the carotid intima media thickness (CIMT), are the two most used, simple and non-invasive methods to demonstrate subclinical atherosclerosis and are useful as independent predictors of future cardiovascular events . EndotheEpicardial adipose tissue has been identified as an important element in the development of cardiovascular disease and may reflect intra-abdominal visceral fat. Therefore, echocardiographic evaluation of epicardial fat could serve as a reliable marker of visceral adiposity. Epicardial fat is also associated with clinical and anthropometric parameters of the metabolic syndrome; therefore, echocardiographic evaluation of epicardial fat is considered a simple tool to stratify cardiovascular risk in clinical practice .Increased CIMT could be related to chronic gluco- and mineralocorticoid treatment or hyperandrogenism. However, a direct association between these variables in patients with CAH has not been precisely demonstrated, although it has been some indications, especially with blood pressure .It is still not clear whether subclinical atherosclerosis is related to CAH itself, its treatment, or both . Thus, tThis is a descriptive prospective cross-sectional study carried out at the National Institute of Endocrinology (INEN), Havana, Cuba; from January 2017 to July 2020.All patients with CAH due to 21OHD who attended or were referred to the INEN during the study period were prospectively considered. The inclusion criteria were a diagnosis of CAH due to 21OHD , age 10 Controls were selected from apparently healthy subjects, matched for age, sex, body mass index (BMI) and Tanner stage from nearby primary health care. For the selection of controls, 40 subjects were examined. To exclude the possibility of CAH in controls, serum 17-hydroxyprogesterone (17OHP) levels were measured.2), waist circumference and abdominal adiposity . The current age, assigned sex, pubertal stage according to Tanner were determined through questioning and physical examination and they were taken into account in the interpretation of the procedures [A detailed personal  and family history as well as physical examination were carried out at INEN including weight, height, BMI ). Epicardial fat was demonstrated by transthoracic echocardiography with patients in left lateral decubitus and is the echo-lucent area between the epicardium of the right ventricle and parietal pericardium, which is seen as a thick line above the right ventricular free wall on echocardiography. Both measurements  were performed three times. There is yet no definite value considered normal for epicardial adipose tissue (EAT) thickness. There are inconsistencies in the literature regarding EAT thickness. In the present study increased EAT thickness was considered 5 mm or more measured in end-diastole in three cardiac cycles using a parasternal long axis or parasternal short axis view, a threshold for subclinical atherosclerosis as Bertaso et al. suggested in a systematic review . All pro2).Variables related to CAH was noted such as time since diagnosis and type of glucocorticoid (hydrocortisone and cortisone acetate), which were converted to hydrocortisone equivalences (cortisone acetate 25 mg = hydrocortisone 20 mg) and daily dose of the hydrocortisone equivalents (mg/mt test (or ANOVA) and Mann–Whitney U test  as appropriate. Categorial parameters were compared using Fisher's exact test or Chi-square test, as appropriate. The association of quantitative variables were done using the Pearson or Spearman correlation coefficient, as appropriate. A p-value < 0.05 was considered significant.The mean ± SD or median and range were used and comparing groups was done with the Student's In total, 44 subjects were included , 36 (82%) were females, with a mean age of 17.1 ± 5.5 years  between 10 and 20 years) (Table p < 0.01) but higher TG and the atherogenic index compared to matched controls (both p < 0.01). A negative correlation was observed between the atherogenic index and the FMD (p = 0.02); as well as with the CIMT (p = 0.03). No relationship was found with epicardial fat (p = 0.33). All other biochemical tests were similar between patients and matched controls (Table Patients with 21OHD had lower blood glucose levels (p = 0.48). The presence of epicardial fat had a positive relationship with total cholesterol levels , the time since CAH diagnosis  and the glucocorticoid dose .The epicardial fat mean in adolescents and young patients with CAH was 1.13 ± 1.63 and in matched controls 1.02 ± 0.66 (p = 0.07) and greater frequency of increased CIMT (p = 0.09), i.e., subclinical atherosclerosis and a non-significant higher percentage of endothelial dysfunction (p = 0.41) , DBP  and the HOMA index , but not with current hydrocortisone equivalent dose . Of the 21 patients with CAH in whom the CIMT were explored, 11 (52%) had it increased. Comparisons between those with CAH and increased vs normal CIMT were made with the only difference being more females in the increased CIMT group  (other data not shown).Adolescents and young adults with CAH had a discreet tendency of increased mean CIMT (1) Table . Unfortur = 0.45, p = 0.03).In relation to clinical variables and cardiometabolic risk factors, it was found that only triglyceride concentrations had a statistically significant positive association with the time since the CAH diagnosis .The characteristics of the patients with CAH are shown according to phenotype in Table This study investigated subclinical atherosclerosis in Cuban patients for the first time, measured as CIMT, had a tendency to be more common in CAH compared to controls matched by age, sex, BMI and Tanner stage. CIMT was associated with hormonal control, diastolic blood pressure and insulin resistance in patients with CAH. However, even though endothelial dysfunction was more than twice as common in these young patients with CAH than in matched controls, this was not statistically significant, probably due to the limited number of participants and the young age. Furthermore, comparing patients with CAH with controls matched by BMI is quite unique in the field of cardiovascular risk in CAH and probably underestimate the differences between patients with CAH and general population.In the management of CAH it is necessary to evaluate the short- and long-term outcomes, especially cardiovascular and metabolic complications which have been shown to be increased in some studies , 10, 26.The main objective of therapy in patients with CAH is to replace the deficient hormones and normalize the adrenal androgen levels, for which glucocorticoids and mineralocorticoids are used , 2. It iIn relation to the biochemical parameters, the lower fasting glucose concentrations in patients with CAH compared to controls is probably a sign of cortisol insufficiency in the morning and have also been reported in other studies , 13. MorGiven the increase in cardiovascular risk in these patients, there is currently a growing interest in detecting vascular disease in its subclinical stage, since intervening in this period is crucial to prevent future cardiovascular events. Among the most used methods for its detection are FMD and CIMT , 22, 23.Endothelial function can be described as a barometer of cardiovascular health, useful for directing patient management in a personalized way and evaluating therapeutic strategies . AlthougIncreased CIMT, is also considered a marker of subclinical atherosclerosis , and hasIn the present study, 18% of patients with CAH had prehypertension or hypertension which was similar to matched controls. Blood pressure measurements in patients with CAH have varied , even thEpicardial fat has emerged in recent years as a relevant target, towards which numerous interventions and therapies are directed today. There are few reports evaluating epicardial fat in patients with CAH. Kim et al. , have beLike all studies, also the current study had limitations. The limited number of included patients with CAH, but still a decent size compared to previous studies , 26, theAdolescents and young adults with CAH had a strong tendency of increased CIMT compared to age-, sex-, Tanner stage and BMI matched controls. CIMT was directly related to 17OHP, diastolic blood pressure and HOMA-index. Epicardial fat was positively associated with total cholesterol levels, duration of CAH and the glucocorticoid dose. Non-classic phenotype may be more affected. Adolescents and young adults with CAH should be regularly assessed for cardiovascular risk and non-invasive methods such as measurement of epicardial fat, CIMT and FMD.


Blood pressure (BP) monitoring is vital in daily healthcare, especially for cardiovascular diseases. However, BP values are mainly acquired through a contact-sensing method, which is inconvenient and unfriendly for BP monitoring. This paper proposes an efficient end-to-end network for estimating BP values from a facial video to achieve remote BP estimation in daily life. The network first derives a spatiotemporal map of a facial video. Then, it regresses the BP ranges with a designed blood pressure classifier and simultaneously calculates the specific value with a blood pressure calculator in each BP range based on the spatiotemporal map. In addition, an innovative oversampling training strategy was developed to handle the problem of unbalanced data distribution. Finally, we trained the proposed blood pressure estimation network on a private dataset, MPM-BP, and tested it on a popular public dataset, MMSE-HR. As a result, the proposed network achieved a mean absolute error (MAE) and root mean square error (RMSE) of 12.35 mmHg and 16.55 mmHg on systolic BP estimations, and those for diastolic BP were 9.54 mmHg and 12.22 mmHg, which were better than the values obtained in recent works. It can be concluded that the proposed method has excellent potential for camera-based BP monitoring in the indoor scenarios in the real world. Blood pressure (BP) is a primary physiological parameter of the human body and is an essential basis for disease diagnosis. Cardiovascular diseases are the leading cause of death globally. Most of them are highly related to hypertension. In this context, convenient ordinary monitoring of blood pressure in daily life becomes critical, especially for long-term bedridden patients, sedentary office workers, etc. Many outstanding works have successfully calculated BP values by extracting the morphology and temporal characteristics of the blood volume pulse (BVP) signals obtained with the photoplethysmography (PPG) technology ,2. A conHowever, the accuracy of BP estimation is easily affected by many factors, including the professional abilities of those conducting it, the height, weight, and age of the subjects, and the seasons and the environments . Apart fAn end-to-end network that uses spatiotemporal maps of facial videos for remote BP estimation is proposed.A BP classifier that transforms a regression problem into a joint problem of classification and regression is proposed.An oversampling training scheme for effectively addressing the unbalanced distribution of BP values in the training process is exploited.Therefore, this study proposes the end-to-end non-contact BP estimation network based on facial videos. The main contributions are summarized as follows:Blood pressure measurement can be classified into invasive and non-invasive measurement. Invasive measurement is the most accurate, but it is not suitable for daily BP measurements. It is used in critically ill patients. Non-invasive measurement indirectly measures BP by using various sensing technologies and signal processing methods. Moreover, non-invasive measurement can be divided into cuff measurement and cuff-less measurement. In general, cuff measurement is more accurate than cuff-less measurement. However, repeated cuff measurements will cause discomfort and even damage people’s bodies. For long-term BP monitoring, cuff-less BP measurements received significant attention in recent years. With the development of PPG technology, researchers have successfully calculated BP based on the features of BVP signals ,14 or thIn recent years, remote photoplethysmography (rPPG) has been proposed as an alternative to PPG technology in some application secnarios ,21. A caUnder these conditions, this paper proposes a non-contact BP measurement method that uses the rPPG technology. Furthermore, since the spatiotemporal mapping of facial videos has abundant physiological information related to BVP signals , this stIn this section, we give detailed explanations of the proposed network for remote blood pressure estimation from facial videos. The change in the brightness of the facial skin caused by periodic heartbeats is very subtle; thus, noise caused by movement of the face and ambient light can easily contaminate the physiological information in facial videos. Considering the goal of obtaining relatively stable pulse wave features, we propose spatiotemporal feature map slices (STSs) to highlight the physiological information in facial videos. An overview of this part is shown in In order to make full use of informative parts containing effective signals and eliminate the noisy parts, such as the eyes, nose, hair, and mouth, four regions of interest (ROIs) are defined by selecting the forehead and cheek, which have rich vascular information. First, the authors used SeetaFace6 to detect the face, localize 68 landmarks, and select seven points to delineate the ROIs in each frame in the video sequence, as shown in t indicates the video frame index, Due to the movement of artifacts and variations in the environmental illumination during signal acquisition, the accuracy of non-contact blood pressure detection is easily affected. Therefore, a data augmentation strategy is required to solve the problem of signal contamination. In 2022, Zhuang et al.  proposedn ROIs of face L because the length of the whole video was too large to be put into the network. All separate time–space fragments m is the index of Noise caused by facial movement and ambient light causes pulse wave distortion over a certain period of time. Time slicing allows a network to eliminate feature maps with great amounts of noise; thus, we propose spatiotemporal slicer to get stable pulse wave feature maps. For the After we generated the  network  is used F. Then, a blood pressure classifier is used to classify the high-dimensional semantic features F to obtain the blood pressure interval. This operation can establish a benchmark for the features and effectively reduce the overfitting phenomenon in the network. Finally, the results of the classifier are integrated with the output of the feature extractor to calculate the specific value of the blood pressure, which can also effectively help in classifier training.Specifically, as shown in We express the whole blood pressure estimation process with the following formula:In addition to designing the network architecture, we also need an appropriate loss function to guide the networks. We used the cross entropy loss function to train the classifier and the L1 loss function to train the calculator. The two loss functions were combined to train the proposed model, and they were formulated as follows:In order to deal with the unbalanced distribution of data in different blood pressure intervals in databases, an oversampling training strategy is proposed. First, according to the distribution and the level of blood pressure, we used different grouping strategies to divide systolic and diastolic pressure data. So, we divided the blood pressure data into four groups based on the values of the blood pressure. Then, we extracted the data from each blood pressure group in order to ensure that equal numbers of samples in each batch were from each blood pressure range. In other words, the ratio of samples from each group in each batch was 1:1:1:1. It is worth noting that we extracted only one sample from one subject. For each batch, four-fifths of the samples were used as the training set, and one-fifth of the samples were used as the validation set.In this section, we provide evaluations of the proposed method, including cross-database testing and an ablation study.We evaluated our method on a public dataset and a private dataset.MMSE-HR [MMSE-HR  is a pubMultimodal Physiological Measurement—Blood Pressure (MPM-BP) is a private dataset for non-contact blood pressure estimation. In this private MPM-BP dataset, the physiological data and corresponding facial videos of 132 people aged 18–24 were collected by using a multi-channel physiological signal acquisition system (Biopac M160), a blood pressure monitor (OMRON HEM-1020), and a mobile phone camera (Huawei Mate30) without a beauty function. Biopac M160 ran the entire time during the data collection. When the mobile phone started to capture video information, Biopac M160 had a corresponding timestamp, which was used to synchronize the physiological signals and video signals. The facial video for each subject was recorded for about 1 min. The frame rate of the videos was 30 fps, the resolution was 1920 × 1080, and the distance between the camera and subjects was about 0.5 m. In addition, the blood pressure signals were collected at the same time as the video signals. The distributions of systolic blood pressure (SBP) and diastolic blood pressure (DBP) for the MPM-BP dataset are shown in Three metrics were used to evaluate the performance of the network, namely, the standard deviation (SD), the root mean square error (RMSE), and the mean absolute error (MAE).For all of the experiments, the facial videos were sampled to 30 fps, the size of all convolution kernels was 3 × 3, the step was 1, and the feature extraction network corresponding to each time domain segment used the same parameters. All of the networks were implemented with PyTorch and trained with NVIDIA-v100. The ADAM optimizer with an initial learning rate of 0.001 was used for training. The maximum epoch number for training was set to 30 for the experiments on the MPM-BP dataset and to 30 for the experiments on the MMSE-HR dataset.We performed an ablation study of our proposed method. All ablation experiments were performed on the MPM-BP dataset using the five-fold cross-validation method.As mentioned before, our experiments proved that the modified YUV color space performed better in blood pressure estimation. As shown in In order to verify the effectiveness of the combination of the spatiotemporal feature map slices and LSTM, we trained our network by using different slice lengths . In the training, we used the oversampling training scheme on systolic and diastolic blood pressure data. Moreover, we used ResNet18 as the backbone network and modified YUV as the color space. In this experiment, we proved that the specific length of the spatiotemporal slicer would greatly affect the final training results, and the optimal scheme of spatiotemporal slicing can be found in the following table.As shown in With the standard data sampling training scheme as a comparison , we tested the effectiveness of the oversampling training scheme. The above results show that the combination of spatiotemporal slices and LSTM was the best when the slice length was 150. Therefore, in this test, a slice length of 150 was used as the primary network structure. Given that systolic blood pressure ranges from 90 mmHg to 160 mmHg with a maximum span of 70 mmHg, while diastolic blood pressure ranges from 50 mmHg to 100 mmHg with a span of only 50 mmHg, the difference in the difficulty levels between the two target tasks had to be considered when selecting the most suitable loss function. Two standard regression loss functions, L1 and L2, were tested.As shown in In the cross-dataset testing, all 132 MPM-BP data samples were used to training the proposed BPE-Net, and then the MMSE-HR dataset was used for testing. The sample ratio of the training dataset and testing dataset was close to 1:1. Recently, some studies provided solutions for blood pressure estimation based on rPPG ,28. In tThis paper presents a novel non-contact end-to-end blood pressure estimation network that only uses facial video information to quickly calculate diastolic and systolic blood pressure in 15 s. In order to compare our results to those of previous work, we performed experiments on the public MMSE-HR dataset and the self-collected MPM-BP dataset, and we additionally evaluated the mean performance. The proposed BPE-Net achieved a proportion of the difference between the predicted and actual blood pressure values of less than 10 mmHg is 74.2% and 78.8% for SBP and DBP, respectively. The results did not meet the requirements defined in the relevant BHS and AAMI standards , which rThis paper innovatively proposed a BP classifier to transform a regression problem into a joint problem of classification and regression. We found that the predicted SBP range of 110–130 mmHg and the DBP range of 60–80 mmHg were more accurate than other BP ranges. The reason may be that the distribution of BP in the MPM-BP dataset was unbalanced, and we repeatedly took samples from the BP groups with ranges of 110–130 mmHg and 60–80 mmHg. Moreover, other factors, such as age and skin status, will also affect the results. Therefore, it is necessary to expand the diversity of the dataset and improve the classification ability of the network for different BP intervals in the future.NCBP is a manual feature extraction method, and our results show that the NCBP’s error was significantly higher than those of the two end-to-end methods. NIBPP’s MAE was similar to that of our method with 90 or 225 frame slices. However, the MAE of our method with 150 frame slices was much lower than that of NIBPP. This shows that the length of the spatiotemporal slices that we adopted allowed the preliminary extraction of physiological signals to be realized without too many non-physiological signals.


Logistic regression models were used to assess the predictors of uncontrolled hypertension. Four hundred (n = 400) hypertensive out-patients (mean age: 50 ± 8 years) participated in this study, with most living in poor sociodemographic environments. The prevalence rate of uncontrolled hypertension was 57%. Obesity , salt consumption , alcohol intake , a smoking habit , alternative medicine use , and comorbidities  were higher in the uncontrolled group than the controlled group, whereas the prevalence of physical activity  was high in the controlled group vs. the uncontrolled. Overall, 85% of the patients moderately adhered to treatment, only 2% exhibited high adherence, and 13% demonstrated low adherence; over half of the patients received tri-therapy treatment. The predictors of uncontrolled hypertension are a number of prescribed antihypertensive therapies , treatment adherence , salt consumption , physical activity , current alcohol use , and current cigarette smoking . The high prevalence of uncontrolled hypertension in this study suggests a need to optimize prescriptions, adherence to BP-lowering medications, and lifestyle modifications. The management of comorbidities such as diabetes could offer considerable benefits in controlling blood pressure. Hypertension is a poorly controlled risk factor for cardiovascular disease in South Africa, particularly among patients receiving care in the public sector who are mostly from low socioeconomic backgrounds. This cross-sectional study investigated uncontrolled hypertension, treatment, and predictors among hypertensive out-patients attending primary health care facilities in Johannesburg, South Africa. The WHO STEPwise approach to the surveillance of non-communicable diseases was used to collect data, including sociodemographic and lifestyle factors, health status, and measurements for anthropometry and blood pressure along with self-reported adherence to treatment, estimated through the general medication adherence scale. Uncontrolled hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg in diagnosed patients receiving anti-hypertensive treatment. Overweight and obesity were defined as a body mass index ≥25 and ≥30 kg/m Hypertension is a leading contributor to the global burden of non-communicable disease (NCD), and it disproportionately affects low- and middle-income countries (LMICs) ,2, whereHypertension is a common NCD across South African population groups, accompanied by comorbidities ,18,19 anA cross-sectional study was conducted among hypertensive out-patients from February 2021 to February 2022. The concept of the study, data collection, and analysis were anchored on a conceptual framework for managing modifiable risk factors for cardiovascular diseases , suggestThis study is set in PHC facilities located in the City of Johannesburg Metropolitan Municipality (COJ). COJ forms part of Gauteng, one of the nine provinces in South Africa, and has an approximated population of 16.1 million people . There aFrom the few studies conducted locally, the prevalence of uncontrolled hypertension is estimated between 13.5% and 75.5%, which we considered to estimate a minimum representative sample , a minimFollowing ethics approval and permission from the relevant bodies to conduct this study, we  started with the recruitment of participants at various facilities with the help of the facility managers. During recruitments, the main researcher informed the patients on the purpose and procedures of the study, as well as the plans for data collection, in addition to distributing information leaflets written in a local language (isiZulu). Patients who met the inclusion criteria and who were receiving care at the selected facilities participated in the study. Eligible participants were chronic hypertensive out-patients enrolled in the CCMDD programme; aged ≥ 30 years; on two or more anti-hypertension drugs for more than six months, defined as a diuretic, calcium-channel blocker, an ACE inhibitor or angiotensin receptor blocker, alpha-blocker, vasodilator, or β-blocker able; residing in COJ; and willing to provide written consent. Any chronic patient with conditions contrary to these criteria was excluded from the study. The WHO STEPwise questionnaire was modified, validated, and administered to the participants by the research team members ; additio2), normal weight (=19–24.9 kg/m2), overweight (≥25–29.9 kg/m2) and obesity (≥30 kg/m2)  were aged 50 years and older. The participants were black Africans living in peri-urban settings, and most of them came from poor socio-demographic backgrounds in terms of being single (43%), unemployed (61%), and living in larger households with five members and more (34%); almost half (46%) were living in households with income of up to USD 26,085/month (ZAR 5000/month) , and males were 168 (42%). Over half of the patients  was the most used control agent, followed by the calcium channel blocker  and angiotensin-converting enzyme inhibitor ; TD was significantly different between the controlled and uncontrolled HBP (p = 0.029). Overall, 85% of the patients moderately adhered to treatment, only 2% exhibited high adherence, and 13% demonstrated low adherence . After controlling for potential confounders , the final hierarchical logistic regression showed significant associations of uncontrolled hypertension with the number of prescribed antihypertensive therapies , adherence to treatment , salt consumption , being physically active , current alcohol use , and current cigarette smoking .This study investigated uncontrolled hypertension, treatment, and predictors among hypertensive out-patients attending primary health care (PHC) facilities in Johannesburg, South Africa. Most participants were living in poor socioeconomic environments, which tend to predispose an individual to chronic diseases compared to the least deprived environments ,57. Part2 test and univariate analysis), similar to other studies [A high prevalence rate of uncontrolled hypertension (57%) was estimated among hypertensive out-patients in this study. Although this prevalence is higher than the prevalence reported in the South African National Health and Nutrition Examination Survey 13.5%) [.5% [3],  studies ,68. Uncontrolled hypertension was more likely among patients on tri therapy compared to those on less than two therapies in this current study. The association of increasing the number of pills and uncontrolled hypertension can be explained as a reversed causality. This happens when BP does not respond to treatment; consequently, more classes are added to the treatment to lower BP, depending on the level of BP and response to medication . Most hyOther predictors of uncontrolled hypertension in this study were salt consumption, being physically active, current alcohol use, and smoking cigarettes, as previously reported ,47,58,74Again, patients who were physically active were less likely to have uncontrolled hypertension. Studies in South Africa, Ethiopia, and Zimbabwe ,7,10,58 The interpretation of these current results is limited by the following points. This study used a cross-sectional design, which can only estimate well-founded inferences and rules out causality. Use of non-probability sampling could have introduced bias, which was mitigated by obtaining a larger sample size of participants. Recall bias, social desirability, and unmeasured confounders might have influenced factors associated with uncontrolled hypertension. Use of dichotomous and trichotomous responses for salt consumption, current alcohol use, cigarette smoking, and physical activity does not provide sufficient information on practices. Therefore, comprehensive and standardized tools that include quantitative measures, such as frequency, quantity, and types, should be considered in future studies, as well as a detailed investigation on comorbidities, including HIV status, and a comprehensive biochemical assessment related to uncontrolled blood pressure. Caution must be taken when generalizing the results of this study, especially in resource-constrained and context-specific settings. Nonetheless, our study has been able to investigate the prevalence, treatment, and predictors of uncontrolled hypertension among hypertensive out-patients attending primary health care facilities in Johannesburg, South Africa. The correspondence of the prevalence, adherence to treatment, and predictors in this study with other studies provides support to these current results. This study reports a high prevalence of uncontrolled hypertension accompanied by comorbidities among out-patients living in environments of poor socioeconomic status and attending selected public PHC facilities in Johannesburg, South Africa. This is irrespective of the common BP control agents  used by patients to treat hypertension, with over half being on tri-therapy, over two-thirds having low to moderate treatment adherence, and almost none with high adherence. Predictors of uncontrolled hypertension are the number of therapies, adherence to treatment, salt intake, physical activity, current alcohol use, and current cigarette smoking. Worth noting is that higher odds of uncontrolled hypertension were more noticeable among patients consuming salt than other predictors. Amidst the legislation of reducing salt intake by the South African National Department of Health , it seem


We examined the changes in variables that could be recorded on wearable devices during the early stages of acute myocardial infarction (AMI) in an animal model. Early diagnosis of AMI is important for prognosis; however, delayed diagnosis is common because of patient hesitation and lack of timely evaluations. Wearable devices are becoming increasingly sophisticated in the ability to track indicators. In this study, we retrospectively reviewed the changes in four variables during AMI in a pig model to assess their ability to help predict AMI onset. AMI was created in 33 pigs by 90-min balloon occlusion of the left anterior descending artery. Blood pressure, EKG, and lactate and cardiac troponin I levels were recorded during the occlusion period. Blood pressure declined significantly within 15 min after balloon inflation  and remained at this low level. Within 5 min of balloon inflation, the EKG showed ST-elevation in precordial leads V1–V3. Blood lactate levels increased gradually after occlusion and peaked at 60 min (from 1.48 to 2.53 mmol/L). The continuous transdermal troponin sensor demonstrated a gradual increase in troponin levels over time. Our data suggest that significant changes in key indicators  occurred at the onset of AMI. Monitoring of these variables could be used to develop an algorithm and alert patients early at the onset of AMI with the help of a wearable device. Acute myocardial infarction (AMI) is a major cause of death and disability worldwide. The risk of death is highest in the first hours after onset of chest pain . TherefoA series of physiological changes occur when an AMI happens. Capturing these changes at the exact moment of symptom onset is difficult . In the We reviewed the data on pigs who underwent AMI induction via balloon occlusion across multiple protocols that had been approved by the institutional animal care and use committee at The Texas Heart Institute. In the AMI protocol, the pig was placed in the supine position under general anesthesia. A 5F hockey stick coronary-guiding catheter  was percutaneously advanced through the aorta and placed at the left main coronary ostium without full engagement under the guidance of C-Arm fluoroscopy. Then, a 20 mm long monorail angioplasty balloon  of 2.25 to 3.5 mm diameter, depending on the diameter of the left anterior descending artery (LAD) , was placed into the LAD between the first and second diagonal branch over a 0.014″ straightforward workhorse guidewire . The balloon was inflated at the minimum pressure needed to ensure occlusion of the LAD distal to the balloon for 90 min. Complete coronary occlusion was confirmed by the absence of distal flow of contrast.p value < 0.05 was considered significant.For the current study, we reviewed the anesthesia records for all pigs, which provided the heart rate (HR) and blood pressure reading every 15 min. Of the 33 pigs in our study, 16 had 12-lead ECG recordings at different time points before and during balloon inflation. Eight pigs were evaluated for lactate  at multiple time points. In these 8 pigs, a transdermal troponin sensor  had also been attached to their ears for non-invasive troponin readings; traditional troponin  and high-sensitivity troponin  analyses were completed at preset time points. All continuous values were expressed as mean ± standard deviation for data analysis. To compare continuous variables at different time points, we used analysis of variance (ANOVA); a This section may be divided by subheadings. It should provide a concise and precise description of the experimental results, their interpretation, as well as the experimental conclusions that can be drawn.p < 0.05): SAP, from 89 ± 14 mmHg to 71 ± 12 mmHg; DAP, from 46 ± 6 mmHg to 40 ± 6 mmHg; and MAP, from 61 ± 8 mmHg to 50 ± 8 mmHg. The decreased levels were maintained until the end of the occlusion.Blood lactate levels gradually increased after occlusion, reaching a peak level around 60 min  or high-sensitivity troponin (ELISA) analyses. However, the Tropsensor showed a trend of a continuous increased optical signal from the point of inflation closely after the onset of ST elevation. The Tropsensor signal was flat before inflation, which serves as a reference .In this retrospective study, we reviewed the hemodynamic data from pigs with AMI at our institution. Specifically, our results provide valuable information on the early changes that occur in the first 90 min after the start of an AMI. We observed several important changes in that early time period. Blood pressure dropped immediately in the first 15 min after balloon occlusion, and the ST elevation on ECG was seen within 5 min after ischemia in the corresponding precordial leads. The upward trend in AMI biomarkers was more gradual over time after AMI. However, we did not see a change in HR; the absence of tachycardia in our study may relate to the general anesthesia and antiarrhythmic medication used during the procedure. These findings provide a clear picture of the early changes seen in AMI and are consistent with the pathophysiological changes seen after AMI in humans .It is difficult to record early AMI data in patients. Currently, there is only one study in humans in which troponin change was examined after the LAD was occluded for up to 90 s ,11,12. WWearable devices continue to be refined and offer a new way to monitor a wearer’s status by continuously and automatically measuring vital signs. When patients have an AMI, vital variables change immediately, as indicated in our preclinical model. A wearable device can detect these sudden changes, predict the risk of AMI based on an algorithm, and trigger an alert to notify the wearer. We believe this approach could dramatically reduce the time that elapses before individuals seek medical treatment at a hospital. Although this specific strategy has not been tested for AMI, several similar applications have been examined. For example, Biobeat, which has sensors that continuously monitor 13 physiological parameters including HR, blood pressure, cardiac output, and single-lead ECG, has been assessed in in-hospital patients for providing real-time monitoring, triggering alerts, and predicting patient deterioration . Zio AT To achieve early AMI detection, a wearable device must first have the capacity to measure multiple key variables. Providing a more comprehensive view of the wearer’s situation not only increases the accuracy of the diagnosis but also decreases false positives. For the reliable detection of AMI and the exclusion of other types of myocardial injury such as tachycardia, our results suggest several pathophysiological changes that occur after AMI , such asA second consideration for devices is the need for all functions to run automatically. Without the need for wearer interference, compliance is increased. A comparison study of a regular Holter monitor with a novel ECG patch that patients did not need to manipulate suggested that the novel patch can achieve 98% patient compliance . Higher For ECGs, most devices require that a wearer touch the device with a finger to start the recording , but somAutomatically and continuously recording multiple variables will help enable the wearable device to monitor all the data needed for the early detection of AMI. According to market research, an estimated 30% of US residents own a smart wearable device . In the Large sample pools of both population and personalized data may be helpful in identifying more significant changes to develop an AI algorithm. This will help in generating auto-alerts for notifying patients about AMI risk. In a recent study, a machine learning algorithm was applied to analyze basic physiological, clinical, and paraclinical data from 150 patients. The algorithm obtained an MI prediction accuracy of 88.67% by using only a blood test, ECG readings, and echocardiography findings . AlthougAlthough the future of wearable devices in AMI detection is promising, many challenges remain. Hardware capable of recording all the necessary functions is still under development. Furthermore, even after sufficient data are generated from the wearable devices, significant investment and resources are needed to design trials to collate, analyze, interpret, and finally develop efficient algorithms. Accurate algorithms will require extensive equipment and the enrollment of large numbers of patients. Moreover, after a practical algorithm is developed, another significant challenge is how to incorporate and transfer the wearable data into the current health system in compliance with existing policies and laws .Our retrospective review has limitations. The major drawback was the small number of animals that underwent lactate and troponin testing, which limits the significance of the results. Our review included data only from pigs with AMI, which means we examined hemodynamic and biomarker changes only under conditions positive for AMI. For further study, we will include more preclinical models to compare how these variables change in different scenarios.Despite the challenges, wearable devices can provide real-time monitoring of key indicators related to AMI. They could alert wearers early at the onset of an MI, which would change the current strategy of AMI diagnosis and dramatically reduce treatment delay.


Background and objectiveThe negligible side effects of paracetamol along with its ease of availability have catapulted paracetamol to be a widely used medication in emergency room management to reduce pain and subsequent elevations in blood pressure (BP). Our study aimed to address the challenges in informed clinical decision-making in the emergency room following paracetamol intravenous infusion.MethodsThis was a retrospective cross-sectional study involving the extraction of data from electronic medical records of patients who received intravenous paracetamol infusion between January 2022 and May 2022. Demographic information and BP-related data were collected for analysis.ResultsWe initially considered a total of 162 patient records, with 132 of them eventually meeting the inclusion criteria. Among patients receiving paracetamol infusion for 15 minutes or less, 34% showed a drop of 1-5 mmHg in systolic BP (SBP), while 26% experienced a drop of 6-10 mmHg. However, infusion time longer than 16 minutes did not significantly reduce SBP. Diastolic BP (DBP) was not significantly affected by the duration of the paracetamol infusion. Analysis of the drop in SBP revealed no significant associations with age, gender, or ethnicity. Mean arterial pressure (MAP) was not significantly affected by the duration of paracetamol infusion.ConclusionOur findings suggest that intravenous paracetamol infusion does not significantly lower BP in adults in the emergency room, except for infusions of shorter durations. However, various factors, including infusion rate, patient characteristics, and concomitant medications, may influence BP measurements. The study emphasizes the need for establishing standardized criteria and conducting further research to assess intravenous paracetamol's hemodynamic effects accurately. Acute pain produces a stress response that causes a transient increase in blood pressure (BP) in adults . In contStudy designThis was a retrospective single-center cross-sectional study performed in the Emergency Department of a tertiary academic medical center in Al Ain, the Eastern Region of the Emirate of Abu Dhabi in the UAE . The extPatient information The medical charts of all patients receiving intravenous paracetamol during the period from January 1, 2022, to May 31, 2022, in the emergency room were analyzed for the study. Patient charts of patients receiving intravenous paracetamol infusion were accessed, and the patients were classified into two groups based on the infusion duration of paracetamol. Group 1 consisted of 50 patients who received intravenous paracetamol for 15 minutes or less, and Group 2 consisted of 82 patients who received intravenous paracetamol for >16 minutes. In fact, the stringent inclusion selection criteria for patients receiving IV paracetamol for 15 minutes or less reduced the numbers in this group. Demographic details data on systolic BP (SBP) and diastolic BP (DBP) were harvested from patient medical records using the International Classification of Diseases, Tenth Revision-Clinical Modification (ICD10-CM) codes.Inclusion/exclusion criteriaThe inclusion criteria were as follows: patients who were ≥18 years old and seen in the ED; chief complaint of acute pain corresponding with a visual analog scale (VAS) score ≥40 mm. Patient charts were excluded if they had any medical history  that would impair accurate pain assessment (as per the clinician’s discretion) or in cases of chronic pain, known or suspected opiate dependence, allergy to paracetamol, any degree of renal or hepatic insufficiency, pregnant patients, or those who had taken paracetamol within the last six hours before presentation.Ethical considerationPatient privacy and data confidentiality were ensured by adhering to the International Conference on Harmonization Good Clinical Practice (ICH-GCP) and local Department of Health Abu Dhabi guidelines. The study was approved (CRD623) by the Tawam Hospital Human Research Ethics Committee (lic#02/2009).Data analysisResults were presented as mean ± standard deviation (SD) for quantitative variables and were summarized as frequencies (percentages) for categorical variables. Analysis of variance was conducted to determine the statistical differences between the groups. Data were analyzed using IBM SPSS Statistics version 23.0 , and p-values less than 0.05 were considered statistically significant.The demographics of the participants are shown in Table Of note, 34% (17/50) of the patients experienced a 1-5 mmHg drop in SBP Table , when thParacetamol infusion failed to significantly lower DBP in the patients, regardless of whether the infusion time was 15 minutes or less or 16+ minutes Table .The drop in the SBP in patients with paracetamol infusion for 15 minutes or less was further analyzed to assess if age, gender, or ethnicity were associated with the outcomes. Thirty patients, irrespective of their ages (30/50), infused for 15 minutes or less showed a drop in their SBP by 1-10 mmHg Table .More than 60%  of the total patients who experienced a drop in SBP were in the age group of 26-40 years (p<0.05), which was very high when compared to the other age groups: 41-60 years: 6/30, 20%; 61+ years: 3/30, 10%; and 8-25 years: 2/30, 6.6%. Ethnicity and gender were not associated with the outcomes of paracetamol infusion for 15 minutes or less in terms of inducing lower SBP. Paracetamol infusion did not significantly lower the mean arterial pressure (MAP) in the patients, regardless of whether the infusion time was 15 minutes or less or 16+ minutes.Intravenous paracetamol is shown to be iso-osmotic with a pH value range of 5.0-7.0, which is similar to plasma values and unlikely to increase pain . The samOur study aimed to assess the hemodynamic effect of intravenous paracetamol infusion in adults in the emergency room of a tertiary care hospital. Paracetamol infusion of less than 15 minutes caused a significant drop in SBP, but not DBP. Approximately 30/50 (60%) of the total patients receiving intravenous infusions for less than or equal to 15 minutes showed a drop in SBP Table . DespiteThe lowering of BP following intravenous paracetamol infusion may be caused by a reduction of both cardiac output and systemic vascular resistance. Notably, the formulations of intravenous paracetamol contain mannitol as a stabilizing compound. It is likely that mannitol contained in the intravenous paracetamol formulations may have contributed to the diuretic effect to reduce BP . Among tOur study has several limitations, which are as follows: (a) preexisting data recorded in the electronic medical records were extracted for this study, and hence selection bias and operator bias may have crept in; (b) the results are representative of the period of the study and may not be generalizable; (c) temporal relationships between the paracetamol infusion and a drop in BP may compound the results; (d) the total effective patient population data gathered were relatively low: only 132 records for the period of study; (e) patient assessment information such as the chief complaint, pain score, and illness score were not available for the study; and (f) retrospective chart reviews are inferior in terms of the strength of the evidence, and can show association but not causation. However, this is perhaps the first study of its kind from the Persian Gulf region, and the emergency department of the hospital where the study was conducted caters to the population of the entire Eastern Region, adding to the strengths of this study.Although our study indicates that the rapid infusion (less than 15 minutes) of paracetamol to manage pain is optimal, it still continues to be a clinical challenge, especially when hemodynamic parameters such as BP changes are determined. Paracetamol infusion and the variability associated with the assessment of BP changes must be carefully addressed by taking into account patient characteristics, the severity of illness, the concomitant fluid administered, and the infusion time, in order to make informed clinical decisions.