BackgroundEarly prediction of hypotension helps to decide appropriate prophylactic measures and, hence, safe anaesthesia for mothers and improved neonatal outcomes. Perfusion index (PI) measured from a standard pulse oximeter has shown positive results in the prediction of hypotension. This study aims to determine if PI can equally predict hypotension in parturients after administration of spinal anaesthesia at different time points.MethodsParturients posted for elective caesarean section belonging to the American Society of Anesthesiology II (ASA II) were divided into two groups based on baseline PI as group A <3.5 and group B ≥3.5. Fifty-six parturients were enrolled in the study. PI and blood pressure were monitored at baseline, every two minutes for 12 minutes and every five minutes until the end of the surgery, after administration of spinal anaesthesia with hyperbaric bupivacaine 10 mg. Incidence of hypotension was compared between groups at all time points of observation. Spearman’s rank correlation coefficient was determined to check the correlation between baseline PI and the number of episodes of hypotension. Receiver operating characteristic (ROC) curve was plotted to determine the ideal cut-off at different time points.ResultsBaseline PI significantly correlated with the number of episodes of hypotension (r-0.525). The overall incidence of hypotension was significantly higher in parturients with baseline PI ≥3.5 (79.16%) as compared to those with PI <3.5 (33.33%). The incidence of hypotension at sixth, 10th and 37th minutes post-spinal anaesthesia administration was significantly higher in the group with PI ≥3.5. The sensitivity and specificity for the 3.5 cut-off of PI were 85.7% and 60%, respectively, at the 6th and 10th minute after spinal administration. A higher cut-off of 3.9 increases the specificity to 69% without much change in the sensitivity.Conclusion Parturients with PI >3.9 at baseline have a higher risk of hypotension in the initial 10-12 minutes following spinal anaesthesia during caesarean delivery. Spinal anaesthesia is the preferred method of anaesthesia for a caesarean section as it avoids the risk of maternal aspiration and drug-induced neonatal respiratory depression and, at the same time, provides good postoperative analgesia without the use of IV opioids . A healtThus, over the years, many strategies have been adopted to prevent or treat hypotension . Fluid lAnother strategy adopted is to predict hypotension by various non-invasive methods such as measurement of heart rate variability, point-of-care ultrasound, cerebral near-infrared spectroscopy, perfusion index (PI), and pleth variability index (PVI) -15. HoweThere are limited studies in India in predicting the incidence of hypotension in parturients undergoing central neuraxial block and correlating baseline PI with an incidence of hypotension at different time points during surgery . TherefoAfter approval by the Institutional Scientific Committee and CDSIMER Institutional Ethics Committee (CDSIMER/MR/0003/IEC/2021), this prospective observational study was conducted over six months at Dr Chandramma Dayananda Sagar Institute of Medical Education and Research, a tertiary care centre. Parturients posted for elective caesarean section belonging to ASA II status with a weight between 40 and 70 kg and height between 140 and 165 cm were included in the study. Parturients with ASA III or IV status, pregnancy-induced hypertension or preeclampsia, twin gestation, parturients with contraindication to spinal anaesthesia, BMI >40, and gestational age <36 weeks or >40 weeks were excluded from the study. After obtaining written informed consent, parturients were included in the study.On the day of surgery, after ensuring adequate fasting of six hours for solids and two hours for liquids, the parturients were premedicated with injection (Inj) pantoprazole 40 mg IV and Inj ondansetron 4 mg IV in the preoperative room. ECG, non-invasive blood pressure and pulse oximeter (MINDRAY multipara monitor) were applied, and baseline data were noted. To maintain uniformity in the recording of PI, a pulse oximeter probe was attached to the left index finger of parturients. An average of three PI values taken five minutes apart was considered as baseline PI value. Based on baseline PI value, parturients were categorized into group A and group B with a PI value of <3.5 and ≥3.5, respectively. The cut-off was based on studies by Toyama S et al.  and DuggParturients were then transferred to the operation theatre, and standard monitors were applied as in the preoperative room (Mindray multipara monitor). They were administered ringer lactate at the rate of 10 ml/kg/hr. Spinal anaesthesia was administered by an anesthesiologist blinded to baseline parameters and study protocol. Spinal anaesthesia was provided in a sitting position using 25 G Quincke’s spinal needle at L3-L4 interspace with 10 mg of 0.5% hyperbaric bupivacaine under strict aseptic and antiseptic precautions. The parturients were then put in a supine position with a wedge placed under the right hip and buttock till the delivery of the baby. Sensory block was checked every two minutes with a cold swab, and after the achievement of the T4 level, surgery was started.PI, heart rate, systolic blood pressure (SBP), diastolic blood pressure, mean arterial blood pressure, and SPo2 were recorded every two minutes for 12 minutes and then every five minutes till the end of surgery by an observer. Hypotension was defined as a decrease in SBP >25% from the baseline value as per institutional protocol  and was Parturients requiring additional uterotonic and with blood loss of more than 500 ml were excluded from the study. Also, parturients whose sensory block was inadequate or converted to general anaesthesia were excluded from the study analysis. The incidence of nausea, vomiting, shivering, or any other complications was noted and managed as per institutional protocol.Statistical analysisThis study included 56 parturients posted for elective caesarean section. The sample size was based on the incidence of hypotension in a previous study , with PIA total of 56 parturients were included in the study. Three parturients were excluded from the study as the sensory level achieved was inadequate and had to be supplemented with general anaesthesia. Two parturients had blood loss of >500 ml and required additional oxytocin for uterine atony were also excluded. Thus, a total of five parturients data were excluded from the final analysis Figure .The demographic variables were comparable between the two groups Table . The senHypotension was observed in 33.33% of parturients in group A compared to 79.16% in group B (P = 0.001). The incidence of hypotension was significantly different between both groups in the sixth, 10th, and 37th minutes Table . BaselinThe change in SBP from baseline showed a significant negative correlation (Pearson’s) to baseline PI at all time points except 17th, 22nd, 37th, and 42nd minutes . The curve yielded 67.9% sensitivity and 79% specificity for a cut-off value of 3.5 Figure , Table 4This study demonstrated that higher baseline PI (≥3.5) is associated with increased incidence of hypotension and increased requirement of vasopressors. The incidence of hypotension in parturients with a cut-off of 3.5 was similar to Toyama S et al. , who hadIn this study, we also could demonstrate that the incidence of hypotension was significantly higher in parturients with baseline PI ≥3.5 at 6th, 10th and 37th minutes post-spinal anaesthesia administration. This analysis is essential to determine the need for prophylactic vasopressors. In a recent study by Pyakurel K et al. , SBP wasIn our study, the ROC curve revealed that the cut-off of 3.5, as determined by Toyama S et al. , is 67.9The usual fall in blood pressure is seen in the first 10-15 minutes  also yiePI is a measure of the ratio of the pulsatile and non-pulsatile blood flow in peripheral tissue and is dependent on the baseline vascular tone. In spinal anaesthesia, the fall in blood pressure is due to sympathetic blockade. The degree of fall in blood pressure depends on the extent of sympathetic blockade and systemic vascular resistance, which is in turn dependent on various factors -4, 21. IPI can be used to predict hypotension in parturients undergoing caesarean section under spinal anaesthesia. Though a 3.5 cut-off is ideal for an overall incidence of hypotension, a new PI cut-off of 3.9 at baseline has higher predictability for the risk of hypotension in the initial 10-12 minutes following spinal anaesthesia. Further studies with PI measured in the lower limb are required to assess the correlation between the degree of change in PI and change in SBP.


The nephrectomy for donation reduces the renal parenchyma and glomerular filtration rate (GFR). It is important to understand the clinical consequences of kidney donation by a living donor.In this single-center, observational, retrospective study, we defined the renal and cardiovascular outcomes of living kidney donors. We analyzed data of 124 donors who donated at the Kidney Transplant Center (TC) of Bari between February 2002 and December 2018. Biometric data collected at visit 0, that is, at the time of the study of the donor candidate, and at visit 1, or rather at the last nephrological checkup (October-2018/August-2019) were compared.An overall drop in GFR of 29 mL/min was observed over the analyzed period of 81+/-59 months. At visit 1, two donors developed chronic renal failure, including one in ESKD who underwent a kidney transplant. No relationship between age at donation and GFR drop was found. A trend toward an increase in obese people was reported; 28% of patients had compensated dyslipidemia and 35% were treated for hypertension. During the follow-up time, 3% had major cardiovascular events and 24% were lost to follow-up. One patient died.The age of the donor does not represent a basic element for reducing GFR or for the occurrence of major cardiovascular events. Furthermore, older donor candidates, in optimal health, should not be excluded from the donation. It is important to promote careful and timely follow-up of the donor, preventing the most common clinical consequences of nephrectomy, in consideration of the poor compliance of a large part of donors over the long-term post-donation period. Kidney transplantation, particularly from a living donor, is the treatment of choice for most patients with end-stage renal disease (ESRD) . The supIn this retrospective single-center observational study, we aimed at defining the renal and cardiovascular outcomes of kidney donors for living donor transplantation.We analyzed clinical and laboratory data of 124 donors undergone to a kidney donation at the Kidney Transplant Center (TC) of Bari during the period from February 2002 to December 2018. Biometric data collected at visit 0, that is, at the time of the study of the donor candidate, and at visit 1, or rather at the last nephrological checkup (from October 2018 to August 2019) were compared.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and of the Declaration of Istanbul and its later amendments or comparable ethical standards. Given the observational and retrospective nature of the study, it was not necessary to obtain informed consent from patients. In any case, all the data were collected digitally, analyzed, and reported in the results in a totally and anonymous manner.n = 57) between 51 and 60 years. Twenty-two percent of patients (n = 28) aged between 61 and 70 years, 20.9% (n = 26) between 41 and 50 years, 7.2% (n = 9) between 31 and 40 years, 2.4% (n = 3) between 71 and 80, and 0.8% (n = 1) between 20 and 30 years.The sample subject of the study was represented by a population of 124 donors, of Caucasian race, 71.7% female , with an average age at the time of donation of 54 years (54.3 years for women and 53.9 years for men) and with a distribution of 45.9% (n = 55) were between mother and son/daughter, 14.5% (n = 18) between wife and husband, and 11.3% (n = 14) between sister and brother/sister. This confirms the previously described predominance of female sex among donors and is of high importance, considering that consanguine donors could have an increased risk of developing chronic kidney diseases.It is interesting to note the degree of relationship between the donor and the recipient. In fact, 44.3% of donations (n = 17) between father and son/daughter, 8% (n = 10) between brother and sister/brother, and 5.6% (n = 7) between husband and wife. Additionally, during the period considered, there was only one case of kidney transplant from a living between an aunt to her niece and another single donation between two young friends. During the analyzed period, there was also the first kidney transplant from a living donor, in crossover modality, of the TC of Bari between a husband in favor of his wife.The remaining transplants studied were 13.7% (n = 28) were performed in the preemptive modality. Regarding the recipient's nephropathy, 44 patients (35.5%) were affected by glomerulonephritis of which, 27 from IgA nephropathy, seven from focal segmental glomerulosclerosis , four from glomerulonephritis with histologically unspecified lesions, three from lupus nephritis, one from membranous-proliferative glomerulonephritis, one from extra capillary glomerulonephritis, and a case of granulomatosis with polyangiitis. Of the remainder, 36 (29%) were late referrals; 17 subjects (13.7%) had a diagnosis of congenital anomalies of the kidney and urinary tract (CAKUT). Autosomal dominant polycystic kidney (ADPKD) was the common pathology in 11 recipients (8.8%) while the remaining nephropathy was secondary to tubulointerstitial nephritis , nephrolithiasis , pre-eclampsia , chronic pyelonephritis , hypertension , cystinuria , renal tuberculosis , and bilateral renal cortical necrosis .Of the 124 living donor transplants analyzed, 22.6%  calculated according to the CKD EPI formula, 24-h proteinuria, fasting blood sugar, total cholesterol and triglycerides, calcium, and phosphorus were, therefore, collected and analyzed according to the in-center laboratory procedures.These parameters were collected at the time of the evaluation of the donor candidate, before nephrectomy (visit 0), and compared with the same ones measured during the last nephrological check (visit 1). During the last outpatient visit, vitamin D and parathyroid hormone (PTH) were also measured in half of the sample.The echocardiograms  of visit 0 and visit 1 were also compared; the latter performed by most of the population.The analysis also compared the body mass index (BMI) and the medical history acquired at visit 0 and visit 1 with particular attention to the onset of cardiovascular events such as the appearance of arterial hypertension or the worsening of this if already existing, the finding of diabetes mellitus, as well as major cardiovascular events such as cases of ischemic heart disease or cardiac arrhythmias reported during follow-up.p < 0.05 values. Statistical analysis of the data was conducted using the statistical software R version 3.6.0.The distribution of variables was studied with the Shapiro-Wilk test of normality. Continuous variables with a Gaussian distribution were expressed as mean and standard deviation, while those with non-Gaussian distribution were expressed as median and interquartile range. Statistical comparisons were made with parametric and non-parametric tests, as appropriate based on the distribution of the variables. Categorical variables were expressed as an absolute numerical value and as a percentage. The multiple linear regression method was used to evaluate the relationship between delta GFR (GFR at visit 1—GFR at visit 0), as dependent variable and numerous independent variables. The effect of age at the time of donation on this relationship was evaluated by comparing the previous model with a mixed model, which included, with the same fixed effects, a random effect represented by the quartiles of age at the time of donation. Statistical significance was set at The mean follow-up time was 81.5 +/- 58.9 months. In the analyzed period, it is possible to describe many kidney transplants from living donors <10 per year, except 2007 and 2008 with 10 and 11 donations, respectively. Subsequently, a significant reduction was observed in these until 2016 with a subsequent progressive increase, which led to a peak in 2018. In fact, in 2015, an outpatient clinic dedicated to living donor transplantation was instituted in our unit. In the group, a psychologist, nutritionist and some dedicated nurses were present who were really important for the study and follow-up process of the couples. This increased the couples being studied. In 2018, thanks to the increasingly better organization of the structure and the greater awareness raising and education about the donation by the team, the number of study couples increased significantly (61 vs. 17 in the 2017). This led to 19 live donor transplants being performed in 2018, thus doubling the annual rate of transplants compared to previous years.The age of the patients was assessed at visit 0 and visit 1, as an absolute value and as quartiles of age. The age quartiles at visit 0 was I quartile: 26–48 years, II quartile: 49–54 years, III quartile: 55–60 years, and IV quartile: 61–72 years. The age quartiles at visit 1 were: I quartile 27–54 years, II quartile: 55–62 years, III quartile: 63–69 years, and IV quartile: 70–80 years.The work showed a percentage of donors lost to follow-up that tends to increase over the years since the donation. In particular, in the first 2 years analyzed (2002 and 2003), the percentage of donors who no longer conduct checks is, respectively, 80 and 75%. The next 9 years, from 2004 to 2012, show an average of 33.7% donors lost to specialist follow-up. Donors who have undergone nephrectomy in the last 6 years result from the analysis to proceed correctly with outpatient appointments; therefore, there are no lost to follow-up, except one case (year of donation 2017).Thirty patients up to 124 included in the study were lost to follow-up, resulting in an overall donor population analyzed of 94 patients.The comparison of the principal anthropometric and biochemical data between visit 0 and visit 1 is summarized in 2, while at visit 1 was 25.9 ± 3.8 kg/m2, p = 0.29. The variation in BMI between visit 0 and visit 1 was also examined in different age quartiles, with reference to the age present at visit 0 and visit 1. A statistical significance was found only in the third-quartile of age (p = 0.004) in which the BMI increased from 24.9 ± 3.2 to 26.9 ± 3.2 kg/m2. No significant differences were found in the remaining quartiles.The change in the BMI of the donors between visit 0 and visit 1 was analyzed. The mean value of BMI at visit 0 was 25.3 ± 3.6 kg/mAnalyzing the distribution of donors in different categories based on BMI, it was found that in the pre-donation period there were two underweight subjects, 37 normal weight, a lot of overweight, and eight with class I obesity. At the last follow-up visit, their breakdown changes as follows: two underweight, 32 normal weight, 32 overweight, 12 with class I obesity, and two with class II obesity. No tests aimed to define a pre-diabetic status have been performed neither before nor after donation.p = 0.002.Donors at visit 0 had a GFR value of 97 ± 11 ml/min  while at visit 1 of 63 ± 15 ml/min , In the observation period, an overall decrease in GFR of 29 ml/min is described.p < 0.001) with changes in the GFR, respectively, from 102.3 ± 10 ml/min  to 77.3 ± 12.3 ml/min  in the second quartile; from 92.5 ± 9.9 ml/min  to 66.7 ± 15.2 ml/min  in the third quartile; and from 91.2 ± 5.9 ml/min  to 62.4 ± 14.5 ml/min  in the fourth quartile.The variation of the GFR was also studied in the age quartiles. Statistical analyses showed a statistically significant variation in the second, third, and fourth quartiles  with the dependent variable  at visit 0 and of 132.91 ± 165.31 mg/24 h  at visit 1. Although the increase in this parameter is statistically significant, the 24-h proteinuria value of the donors observed at follow-up is not clinically relevant.p = 0.008).The fasting blood glucose value of the donors at visit 0 was of 92.7 ± 10 mg/dl, while the blood glucose at visit 1 was 88.2 ± 14 mg/dl (p = 0.007).Total cholesterol at visit 0 was 199 ± 36 mg/dl, while at visit 1 it was 186 ± 28 mg/dl (p = 0.04).The triglyceride values were at visit 0 was 98 ± 51 mg/dl, while at visit 1 it was 114 ± 61 mg/dl .At visit 1, the native vitamin D levels were 25 ± 10 ng/ml (n = 60).At visit 1, PTH was 35.5 ± 15.8 pg/ml  of the subjects analyzed in the study presented a diagnosis of arterial hypertension at visit 1. Of them, 25 patients were not hypertensive at visit 0. Specifically, it is possible to describe at visit 1 two cases in which the worsening of hypertension required the enhancement of antihypertensive therapy, from mono to dual therapy in one situation and from dual to triple therapy in the other.Twenty-eight percent of the donors in the sample showed dyslipidemia under pharmacological treatment, in all cases, except one, of new onset at visit 1 compared to 0. Additionally, 35.1%  while in 12% of cases, there is a decrease in GFR <60 ml/min. The increase in proteinuria could be secondary to the hyperfiltration mechanism that the nephrons of the residual kidney undergo. This compensatory mechanism tends to increase over the years after nephrectomy and could finally lead to impaired renal function .It would be important to define the prognostic value of proteinuria and GFR reduction in the donor population. In particular, for example, the use of GFR calculated with other methods (eGFRcys or mGFR) could give a more precise value of effective GFR in patient with < 90 ml/min.Considering also that the mortality of donors is lower than that of the general population , the finIt is also important to consider how some consanguineous donors may have an unknown genetic predisposition to the development of kidney disease that can lead them to a condition of terminal uremia. In fact, consanguineous donors could share with the recipients some genetic traits and environmental factors. This could be the case of the only patient in our sample, a donor to her daughter suffering from IgA-deposited glomerulonephritis, who subsequently developed end-stage chronic renal failure and therefore underwent a preemptive kidney transplant from a cadaveric donor. In this case, no genetic test was available, so an eventual genetic predisposition could not have been excluded.The remainder of our sample showed an overall decrease in GFR of 29 ml/min in the mean observation period of 81.5 months. It was impossible to compare this decrease in the filtration rate with that expected in the general population, equal in age and comorbidity of a control group. It should be considered that this reduction in GFR is affected by various comorbidities that have occurred over time, the aging of the population, as well as a very variable post nephrectomy observation time, from months to about 17 years. Furthermore, it was impossible to describe the trend of reduction of GFR per year with respect to the expected slope for aging because many donors analyzed did not perform regular annual laboratory checks. The analysis of the variation of the GFR by age quartiles, however, allowed us to observe how the reduction of this is not significantly influenced by the age of the donor. This result could have an important clinical value, confirming a good outcome of older donors.Of note, according to literature, age should not be a parameter to exclude donors in the process of living kidney transplantation, but an estimation of lifetime ESRD risks for young individuals and late-life onset of end-stage kidney diseases must be addressed .Of the 94 subjects studied, only in one case the presence of a GFR <30 ml/min was found at visit 1. This is a 63-year-old male patient, in post-donation follow-up for about 14 years, who developed major cardiovascular complications such as myocardial infarction, hypertension, diabetes, and dyslipidemia, which could be the cause of the development of the insufficiency pattern. Renal.Concerning the appearance of proteinuria, in our sample, the mean value in the urine of 24 h at visit 1 is clinically insignificant (132.91 ± 165.31 mg/24 h); it can be added, however, that six donors presented at visit 1 a determination of 24 h proteinuria> 300 mg/day; of these, half has been in post-donation follow-up for more than 14 years and only one of them has a GFR <30 ml/min.The remaining laboratory parameters examined showed how donors, regardless of their age group, retain an excellent metabolic compensation. Although there is a reduction in GFR, this is not associated with significant changes in calcium, phosphorus or with an increase in parathyroid hormone or a decrease in vitamin D. This confirms that donors do not always develop signs of chronic kidney disease –18.Concerning cardiovascular risk, the analysis of the variation in BMI highlighted a redistribution in the various categories, which saw a reduction in normal weight subjects in favor of an increase in obese. The increase in body mass incidence represents an important cardiovascular risk factor as well as worsening of renal function indices .With respect to major cardiovascular events, three subjects with ischemic heart disease and four with arrhythmic episodes are described in the entire population. There were two cases of new-onset diabetes mellitus, while 35% of the sample was affected by arterial hypertension and 28.7% by dyslipidemia.The lack of the control group does not allow to compare these results with those expected in a general population. The literature does not show an increase in cardiovascular risk in donors, particularly in the first decade after nephrectomy.On the subsequent observation period, there are currently no univocal data in this regard. In fact, it is possible that a reduction in GFR in these subjects may still lead to cardiovascular manifestations, but probably in a longer time .The main elements on which to intervene in cardiological prevention are arterial hypertension, dyslipidemia, and BMI. The results of the work show that our donors therefore have risk factors that should be monitored clinically.It is essential to promote adaptation to a correct lifestyle, awareness of the possible consequences, as well as a precise clinical-laboratory follow-up. The information must start in the study phase, before the donation, to continue during the outpatient checks. In fact, the periodic execution of blood chemistry tests and outpatient nephrological visits, repetition of annual cardiologic checks, monitoring of BP, and body weight are recommended , 22.The work showed that there is a percentage of donors lost to nephrological follow-up equal to 24%. This value has a certain distribution of study time and therefore tends to increase with the passage of time from the donation. In the last 6 years, the subjects have all been compliant with the scheduled checks. If we also refer to cardiological follow-up, the subjects who have performed a cardiological visit in the last year are just 25.5%. Difficulty in accessing care is often reported by kidney donors; in fact, not all centers create a care path dedicated to the follow-up of the donor; the long waiting times for executing controls, not specifically nephrological, often discourages the execution.The birth recently of surgery dedicated to living transplantation at the Kidney TC of Bari could justify the increase in compliance with the follow-up recorded in the most recent period. The awareness of the subjects toward the gift has been increased, as well as information about any risks and possible consequences. Couples are welcomed when they express their will to undertake this path, then guided in the preparation phase and conducted until the time of surgery. Attention is paid, in particular, to the donor, the aims are to identify any causes of clinical contraindication to the donation and probe the real motivation to perform the gesture.Living donor kidney transplantation is the best therapeutic choice for patients suffering from end-stage chronic renal failure as it reduces waiting times in the transplant lists, thus minimizing the patient's exposure to uremic status, limiting complications related to replacement treatments and in particular delays the onset of cardiovascular risk. Ultimately, it improves the recipient's outcome thanks to greater survival, higher quality of life, and cost reduction. However, the donor increases his self-esteem, undergoes a complete health checkup with subsequent periodic checks and improves the quality of life of his family.In our population, it particularly emerged that age does not represent a discriminating element for reducing GFR or for the appearance of major cardiovascular events. This prompts us to affirm that donor candidates of advanced age, in the presence of an optimal state of health, ascertained in the pre-donation study phase, should not be excluded.Furthermore, the importance of promoting a careful and timely follow-up of the donor emerges aimed at preventing the appearance of the most common clinical consequences of nephrectomy and the main cardiovascular risk factors such as an increase in BMI, BP, and dyslipidemia. The existence of a clinic figure dedicated to living donor study for the donation process can significantly increase the number of couples being studied and finally of donations. It is also necessary to take charge of the donor by a dedicated health team.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by University of Bari. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.LG and GC participated in research design. VC, PG, SS, LM, and CA participated in the writing of the paper. VC and PG participated in the performance of the research and in data analysis. All authors contributed to the article and approved the submitted version.This study was  funded by Italian Ministry of Health—Current Research IRCCS.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Results: Knowledge of kidney function had a significant difference across patient groups with varying employment status. Monthly income is a significant factor for the patient attitude on healthcare towards preventing kidney disease. On the other hand, educational level significantly affects the overall attitude of patients towards preventing kidney disease. Conclusion: Understanding knowledge, attitudes, and practices associated with CKD is vital to informing optimal policy and public health responses in the country.Context: Chronic kidney disease (CKD) is characterized by the presence of kidney damage or decreased kidney function. In the Kingdom of Saudi Arabia, the prevalence of CKD is at 5.7%, which represents a high burden on health care systems. Aims: This study aimed to assess the knowledge, attitudes, and practices of high-risk patients towards prevention and early detection of chronic kidney disease in Saudi Arabia. Setting and Design: Descriptive cross-sectional study in Saudi Arabia. Methods and Material: This study was designed using a newly developed instrument, the CKD Screening Index. It was conducted from December 2021 to May 2022 by a self-administered questionnaire. The questionnaire has three parts: socio-demographic data, clinical factors, and the CKD screening index tool. Statistical analyses used: Independent  Kidney damage refers to pathologic abnormalities, whether established via kidney biopsy or imaging studies, or inferred from markers such as urinary sediment abnormalities or increased rates of urinary albumin excretion. Globally, the prevalence of CKD is 9.1%, and there were 697.5 million cases of CKD  reported worldwide [Chronic kidney disease (CKD) is defined as the presence of kidney damage or decreased kidney function (defined as estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 mHowever, there is limited information on the knowledge, attitudes, and practices towards prevention and early detection of CKD in Saudi Arabia. As such, this study aimed to assess the knowledge, attitudes, and practices of high-risk patients towards prevention and early detection of chronic kidney disease in Saudi Arabia and to find out the association between the participants’ knowledge and attitude with their socio-demographic characteristics.This descriptive cross-sectional study was designed to assess knowledge, attitudes, and practices perceived by Saudi patients at risk for CKD using a newly developed instrument, the CKD Screening Index, which was validated, and its reliability was checked in previous studies. In the previous studies, its internal consistency was 0.87 and 0.8 in Palestine  and JordAs well as the clinical factors, in the CKD screening index tool tests, participants were asked about their knowledge regarding kidney function, risk factors or causes of kidney disease, kidney disease symptoms, and management of kidney disease as well as the current practice and attitude of patients towards preventing kidney disease, such as eating a well-balanced diet, maintaining regular exercise, following certain restrictions, seeking medical help if needed. It was conducted from December 2021 to May 2022 by a self-administered questionnaire.The sampling of this study was non-probability convenience sampling. According to the sample size calculation, the sample size was 385 or more. All adult (age ≥ 18 years) hypertensive, and/or diabetic patients, with a family history of CKD, having chronicity with analgesia, or aged more than 65 years were included in the study. However, any patient younger than 18 years old was excluded.Continuous data were checked for normality and a comparison of means was done using parametric or non-parametric tests. The Statistical Package for the Social Sciences (SPSS) Software was utilized to analyze the data. The data were presented as frequency and in tables; chi-square test, which is a feature of SPSS under cross table or nonparametric analysis, was used to attain a p-value between categorical data-dependent and independent to estimate the association where p-value ≤ 0.05 is considered significant. The data were kept confidential and only used for the purposes described in the study objectives.This study was approved by the institutional review board (IRB) of Imam Mohammad Ibn Saud Islamic University with approval number (181-2021). Additionally, this research was carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki 2013) for experiments involving humans. All participants were aware of the study aims, and written electronic consent was taken before answering the electronic questionnaire. All the data collected from this study were highly confidential and only used for the purposes described in the study objectives. Any identifying information such as names, phone, or fax numbers, medical record number, initials, anywhere in the paper were concealed. No personal information was taken, to ensure privacy.Two hundred and ninety-three participants  took part in this study, as shown in p = 0.034) in terms of knowledge about kidney function was observed across patients with varying employment status. For other questions on knowledge about CKD prevention and early detection, no statistical difference was observed across patient groups with different employment statuses.Each participant was tested in terms of their knowledge about CKD prevention and early detection as shown in p = 0.045). Monthly income (p = 0.003) plays a significant factor in the patient attitude about healthcare towards preventing kidney disease. On the other hand, educational level (p = 0.012) significantly affects the overall attitude of patients towards preventing kidney disease. Each participant was also asked questions on their current practices to prevent kidney disease as exemplified in Each participant was also tested in terms of their attitude towards preventing kidney disease as provided in CKD is a serious worldwide health problem with a rising incidence and prevalence . PatientBased on the results, knowledge about kidney function had a significant difference across patient groups with varying employment status. Monthly income is a significant factor in patient attitude about healthcare towards preventing kidney disease. On the other hand, educational level significantly affects the overall attitude of patients towards preventing kidney disease. In a study conducted by Yusoff and colleagues in Malaysia, the majority of respondents had poor knowledge, but most of them had a good attitude and good practices towards the risk of CKD. Monthly income, occupation, and educational attainment were found to be significantly correlated with knowledge about CKD . In PaleIn Saudi Arabia, it has been reported that there was a relatively high positive attitude toward CKD prevention and control among the educated Saudi population . Based oKhalil and Abdalrahim  had founBased on the study results, chronic disease, age, gender, educational level, employment status, and monthly income did not pose a significant difference for the current practices of patients to prevent kidney disease. On the other hand, patients with higher knowledge and attitudes scores, a male gender, and normal body mass index, were statistically significantly associated with a higher practice score towards CKD prevention . FurtherSocio-demographic factors can play a pivotal role for the understanding of high-risk patients towards prevention and early detection of chronic kidney disease. Understanding knowledge, attitudes, and practices associated with CKD is vital to informing optimal policy and public health responses in the country.


IntroductionCapillary blood glucose (CBG) monitoring remains the most used testing form in hospitals and allows for “points in range (PIR)” metric calculation. This study was conceived to evaluate the metabolic control in patients with diabetes mellitus (DM) at a hospital through PIR metrics.MethodsThis was an observational cross-sectional study conducted on October 9, 2020, that included non-critical adults admitted to Centro Hospitalar Universitário do Porto (except pregnant/postpartum women) with DM under CBG monitoring and a minimum of 24 hours of hospitalization. Glycemic control was evaluated by previous day CBG monitoring.ResultsThe study sample consisted of 110 patients with DM (93.6% type 2) with a median number of CBG tests of 4.00 (1.00) and a median CBG of 166.20 (69.41) mg/dL, SD 41.93 ± 27.20 mg/dL, and variation coefficient of 22.56 ± 12.51%. Points below range were 0.5%, with 0% below 54 mg/dL. The points in ranges 70-140 mg/dL and 140-180 mg/dL were 32.8% and 22.0%, respectively, and the total number of patients with all points in range 70-180 mg/dL was 19 (17.3%), with only 3 (2.7%) having all points in range 140-180 mg/dL and 10 (9.1%) in range 70-140 mg/dL. Regarding points above range (PAR), 29.9% and 14.8% points were at levels 1 and 2 hyperglycemia, respectively, and 15 (13.6%) patients had all points above 180 mg/dL. Correlations were identified between PAR and the total number of CBG assessments .ConclusionWe conclude that in-hospital glycemic control remains suboptimal: only few have adequate control according to the PIR metrics despite low glycemic variability. PIR metrics are a new, valuable, simple and valid way to take better advantage of CBG monitoring at no added cost. Capillary blood glucose (CBG) and continuous glucose monitoring (CGM) provide different information about the glucose regulatory situation of a certain patient. CBG monitoring provides an accurate static value that reflects glucose concentration in the body’s transport system but does not report on its variations over time. Instead, CGM offers a dynamic measurement of the interstitial fluid glucose levels. These two forms measure glucose levels in different compartments, which can be associated with some degree of discrepancy especially in situations of high glycemic variability .We have been witnessing the exponential growth in forms of CGM worldwide and this has led to the emergence of the concepts of glycemic variability (GV), time in range (TIR), time above range (TAR), time below range (TBR) and other CGM metrics that complement the value of HbA1c ,3. In 20Nonetheless, CBG testing remains the most widely used form of inpatient monitoring because it is associated with lower costs and there are some doubts about CGM accuracy in hospitalized patients. However, despite the usefulness of CBG in daily decision making in hospitalized patients, the evaluation of the global metabolic control in these patients is difficult to assess based on individual CBG testing. During the COVID-19 pandemic, there was a need to develop strategies for the remote monitoring of glucose in hospitalized patients, which led to greater liberalization of the in-hospital temporary use of CGM. After April 2020, when the Food and Drug Administration (FDA) made the use of CGM available in hospitalized COVID-19 patients, several studies sought to assess its accuracy and safety in inpatient settings with favorable results, although there is still not enough evidence to prove the cost-benefit of its more indiscriminate use in this context . TherefoThe analysis of self-monitoring CBG values by Diabetes Management Systems (DMS) led to the perception that those isolated values could be pooled to provide additional information on glycemic control, similarly to what is done with CGM systems. This way, these new CBG monitoring metrics, the “points in range (PIR)”, were created seeking to bypass its limitations compared to CGM but considering that CBG only provides isolated glucose values. The PIR metrics are interpreted similarly to CGM’s TIR and provide additional information on the isolated value of CBG .The primary objective of this study was to describe CBG monitoring in PIR metrics and to assess the metabolic control in patients with diabetes mellitus (DM) in the hospital through PIR metrics. Furthermore, we also intended to compare PIR metrics in the infection/non-infection subgroups and with respect to the length of hospitalization.The results of this study were previously presented as a meeting abstract at the Portuguese Congress of Endocrinology , January 29-31, 2021.This was an observational cross-sectional study conducted on October 9, 2020, at Centro Hospitalar Universitário do Porto, a central hospital in Portugal, and included non-critical adult patients (except pregnant/postpartum women) with diagnosis of DM , hospitalized for a minimum of 24 hours and under CBG monitoring. A total of 31 patients with insufficient clinical information in the process were excluded. The study protocol conformed to the World Medical Association’s Helsinki Declaration and was approved by the Ethics Committee of Centro Hospitalar Universitário do Porto, approval number 2021.079 (065-DEFI/068-CE). Informed consent was waived by the Ethics Committee based on the retrospective nature of the study and full data anonymization. The following data were collected from the electronic clinical record: demographic information, day of hospitalization, main diagnosis (infection/non-infection), type of DM and its microvascular/macrovascular complications, and CBG monitoring of the previous day.To define the total points in each of the intervals, we took into account both the American Diabetes Association (ADA) recommendations regarding glycemic control in hospitalized patients and the CGM-based targets defined in the 2019 ATTD consensus ,7. This GV was assessed by standard deviation (SD) of the mean glucose value of each patient and the value of coefficient of variation (CV)  . An analData analysis was performed using the statistical package IBM SPSS Statistics, version 20.0.0 . Categorical variables were presented as frequencies and percentages, and continuous variables as means and SD or medians and interquartile ranges (IQR) for variables with skewed distributions. Normal distribution was checked using the Shapiro-Wilk test or skewness and kurtosis as appropriate. All reported p-values are two-tailed, with a p < 0.05 indicating statistical significance. Spearman’s correlation coefficient (ρ) was used to assess the correlation between PIR metrics and other parameters under analysis, namely, the length of hospital stay and the number of CBG tests. The interpretation of correlations’ strength was made using the reference values provided by Bryman and Cramer . For theThe sample description is shown in Table Table Table Regarding the subgroup analysis by main diagnosis (infection/non-infection), we found a greater number of CBG tests in the infection group, 4.0 (0.0) vs. 3.0 (1.0), p = 0.011, although there were no significant differences in relation to the total PIR, 3.0 (2.0) vs. 3.0 (1.0), p = 0.910, or PAR, 3.5 (2.0) vs. 3.0 (1.0), p = 0.680. With respect to the length of stay subgroup analysis, no differences were found in terms of the number of CBG tests (p = 0.062), total PIR (p = 0.167) or PAR (p = 0.199).Using the 2019 ATTD consensus, these results showed that inpatient glycemic control remained suboptimal because only a minority of the patients had adequate control according to PIR metrics: the total of points in the range 70-180 mg/dL was 54.8% with a minimum percentage of PBR, which means that hyperglycemia continues to keep us from reaching our glycemic targets. This is supported by the low percentage of patients with all points in the range 70-180 mg/dL, thus indicating that the number of patients with at least one assessment corresponding to hyperglycemia is quite high.We found a positive significant and moderate correlation between CBG tests and PAR. One possible explanation might be the tendency to intensify CBG monitoring in face of poor glycemic control. Yet, the opposite would be expected for PIR, that is, a negative correlation between the number of CBG tests and the total of PIR, which was not verified. Thereby, the results of the subanalysis by main diagnosis are also interpretable along this line of thinking: there was a significantly higher number of CBG tests in the infected group in which worse glycemic control would be expected, but probably not sufficiently higher to reflect a difference in the total PIR/PAR. Besides, the lack of correlation between PIR/PAR and length of stay combined with the absence of significant differences in the subanalysis by day of hospitalization suggests that the length of stay might be a less important factor compared to infection diagnosis to take into account as a potential interfering factor in glycemic control.This was the first study to apply the PIR metrics to inpatients and demonstrate its relevance in a real context for the assessment of glycemic control. Despite the existence of FDA-approved CGM devices for non-critical patients, their widespread use is not possible in clinical practice mainly for reasons of cost . It was As limitations of this study, the following should be noted: it was cross-sectional in nature that only allowed a punctual assessment of glycemic control by this new metrics; the sample size may still have been insufficient to obtain significant correlations between some variables under study and the PIR metrics. In addition, it is also worth to mention that this study was carried out in hospitalized patients and the use of CBG monitoring in this population has limitations, because numerous factors, such as the patient's perfusion status, can influence the accuracy of this measurement .In light of the results found in this study, in-hospital glycemic control seems to remain suboptimal: only few have adequate control despite low glycemic variability, which points to the relevance of finding ways to improve it without additional costs. In conclusion, PIR metrics are a new, valuable, simple and valid way to take better advantage of CBG monitoring and overcoming its limitations at no added cost. Further longitudinal studies are still desirable to confirm and eventually extend these results.


BackgroundAsthma is a reactive airway disease that has a high prevalence across the globe. Asthma exacerbations can occur due to various bacterial and viral infections that irritate nerve endings in the airways. With time, airway obstruction follows, and patients with asthma have various symptoms that occur intermittently. Asthma symptoms primarily include breathlessness, wheezing, coughing, and chest tightness. This research focused on the association between the Asthma Control Test (ACT) score and number of exacerbations per year.Methods A questionnaire-based, cross-sectional study was conducted at the outpatient pulmonary clinic, King Abdulaziz Medical City, a tertiary hospital in Riyadh. The study included 227 adult patients who were diagnosed with asthma and had no other pulmonary diseases or other medical diseases that could mimic asthma exacerbation. Data was collected by direct interview with the patients and through the BESTCare system in King Abdulaziz Medical City. All the data were collected through Microsoft Excel 2010  and analyzed using Statistical Package for Social Sciences (SPSS) Statistics version 23 . The categorical data we used were presented by percentages and frequencies such as gender, whereas the numerical data were prescribed as mean and standard deviation such as age and number of exacerbations. For inferential statistics, Chi square was used to find the association between the categorical variable while T-test and ANOVA test were used to find the relationship between asthma control test score of asthmatic patients, which was divided into three different groups based on their scores that include: well-controlled, partially controlled, or uncontrolled, and the number of exacerbations per year. ResultsA total of 227 adult asthma patients were enrolled in this study, most of them were females (72.7%). Average age of the participants was 47.3 ± 13.8 years. The average ACT score was found to be 18.5 ± 4.9 out of 25. Uncontrolled asthma was present in 26% of the patients, 22.9% were partially controlled and 51.1% had well-controlled asthma; to relieve the exacerbation most of the patients used salbutamol (51.5%), 35.2% used oxygen and 30.4% did not use any medication. Gender and age were not associated with ACT score , whereas number of exacerbations was significantly associated with ACT score (P = 0.000), as fewer exacerbations were reported with higher ACT scores.ConclusionAbout one-quarter of the patients had uncontrolled asthma, slightly less than one-quarter of the patients had partially controlled asthma while more than half of the patients had well-controlled asthma. Number of exacerbations was found to be significantly associated with asthma control test score as fewer exacerbations were reported in well-controlled asthmatic patients. Asthma is a disease of airway hyperreactivity and bronchospasm. Asthma exacerbations can occur due to various bacterial and viral infections that further irritate nerve endings in the airways . With tiAsthma is considered one of the most identified chronic diseases in Saudi Arabia. The prevalence of asthmatics in Saudi Arabia is 11.3%, while it is about 4.3% of the worldwide population, and both numbers are rising annually . AverageThe Asthma Control Test (ACT) is used to measure how well-controlled a patient’s asthma is. Asthmatics with higher ACT scores predict that the likelihood of asthma exacerbations is lower. The plan was to understand how effective the ACT score is in predicting the outcome of patients to optimize its benefits. Moreover, there was a lack of studies regarding the association of emergency department visits related to asthma exacerbations. Therefore, we thought of its importance as well as looked forward to understanding the relationship between ACT and the number of exacerbations.Based on the ACT of asthmatic patients, we aimed to have a clear vision of controlled and uncontrolled asthmatic patients and to understand the association between asthmatic patients’ ACT and the possible number of exacerbations per year. The aim of the study was to determine the association between the ACT score and the number of exacerbations per year at King Abdulaziz Medical City (KAMC) in Riyadh.A questionnaire-based, cross-sectional study was conducted at the outpatient pulmonary clinic, King Abdulaziz Medical City, a tertiary hospital in Riyadh. The sample size was designed to ensure 95% confidence interval, with a margin of error of 5%. The number of asthmatic patients in Saudi Arabia from the ages of 15 to 60 years old is estimated to be 530,000 patients as of 2016 . The preData was collected by direct interview with the patients and through the BESTCare system in KAMC. The first step was to use the ACT to detect the score for each patient that visited the pulmonary clinic, and the second step regarding the number of exacerbations we used a data collection sheet that was prepared by the research team based on the abstraction of data from the BESTCare system. The Arabic version of the asthma control test is valid, reliable, and has been used in the assessment of asthma since its validation . It has All the data were collected through Microsoft Excel  and transferred to Statistical Package for Social Sciences (SPSS) version 23  for analysis. Data were checked for any missing information and new variables were recorded and computed based on the data extracted. The categorical data we used were presented by percentages and frequencies such as gender, whereas the numerical data were prescribed as mean and standard deviation such as age and number of exacerbations. For inferential statistics, Chi square was used to find the association between the categorical variable while T-test and ANOVA were used to find the relationship between asthma control test score of asthmatic patients, which was divided into three different groups based on their scores that include: well-controlled, partially controlled, or uncontrolled, and the number of exacerbations per year. Regarding ethical consideration, all patients were given an informed consent before the ACT was conducted, and King Abdullah International Medical Research Center (KAIMRC) issued approval SP20/342/R.Demographic and clinical characteristics of the study participantsA total of 227 adult patients who were diagnosed with asthma were included in this study. Most of them were females (72.7%). The average age of the participants was 47.3 ± 13.8 years (range from 18 to 68). Most of the participating patients (81.5%) had no visits to KAMC Emergency Department and 38 (16.7%) had less than five visits.The average ACT score among the study population was found to be 18.5 ± 4.9 out of 25. Uncontrolled asthma was present in 26% of patients, partially controlled asthma was present in 22.9% while the majority of patients (51.1%) had well-controlled asthma  followed by Symbicort (44.1%), Seretide (39.6%), montelukast (37.4%) and mometasone (15%) . Our results showed that lower number of exacerbations (0 to four) was predominant among well-controlled patients while higher number of exacerbations (five to 10) was predominant among uncontrolled patients Table .Association between gender and number of exacerbationsThe results of the analysis showed that there was no significant association between gender and number of exacerbations, as the calculated P value was recorded as 0.620 Table .Control of asthma is one of the most important determinants of progression of the disease and it was proven to be a critical factor affecting the frequency and severity of exacerbations. The aim of this study was to study and demonstrate the association between the patient's asthma control test score and the number of exacerbations per year.In the current study more than two-thirds of the respondents were females, and the remaining were males, and this could be attributed to the relatively higher prevalence of asthma among females that has already been reported in many international registries as reported in other study showing prevalence of asthma among females is nearly two times its prevalence among males . The aveRegarding the average ACT score among the study population, it was found to be 18.5 ± 4.9 out of 25. About one-quarter of the patients had uncontrolled asthma, slightly less than one-quarter of the patients had partially controlled asthma while more than half of the patients had well-controlled asthma, and this was found to be contradictory to another study which was conducted in Saudi Arabia showing that more than half of the patients had uncontrolled asthma . About half of the patients had a previous visit or needed to go to the emergency department, this was reported in another parallel study which was conducted in the UK but with a lesser percentage of patients compared to the current study and this study showed only one-third of the patients needed emergency visit .Regarding the number of exacerbations in the last year, nearly one-third of the patients had no exacerbation last year. Concerning the agent used to relieve the exacerbation; nearly half of the patients used salbutamol, about one-third used oxygen and slightly less than one-third did not use any medication. Similar results were found in another study which was conducted in the USA showing the most commonly used drug in treatment of acute exacerbations of asthma was found to be nebulized beta-2 agonist as salbutamol .Concerning the most common drug used, the most used one was salbutamol which was reported by about two-thirds of the patients followed by Symbicort which was stated by nearly half of the patients, then Seretide, montelukast and mometasone each reported by more than one-third of the patients, controller therapy is most effective if administered as combination therapy rather than monotherapy as demonstrated in another study conducted in the Netherlands by Loymans et al. showing a combination of long-acting beta-2 agonist (LABA) and inhaled corticosteroids (ICS) is more effective and secure in preventing asthma exacerbations .Regarding association of gender and age with ACT, gender and age were not found to be associated with ACT score, also the results of the analysis showed that there was no significant association between gender and number of exacerbations, and this was in contradiction to a parallel study conducted in Saudi Arabia showing association of gender with ACT with females having uncontrolled asthma more than males .The number of exacerbations last year was found to be significantly associated with ACT score and our results showed that a lower number of exacerbations (0 to four) was predominant among well-controlled patients while a higher number of exacerbations (five to 10) was predominant among uncontrolled patients. The same results were found in another study conducted by van Dijk et al. in the Netherlands showing decreased number of exacerbations with increased asthma control score .The limitations of the current article were the reality that information was just gathered from one center, potentially restricting the generalizability of the discoveries. This subject requires more exploration to be done in the area, with a bigger sample size and multiple centers involved to achieve an accurate estimation of how well asthma is controlled and what possible influencing factors causing exacerbations at the local and international levels are in order to achieve better control.About one-quarter of the patients had uncontrolled asthma, slightly less than one-quarter of the patients had partially controlled asthma while more than half of the patients had well-controlled asthma. Half of the patients had a previous visit or went to the emergency department. Nearly one-third of the patients had no exacerbation last year nearly half of them had one to four exacerbations. The most common drug used to relieve acute asthmatic exacerbations was salbutamol. Gender and age were not found to be associated with ACT score. Number of exacerbations last year was found to be significantly associated with ACT score as a lesser number of exacerbations was reported in well-controlled asthmatic patients.


Aims: We aimed to assess trends in glycosylated hemoglobin A1c (HbA1c) and systolic blood pressure (SBP) thresholds at initiation of glucose- and blood pressure-lowering medication among patients with type 2 diabetes and assess the influence of age and sex on these trends.Materials and Methods: We used the Groningen Initiative to ANalyze Type 2 diabetes Treatment (GIANTT) primary care database. Patients initiating a first non-insulin glucose-lowering or any blood pressure-lowering medication between 2015 and 2020 with an HbA1c or SBP measurement in the 120 days before initiation were included. We used multilevel regression analyses adjusted for potential confounders to assess the influence of calendar year, age or sex, and the interaction between calendar year and age or sex on trends in HbA1c and SBP thresholds at initiation of medication.Results: We included 2,671 and 2,128 patients in the analyses of HbA1c and SBP thresholds, respectively. The overall mean HbA1c threshold at initiation of glucose-lowering medication significantly increased from 7.4% in 2015 to 8.0% in 2020 (p < 0.001), and particularly in the younger age groups. Compared to patients ≥80 years, patients aged 60–69 years initiated medication at lower levels mainly in the early years. Patients <60 years and between 70–79 years initiated medication at similar levels as patients ≥80 years. Females initiated medication at lower levels than males throughout the study period (p < 0.001). The mean SBP threshold at initiation of blood pressure-lowering medication varied from 145 to 149 mmHg without a clear trend (p = 0.676). There were no differences in SBP thresholds between patients of different ages or sex.Conclusion: The rising trend in the HbA1c threshold for initiating glucose-lowering medication in the lower age groups was unexpected and requires further investigation. Males appear to receive less timely initiation of glucose-lowering medication than females. The lack of higher thresholds for the oldest age group or lower thresholds for the youngest age group in recent years is not in line with the age-related recommendations for personalized diabetes care and calls for health systems interventions. Adequate treatment of risk factors, including glycosylated hemoglobin A1c (HbA1c) and systolic blood pressure (SBP), is important for people with type 2 diabetes mellitus (T2DM) to lower the risk of micro- and macrovascular complications . When paTo facilitate the effective and safe use of medication treatment, it is relevant to study drug utilization trends in the whole population as well as among specific subpopulations. A study looking at trends among Dutch T2DM patients showed that mean HbA1c and blood pressure levels decreased between 1998 and 2008 and were similar for different age categories . AnotherLittle is known about these treatment trends in the recent years. Our aim was to 1) assess trends in HbA1c and SBP thresholds at initiation of glucose- and of blood pressure-lowering treatment between the years 2015 and 2020, and 2) assess the influence of patients’ age and sex on these trends.www.giantt.nl) database, which contains anonymous electronic medical records data from T2DM patients treated in primary care in the north part of Netherlands. In Netherlands, the majority of T2DM patients are managed in primary care, often receiving 3-monthly check-ups by a nurse practitioner and yearly check-ups by their general practitioner. The methods used in this study were similar to those used in previous trend studies using the same database  classification codes A10B] or any blood pressure-lowering medication  without a known prescription for any glucose- or blood pressure-lowering medication, respectively, in the preceding 365 days. We excluded patients who were diagnosed with diabetes before the age of 35 years because of the possibility that these were type 1 diabetes patients . PatientOur two outcomes were the patients’ most recent HbA1c or SBP level in the 120 days before or on the day of glucose- or blood pressure-lowering medication initiation, respectively.We included the following explanatory variables: calendar year of medication initiation, patients’ age or sex and the interaction between calendar year and age or sex. Age was calculated on 1 January of the calendar year in which the patient initiated treatment and was categorized in four groups  based on the different cut-offs observed among guidelines . Sex was2 or >60 ml/min/1.73 m2), presence of albuminuria , body mass index , lipid-lowering treatment (no treatment or ≥1 classes) and number of all other prescribed chronic medications at initiation (used as a continuous variable). Additionally, the analyses of HbA1c thresholds were adjusted for SBP level (<140 mmHg or ≥140 mmHg) and blood pressure-lowering treatment  and the analyses of SBP thresholds for HbA1c level (<7% or ≥7%), history of cardiovascular events , number and type of glucose-lowering treatment  and smoking. More details about definitions and calculations of these variables have been described previously , presence (yes/no) of dyslipidemia [defined as low density lipoproteins (LDL) ≥2.5 mmol/L], estimated glomerular filtration rate . Imputing variables with large amounts of missing data would be expected to end up with larger error terms. For albuminuria, where more than 20% of patients had a missing value, we assumed these patients did not have albuminuria, since conducting this test is less common in patients without suspected kidney problems.p < 0.0125 for age and p < 0.025 for sex. Last, to assess the effect of age and sex over time, we added age or sex and the interaction between year and age or sex to the model. All analyses were conducted in Stata V.14 .The same analyses were used for the HbA1c and SBP thresholds. Patient characteristics were analyzed descriptively per calendar year, age, and sex group. We conducted multilevel regression analyses with a two-level random intercept model to account for patients being nested within general practices. First, using the empty model which includes only the outcome, we calculated the intraclass correlation coefficient to assess the variance that is attributed to general practices. Next, we added the potential confounders to assess the overall trend over the years. This model was also used to analyze the trends in each age and sex group separately, where after applying Bonferroni correction for multiple testing the significance levels were set at There were 2,671 and 2,128 patients who met our in- and exclusion criteria included in the analyses of HbA1c and SBP thresholds, respectively . The numThe number of patients initiating glucose-lowering medication per year ranged from 348 to 551 . Thirty-β (year) = 0.093, 95% CI 0.062, 0.124; p < 0.001; β (year) = 0.086, 95% CI 0.026, 0.147; p = 0.005] and those aged 60–69 years . No statistically significant linear nor quadratic trends were seen in the older age groups. In the analyses by sex (β (year) = 0.087, 95% CI 0.044, 0.130; p < 0.001] and females .The overall mean HbA1c thresholds at initiation of glucose-lowering medication significantly increased over the years from 7.4% in 2015 to 8.0% in 2020 [linear trend, s by sex , the meaPatients younger than 60 years initiated glucose-lowering treatment at somewhat higher HbA1c levels than older patients in most years , but thiThe number of patients initiating blood pressure-lowering medication included in our analysis ranged from 272 to 419 . Twenty-The mean SBP level at initiation of blood pressure-lowering medication rose from 145 mmHg in 2015 to 148 mmHg in 2017, dropped to 145 mmHg in 2019 and went up to 149 mmHg in 2020 . This waNo significant differences in SBP levels at initiation of blood pressure-lowering medication based on age  and sex This study shows that the HbA1c thresholds at initiation of glucose-lowering medication increased over the years 2015–2020. This increase was particularly seen in younger age groups and in both males and females. Females generally initiated medication at lower HbA1c thresholds than males. Patients aged 60–69 years initiated medication at lower levels in the first years and at similar levels in the later years compared to patients aged 80 years or older. Patients under 60 years and between 70–79 years initiated medication at similar levels as patients of 80 years and older. The SBP thresholds at initiation of blood pressure-lowering medication remained relatively stable over the study period regardless of age or sex.We previously observed a rising trend in HbA1c thresholds for medication initiation between 2011 and 2014 . The curMost guidelines recommend initiating glucose-lowering medication at HbA1c levels above 6.5% or 7% in younger patients and above 8% or 8.5% in older patients . SurprisThroughout the study period, we observed higher HbA1c thresholds at initiation of glucose-lowering medication in males compared to females. A post-hoc analysis of sex differences in the years 2008–2014 showed the same differences . DiffereAn intriguing finding was that both mean HbA1c and mean SBP thresholds were highest in 2020. For the HbA1c threshold this could be a continuation of the rising trend over the years, but this is not the case for the SBP threshold. There are indications that the COVID-19 pandemic influenced diabetes care in the year 2020 in Netherlands . Other sA strength of our study is the use of a large database of real world data from electronic medical records, representing a range of Dutch general practices from urban and rural areas. Data undergo data entry error checks before being imported in the GIANTT database, increasing the internal validity. Using medical record data also brings some limitations. First, this is a dynamic cohort and the variation between years could in part be due to a variation between the participating general practices. We conducted additional analyses of trends in HbA1c and SBP thresholds including only the 59 general practices that were present in the whole period up to the year 2020, which showed similar results (data not shown). Secondly, some patients may not be true initiators but people who moved to a general practice participating in GIANTT while already using medication. Although we included only patients with a medical history of 1 year, this may not prevent the inclusion of some patients that have been treated with glucose-lowering or blood pressure-lowering medication by other healthcare professionals in the past. We used an arbitrary cutoff of 10 years to exclude patients that were unlikely to be initiators. A previous study conducted in Netherlands showed that around 20% of patients have not yet started medication treatment 3 years after their diagnosis . Since iTo conclude, the rising trend in the HbA1c threshold for initiating glucose-lowering medication in the lower age groups was unexpected and requires further investigation. The lack of lower thresholds for the youngest age group and higher thresholds for the oldest age group at initiation of glucose- and blood pressure-lowering drugs calls for interventions to support age-related personalized diabetes treatment. Multicomponent interventions targeting clinicians are seen as effective type of interventions . This co


To examine the association of hypertension (HBP) and its control with atrial fibrillation (AF) and how patient sex affects this association.A case control study of patients admitted to our hospital from 2015 to 2019 was conducted. Patients were divided into subgroups according to their blood pressure (BP) levels and control status, in which odd ratios (OR) by sex for AF was estimated using a logistic regression model and restrictive cubic splines before and after propensity score matching.A total of 3,212 patients with AF and 8,307 without AF were investigated. Compared to patients with normal BP, patients with HBP had more AF . In HBP patients with grade 3, the OR of AF was much higher in women than in men . BP over 133.1/79.9 mmHg in men or 127.1/75.1 mmHg in women was positively associated with AF. In patients with HBP, uncontrolled BP was more associated with AF , especially in women . BP and prevalence of AF correlated with each other positively in patients admitted to a cardiology ward. Lowering BP to 145.1/85.8 mmHg in men or 140.5/82.5 mmHg in women led to less AF.There is more significant relationship between HBP and AF in female patients. A lower and individualized BP target may be formulated to prevent AF in women. Arterial hypertension (HBP) and atrial fibrillation (AF) are closely related and often coexist clinically . About 6However, it is uncertain above which BP level the risk of AF is significantly increased. Also, the extent to which BP control reduces AF in hypertensive patients is unknown, despite clear evidence that BP control reduces target organ damage and improves overall survival –11. ThouIn many diseases, clinical manifestations vary by sex. Specifically, females have a lower overall rate of HBP than males , but posIn this study, we aimed to examine in detail the association of BP and its control status with AF using a large case-control patient population. We also investigated sex differences in the relationship of BP and AF to provide more personalized suggestions for clinical treatment.All patients admitted to the Cardiology Department of the Third Xiangya Hospital of Central South University during 2015–2019 were eligible. Among them, we included patients who were (a) ≥ 18 years of age and (b) had BP recorded at least daily for three consecutive days after admission. We excluded those diagnosed with (a) secondary HBP and (b) AF due to transient and reversible causes . Those missing necessary data were also excluded. The included patients were assigned to case group or control group according to the presence or absence of AF. A flowchart for screening patients for analysis is shown in We collected basic patient characteristics , medical history , and renal insufficiency), BP, and heart rate (HR). For patients with two or more admissions, only the data from the last admission were collected for analysis.Blood pressure (BP) and HR were measured by professional nurses or doctors using the Omron HBP-1300. The BP monitoring device was calibrated annually. The BP and HR records were obtained from the Hospital Information System (HIS), and the average of the BP and HR records for three consecutive days after admission was calculated as the final BP and HR for analysis.A patient is considered to have a history of AF if he/she had a clear history of AF or if the electrocardiogram showed AF during hospitalization, but was excluded if the exclusive criteria were met.A patient is considered to have a history of HBP if he/she had a clear history of HBP or if BP monitoring during hospitalization met the diagnostic criteria for HBP (including office BP or ambulatory BP).Grade 1 is systolic and diastolic BP (SBP/DBP) ≥ 140/90 mmHg and < 160/100 mmHg; Grade 2 is SBP/DBP ≥ 160/100 mmHg and < 180/110 mmHg; and Grade 3 is SBP/DBP ≥ 180/110 mmHg.A patient with a history of HBP is considered BP controlled if BP was < 140/90 mmHg at the time of admission after lifestyle adjustment or medication; Otherwise, the patient is considered BP uncontrolled.Refers to moderate to severe mitral stenosis, mitral insufficiency, aortic stenosis, and aortic insufficiency.Includes dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, myocardial amyloidosis, and other confirmed cardiomyopathies.2.Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 mt-test to compare continuous variables and the Chi-square test (χ2) to compare categorical variables. Odd ratios (OR) between AF and Non-AF groups were analyzed using logistic regression and restricted cubic splines (RCS).We used the independent To address the confounding of patient demographics in this observational study, we estimated propensity scores for the likelihood of developing AF, and based on the estimated propensity scores, we matched patients with AF with those without AF using a 1:2 ratio without replacement . We thenFor patients with or without AF, we used propensity score models adjusted for the following variables–sex, age, BMI, HR, smoking, alcohol drinking, diabetes, stroke, coronary artery disease, heart failure, valvular heart disease, cardiomyopathy, COPD, and renal insufficiency. PSM was implemented using a nearest-neighbor strategy. If the unspecified approach did not produce a satisfactory balance, the caliper for the matching was specified in the nearest-neighbor strategy. We then estimated comparative AF-vs.-Non AF ORs using conditional logistic regression and RCS.P-value less than 0.05 was considered significant.Analyses were performed using RStudio version 2022.02.3 (with the packages MatchIt and rms). A The Institutional Review Board of the third Xiangya Hospital approved the waiver of informed consent (No. I22317). All data were collected anonymously from the HIS and all authors ensure the confidentiality of patient data.Of the 16,122 hospitalized patients, 11,519 were included in the study for further analysis after excluding those who met the exclusion criteria. Among these included patients, 3,212 were assigned to the case group (with AF) and 8,307 to the control group (without AF) .P = 0.025), HBP , smoking , diabetes , stroke , coronary artery disease , heart failure , valvular heart disease , cardiomyopathy , COPD , renal insufficiency , mean age , SBP , DBP , and HR . There were no significant differences in mean body mass index (BMI) and proportion of drinkers between the two groups. Compared to controls without AF, the AF case group had significantly higher proportions of the following patient variables: female , age , HR , HBP , stroke , valvular heart disease , COPD , and renal insufficiency . Smoking , diabetes , and heart failure  were positively correlated with AF, but not statistically significant. BMI, drinking, coronary artery disease and cardiomyopathy were not correlated with AF .Elevated BP was significantly highly correlated with AF risk. Compared with patients with normal BP, patients with grade 1 HBP had a 1.75 (95% CI: 1.52–2.02)-fold increase in the exposure ratio of AF, and in patients with grade 2 and 3 HBP, the ratio was further increased to 2.66 (95% CI: 2.24–3.15) and 4.30 (95% CI 3.40–5.44), respectively . EspeciaIn the sex subgroup, the results maintained the same trend, but the relationship appeared to be stronger in female patients. While the risk of AF in females with grade 1 and 2 HBP was slightly higher than that in males, the OR of AF was significantly higher in females with grade 3 HBP than in males  . Also, tIn HBP patients, BP uncontrolled was highly correlated with AF , which appears to be more obvious in females . However, with good BP control, the OR of AF was reversed in both sex subgroups. Compared with HBP uncontrolled patients, controlling HBP reduced the OR of AF in HBP controlled patients to 1.62 (95% CI: 1.34–1.96), in particular, controlling HBP reduced the OR of AF in females and males to 2.02 (95% CI: 1.44–2.83) and 1.29 (95% CI: 0.89–1.98), respectively . FurtherThe prevalence of AF increased with age . FemalesThere is a strong relationship between HBP and AF, and the two share many common risk factors. HBP is also a key risk factor for AF. However, neither previous studies nor current guidelines clarify what high levels of BP should be controlled to reduce the occurrence of AF –16. In tStudies have shown that multiple risk factors are closely related to the occurrence of AF, including uncontrollable factors such as age, sex, family history, race, height, and genetics , 22, conIn the general population, the occurrence and recurrence of AF were associated with BP , 27. EveIn hypertensive patients, BP control can significantly reduce the incidence of AF. Compared with the non-hypertensive patients, the OR of AF in patients with uncontrolled BP was 3.00 times, which decreased to 1.62 times after BP control, fully demonstrating the importance of BP control. In hypertensive patients, lowing BP to 145.1/85.8 mmHg had a significant effect on the OR of AF, whereas in female patients, it should be lowered to 140.5/82.5 mmHg.After BP control, the risk of AF decreases. On the one hand, the remodeling of the atrial myocardium by HBP is fundamentally released after BP reduction, . On the Left atrial remodeling is the main cause of AF in hypertensive patients. Verdecchia et al. conducted a 16-year follow-up of 2,482 patients with primary HBP and found that the risk of AF increases with patient age and left ventricular size, and that increased left atrial volume predisposes to chronic AF . This isSex differences in the relationship of HBP and AF is the highlight of this study. On the one hand, women tend to have lower BP for reasons such as estrogen , weight In this study, to minimize the information loss caused by data grouping, in addition to logistic regression, we also conducted RCS to directly process the data. The RCS results showed that unexpectedly, the BP cut-off values for a significantly increased OR of AF due to elevated BP and a reduced OR of AF after BP control in hypertensive patients were not 140/90 mmHg and 130/80 mmHg, respectively  over 133.1/79.9 mmHg in male patients or 127.1/75.1 mmHg in female patients was significantly associated with the prevalence of AF. In HBP patients, a BP lower than 145.1/85.8 mmHg in men or 140.5/82.5 mmHg in women was associated with reduced prevalence of AF. These data suggest that BP targets to reduce the risk of AF may consider sex differences, and that a lower and individualized BP target may be established to protect against AF in women.tangxh007007@163.com.The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Requests to access these datasets should be directed to XT, The studies involving human participants were reviewed and approved by IRB of The Third Xiangya Hospital of Central South University. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.XZ and QF established the idea and helped in wrote main ideas for this research, main results, and discussion of the findings. AW was a major contributor in wrote the manuscript. XZ and WJ interpreted statistical analysis to prove the main findings of this project. QF, XW, and JW collected data. XT contributed on editing this manuscript and giving advice for the main authors to organized the manuscript and ideas of the project. All authors contributed to the article and approved the submitted version.


Cardiovascular diseases (CVDs) are a group of diverse pathological conditions of the heart and the vascular system with different etiology. CVDs are the number one cause of human mortality and per the WHO’s latest estimates, 32% of global mortality is due to cardiovascular-related diseases . The cardiovascular system (CVS) is greatly influenced by our endocrine system in multiple ways, ranging from the regulation of blood pressure through an intricate network of hormonal signaling involving the Renin-Angiotensin system (RAS) to the positive or negative chronotropic effect . SeveralEndocrine-related Cardiovascular Diseases: Recent Advances in Diagnosis and Treatment”. This issue was launched with the aim to provide a platform for the research community working in the areas of CVDs to share their findings on our recent understanding of the role of the endocrine system in CVDs, its diagnosis, and treatment. A total of five articles; four original and one systematic review were selected for publication among the numerous submissions received. A brief summary of each contribution is highlighted below.This editorial summarizes the contribution to the special issue of Frontiers of Endocrinology “Gan et al. explored the relationship between lipocalin-2 (LCN-2), an acute phase protein released by neutrophils in response to multiple stresses  in essential hypertension. The authors show that there is selective dysfunction of alpha 1 receptors in mediating systolic blood pressure hyperreactivity to norepinephrine infusion, whereas these receptors mediate diastolic blood pressure hyperreactivity in essential hypertensive individuals, which can be inhibited by a non-selective alpha receptor blocker. Thus, either the alpha receptors do not mediate systolic hyperreactivity or else their function is impaired, which sets the stage for investigating the underlying molecular mechanisms and its possible implications for appropriate therapeutic approaches.The adrenal glands, especially the medulla, is an important mediator of endocrine regulation of blood pressure and cardiovascular function through circulating epinephrine and norepinephrine. The relationship between mental stress and blood pressure is well established. However, the mechanisms of adrenergic receptors, especially alpha receptors, in hyperreactivity to circulating catecholamines in essential hypertension are not known. In the second article of this collection entitled “Alpha-adrenergic mechanisms in the cardiovascular hyperreactivity to norepinephrine-infusion in essential hypertension”, Wang et al. performed a meta-analysis on the effect of empagliflozin on DMF. Empagliflozin belongs to the growing list of antidiabetic drugs that inhibit sodium-glucose cotransporters (SGLTs) but have also been shown to possess cardiovascular benefits, including a reduction in DMF  poses an increased health risk of progressing towards heart failure due to several adverse changes that occur in the heart, such as diastolic dysfunction, increased myocardial stiffness, and left ventricular remodeling . If stopn in DMF . Out of Feng et al. demonstrated the use of the coronary angiography-derived index of microcirculatory resistance , a less-invasive and pressure-wire free index to assess the coronary microvascular function in the chronic coronary syndrome (CCS) patients with obesity. The authors found that calMR value of >=25 was independently associated with major adverse cardiac events in obese patients but not in non-obese patients. Their data supports a significantly higher prognostic value of calMR in obese patients suffering from CCS, thus a potential biomarker of CCS in obese patients.The development of easy, fast, cost-effective, reliable, and preferable non-invasive methods is the ultimate aim of modern disease detection approaches. It becomes more imperative when detecting life-threatening diseases, including cardiovascular diseases. Over several decades of technological innovation, many techniques have been developed to assess cardiac function. The use of invasive coronary flow rate (CFR) and microcirculatory resistance (IMR) techniques to assess coronary microvascular function is quite prevalent with each technique having its own merits and demerits, especially when assessing coronary microvascular function in obese patients . In the Liu et al analyze the association between thyroid hormone sensitivity and risk of carotid plaque in patients with coronary heart disease (CHD) and further explore this association based on baseline characteristics and lifestyle. This was a retrospective cross-sectional study and included 6679 CHD patients (aged 35-75). Central sensitivity to thyroid hormone was evaluated by the thyroid feedback quantile-based index (TFQI), thyroid-stimulating hormone index (TSHI), and thyrotroph thyroxine resistance index (TT4RI). Peripheral sensitivity to thyroid hormone was assessed by the free triiodothyronine/free thyroxine (FT3/FT4) ratio. Out of 6679 CHD patients, 72.50% had a carotid plaque. In the multi-adjusted models, the TFQI, TSHI, and TT4RI were positively associated with the risk of carotid plaque. Compared with females and people > 60 years, the odds ratio (OR) value for the carotid plaque was higher in males and people ≤ 60 years. smokers and drinkers had higher OR values for carotid plaque than non-smokers and non-drinkers. FT3/FT4 ratio was negatively associated with carotid plaque, and the OR value for the carotid plaque was lower in males, patients ≤ 60 years, smokers, and drinkers. In conclusion, this study showed that thyroid hormone sensitivity is associated with carotid plaque in patients with CHD. This association is more significant in male smokers and drinkers aged ≤ 60 years.In the fifth article entitled “Impaired sensitivity to thyroid hormones and carotid plaque in patients with coronary heart disease: A RCSCD-TCM study in China” AB was the guest associate editor and wrote the paper text. AD was the guest associate editor of the Research Topic and edited the text. KD was the guest associate editor of the Research Topic and edited the text. All authors contributed to the article and approved the submitted version