To assess the relation between socioeconomic status and achievement of target blood pressure in hypertension.Retrospective longitudinal cohort study between 2001 and 2014.Primary health care in Skaraborg, Sweden.48,254 patients all older than 30 years, and 53.3% women, with diagnosed hypertension.Proportion of patients who achieved a blood pressure target <140/90 mmHg in relation to the country of birth, personal disposable income, and educational level.Patients had a lower likelihood of achieving the blood pressure target if they were born in a Nordic country outside Sweden , or born in Europe outside the Nordic countries , compared to those born in Sweden. Patients in the lowest income quantile had a lower likelihood to achieve blood pressure target, as compared to the highest quantile . Educational level was not associated with outcome. Women but not men in the lowest income quantile were less likely to achieve the blood pressure target. There was no sex difference in achieved blood pressure target with respect to the country of birth or educational level.The association between socioeconomic status and achieving blood pressure targets in hypertension has been ambiguous.•In this study of 48,254 patients with hypertension, lower income was associated with a reduced likelihood to achieve blood pressure control.•Being born in a foreign European country is associated with a lower likelihood to achieve blood pressure control.•We found no association between educational level and achieved blood pressure control.In this real-world population of primary care patients with hypertension in Sweden, being born in a foreign European country and having a lower income were factors associated with poorer blood pressure control. Hypertension is a leading and modifiable risk factor for global disease burden . There iThe current study aims to enlighten the association of attaining blood pressure target achievement and socioeconomic status in a hypertensive population in a Swedish primary care setting. More specifically, the study assessed the association between achieved blood pressure and markers of socioeconomic status , and the relation to sex.The Swedish Primary Care Cardiovascular Database (SPCCD) is a research project including patients who attended primary care in two Swedish regions (Skaraborg and Stockholm) 2001–2008 with a registered diagnosis of hypertension . A focusThis retrospective observational study includes individuals with a diagnosis of hypertension (ICD-10: I10–15) and a documented initial blood pressure value included in SPCCD-SKA between 1 January 2001 and 31 December 2014. Socioeconomic status was assessed at the time of inclusion in SPCCD-SKA (baseline). Definitions for country of birth, educational level, and personal disposable income are given in The study outcome was defined as achieved blood pressure target <140/90 mmHg, as suggested in the national and international guidelines at the time of the study. According to prevailing national recommendations by the time of the study, blood pressure should be measured in the supine or seated position by a nurse or a physician by an oscillometric device or by the auscultatoric method as an average of two or more recordings. There are currently no home blood pressure measurements included in SPCCD. All patients were followed until 31 December 2014 or death. Achieved blood pressure was defined as the most recent blood pressure registered in SPCCD-SKA.SD), as appropriate. Multiple logistic regression was used to calculate risk ratios and 95% confidence intervals (CI) for the relationship between socioeconomic variables at baseline and achieved blood pressure target. These analyses were conducted in five different models. In models 1–3 the relationship was evaluated separately for each socioeconomic variable, adjusted for age, sex, and index year. In model 4 all three socioeconomic variables were included in the same analysis adjusted for age, sex, index year, and in addition for marital status and comorbidities . In model 5 sex-stratified logistic regression models adjusted for age, index year, marital status, and comorbidities were performed as well. A sensitivity analysis investigated the results in models 1–4 when the blood pressure target was set as ≤140/90 mmHg (instead of <140/90 mmHg) to account for bias due to digit preference. All analyses were conducted using SAS version 9.3 .Data are presented as proportions or as mean values ± standard deviation , and the mean follow-up time was 6 years. Half of the individuals had the last blood pressure measurement in 2014. Baseline characteristics are presented in At follow-up 24,114 individuals (50.0%) achieved blood pressure target; 12,306 (47.8%) of the women, and 11,808 (52.4%) of the men. Three logistic regression models  were used to estimate the risk ratio for achieved blood pressure target, in relation to indices of socioeconomic status . First, The fourth logistic regression model, including all socioeconomic variables, was conducted with additional adjustment for marital status and history of comorbidity. The relations are presented in A sensitivity analysis with ≤140/90 as blood pressure target showed that 63.6% of the patients reached target blood pressure. The association of country of birth and educational level to achieved blood pressure remained the same. However, the effect of the income was attenuated and no longer significant with a blood pressure target set to ≤140/90 mmHg.There are three major findings of this observational study among almost 50,000 patients with hypertension in Swedish primary care. First, lower disposable income was associated with a lower likelihood of achieving the blood pressure target. Second, individuals born in a European country other than Sweden had a lower likelihood of achieving the blood pressure target. Third, educational level was not associated with achieving the blood pressure target.The large size of this contemporary real-world study population, the longitudinal design, and the robust data of the conditions for exposure  are strengths of the present study. However, some important limitations need to be acknowledged. First, patients were treated according to standard clinical practice, which may result in treatment bias by indication. Second, the observational retrospective study design is sensitive for confounding. We attempted to adjust for potential confounders by multiple analyses to reduce the risk of confounding. We have included cardiovascular comorbidity and diabetes mellitus in the adjustments since those diagnoses result in a more structured follow-up that can affect achieved blood pressure. However, data about diet, alcohol consumption, exercise habits, and other possible factors affecting blood pressure were not available to us, a common challenge in large observational studies. Third, the personal disposable income might misclassify patients with low personal income who live in a rich households. Therefore, we have adjusted our analyses for marital status. Finally, the results may not be valid in other contexts, where different conditions may prevail.The main finding of this study is the independent association between low personal disposable income and lower likelihood to achieve blood pressure target. This is in agreement with our previous findings, where patients with higher income had lower discontinuation rates of antihypertensive drug treatment, while there was no association between educational level and treatment persistence . This maIn this study, hypertensive patients born in a European country outside Sweden were less likely to achieve blood pressure targets. Being a foreigner might be an obstacle in establishing good contact with the healthcare system, although Sweden provides equal subsidised accessible universal healthcare for all citizens. Previous studies have shown differences in the prevalence of hypertension among immigrants , and ethWe found no association between educational level and blood pressure control. Low socioeconomic status  has been associated with an increased prevalence of hypertension . HoweverUp to now, education has been looked upon as a more reliable entity while income may vary during a lifetime. The organisation, or change in organisation, of the educational system, may, however, be of major concern when the association between educational length and health is evaluated. In Sweden, such a change has been implemented during the last 30 years. Earlier, an education length of 12 years was almost identical to a later university degree. Today education of 12 years may include craft training to achieve a vocational degree. This change in the content in the educational system may partly explain why income and not educational length are closely related to blood pressure control. Thus, whereas income, educational level, and occupation are all established markers for socioeconomic status, our findings suggest that personal disposable income has a stronger association than educational level to achieve blood pressure control in a hypertensive population in Sweden.This study shows that one-half of people attending Swedish primary care in 2001–2014 with a diagnosis of hypertension achieved a blood pressure target of <140/90 mm Hg. This is an encouraging improvement from our previous findings  . NotwithThis real-world population study of patients with hypertension attending primary care in Sweden shows that socioeconomic status, i.e. low income, and country of birth in a foreign European country, was associated with inferior blood pressure control in both women and men. Thus, health care providers are advised to provide additional support for those patients to achieve proposed blood pressure targets and thereby reduce future cardiovascular risk.


Among all participants, 24 (14.5%) had decreased eGFR (<90 mL/min/1.73 m2). A significant positive correlation between β2M/Cr. ratio and body mass index  was found. Furthermore, higher levels of urinary β2M were detected among CCS with a longer follow-up time (over 5 years) after treatment. Subjects with decreased eGFR showed statistically higher urinary β2M levels  compared with the healthy peers. Twelve survivors (7.2%) presented hyperfiltration and they had higher urinary β2M levels than CCS with normal glomerular filtration . This study did not reveal an association between potential treatment-related risk factors such as chemotherapy, surgery, radiotherapy, and the urinary β2M level. The relationship between treatment with abdominal radiotherapy and reduced eGFR was confirmed (p < 0.05). We demonstrated that urinary beta-2-microglobulin may play a role in the subtle kidney injury in childhood cancer survivors; however, the treatment-related factors affecting the β2M level remain unknown. Further prospective studies with a longer follow-up time are needed to confirm the utility of urinary β2M and its role as a non-invasive biomarker of renal dysfunction.The objectives of this study were to evaluate urinary beta-2-microglobulin (β2M) levels in long-term childhood cancer survivors and to establish its association with anticancer drug-induced nephrotoxicity. The study consisted of 165 childhood cancer survivors (CCS) who were in continuous complete remission. We reported that CCS had a significantly higher level of β2M ( Improvements in the diagnosis and treatment of pediatric cancers have now resulted in significantly higher survival rates. However, childhood cancer survivors (CCS) are at greater risk of experiencing many treatment-related adverse effects that substantially affect later quality of life ,2. NephrThe extent of renal impairment can vary and depends on many factors. In some cases, the only sign of kidney damage is renal hypertension or Fanconi syndrome, while others develop chronic kidney disease (CKD) from mild damage to complete kidney failure at various ages in life. Based on available methods, it remains difficult to predict which patients will develop kidney disease after anticancer treatment. The primary parameter assessing renal function is estimated glomerular filtration rate (eGFR) based on creatinine level. However, there are many limitations affecting its level which include age, sex, race, muscle mass, diet, hydration status, physical activity, and medications taken regularly. New markers are being sought to identify individuals with early renal function impairment before it is clinically detectable by standard techniques. In recent years, there has been an increasing number of studies on the role of beta-2-microglobulin (β2M) in the development of acute kidney injury (AKI) and CKD. Some of them, but not all, reported its elevated levels following treatment with nephrotoxic drugs ,6. StillBeta-2-microglobulin is a small protein 18 kDa) encoded by gen located on chromosome 15. In healthy subjects it is filtered by glomeruli and subsequently reabsorbed in the proximal tubule of the nephron, resulting in minimal urine concentration ,8. Tubul kDa encoThe aims of this study were to evaluate urinary beta-2-microglobulin levels in long-term childhood cancer survivors and determine its relationship with the type of anticancer treatment used.The study included 165 childhood cancer survivors  visiting the follow-up outpatients’ clinic at the Department of Pediatric Oncology and Hematology, Medical University of Bialystok (Poland). All participants were in complete first continuous remission. Exclusion criteria included: congenital anomalies of kidney or urinary tract, current infection, relapse of cancer. All the children were treated according to the international protocols in line with the diagnosis, approved by the Polish Pediatric Leukemia and Lymphoma Group, and Polish Pediatric Solid Tumors Group. Written informed consent was obtained from the participants or their parents/guardians. The study was approved by the Ethical Committee of the Medical University of Bialystok in accordance with the Declaration of Helsinki (permission number: R-I-002/62/2018).2). Blood pressure was measured using a standardized sphygmomanometer ; before the measurement, the participant rested peacefully for five minutes. Hypertension was defined as mean systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) level ≥ 95th percentile adjusted for age, sex, and height [Clinical history, including demographic information, comorbidities, anticancer treatment used in each patient, especially cumulative dosage of nephrotoxic drugs , and abdominal radiotherapy was obtained from the CCS database. All the participants underwent a clinical examination and anthropometric measurements. Body mass index (BMI) was calculated as weight in kilograms divided by height in squared meters (kg/md height . The con2) was calculated using the updated Schwartz formula: eGFR = 0.413 × (height in cm/serum cr. in mg/dL). Urinary beta-2-microglobulin level was measured using commercial immunoassays  according to the instructions for the ELISA kit. The tested urine biomarkers were calculated per milligram urine creatinine (cr.) in order to avoid the effect of urine dilution (β2M/cr. ratio). Urine albumin concentration was determined by Lowry’s method. Subjects with a urinary albumin/creatinine ratio between 30 to 300 μg/mg were considered to have albuminuria. The stages of CKD were classified according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, defined by structural or functional abnormalities of the kidney for ≥3 months, with or without decreased eGFR or eGFR < 60 mL/min/1.73 m² for ≥3 months, with or without kidney damage [2 [All participants had an abdominal ultrasound to assess the kidney and urinary tract performed by a qualified radiologist. After a 12 h night, fasting peripheral blood was collected from each participant for routine laboratory testing. Clean catch urine samples were stored at −80 °C for further analysis. The serum creatinine level was measured by enzymatic method, and the estimated glomerular filtration rate  was used to perform statistical analysis, and statistical significance was determined at 0.05.Statistical analysis. Normal distribution was tested by using the Shapiro–Wilk test. Mean and standard deviation (SD) or median (Me) and interquartile range (IQR) were used to presented data. The The clinical characteristics of the childhood cancer survivors (CCS) are presented in p = 0.035) as well as urine creatinine levels  than the healthy peers. However, we did not observe any difference in the eGFR . Childhood cancer survivors revealed increased serum creatinine levels  and β2M/Cr. ratio  compared to the control group  and β2M/Cr. ratio  concentrations according to sex. Both genders had significantly higher values of urine creatinine  and urinary β2M  when compared to the control group, but no gender differences were found within the study group. Of note, HSCT treatment had no effect on urinary β2M levels (p < 0.05).We found no differences in β2M  in CCS, but no correlations between both the β2M level and β2M/Cr. ratio and eGFR were found. Among the whole study group, there were twelve individuals (7.2%) who presented hyperfiltration. Compared to those with normal glomerular filtration, they showed higher urinary creatinine  and β2M  levels.Twenty-four of the study participants (14.5%) presented eGFR below 90 mL/min/1.73 m2) in each group according to whether or not they were exposed to a particular nephrotoxic agent. Survivors who had radiation therapy in childhood were statistically more likely to have decreased eGFR at the time of the study compared to those who had never received RT . We also investigated the association between the type of cytostatics used, abdominal radiotherapy, and the number of patients with reduced eGFR (<90 mL/min/1.73 mp < 0.0001), uCr , β2M , β2M/Cr. ratio , and lower eGFR  than participants who were under 5 years from the end of treatment at follow-up  over 5 years after the end of treatment with significantly higher levels of sCr , systolic blood pressure , diastolic blood pressure , and β2M level were found; however, the strength of relationships was very weak (r < 0.3).In the whole group, positive correlations between urine creatinine (n = 105), Hodgkin lymphoma (n = 10), and solid tumors (n = 50). No significant differences in eGFR (p = 0.149), β2M level (p = 0.936), and β2M/Cr. ratio (p = 0.573) were found between subgroups.Participants were also divided based on their initial diagnosis and treatment as follows: leukemia and non-Hodgkin lymphoma (p > 0.05). Moreover, no correlations between the β2M level and β2M/Cr. ratio, and the cumulative dose of cyclophosphamide, ifosfamide, cisplatin, and methotrexate were found (p > 0.05).The β2M level and β2M/Cr. ratio were investigated depending on whether or not the patients received a specific cytostatic drug during the treatment ; however, no relationships were revealed (2). However, none of them showed any diagnostic value (the AUC for the β2M level was 0.46 and for the β2M/Cr. ratio was 0.43).Receiving operating curve (ROC) analyses were conducted to determine the diagnostic profile of β2M level and β2M/Cr. ratio in identifying participants with decreased eGFR . Other potential confounding factors such as abdominal radiotherapy, cumulative dose of nephrotoxic cytostatics, age at diagnosis, age at study, eGFR, albumin-to-creatinine ratio, and solitary functioning kidney did not affect the β2M level or β2M/Cr. ratio . However, there is a population of CCS who had never experienced AKI but who developed CKD many years after treatment. In recent years, much effort has been concentrated on identifying those survivors who are at risk for developing kidney failure during adolescence and adulthood.The available methods for accessing renal function have many limitations, and, thus, new biomarkers to access early kidney deterioration are needed. There are several urinary markers (highly sensitive and specific) for monitoring drug-induced kidney injury that have been approved in preclinical studies by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA). The best candidates include β2-microglobulin (β2M), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), clusterin, and trefoil factor-3 (TFF-3) ,14. Most2) accounted for 14.5% and this decreased in subsequent tests performed at least every 3 months. Our results are in accordance with one of the largest available studies conducted on a cohort of 1122 survivors, in which the probability of reduced eGFR among CCS treated with nephrotoxic agents was 6.6% by age 35 years compared to those who had never received such treatment, and eGFR continued to fall with time. The greater risk of nephrotoxicity was observed in survivors given ifosfamide and cisplatin, and with nephrectomy [In the overall group of CCS, subjects with reduced eGFR , which has not been investigated so far. These individuals were analyzed separately but did not differ from CCS with other cancer types.Higher levels of urinary β2M were observed in subjects with a follow-up time of more than 5 years. Interestingly, in the univariable linear regression analysis, significant positive correlations between β2M/Cr. ratio and BMI were observed. These results may suggest that urinary β2M level depends on age and body weight, as postulated by some authors; however, reference values are not available ,28.Reviewing the literature, there are many data reporting elevated serum β2M levels at the time of diagnosis in many types of cancer, as well as being a predictor of relapse in some of them ,30,31. IFurthermore, there are many studies investigating the role of β2M in kidney diseases of different etiology. It has been demonstrated that β2M concentration is elevated among individuals with systemic lupus erythematosus, beta thalassemia major, type 1 diabetes, acute appendicitis, and congenital lower urinary tract obstruction, among others ,34,35,36Finally, there are several limitations that need to be considered. First, single-center studies may influence the occurrence of bias. Second, the heterogeneity of the study group in terms of different types of cancers made it unfeasible to analyze the effect of some specific treatment protocols . For this reason, we targeted the impact of specific treatments modalities, such as cytostatic agents and radiotherapy. Third, we used the GFR estimated from creatinine level rather than measured by standard techniques such as plasma clearance of iohexol. Another limitation of the study is the non-inclusion of other markers for assessing renal function, such as cystatin C, which is considered to be more resistant to various confounding factors, such as body mass index. The authors did not use Gao’s quadratic equation in addition to Schwartz’s formula when glomerular hyperfiltration was suspected; however, the number of subjects with hyperfiltration was very limited .The strengths of the study include the relatively large number of participants, long follow-up time, and ethnic homogeneity of the group.Pooling all data, we demonstrated that 14.5% of childhood cancer survivors had reduced eGFR value, and the most adverse factor affecting renal function was abdominal radiotherapy used during the treatment. We also provided new data that this particular population has elevated urinary beta-2-microglobulin level regardless of initial diagnosis. Of the factors tested with potential effects on renal function, only a longer time of follow-up and high BMI were positively correlated with the level of urinary β2M. The results of this study do not explain what urinary β2M level depends on. None of the factors investigated, including type of cancer, cumulative dose of cytostatics used, radiotherapy, nephrectomy, or age at diagnosis significantly affected biomarker levels. It cannot be ruled out that genetic background is also relevant. Furthermore, in light of recent studies demonstrating premature aging of survivors, it is important to note that nephrotoxicity is a multifactorial process involving both environmental and genetic factors ,40. Sinc


The primary objective of this study aims to test patient factors, with a focus on cardiometabolic disease, influencing the performance of the Cockcroft-Gault equation in estimating glomerular filtration rate.A cohort study was performed using data from adult patients with both a 24-h urine creatinine collection and a serum creatinine available. Creatinine clearance was calculated for each patient using the Cockcroft-Gault, Modified Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations and estimates were compared to the measured 24-h urine creatinine clearance. In addition, new prediction equations were developed.n = 484), 44.2% of patients were obese, 44.0% had diabetes, and 30.8% had dyslipidemia. A multivariable model which incorporating patient characteristics performed the best in terms of correlation to measured 24-h urine creatinine clearance, accuracy, and error. The modified Cockcroft-Gault equation using lean body weight performed best in the overall population, the obese subgroup, and the dyslipidemia subgroup in terms of strength of correlation, mean bias, and accuracy.In the overall study population (Regardless of strategy used to calculate creatinine clearance, residual error was present suggesting novel methods for estimating glomerular filtration rate are urgently needed. Creatinine clearance (CrCl) is used to estimate glomerular filtration rate (GFR) to assess renal function. Numerous medications require dosage adjustment in the setting of reduced GFR and CrCl is often used to guide dosing of medications cleared by the kidney. The most accurate and clinically feasible estimate of CrCl is the measured 24-h urine CrCl; however, this method is not often practical and is time consuming. The Cockcroft-Gault equation published in 1976, , 4. BothThe appropriate assessment of renal function is critical for drug dosing. More than half of all medications are cleared by the kidneys and inappropriate dose adjustment to account for potential drug accumulation may lead to drug toxicity. Therefore, an adept understanding of the accuracy, reliability, and nuances of the Cockcroft-Gault equation is necessary. Moreover, strategies to correctly classify the degree of renal dysfunction are likely to improve patient outcomes. The reliability and application of the Cockcroft-Gault equation (see equation below)hreshold . The quehreshold , 15, 16.hreshold . There ihreshold . OverallA retrospective cohort study was performed using data extracted from the electronic discharge database and medical records at community medical center between January 2009 and July 2019. All consecutive adult patients (aged 18 years or older) with both a 24-h urine creatinine collection and a serum creatinine obtained within 24 h of each other were screened for inclusion. The institutional standard for measurement of creatinine is the Jaffe method. Only patients with comorbidities recorded in the electronic health record were further considered for inclusion. Patients were required to have a stable serum creatinine defined as less than a 20% fluctuation between two serum creatinine values measured within 48 h. Patients who were pregnant, had undergone amputations, in acute renal failure, or those on hemodialysis were excluded. Individuals with a serum creatinine greater than 2.5 mg/dL were excluded from the analysis since this would suggest Stage 5 Chronic Kidney Disease and previous data reported inaccuracies in estimation of CrCl using traditional equations in this population  index above 37 kg/m2) . We placp < 0.05 in the regression analysis. Only disease states present in at least 15% of patients in the analytic dataset were considered for evaluation in the regression.Second, we performed multivariate regression analysis. For multivariate eq. 1, measured 24-h urine CrCl was divided by body surface area and then coefficient values for serum creatinine, age, and sex were estimated. For multivariate eqs. 2, 3, and 4 total, adjusted, or lean body weight were included with coefficient values to develop equation, respectively, as well as serum creatinine, age, and sex. After estimating coefficient values from base equations, disease states  and race (white or non-white) were tested and included if All results were summarized using descriptive statistics. Mean and standard deviation were reported for normally distributed continuous data and median and range were reported for data that were not normally distributed. Normality of data was assessed using visual inspection of histograms and the Shapiro–Wilk test. Binary data were reported as counts and proportions. The Pearson’s correlation coefficient between each of the calculated CrCl values and the measured 24-h urine CrCl and corresponding 95% confidence intervals were calculated using Fishers Z methods. The mean bias between the measured 24-h CrCl and various methods for calculated CrCl was defined as the difference between the two values and the precision was described using the 95% confidence interval for the difference. Root mean square error (RMSE) was calculated for each outcome in order to assess the degree of bias. Calculated CrCl not deviating more the 30% from the 24-h urine CrCl was considered to be accurate. This definition of accuracy was based on the original study validating the Cockcroft-Gault equation, which reported that Cockcroft-Gault calculated CrCl was within 30% of the 24-h urine CrCl  and otheFigure The estimation of GFR using calculated CrCl is critical to select optimal medication dosing regimens. Individuals with obesity, diabetes, and dyslipidemia often are on many medications and have altered kidney function making calculating CrCl more critical. The overall purposes of this study were to identify the influence of cardiometabolic disease on GFR estimation and to enhance and develop CrCl equations. The current study identified several limitations with current practices in the calculation of CrCl. First, the Cockcroft-Gault equation uses the total body weight in calculating CrCl. There has been conflicting data regarding substituting adjusted body weight into the equation. We provide evidence that adjusted body weight is a reasonable consideration. Using this weight produced similar and, in some situations, better correlation, lower bias, and improved accuracy. Moreover, we demonstrate that the inclusion of obesity, diabetes, dyslipidemia, and race into a modified Cockcroft-Gault equation improves performance relative to the original Cockcroft-gault equation.Previous studies have investigated the precision, bias, and accuracy or overall performance of GFR estimation using calculated CrCl in a variety of populations , 33, 34.Some limitations to our study must be considered. First, 24-h CrCl was used as the reference value, an alternate to the gold standard. Ideally, injection of inulin and capturing its clearance by the kidneys would be preferable; however, this approach is seldom applied in the clinical setting due to its invasiveness, cost, time commitment, and lack of availability in retrospective data . There aGiven that half of all medications or their metabolites are cleared by the kidney and roughly 3 billion prescriptions for medications are written annually many individuals may be at risk for underdosing (or overdosing) if renal function isn’t appropriately assessed , 40. WhiFurther research is warranted to identify novel biomarkers to accurately estimate CrCl. Despite improvement of estimation using a modification of the Cockcroft-Gault or development of new equations using nonlinear regression to estimate CrCl, there remains residual error that cannot be explained. This error may be related to inherent limitations of using serum creatinine in the equations . Future studies should aim at identification of biomarkers that can accurately estimate renal function.Based on our study, total body weight is the appropriate weight descriptor to use in the original Cockcroft-Gault equation. Our modified Cockcroft-Gault equation using lean body weight outperforms other methods of calculating CrCl in terms of correlation, accuracy, mean bias, and RMSE value. Additional research is warranted to determine if this equation is correlated to drug exposure, toxicity, and efficacy.


Approximately 67% of the patients reported “high adherence” on Visit 2, and 70% of them reported “high adherence” on Visit 3. The percentage of patients with ACQ-6-uncontrolled asthma decreased from 79.1% on Visit 1 to 22.3% on Visit 2 and further decreased to 6.7% on Visit 3. Significant improvements were also observed in the total AQLQ score, predicted FEV1% and reduction in rescue medication use. Conclusions: The NEXThaler device, delivering a combination of BDP/F, achieves satisfaction and high adherence in patients with asthma not well controlled with low-dose ICS. Asthma control, QoL, lung function and rescue medication use were improved in a Greek real-world setting.Background: The fixed combination of extrafine beclometasone dipropionate 100 μg/formoterol 6 μg (extrafine BDP/F) delivered by NEXThaler has proved to be effective in patients with moderate-to-severe asthma in terms of lung function, symptoms and asthma control. The aim of this study was to investigate the usability/satisfaction of NEXThaler and adherence to treatment in asthma patients not well controlled by low-dose inhaled corticosteroids (ICS). Methods: This was a 6-month prospective, multicenter, open-label, observational study in 661 patients with asthma not well controlled by low-dose ICS according to the physician’s clinical assessment, which have received regular treatment with extrafine BDP/F NEXThaler. Feeling of Satisfaction with Inhaler (FSI), treatment adherence with self-reported Morisky scale, asthma control, lung function and QoL were recorded at baseline, 3 and 6 months after treatment with extrafine BDP/F. Results: The percentage of patients at least “fairly” satisfied with NEXThaler usability (FSI-10 score 40 to 50) was 96.3%. The mean FSI-10 total score was 46.8 ± 4.4 on Visit 2 and increased to 48.1 ± 3.3 on Visit 3 ( Asthma is a heterogeneous chronic inflammatory disease of the airways that represents a major global public health issue affecting all age groups. Due to its increasing prevalence rates and rising treatment costs, it imposes an unacceptable burden to the patients and the community ,2,3. It Regular controller treatment particularly with inhaled corticosteroid (ICS) containing medications markedly reduces the frequency and severity of asthma symptoms and the risk of having a flare up . InternaRecently, an additional delivery device option apart from pMDIs has been developed to provide the extrafine formulation of beclometasone dipropionate 100 μg/formoterol 6 μg (BDP/F) through a DPI, the NEXThaler. NEXThaler is a pocket-sized, breath-actuated, medium resistance, multi-dose DPI that proved to be an effective and well-tolerated delivery device for the treatment of patients with asthma who require maintenance treatment . In a reThe NEXThaler device has significant benefits compared to other DPIs, such as that dose counter does not decrement after preparation of the dose but only after delivery of the full therapeutic dose, acting like an “inhalation counter” . The breThe aim of this study is to investigate the usability and satisfaction of NEXThaler delivering extrafine formulation of BDP/F and explore adherence to treatment, in patients with asthma not well controlled by low-dose ICS. Moreover, the improvement of asthma control with the use of BDP/F extrafine formulation and the quality of life will be assessed as well as lung function and use of rescue medication.Patients were eligible if aged ≥18 and ≤75 years old with a physician-confirmed clinical diagnosis of persistent asthma according to GINA guidelines. They were all receiving low-dose ICS and, as needed, short-acting beta2 agonists (SABA) but had inadequate control of asthma according to the physician’s clinical assessment. A documented decision in the patient’s medical file on NEXThaler DPI BDP/F as the treatment of choice was needed before the patient being informed about their potential participation in the study.Exclusion criteria included diagnosis of chronic obstructive pulmonary disease (COPD), cystic fibrosis, respiratory infection, or antibiotic intake the last 4 weeks before enrolment, other clinically significant medical conditions interfering with the patient’s compliance, pregnancy or lactating women. Moreover, patients who participated in interventional studies were excluded because their data do not reflect the standard clinical practice.All patients were informed in detail about this study and gave their consent to the use of their data for processing and derivation of collective results.The primary endpoint was the assessment of usability and patient satisfaction with the NEXThaler device. These were assessed using the FSI-10  questionnaire. The FSI-10 questionnaire is a self-report instrument containing 10 questions, each with five possible responses on a five-point Likert scale: 5 = very, 4 = fairly, 3 = somewhat, 2 = not very, 1 = hardly at all . It asseThe co-primary endpoint was the evaluation of treatment adherence to BDP/F using the four-item Morisky Scale. The total score of the four-item Morisky Scale is the sum of the answers to the four items , with 0 points representing high adherence, 1–2 points representing intermediate adherence and 3–4 points representing low adherence .Secondary outcomes were asthma control according to the six-item ACQ-6 questionnaire and quality of life as assessed by the AQLQ using the Greek abbreviated version of it. According to the ACQ score, asthma is classified as controlled when the ACQ score ≤ 0.75, partly controlled when 0.75 < ACQ score < 1.5 and uncontrolled when ACQ score ≥ 1.5 . The GreThis was a multicenter, non-interventional, prospective, open label, observational study of recording and analyzing data from patients with asthma receiving a BDP/F NEXThaler according to the standard clinical practice for managing inadequately controlled or uncontrolled asthma by low-dose ICS plus SABA as needed. In total, sixty-two (62) private care sites participated in this study, coordinated by one hospital/site. This study was conducted as per the guidelines of the Declaration of Helsinki and was approved by the Institutional Review Board of the coordinating hospital.Data were collected from December 2015 to January 2017 and chronologically covered 6 months, from the commencement of the treatment with BDP/F  and 3 and 6 months following patients’ enrolment and initiation of the study . Patients’ demographic and social data were collected at visit 1, including gender, age, family history, smoking status and height and weight in order to calculate BMI at the phase of statistical analysis. Medical history data on comorbidities were collected, with an emphasis on atopy and chronic rhinitis. During every visit, the following data were collected: treatment with study medication, usability satisfaction with the device (FSI-10), evaluation of treatment compliance , asthma control (ACQ-6), asthma quality of life (AQLQ), lung function test results (if spirometry data were available), rescue medication use and other concomitant medications.Analysis included all patients who gave their informed consent and met the inclusion criteria. Continuous parameters were presented using mean ± standard deviation, median, while the nominal ones  were presented using tables of frequencies. The ordinal study parameters were presented using both descriptive measures  and tables of frequencies.t-test was used to compare the corresponding mean values of the two study visits.The percentage of patients with a total FSI-10 score on the 3rd Visit between 40 and 50 (≥40 and ≤50) was calculated. All Confidence Intervals (CIs) to be calculated were of normal approximation, 95%, two-sided, and for all statistical tests: α = 0.05. Regarding the primary study variables, a 95% CI was computed for the estimation of the percentage of patients with total FSI-10 score on the 3rd Visit between 40 and 50 (≥40 and ≤50). For each primary variable, a Multiple linear regression (stepwise selection) tested the relationship of the average FSI-10 score (dependent variable) with the main individual data and average Morisky score (independent variables). Multiple linear regression (stepwise selection) also tested the relationship of the average Morisky scale (dependent variable) with the main individual data and average FSI-10 score (independent variables).t-test was applied for the (three) pairwise comparisons between study visits.Regarding the secondary study variables, a multiple linear regression (stepwise selection) tested the relationship between the baseline values of each secondary variable (dependent variable), with the main individual data (independent variables). Repeated measures analysis of variance tested the change of each secondary variable over time. Paired samples t-test samples were applied for the pairwise comparisons between the mean scores of the four AQLQ domains. Regarding ACQ-6 and AQLQ differences between the 1st and the 3rd Visit (dependent variables) multiple linear regression (stepwise selection) was applied to test the relationship of these differences, with main demographic data, average Morisky score, average FSI-10 score and baseline values of the corresponding dependent variable.Friedman’s technique tested the change of ACQ-6 asthma classification over time. A Wilcoxon test was used for the (three) pairwise comparisons between visits. Paired A total of 661 patients with asthma participated in the study, in a recruitment period that lasted 7 months. Only five patients (0.8%) prematurely discontinued treatment. The main demographic data and characteristics of the study group are shown in p < 0.001). The percentage of patients who were at least “fairly” satisfied with the usability of the NEXThaler device (FSI-10 score between 40 and 50) was 96.3%  on Visit 3. In all 10 questions of the FSI-10 Questionnaire, the percentage of patients who answered “very” increased in Visit 3 compared to Visit 2 by approximately 10%. Moreover, the median value of all items of the FSI-10 Questionnaire was 5.0 (“very”) at both Visits 2 and 3 . The items with the lower “very” percentages for both study visits were “Was it easy to carry the inhaler with you?” (corresponding percentages on Visits 2 and 3: 64.3% and 76.5%) and “Was using the inhaler easy in term of size and weight?” (corresponding percentages on Visits 2 and 3: 68.9% and 79.7%) .According to Multiple Linear Regression, Morisky scale and age were significantly related with the average total FSI-10 score. Patients with a lower Morisky scale (greater compliance) and younger patients showed a higher FSI-10 total score see .p = 0.937)  . It mustAccording to Multiple Linear Regression, the average FSI-10 total score, age and ACQ-6 score were significantly related with the total average score on the Morisky scale. Patients with a higher total FSI-10 score, older patients and patients with a higher baseline ACQ-6 score (less controlled) showed a lower total Morisky scale score (higher adherence) see .p < 0.001 and t-test p < 0.001 for all pair comparisons between the three visits). The mean ACQ-6 values decreased from 2.3 on Visit 1 to 0.9 on Visit 2 and 0.5 on Visit 3 (average decrease (±SD) on Visit 3 compared to Visit 1 = 1.8 ± 1.0). The percentage of patients with ACQ-6-uncontrolled asthma decreased from 79.1% on Visit 1 to 22.3% on Visit 2 and further decreased to 6.7% on Visit 3. Accordingly, the percentage of patients with ACQ-6-controlled asthma increased from 3.2% on Visit 1 to 44.1% on Visit 2 and further increased to 74.1% on Visit 3   and further decreased on Visit 3 (Hotelling’s test  visits) . Accordi visits) .p < 0.001, and t-test p < 0.001 for all pair comparisons between the three visits). The mean AQLQ total score increased from 4.6 on Visit 1, to 5.9 on Visit 2 and 6.4 on Visit 3 (average increase on Visit 3 compared to Visit 1 = 1.8 ± 1.1). The Domains “Symptoms” and “Environment” presented the largest increase (The mean (and median) values of all 18 AQLQ items were increased in Visits 2 and 3 compared to baseline. The mean score of each of the four domains of AQLQ and the mean total score increased substantially on Visit 2 compared to Visit 1, and further increased on Visit 3 . The mean predicted FEV1% increased from 80.7% on Visit 1 to 87.0% on Visit 2 and 88.5% on Visit 3 (average increase on Visit 3 compared to Visit 1 = 9.7 ± 12.5)   see . Mean FEits) see . The aveits) see .p < 0.001. t-test p < 0.001 for the pairs Visit 1-Visit 2 and Visit 1-Visit 3, p = 0.002 for the pair Visit 2-Visit 3). The percentage of patients who used short-acting beta-2 agonists (the last month before each Visit) decreased over time. During Visit 1, the corresponding percentage was 56.9%, during Visit 2 this was 16.2%, while during Visit 3 this was only 10.4% . During In the present study, we evaluated the usability and patient satisfaction of the NEXThaler device delivering the inhaled combination of BDP/F extrafine formulation in patients with asthma not well controlled by low-dose ICS. We found that the percentage of patients who were at least “fairly” satisfied with the usability of the NEXThaler device presenting an FSI-10 score between 40 and 50 surpassed96%. Furthermore, the usability/satisfaction was indicated by the median value of 5 corresponding to “very” in each of the 10 individual items of the FSI score. Moreover, the adherence to treatment was quite high, and almost 70% of the patients with asthma presented high adherence after 3 and 6 months of treatment. Furthermore, we showed that this ICS/LABA combination is very effective in improving the level of asthma control, quality of life and lung function in patients not well controlled on low-dose ICS monotherapy and also led to lesser use of rescue medication (SABA).Fixed combinations of ICS/LABA are considered convenient and are the mainstay of asthma treatment. They are available in many different formulations and devices and have helped in achieving better compliance and better control of the disease. Not all patients with asthma are equally capable of using a particular device that delivers the inhaled combination. Therefore, the availability of the same medication in different formulations, such as pMDIs and DPIs, offers both physicians and patients a broader range of therapeutic options to treat asthma and improve compliance.An additional delivery device option apart from pMDI has been developed to provide the extrafine formulation of BDP/F through a DPI, the NEXThaler. NEXThaler was proved to be an effective and well-tolerated delivery device for the treatment of patients with asthma who require regular treatment with ICS/LABA and was shown to be non-inferior to extrafine BDP/F administered via pMDI in terms of lung function, asthma control and use of rescue medication .Personalized medicine, having a broader meaning than precision medicine, includes all features associated with “the person” . In thisNEXThaler device has significant advantages such as that the dose counter works as an “inhalation counter”, decrementing only after delivery of the full therapeutic dose, but most importantly, the breath-actuated mechanism of the device is triggered by variable inhalation flows. That provides the opportunity to the patients to use the device effectively irrespective of asthma control and severity .The self-reported Morisky Scale has been used in many studies to assess the adherence to treatment among patients with asthma ,15. We fA correct inhaler technique is the key factor to ensure that the inhaled drug reaches the bronchial tree, exerts its pharmacological effects and, therefore, improves asthma control. Asthma control is the main target of asthma care and pharmacotherapy according to asthma guidelines . We founThe improvement in quality of life observed in our study accompanying the improvement in asthma control is compatible with other studies showing a positive correlation between asthma control and quality of life . It is wNEXThaler is substantially unaffected by flow rate through the inhaler in terms of both delivered dose and fine particle mass , and thiInhaler device selection can have an impact on asthma clinical outcomes and the use of healthcare resources. Although we did not assess the use of healthcare resources in the present study, we showed that BDP/F NEXThaler improved all outcomes after 6 months of treatment in patients with asthma not well controlled by low-dose ICS. This could be attributed to the high satisfaction/usability and high adherence achieved by the NEXThaler device and in every day clinical practice the latter is of great significance in attaining better clinical outcomes. Importantly, our study showed that higher FSI scores correlated with lower Morisky scale scores, meaning greater compliance, in the Greek population studied. Our results seem to show cohesion with other studies reporting positive correlations between patients’ satisfaction, treatment adherence and clinical outcomes ,25.Our study was conducted as per GINA 2015 recommendations , and patIn terms of study limitations, it must be highlighted that a step-up approach was followed during this study in terms of escalating asthma treatment according to GINA recommendations and everyday clinical practice, which could have an impact on asthma control. Furthermore, rescue medication was assessed by the number of puffs/week of SABA needed by the patient during the last month before each visit. We acknowledge the use of diaries or e-diaries in assessing such clinical outcomes; nevertheless, we consider that the study population could have successfully recalled any use in the recent past.In conclusion, we showed that the fixed combination of BDP/F delivered by NEXThaler is a rational choice for the treatment of patients with asthma who feel very satisfied with the device and present high adherence, while being at the same time very effective in clinical outcomes such as asthma control, quality of life, lung function and use of rescue medication.


Variability in chronic kidney disease (CKD) progression is a well-known phenomenon that underlines the importance of characterizing the said outcome in specific populations. Our objectives were to evaluate changes in the estimated glomerular filtration rate (eGFR) over time and determine the frequency of dialysis admission and factors associated with this outcome, to estimate the rate of program's loss-to-follow-up and the probability of transition between CKD stages over time. 2/year was estimated using the ordinary least-squares method. Dialysis initiation and program's loss-to-follow-up rates were calculated. Heat maps were used to present probabilities of transitioning between various CKD stages over time. Survival model with competing risks was used to evaluate factors associated with dialysis initiation.  The study type was an observational analytic retrospective cohort in patients treated in a CKD prevention program in Bogota, Colombia, between January 1, 2009, and December 31, 2013, with follow-up until December 31, 2018. Adult participants of 18 years of age or older with diagnosed CKD stages G3 or G4 were enrolled into a prevention program. For each patient, the rate of progression of CKD in ml/min/1.73 m2 per year, and in the diabetic population, it was −1.55 ml/min/1.73 m2 per year. The program's loss-to-follow-up rate was 2.6 events per 100 patient-years (95% CI 2.3 to 2.9). Probabilities of CKD stage transitions are presented in heat maps. Female sex, older age, baseline eGFR, and serum albumin were associated with lower risk of dialysis initiation while CKD etiology diabetes, cardiovascular disease history, systolic blood pressure, blood urea nitrogen, and LDL cholesterol were associated with a higher likelihood of dialysis initiation.  A total of 2752 patients met inclusion criteria and contributed with 14133 patient-years of follow-up and 200 dialysis initiation events, which represents a rate of 1.4 events per 100 patient-years (95% CI 1.2 to 1.6). The median change of the eGFR for the entire cohort was −0.47 ml/min/1.73 m A CKD secondary prevention program's key indicator is reported here, such as dialysis initiation, progression rate, and program drop-out; CKD progression appears to be correlated with diabetic status and timing of referral into the preventive program. Chronic kidney disease (CKD) is a syndrome that today has important implications for the health of populations and the economic sustainability of health systems around the world . In 2012The literature shows a significant variability in CKD progression rates, with substantial proportions of populations that progress less than −1 ml/min/year, other populations with progression rates at around −4 ml/min year, and groups that evolve quickly and reach −10 ml/ml/year . Linear 2 per year, with an incidence cumulative renal failure in the 10 years of 0.04 (95% CI 0.03–0.06) [Based on this class of methods, a population follow-up study with 10-year follow-up in 3047 patients in Norway reported a rate of progression of CKD of −1.03 ml/min/1.73 m03–0.06) . A study03–0.06) .There is scarcity of data about the transition between CKD stages over time; however, extensive research has been done regarding models that predict the progression of this disease , as wellIn Colombia, a prevention program for CKD was implemented to identify patients early with a high risk of progression and with uncontrolled risk factors such as hypertension out of goals, poor glycemic control, and proteinuria and to offer multidisciplinary care interventions , to improve control of their disease and outcomes .For context, Renal Therapy Services (RTS) in Colombia is a renal care provider network caring for approximately 9500 patients in CKD prevention programs. Compensar is a Colombian Health Maintenance Organization that provides and insures healthcare for 1.5 million patients. More than a decade ago, RTS and Compensar established a CKD prevention program, with the goal of early detection of CKD patients in stages G3 or G4 and intervening to reduce the rate of progression and ensure a gradual, planned transition to initiate kidney replacement therapy, when needed.The study aimed to evaluate changes in the estimated glomerular filtration rate (eGFR) over time, as well as to determine the frequency of dialysis initiation and factors associated with this outcome, to determine the rate of program's loss-to-follow-up, and the probability of transition between CKD stages over time.The study type was observational, analytic, historical cohort.2 and a diagnosis of CKD by a nephrologist; follow-up duration was a minimum of 5 years. The presence of metastatic disease was considered an exclusion criterion. Patients entered the cohort on the date of first estimate of the GFR. The main outcomes of the study were initiation of dialysis, transitions between CKD stages, and loss-to-follow-up. Censoring occurred for the following events: referral to primary care, change of provider/insurance, death, suspension from the program, palliative care, and kidney transplant.All patients admitted to the CKD prevention program of Renal Therapy Services (RTS) and Compensar between January 1, 2009, and December 31, 2013, with CKD stages G3 or G4, older than 18 years, were assessed for inclusion; the end of the follow-up duration was December 31, 2018. To be included in the study cohort, patients had to have at least two eGFR <60 ml/min/1.73 mAt least four estimates of the glomerular filtration rate with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation  were reqRTS CKD prevention program was an integrated approach between the primary and secondary levels of care . In its The interventions encompassed laboratory monitoring, nephrology consultation, nutritional evaluation and treatment, and comprehensive CKD education by a nurse and social worker to decrease CKD progression and prepare the patient for eventual kidney replacement therapy.2 and clinical diagnoses of CKD.Patients were admitted to the program when they had at least two eGFRs measuring <60 ml/min/1.73 mThe variables measured in the study were extracted from the RTS electronic medical records system (Versia®), which systematically records the measurements that are part of standard clinical care of these patients on a quarterly or monthly basis according to the standard of care protocols. A project information engineer and a quality information assurance person were responsible for building and validating the research database. Data corresponding to variables measured in this study were transferred from Versia® to an Excel file and then exported to a Stata format for statistical analysis, using STATA 14®  and R version 3.6.2 program.For the descriptive component, the following variables were captured: age, sex, ethnicity, education level, CKD etiology, history of cardiovascular disease, glomerular filtration rate estimated by the CKD-EPI formula , CKD sta2/year, as the slope of the individual linear regression line of eGFR over follow-up using the ordinary least-squares regression; as used in other studies [The follow-up duration was divided into 6-month periods. Permanence counts were made at the end of each period. The counts were presented in figures as proportion of CKD stage for every period. For each patient, the CKD progression rate was estimated in ml/min/1.73 m studies  a negatiThe rate of dialysis initiation and the program's loss-to-follow-up were estimated as incidence rates and reported as events per patient-year, with its respective 95% CI. Additionally, the transition probabilities between the different CKD stages over six-month periods were estimated and this information was presented using heat maps; each cell contains the probability expressed as percentage . Probabilities of transition were estimated for the total CKD population, diabetic, hypertensive, and glomerulonephritis.We followed the Fine & Gray approach to fitting a survival model with competing risks. No data imputation procedure was performed, as the models were built on patients with complete information. The survival model incorporating competing risk of death, kidney transplant, and palliative care included the following variables: time to start dialysis, age, sex, education level, cardiovascular disease history, CKD etiology, body mass index, systolic and diastolic blood pressure, estimated glomerular filtration rate, serum albumin, hemoglobin, blood urea nitrogen, uric acid, and LDL cholesterol.The study was approved by the RTS Ethics Research Committee, approved on January 20, 2015, that exempted the use of informed consent as this study does not contain identifiable information and is an observational study.2 (SD = 9.8); CKD etiology consisted of 60.3% (n = 1660) hypertensive nephropathy and 18.4% (n = 506) diabetes mellitus; details of baseline demographic and clinical characteristics are presented in n = 200) of patients started dialysis, 13.6% (n = 373) had been lost to follow-up, 7.5% (n = 206) died, and 20.8% (n = 573) were referred to ordinary primary consult; patient's flow within the study is presented in A total of 2752 patients were included for analysis. The mean baseline eGFR was 43.2 ml/min/1.73 mUpon admission into the study cohort, most of patients were in CKD stage G3; and throughout the study, 43.2% of patients' eGFR counts observed in periods of 6 months belong to stage G 3A see . In addiThe median number of days in CKD stage G5 without dialysis was 278.5; see All patients contributed 14,133 patient-years of follow-up; there were a total of 200 events of dialysis initiation, which represents an incidence rate of 1.4 events per 100 patients-years (95% CI 1.2 to 1.6); this rate was 3.6 per 100 patient-years for diabetics; otherwise, the program's loss-to-follow-up rate was 2.6 events per 100 patient-years (95% CI 2.3 to 2.9); characteristics of the patients who initiated dialysis are presented in 2 per year, and in diabetic population it was −1.55 ml/min/1.73 m2 per year. In the 75th percentile, there is a proportion of patients maintaining their eGFR, some even with improvement; see The median change of the eGFR of enrolled patients was −0.47 ml/min/1.73 mProbabilities of transition between CKD stages in six month intervals are shown in Multivariable analyses were conducted to assess the effect of demographic, clinical, and laboratory variables on the risk of dialysis initiation adjusting for the competing risks death, kidney transplant, and palliative care. Female sex, older age, baseline eGFR, and serum albumin were associated with lower risk of dialysis initiation while CKD etiology diabetes, cardiovascular disease history, systolic blood pressure, blood urea nitrogen, and LDL cholesterol were associated with a higher likelihood of dialysis initiation; see 2 per year showing that the patients of this program behave in a stable manner in terms of maintaining eGFR. This can be seen indirectly with the low rate of dialysis initiation, close to 1.5 events per 100 patient-years. These results may be related to the fact that a significant proportion of patients entered the CKD prevention program relatively early in their disease course at CKD stage G3, with a median eGFR at baseline of about 43 ml/min/1.73 m2.The nephrology community has walked a journey in identifying, understanding progression, and estimating the prognosis of patients with CKD , 19. ThiThe speed of progression is lower than other studies reported in the literature , 20 whicOn the other hand, other studies report different progression characteristics and probabilities . This vaA salient characteristic of this population is the low rate of patients being lost to follow-up, which suggests high adherence to this prevention program where most patients remained in CKD stages G3 and G4. The emphasis on adherence to the program is one of the pillars of its success, since the drop-out of preventive interventions is one of the barriers in health systems. Better results can be achieved with educational and awareness programs for CKD patients. On the other hand, high adherence may reflect additional characteristics that were not measured, as greater tendency to self-care, have healthy life habits, and have adequate health insurance.This study strengths include data originating from an established CKD prevention program in a large population of patients, standardized interventions/assessments, and a minimum follow-up period of 5 years.Our study found several factors, similar to prior literature, associated with a lower risk of start dialysis, such as older age, female sex, serum albumin, and baseline estimated glomerular filtration rate , 11, 13.Study limitations include lack of data on micro-albuminuria, proteinuria, or serum bicarbonate during the study which lead to the inability to analyze these important markers of progression.Key indicators of a CKD secondary prevention program's performance are reported in this study, such as rate of initiation of dialysis therapy, drop-out of the program, rate of CKD progression, and the probability of change between stages. CKD progression was associated with diabetic status and the time of entry into the preventive program. These kinds of prevention programs can be a suitable tool to improve patient and health system outcomes.


There is a need to identify the asthma inflammatory phenotypes of patients to facilitate personalized asthma treatment. Sputum induction is time-consuming and requires expert clinical technique. This study aimed to assess the distribution and characteristics of asthma inflammatory phenotypes in Jilin Province, China; it also aimed to identify an easier method for characterization of an asthma phenotype, rather than sputum cellular analysis.In this study, 232 asthma patients underwent sputum induction following clinical assessment and blood collection. Inflammatory cell counts in sputum were used to classify asthma inflammatory phenotypes. Receiver operating characteristic curve and Spearman correlation coefficient analyses were used to identify correlations between clinical parameters.9/L and 30.25 ppd (area under the curve (AUC) = 0.744; AUC = 0.653, p < 0.001). AUCs did not significantly differ between FeNO and blood eosinophil count (p = 0.162), but both exhibited poor specificity . To identify the presence of sputum neutrophil proportion ≥ 61%, the optimal cut-off value for blood neutrophil proportion was 69.3% ; however, this exhibited poor sensitivity (50%).Among the included patients, there had 52.1% paucigranulocytic, 38.4% eosinophilic, 4.3% neutrophilic, and 5.2% mixed granulocytic asthma phenotypes, respectively. In total, 129 (55.6%) patients had asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO); these patients had higher proportion of smokers, higher sputum neutrophil count, worse lung function, and worse asthma control, compared with patients who had asthma alone (p < 0.05). Sputum eosinophil/neutrophil counts were positively correlated with blood eosinophil/neutrophil counts (p < 0.01). To identify the presence of sputum eosinophil proportion ≥ 3%, optimal cut-off values for blood eosinophil count and fractional exhaled nitric oxide (FeNO) were 0.2 × 10Paucigranulocytic asthma was the most common phenotype, followed by eosinophilic asthma. Higher proportion of smokers, poor patient compliance, insufficient treatment, and poor asthma control may have been the main causes of high ACO proportion among patients in this study. Blood eosinophil/neutrophil counts exhibited poor specificity and sensitivity for prediction of airway eosinophilic/neutrophilic inflammation. Asthma is a complex and heterogeneous disease  that affThis study assessed the distribution and characteristic of asthma inflammatory phenotypes in Jilin Province, China, through analysis of inflammatory cells in sputum; it also identified factors related to sputum eosinophilia/neutrophilia in patients with asthma. The results will aid in research regarding alternative methods for sputum cell analysis to predict airway eosinophilic/neutrophilic inflammation and provide guidance for the individualized clinical treatment of patients with asthma.This cross-sectional study included eligible patients with asthma in the Department of Respiratory Medicine of Jilin University Second Hospital between June 2016 and December 2019. Each recruited patient underwent examinations of lung function, sputum induction, FeNO measurement, and routine blood analyses. Each patient completed the following questionnaires: 6-item Asthma Control Questionnaire (ACQ6), Asthma Control Test Questionnaire (ACT), Asthma Quality of Life Questionnaire (AQLQ), and Hospital Anxiety and Depression scale (HADS). The study protocol was approved by the ethics committee of the Second Hospital of Jilin University (2016-34), and all patients provided informed consent to participate.Patient selection criteria were as follows: age ≥ 18 years; diagnosis of asthma in accordance with 2012 GINA criteria ; stable The main exclusion criteria for patients and healthy controls were pregnancy, cognitive impairment, malignant tumors and chronic diseases of various systems and organs, severe irreversible organ failure, chronic obstructive pulmonary disease (COPD) (except for asthma and COPD overlap [ACO]), or pulmonary diseases (except for Asthma).Severe asthma, as defined in the 2019 GINA guidelines , refers Induced sputum was collected and processed using validated methods , 14. BriBased on published criteria , a cutofThe study used IBM SPSS Statistics, version 25.0, for statistical analysis. The normally distributed data were expressed as mean ± SD; skewed data were expressed as median (interquartile range). Subgroups were compared using analysis of variance with a least significant difference test or a Kruskal–Wallis test, accompanied by Bonferroni correction. Spearman correlation coefficients were used to identify correlations between clinical characteristics. Categorical variables were presented as numbers (proportions) of observations, and were analyzed using the Chi-squared test. Receiver operating characteristic (ROC) curves were used to determine the optimal blood cell count values that best identified sputum neutrophilic/eosinophilic inflammation. Differences with p < 0.05 were considered statistically significant.Forward logistic regression analysis was used to determine whether multiple covariates  could predict sputum neutrophilic/eosinophilic inflammation.In total, 232 patients with asthma were enrolled and successfully underwent sputum induction in this study Table . ApproxiThe male/female ratio did not significantly differ among the four asthma inflammatory phenotypes (p > 0.05). Notably, the average age and average age at diagnosis were highest in patients with NA, followed by those with MGA (p < 0.01) Table . There w1/FVC value of PGA group was significantly higher than that of MGA group (p = 0.046). Patients with PGA tended to have the best lung function (post-FEV1/FVC and post-FEV1% predicted), but the difference between the groups was not statistically significant. However, patients with EA had higher FeNO levels, compared with patients with PGA and those with NA (p < 0.001); they had lower ACT scores, compared with patients with PGA (p < 0.05). Patients with EA had the greatest numbers of blood eosinophils and blood lymphocytes, compared with patients with NA and those with PGA (p < 0.001). Furthermore, patients with EA had greater numbers of blood basophils, compared with patients with MGA and those with PGA (p < 0.05). Compared with patients with NA and those with MGA, patients with EA had greater numbers of sputum basophils, but this number was significantly lower than in patients with PGA (p < 0.001). Moreover, the proportions of blood neutrophils were significantly higher in patients with NA and those with MGA than in patients with EA or PGA (p < 0.001); however, the increase in blood neutrophil count was not statistically significant (p = 0.052)  Table . Patient9/L or 2.5%  , whereas the ACT score was negatively correlated with the sputum eosinophil count      Table . Howevert p > 0.0 , eosinophilic (40%), mixed granulocytic (6.7%), and neutrophilic (5.4%) . In contIn our study, ICS treatment and age were correlated with sputum neutrophilia among patients with asthma. Notably, age was positively correlated with sputum neutrophilia; patients with NA were significantly older than those with EA or PGA. Our findings are similar to those previously reported by Thomas et al. and Brooks et al. These prior studies revealed that age was significantly associated with sputum neutrophilia in adults, and that older patients more frequently exhibited NA , 26. Fur1/FVC, and FEV1% predicted value exhibited negative correlations with sputum neutrophil counts, which confirmed that the sputum neutrophil count was associated with severe [1/FVC, and FEV1% predicted value were not independent risk factors for sputum neutrophilia in our study.Consistent with the findings in previous reports , we founh severe , 35 and h severe  disease h severe . WhetherPrevious studies have shown that PGA is a mildly inflammatory asthma phenotype , 23. In Patients with EA exhibited the highest FeNO level and worse asthma control; additionally, these patients included a lower number of smokers. Among patients with EA, 45.9% exhibited severe disease. In addition, ICS treatment has been shown to successfully reduce eosinophilic airway inflammation in patients with asthma, consistent with the results of a prior study ; fewer p3 and 3%) [9/L and 2.7%) [Our results showed that the sputum eosinophil count was negatively correlated with ACT score and lung function. Importantly, blood eosinophil count and FeNO level were positively correlated with sputum eosinophil count. Sputum eosinophil count also showed a stronger correlation with blood eosinophil count, compared with FeNO level; however, both correlations were not strong. The blood eosinophil thresholds demonstrated effectiveness similar to that of FeNO level for prediction of sputum eosinophilia. Our blood eosinophil thresholds were similar to the results reported by Schleich et al. (220/mm and 3%)  and Zhannd 2.7%)  and Alvand 2.7%) . Therefond 2.7%) . Moreovend 2.7%)  and Alvand 2.7%)  found thnd 2.7%) , althougnd 2.7%) , 41. BloThe inflammatory phenotype of patients with asthma is reportedly influenced by treatment, especially involving ICS . An impoThe most common asthma phenotype in this study was PGA, followed by EA. Higher proportion of smokers, poor patient compliance, insufficient treatment, and poor asthma control may have been the main causes of high ACO proportion among patients in this study. Blood eosinophil/neutrophil counts exhibited poor specificity and sensitivity for prediction of airway eosinophilic/neutrophilic inflammation. Further studies are needed to confirm whether full blood cell counts can achieve sufficient accuracy to predict asthma inflammatory phenotype.


Bisphenol A (BPA) is a compound that is especially widespread in most commonly used objects due to its multiple uses in the plastic industry. However, several data support the need to restrict its use. In recent years, new implications of BPA on the renal system have been discovered, which denotes the need to expand studies in patients. To this end, a systematic review and a meta-analysis was performed to explore existing literature that examines the BPA-kidney disease paradigm and to determine what and how future studies will need to be carried out. Our systematic review revealed that only few relevant publications have focused on the problem. However, the subsequent meta-analysis revealed that high blood concentrations of BPA could be a factor in developing kidney disease, at least in people with previous pathologies such as diabetes or hypertension. Furthermore, BPA could also represent a risk factor in healthy people whose urinary excretion is higher. Finally, the data analyzed from the NHANES 03-16 cohort provided new evidence on the possible involvement of BPA in kidney disease. Therefore, our results underline the need to carry out a thorough and methodologically homogeneous study, delving into the relationship between urinary and blood BPA, glomerular filtration rate, and urine albumin-to-creatinine ratio, preferably in population groups at risk, and subsequently in the general population, to solve this relevant conundrum with critical potential implications in Public Health. Bisphenol A (BPA) is a phenolic compound widely distributed in many everyday objects due to its multiple uses in the plastic industry . FundameCurrently, the European Food Safety Authority (EFSA) has delimited a tolerable daily intake (TDI) up to 4 µg/kg body weight/day, based on studies by Tyl et al. 2008) on the ability of BPA to affect the kidneys ,7. Howev on the aIn parallel, other works by our team determined that BPA could influence the development of arterial hypertension, a disease closely related to kidney pathologies. When mice were treated with BPA in drinking water (20–25 mg/kg/day), significant increases in blood pressure were observed even at low doses , in whicThese data suggest that BPA could play a role in the pathogenesis and progression of renal diseases. Consequently, it is essential to study the possible implications of BPA in the renal system of the healthy population and patients with kidney disease. A preliminary search was conducted to verify whether there is any systematic review or meta-analysis in the academic literature, using the keywords “bisphenol AND  AND ”.The preliminary analysis only showed one relevant article . The pubStudies that reported the association between high exposure to BPA in humans (in urine or blood) and risk of kidney disease were eligible for inclusion. Due to the small number of existing publications, all available population groups and age ranges were studied. To carry out the meta-analysis, all those studies with an available odds ratio (OR) and confidence interval (CI) or, at least, with sufficient data allowing calculation of the latter parameters were selected. All publications with any degree of relationship between BPA and kidney disease were selected.pubmed.ncbi.nlm.nih.gov, accessed on 5 July 2021) and Web of Science . To optimize the search strategy, we combined the terms “Bisphenol AND  AND ”, without year restriction.This search was carried out during July 2021 using the reference academic search engines PubMed  accepted and published.Studies in human populations (adults or children).Quantification of BPA in urine or serum and its correlation with any predisposition or susceptibility marker of kidney damage or disease.Studies published in English.After eliminating the repeated articles, using Mendeley  manager and organizer, we evaluated the resulting academic papers by title/abstract , whose decisions in each of the bibliographic search and evaluation steps were determined by consensus, evaluated all the publications.Once the publications of interest were selected, they were classified according to the study variable. Three studied BPA in the blood, while the rest analyzed it in the urine. Simultaneously, other important parameters for determining kidney damage were also considered since two articles explored the concept of “low-grade albuminuria,” while others investigated the estimated glomerular filtration rate (eGFR). Notably, the studies that evaluated blood BPA were carried out on diagnosed or developing pathologies, while the urinary studies mainly presented data from the healthy population.At the statistical level, the objective was to perform the inverse analysis of variance to unify the studies related to each other, introduced in a random-effects model. The steps followed for the analysis of each subgroup are detailed below.In order to calculate the OR, we analyzed the following articles: Krieter et al. , Hu et a2). The four subgroups analyzed correspond to stages 3, 4, 5, and stage 5 undergoing hemodialysis was used to calculate the standardized mean difference comparing the control group with the different concentrations of BPA in stages 3 to 5 of chronic kidney disease (CKD) . In this regard, Li et al.  and TrasOn the other hand, in the following two studies conducted by Malits et al.  and KangSecondly, the relationship between BPA and the eGFR has also been studied in the studies by You et al. , Malits 2 and I2 tests. The I2 statistic was calculated as a percentage, and they were interpreted as low, medium, or high heterogeneity, reaching 25, 50, and 75%, respectively [p-value < 0.05 was considered statistically significant for all the analyses performed. The statistical program used to carry out the analyses was Review Manager (RevMan 5.3).Next, the OR with its 95% CI was used to calculate the estimated pooled effect. Heterogeneity between studies was calculated by applying the Chiectively . The p-vAfter studying the academic literature, the absence of studies using all the BPA values in the NHANES 2003–2016 cohort was observed, and the analysis of the subpopulations classified as kidney disease during the patient evaluation process undiagnosed kidney disease whose eGFRs are abnormal. Therefore, this section aims to unify in a single database all the American populations’ urinary BPA measurements studied from 2003 to 2016 (data currently available) to carry out the statistical study on the relationship between BPA and kidneys with the largest sample size described to date.https://wwwn.cdc.gov/ (accessed on 16 July 2021)” Once the data had been extracted, unified, and classified according to each patient’s numerical code, a table was obtained with 72,697 people . The adults (age > 18 years) were selected, and all those in whom urinary BPA was not quantified were eliminated, obtaining a sample size of 12,757 people.Patient files containing elements like urinary bisphenol, albumin and creatinine levels, plasma creatinine, sex, weight, age, kidney diseases, or dialysis patient were first collected to correlate urinary BPA with renal function. All files can be found in Xps Transport File Format (.XPT) and downloaded from “Spot urine samples are unable to determine urinary volume or albuminuria excreted within 24 h. Therefore, the ACR  was used to estimate albumin excretion. Similarly, the excretion of BPA to urinary creatinine (µg BPA/g creatinine) was also adjusted for the same reason. The MDRD-4 and the CKD-EPI equations (the most widely used formulas) are used to calculate the eGFR ,40,41.p < 0.05.NHANES data were analyzed using the GraphPad Prism 7.0 software . The data were analyzed using the D’Agostino & Pearson and Kolmogorov–Smirnov normality tests. As they did not follow a normal distribution, the data are expressed as median (95% CI) in the tables and the graphs. The Kruskal–Wallis test followed by Dunn´s multiple comparisons test or Mann–Whitney test was performed. Differences were considered statistically significant at The initial search identified 102 articles in PubMed and 86 in Web of Science. After exporting all references to the Mendeley application and eliminating duplicates, 134 items were placed. The selection process was carried out based on the information contained in the title/abstract . Publications related to quantification methodologies were eliminated, as well as those that studied organs/compounds different from kidney/BPA. After the first screening, 38 articles were identified, and the full texts were reviewed. Of these, twelve were included in the systematic review .We will proceed to briefly describe the most interesting aspects of the academic publications used in the meta-analysis  into four quartiles, it has been observed that those subjects who were in quartile four could have a greater predisposition to specific pathologies, such as cardiovascular disease . Within 2, normal kidney function; 60–90 mL/min/1.73 m2, mild alteration; ≤60 mL/min/1.73 m2, CKD. They performed regression models and adjusted for factors related to health, socioeconomic factors, and urinary creatinine. The results showed a positive and statistically significant relationship between urinary BPA excretion and the eGFR so that pathological situations, those with a lower GFR, presented lower concentrations of urinary BPA. The second publication compared a cohort of children with CKD with a general cohort (NHANES), determining that children with CKD have urinary BPA concentrations lower than those observed in healthy children. However, multivariate linear regression  showed a negative relationship between urinary BPA and eGFR.Within the other group can be found the works of You et al. , Malits Kang et al.  shows a As previously mentioned, the BPA-kidney damage paradigm comprises a small number of quite heterogeneous but potentially significant publications.Once all the ORs and their respective standard errors were obtained, the inverse variance method was calculated. As shown in The unified works by Li et al.  and TrasIn the study between urinary BPA and ACR, the combined effect is slightly positive. There are large SEs in some studies, so the weight of the study falls on three works ,34. The Finally, in studying the relationship between BPA and eGFR, four studies show a negative relationship between both parameters in their respective multiple linear regression studies . Only the work of You et al.  showed aAs can be seen in By analyzing the data based on BPA/creatinine quartile, a significant increase in the ACR was manifested when comparing the group with higher levels of urinary BPA (Q4) with those with the lowest amount (Q1) A. SimilaWhen analyzing urinary BPA concentrations as a function of ACR, no differences were observed between individuals with non-pathological values  vs. individuals with pathological values  A. HoweveAmong the individuals in the cohort were patients with kidney disease and some on dialysis. When studying BPA corrected for creatinine, significant increases were observed in patients with kidney disease vs. healthy subjects, and patients undergoing dialysis vs. patients without treatment .Firstly, the systematic review shows an evident scarcity of publications that study the BPA-kidney paradigm in humans. However, it is interesting to note that the limitations on exposure to BPA proposed by the EFSA base their model on animal models that study how this compound affects the kidney ,7.Secondly, the meta-analysis shows that the high concentration of BPA in the blood could be a warning sign for kidney disease. Increasing the concentration of a compound in the blood due to the kidney’s reduced filtering capacity is logical from a functional point of view. If we only look at the work of Krieter et al.  and ShenOn the other hand, a high urinary BPA concentration could be related to an increase in the excretion of albuminuria in the healthy population. Perhaps it would be possible that in the healthy population, whose filtering capacity is standard, the increase in excreted BPA could be related to a greater predisposition to increased albuminuria, which could be an early indication of kidney damage. However, some publications suggest that BPA could bind to proteins , which wBPA is a compound whose metabolism is fundamentally characterized by phase II reactions, biochemical mechanisms capable of modifying its structure to facilitate its excretion . This deWithin the study’s limitations, it must be considered that the blood studies were carried out on specific population groups, such as patients with kidney disease, type 2 diabetes, and hypertension. In contrast, the urinary studies were carried out in the general population, except that of Malits et al.  and JacoThe analysis of eGFR and blood BPA suggests that higher concentrations of BPA present a greater probability of suffering kidney damage (or lower eGFR). However, in the works of You et al.  and MaliKidney disease is closely related to diseases such as hypertension. In this sense, it has been observed that BPA could be a predisposing factor for the development of hypertension in animal models  or epideThe main conclusion that can be drawn from the meta-analysis is the need to carry out a complete study, which delves into the relationship between urinary and plasma BPA, glomerular filtration rate, and albuminuria, both in population risk groups (in patients with diabetes or hypertension) and in the general population. This study must be placing a particular emphasis on the particularities related to the ACR and glomerular filtration . Finally, the data analyzed from the NHANES cohort show new evidence that reinforces the hypothesis that BPA acts as a factor involved in kidney damage. It is interesting to highlight the importance of creatinine correction in studying urinary metabolites, such as BPA. Thus, a significant increase in urinary BPA has been observed in men, expressed in µg/mL, while women presented higher BPA values corrected for creatinine. In the absence of the absolute volume of urine excreted in 24 h, correction for creatinine allows a better estimation of urinary metabolites, taking into account the renal filtration capacity.Regarding the analysis of the population, classified according to urinary BPA, evident and significant differences have been observed between people with lower and higher concentrations of urinary BPA (Q1–Q4). In the study of the complete cohort and the study of the healthy population , significant increases in the ACR between Q4 and Q1 have been observed. Similarly, significant increases in urinary BPA were observed in those individuals with low-grade albuminuria. This data is consistent with the results observed by Li et al.  and TrasIn short, the body of evidence in the present work takes a further step towards the relationship between BPA and the predisposition to develop kidney diseases. BPA may bind to proteins, limiting the correct analysis of parameters such as ACR, and it seems that the glomerular filtration capacity conditions its excretion rate. However, the joint analysis of the studies on BPA in blood, together with the urinary concentrations observed in the NHANES cohort patients, provides new evidence that supports this possible causal relationship. Although experimental data fully support a pathogenic role of BPA exposure on hypertension and renal disease, further epidemiological studies need to clarify this critical issue.Despite the importance of the BPA-kidney paradigm in the context of human exposure, few works explore the issue.In the study of blood BPA and kidney disease, solid evidence correlates high concentrations of BPA in the blood with a greater predisposition to develop kidney disease, at least under pathological conditions.In the study of the ACR and urinary BPA, a positive relationship was observed in healthy subjects. The same trend was observed in the NHANES cohort. Similarly, subjects with low-grade albuminuria showed a significant increase in urinary BPA.Despite inconsistencies observed in urinary BPA concentration from patients with kidney disease, statistical correlations with eGFR support an important relationship between BPA and glomerular filtration.The results, consistent with the experimental models, show interesting evidence that positions BPA as a possible environmental factor inducing kidney damage.


Hypertension is a risk factor for both cardiovascular and cerebrovascular disease, with an increasing incidence with advancing patient age. Exercise interventions have the potential to reduce blood pressure in older adults, however, rates of exercise uptake and adherence are low, with ‘lack of time’ a commonly cited reason. As such, there remains the need for time-efficient physical activity interventions to reduce blood pressure in older adults.To compare the effect of three, novel time-efficient physical activity interventions on resting blood pressure in older adults.Forty-eight, healthy, community-dwelling older adults (mean age: 71 years) were recruited to a 6-week randomised control trial. Resting blood pressure was measured before and after one of three supervised, time-efficient interventions: high-intensity interval training (HIIT) on a cycle ergometer; isometric handgrip training (IHG); unilateral, upper limb remote ischaemic preconditioning (RIPC) or non-intervention control.Both HIIT and IHG led to a statistically significant reduction in resting systolic blood pressure (SBP) of 9 mmHg, with no significant change in the RIPC or control groups. There was no change in diastolic blood pressure or pulse pressure in any group.Supervised HIIT or IHG using the protocols described in this study can lead to statistically significant and clinically relevant reductions in resting SBP in healthy older adults in just 6 weeks. Six-week high-intensity interval training can reduce the systolic blood pressure (SBP) of older adults.Six-week low-exertion isometric handgrip training can also reduce the SBP of older adults.The reductions in SBP elicited by both these interventions are of a clinically relevant magnitude.The control of hypertension is key to the management of cardiovascular risk throughout national guidelines . Meta-anEthical approval was obtained to recruit healthy (American Society of Anesthesiologists grade 1 or 2) adults aged 65–85 years to participate in a trial of 6-week fully supervised HIIT, RIPC, IHG or non-intervention control (CON) (NCT03019146). All participants gave written informed consent. Participants already prescribed antihypertensives were included, providing no alterations were made between 3 months prior to enrolment and study close. The primary outcome of the study was resting SBP.Resting blood pressure (BP) was measured at the start and end of the study using oscillometry  and a blood pressure cuff of appropriate size, according to current clinical guidelines  using thsealedenvelope.com), stratified to baseline SBP (<140 mmHg or ≥ 140 mmHg) and antihypertensive medication.After their baseline measurement, participants were randomised to either HIIT, RIPC, IHG or control using computerised randomisation , placed on their dominant arm and inflated to 200 mmHg for 3 min before deflating. This was repeated three times in each session with 3-minute rest between each inflation.IHG subjects completed four 2-minute repetitions of isometric handgrip at 30% of maximum voluntary contraction (MVC) on an electronic hand dynamometer  using their dominant hand, with 2-minute rest between each contraction. MVC was measured according to the American Society of Hand Therapists clinical assessment recommendations, with the participant seated, the shoulder adducted and neutrally rotated and the elbow flexed to 90 degrees . Each paa priori power calculation determined a sample size of 48 was required for 90% power to detect a reduction in SBP of 10 mmHg. All calculations were performed using Graphpad Prism Version 7.02 . Data are presented as mean [standard deviation SD]. Outcome data were compared using two-way analysis of variance with Sidak’s multiple comparisons post-hoc testing. Significance was taken as an alpha of P < 0.05.An Forty-eight participants of mean age 71(4) years  were randomised and none were lost to follow-up. Users of anti-hypertensive medication were equally distributed throughout the groups , with equal sex distribution . Mean (SD) training compliance was 99(3)%, and there were no adverse events. The study consort diagram is displayed in P = 0.15) or DBP (P = 0.30). For SBP, there was a main effect of time (P < 0.001) and a significant group x time interaction (P = 0.04), with significant reductions in both the HIIT (142(15) vs. 133(11); −9(9) mmHg, P < 0.001) and IHG (139(15) vs. 130(12); −9(9)mmHg, P = 0.002) groups. There was no significant change in either the RIPC (138(15) vs. 134(14); −4(5), P = 0.17) or control (130(10) vs. 128(10); −1(6), P = 0.96) groups. For DBP, there was a main effect of time (P = 0.01), however, no group x time interaction (P = 0.83). There was no effect of either time (P = 0.09) or group x time interaction on pulse pressure (P = 0.33).Data for both resting SBP and diastolic blood pressure (DBP) at baseline and after intervention are displayed in et al., asked their volunteers, with a mean age of 62 years, to perform nine sessions of HIIT over a 6-week intervention period, with each session comprising six 30-second sprints on a cycle ergometer, at 40% of peak power output determined using a 6-second test , intersThe effect of the IHG protocol on SBP in this study was approximately equal to the mean change found in the meta-analysis of the two previous trials of IHG in older adults, which were conducted over 8  and 10 wet al. [It would appear that RIPC conducted using a unilateral arm 3 × 3-minute occlusion protocol does not have any effect on BP. This was the first RCT to examine the effects of unilateral upper limb RIPC with only 3-minute ischaemic periods in older adults and did not reproduce the significant reduction in resting BP found by Jones et al. . It may As with almost all research, we must consider limitations to our study design. Despite stratified randomisation for hypertension and medication status, our relatively small sample size led to some baseline imbalances in starting blood pressure and precluded across-group effect comparisons. In addition, no data on compliance with antihypertensive medication was recorded, with participants simply instructed not to make any changes to this. Other key limitations of this study are that only two participants were aged over 80 and that none had significant comorbidity, limiting the interpretation of this study with regards to these groups.It is, however, promising that two time-efficient interventions, one of which is relatively ‘static’ in nature, appear to have potential as tools to reduce blood pressure in older adults. Future work should examine the possibility of using HIIT and IHG interventions as home-based, unsupervised interventions and conduct longer duration follow-up to assess the durability of these adaptions.