No validated screening method currently exists for Chronic Obstructive Pulmonary Disease (COPD) in smokers. Therefore, we constructed a predictive model with simple parameters that can be applied for COPD screening to detect fixed airflow limitation. This observational cross-sectional study included a random sample of 222 smokers with no previous diagnosis of COPD undertaken in a Spanish region in 2014–2016. The main variable was fixed airflow limitation by spirometry. The secondary variables (COPD factors) were: age, gender, smoking (pack-years and Fagerström test), body mass index, educational level, respiratory symptoms and exacerbations. A points system was developed to predict fixed airflow limitation based on secondary variables. The model was validated internally through bootstrapping, determining discrimination and calibration. The system was then integrated into a mobile application for Android. Fifty-seven patients (25.7%) presented fixed airflow limitation. The points system included as predictors: age, pack-years, Fagerström test and presence of respiratory symptoms. Internal validation of the system was very satisfactory, both in discrimination and calibration. In conclusion, a points system has been constructed to predict fixed airflow limitation in smokers with no previous COPD. This system can be integrated as a screening tool, though it should be externally validated in other geographical regions. Despite its associated morbidity and mortality and the considerable expenditure of resources generated by COPD, it is underdiagnosed worldwide4.Chronic obstructive pulmonary disease (COPD) is a major public health problem, making it the fourth leading cause of death worldwide5. Other factors include age, male gender and respiratory symptoms6. COPD has also been associated with certain chronic comorbidities such as hypertension, cardiovascular problems, and diabetes8.The main risk factor for COPD is smoking1)/forced vital capacity (FVC) ratio < 0.7. This is a simple, reproducible technique with low individual cost10. Although it is indicated in patients with respiratory symptoms, in normal clinical practice it is underutilized11, thereby explaining part of the underdiagnosis. Thus, forced spirometry does not appear to be a good screening technique that can be applied in all smokers regardless of their symptoms because, in most cases, these symptoms become evident when the disease is already established or when they already affect quality of life, which is associated with a greater severity of the disease13.The most commonly accepted method to confirm COPD is forced spirometry, which is considered positive with a post-bronchodilator forced expiratory volume in the first second , which could be used even by patients. With all this, we will have a screening tool that, provided it is externally validated in other populations, could be integrated into the protocols and clinical guidelines for COPD, prior to the definitive diagnosis by forced spirometry and respiratory symptoms. Whilst COPD screening is not currently recommended in smokers, this is because the techniques to do so are time consuming and expensive. Therefore, in this study we present an alternative that overcomes these limitations and leaves spirometry for confirmation in high-risk cases.As a response to the need to implement a screening method that can differentiate smokers with a higher risk of fixed airflow limitation prior to onset of established symptoms, the objective of this study was the elaboration and internal validation (bootstrapping) of a prediction model for fixed airflow limitation, using the recommended statistical methodologySmokers aged 40–75 years with no previous diagnosis of COPD whose primary health care is delivered at the Raval Health Centre in Elche (Alicante). This centre covers a population of 20,284 adults and is a primary care centre of the Spanish Public Health System which provides universal and free coverage.This cross-sectional observational study was carried out during 2014–2016 with the objective of determining the underdiagnosis of COPD resulting from the underuse of forced spirometry and with this to construct a predictive model. We consulted the outpatient database of this centre and excluded those patients who did not meet the following inclusion criteria: smokers, age 40–75 years, and with no active diagnosis of COPD in their medical record. From the list obtained in this consultation, a group of patients was selected by random sampling (random number table) and contacted by telephone, asking them over the phone for their informed consent to participate in the study. The patients who agreed to participate were asked to perform forced spirometry, fill out questionnaires on COPD risk factors, and sign the written informed consent. Just under 10% of those selected refused to participate . These patients were passed over and the next person in the random table was selected.1/FVC ratio < 0.7)17.The primary variable was fixed airflow limitation performed with a validated Datospir 110 A spirometer, according to the regulations of the main Spanish medical societies and the criteria established in the GOLD guide ; smoking history in pack-years, calculated as the number of cigarettes smoked per day multiplied by the number of years smoking divided by 20; Fagerström test, considering three levels of dependence: mild (0–3 points), moderate (4–6 points) and severe (7–10 points)21; presence of symptoms or respiratory problems  requiring medical consultation during the last year and level of exacerbation, described as a sustained deterioration in the patient’s baseline clinical condition, beyond the usual daily variability, which appears acutely, and is accompanied by increased dyspnoea and expectoration and a change in the appearance of sputum, or any combination of these three symptoms, requiring a therapeutic change and classified as mild (no episodes of bronchitis in the last year), moderate (episodes treated by primary care physician) and severe 22.Secondary variables were collected according to the risk factors associated with the diagnosis of COPD: older age, male gender, number of cigarettes smoked and for how long, low body mass index (BMI), low educational level, presence of respiratory symptoms and exacerbations during the last year23.Since the objective of this study was to construct a predictive model of a binary event through a binary logistic regression model, the sample size had to verify that the ratio between the number of events and the number of predictors of the model was greater than or equal to 102 test and the t-test. A logistic regression model was constructed with a maximum number of five predictors (57 patients with fixed airflow limitation). Taking into account that we had a total of 8 predictors , we checked all possible combinations of 1 to 5 predictors, selecting the one with the highest discriminating capacity, that is, the one that gave a maximum area under the receiver operating characteristic curve (AUC). Thus, the AUC was calculated in a total of 218 combinations. The optimum combination was adapted to a points system using the Framingham study methodology24 which, through a weighting of the model coefficients and a categorization of the predictors, associates a score to each variable and the sum of these scores gives an event probability. Once the points system was developed, it was internally validated through bootstrapping (1000 random samples), since this is the most recommended technique25. Discrimination was determined in each of the 1000 samples (the points system can differentiate fixed airflow limitation) and calibration . Discrimination is addressed by calculating the AUC, whilst calibration is evaluated through the construction of smooth curves (linear splines) with the Hosmer-Lemeshow test, which is appropriate for the recommended level of calibration (moderate)15. All analyses were performed with a type I error of 5%, and for each relevant parameter its associated confidence interval (CI) was calculated. Statistical packages used were SPSS Statistics 24 and R 2.13.2.Qualitative variables were described using absolute and relative frequencies, whilst quantitative variables were expressed through means and standard deviations. Our variables had no missing data. Associations between the primary variable and the secondary variables were assessed using the XThis project was approved by the Clinical Trials Ethics Committee of the Department of Health of the Generalitat Valenciana  at its meeting on 20 March 2014, in accordance with the International Guidelines for Ethical Review of Epidemiological Studies and the recommendations of the Spanish Society of Epidemiology on the review of the ethical aspects of epidemiological research studies, respecting the rules set forth in Law 15/1999 on Personal Data Protection in research studies. The committee approved the age range of the patients in the study (40–75 years), as the highest prevalence of COPD occurs at these ages.The diagnosis of COPD is customarily made using forced spirometry and respiratory symptoms, but this does not appear to be a good screening technique that can be extended to all smokers. We elaborated and internally validated a prediction model for fixed airflow limitation with simple parameters that can be implemented in routine clinical practice in a systematic way. Care time would not be increased, since the model will be implemented in a mobile app for Android. With all this, we will have a screening tool that could be integrated, after external validation, in the protocols and clinical guidelines for COPD.Spirometry was performed in a total of 222 patients, of which 119 (53.6%) were men; 57 (25.7%) patients had fixed airflow limitation. Table The internal validation of the points system using the bootstrap technique was very satisfactory. First, in Fig. This study developed a simple prediction tool to assess fixed airflow limitation in smokers with no previous diagnosis of COPD. The model is simple to use because the variables are easy to measure, risk is assessed by a points system and its implementation in a mobile application makes calculations even easier. The model has been internally validated in our setting through the most recommended statistical methods. Underdiagnosis of COPD in our population was 25.7% (fixed airflow limitation), with the following associated risk factors: male gender, older age, lower educational level, higher level of nicotine dependence (Fagerström), higher cigarette consumption, presence of respiratory symptoms and high level of exacerbations.25.The main strength of our study is the development and internal validation of a prediction model for COPD screening in patients prior to diagnostic confirmation by spirometry and respiratory symptoms. Although others have developed a prediction model, their models have several limitations for use in clinical practice Table . We alsoSelection bias was minimized by randomly choosing the sample from among all smokers in the corresponding health area, with very low exclusion for not wanting to participate (about 10%). To minimize information bias, the tests were conducted by the principal investigator using validated questionnaires and instruments. To avoid possible confounding bias, we applied well-calibrated multivariate models with high discriminating capacity. Our main limitations were sample size (limiting the number of predictors) and lack of external validation (future line of research).1/FVC ratio threshold at 0.7. However, it has been seen in populations similar to ours that establishing the diagnosis of COPD with the lower limit could exclude a high number of patients with significant clinical impact and high consumption of healthcare resources26. We have also used a total of 8 explanatory variables to predict fixed airflow limitation, with a greater number of factors contributing to this problem. Nevertheless, the mathematical model had very good discrimination and good calibration.We could have used the lower limit criterion instead of setting the FEV16. Our team is collecting a new sample for this purpose, and this type of study should also be carried out in other geographical areas to determine whether the predictive model is satisfactory for detecting fixed airflow limitation.Another point to take into account is that we did not have a sufficient sample size to externally validate the points system constructed. For this, a completely different sample should be available with at least 100 patients with fixed airflow limitationWe would like to note that our points system is only applicable to patients without COPD who are current smokers and between the ages of 40 and 75 years. Patients with COPD who have no history of smoking have also been excluded, as they already have the disease and there is no point in screening. The exclusion of ex-smokers and elderly people could lead to an increase in the prevalence of fixed airflow limitation, and it should be verified in another study whether the model is applicable to these people, since the variables age, Fagerström test, and pack-years can be evaluated in these excluded patients. If similar results are obtained, the target population of our predictive model could be expanded.12, but its use is limited and the effectiveness of extending it to the entire population is unknown11. Consequently, several authors have proposed the possibility of first using questionnaires aimed at detecting and classifying patients at high risk of COPD, in conjunction with the intermediate use of a pocket spirometer, and followed by confirmation with conventional spirometry in cases with low FEV1/FEV6 figures27.The technique used to confirm the presence of COPD is still spirometry and respiratory symptoms16 in order to develop a simple algorithm based on the data obtained in our study indicating the population at risk of COPD and that could go undetected. The tool can be used quickly in daily clinical practice by the primary care physician, or even with the development of a mobile application (app) that facilitates self-diagnosis by the patient (fixed airflow limitation), leading directly to the need for spirometry and assessment of respiratory symptoms to confirm the presence or absence of COPD and thus preventing the high levels of underdiagnosis. Consequently, this tool can be very useful, since the estimated worldwide prevalence of COPD is 1% in the general population and 8–10% in those aged over 40 years28, and between 2.1% to 26.1% in Europe depending on country, method and population29.The older predictive models had major statistical limitations Table . We used34. Other studies refer to a higher risk of underdiagnosed COPD in cases of low educational level3, low socioeconomic status20, previous respiratory symptoms or high BMI (≥30 kg/m2)2, whilst others associate it with low BMI11. Underdiagnosis has also been associated with increased comorbidity, especially cardiovascular36. Therefore, we can confirm correspondence with the data found in our study.Regarding risk factors associated with underdiagnosis, age and smoking are already recognized as the main risk factors for underdiagnosis37. Because of its ease of use, this scoring system can be extended to the entire population through mobile applications (apps), enabling patients to easily understand their risk and thus serving as a coercive measure for quitting. In other words, the points obtained for age cannot be modified, but it is visible on the scale that quitting smoking can improve scores, both in nicotine dependence and in respiratory symptoms. It is also a tool that can save time in primary care consultations and in the use of spirometry by applying the technique only in cases with a high probability of fixed airflow limitation. Finally, this model , the physician must evaluate the need for confirmation by spirometry, according to patient characteristics and cost-effectiveness. In addition, understanding their COPD risk may well encourage smokers who are already considering quitting to take the definitive step


Acute kidney injury (AKI) is a challenging problem in developing countries due to late presentation of its victims to health care facilities. Data on the pattern of AKI, its outcome and factors associated with its recovery is scanty in developing countries therefore impeding AKI management. Aim: to study AKI recovery rate and its associated factors.An observational study conducted from September 2013 to June 2014 at Korle-Bu Teaching Hospital (KBTH). Participants were adults, admitted with AKI at KBTH. Kidney Disease: Improving Global Outcomes (KDIGO) criteria was used to diagnose and stage AKI.Mean age (SD) of the participants was 41.9 (± 19.2) years. About a third of the patients (34.6%) were less than 29 years with 30-39 years and 40-60 years constituting 23.0% and 23.6% respectively. Females were in the majority (56.0%). AKI stages I, II and III accounted for 11.0%, 6.8% and 70.7% respectively. Majority, 82.2% of the patients recovered their kidney function. Stage III AKI was significantly associated with decreasing odds of recovery . In addition, normal blood sodium was associated with recovery from AKI . Almost half (45.5%) presented with fever whereas 32.5% and 22.5% presented with peripheral oedema and pulmonary oedema respectively.The study demonstrated high kidney function recovery following AKI. Dominant clinical features were fever, peripheral and pulmonary oedema. Advanced stage was associated with poor recovery whereas normal serum sodium level improves kidney function recovery. Accoare unit  develop are unit , 6. AKI are unit . AKI is are unit . Howeverare unit .The prognosis of AKI depends hugely on the underlying aetiology. Knowledge of the factors associated with renal recovery are important. In-depth knowledge of the recovery rate and its associated factors will help to guide decisions concerning treatment and prognosis. The overall aim of this study was to gain insight into the demographics, pattern and outcome of patients with AKI admitted to a tertiary hospital in Ghana. We hope to create awareness on AKI by educating the general public on the demographics, clinical presentations, factors associated with recovery of kidney function and its outcome. More importantly, the findings from this study will enable policy makers; both governmental and non-governmental to make decisions concerning prevention and factors that significantly affect recovery from AKI.Study design and setting: this was an observational prospective study carried out at Korle-Bu Teaching Hospital (KBTH). KBTH is a tertiary referral centre located in the capital of Ghana, Accra. The hospital has a 1,600 bed capacity and twelve different departments. Being the largest hospital in Ghana, it receives referrals from all other hospitals in the country. This study was conducted from September 2013 to June 2014.Study population and subject recruitment: any patient who met the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for AKI was eligible for recruitment. In accordance with this guideline, patients were deemed to have AKI if their calculated baseline serum creatinine increase by 26umol/l within 48 hours, an increase in serum creatinine by > 1.5 times the baseline value within 7 days and/or a fall in urine output of <0.5ml/kg/hour for more than 6 hours. Patients with a previous history of chronic kidney disease, patients with ultrasonography evidence of chronic kidney disease (i.e. shrunken kidneys), patients already on chronic haemodialysis therapy and/or patients aged less than 14 years were all excluded from the study. In all, 230 patients were recruited but 39 were lost to follow-up and were therefore excluded from analysis. One hundred and ninety one patients were therefore included in the analysis. Patients were contacted at or after 3 months (ninety days) following diagnosis for a repeat serum creatinine. Patients who had abnormal serum creatinine levels were referred for follow up as chronic kidney disease at the Renal Unit.Recovery assessment: outcome measures were mortality at 30 and 90 days and recovery of renal function at 3 months. For the purpose of this study, full recovery from AKI was considered and was based on the return of a patient's serum creatinine levels to the calculated baseline levels within the KDIGO criteria (absence of AKI) at 3 months [3 months .Ethical consideration: formal approval was obtained from the Ethical and Protocol Committee of the University of Ghana Medical School. Participation was voluntary and the participants were at liberty to withdraw from the study at any time with no consequence. Patients were fully informed about the nature of the study. Follow up of patients were done within the patient scheduled review period so as to avoid extra burden.Data collection: socio-demographic characteristics including age, gender and clinical presentations were retrieved from participants' clinical records.Blood pressure measurement: blood pressure (BP) measurements were done using the Omron M5-I digital fully automatic blood pressures monitor ; at least two measurements were taken and averaged. Hypertension was defined if the averaged BP was greater than 140/90mmHg.Blood sampling, processing and biochemical assays: whole blood samples were drawn by venipuncture by competent personnel and collected into both serum separator gel and EDTA tubes, maintained at 0°C - 4°C during delivery to the laboratory. Whole blood was analyzed for haemoglobin concentrations with Sysmex haematology analyzer whereas serum was used for the measurement of creatinine concentration with Cobas C 11 chemistry analyzer.Data analysis: data from patients were analysed using Statistical Package for Social Scientists (SPSS version 20.0). Numeric data were summarized by means and Standard deviation. Categorical data was summarized by frequencies and percentages. Binary logistic regression was used to assess associations between variables with the levels of associations presented as Odds Ratio (OR) and 95%CI. Graphical presentations were provided to highlight the level of differences. Proportions of categorical variables were compared using chi-square test. Significant level was set at α=0.05, thus all statistical tests were declared significant for p-value <0.05.The mean (±SD) age of the participants was 41.9 (± 19.2) years with 34.6% being ≤ 29 years . FemalesIncidence of AKI is on the rise in developing countries including Ghana . PlethorThe study recorded a kidney function recovery rate of 82.2% . This isIn assessing factors associated with recovery from acute kidney injury, the results showed that normal serum sodium concentration significantly increased the likelihood of kidney function recovery . Acute kSimilar clinical presentations albeit slight variations were reported in a retrospective study conducted among AKI patients in a University Hospital of Kinshasa, Congo in which fever accounted for 80.3% followed closely by jaundice (73.2%) . UnsurprThe study demonstrates a considerably high recovery rate among the studied AKI participants. This was found to be due to the relatively young nature of AKI diseased patients. Most of the participants were in Stage III AKI. Significant factors found to be associated with recovery from AKI were serum sodium levels and Stage III AKI; whereas normal sodium levels increase odds of recovery, stage III AKI suggests a lesser chance of recovery. Dominant clinical features found in the participants were fever, peripheral and pulmonary oedema. In addition, anaemia and hypertension were important co-morbidities found among the studied participants. Further studies which employ robust study design involving longer follow-ups with recruitment from peripheral health centres are warranted to fully understand the mechanism behind these associations.Incidence of acute kidney injury is considerably high in Ghana and other under-resourced countries;Acute Kidney Injury is a major risk factor of chronic kidney disease, morbidity and mortality;Acute Kidney Injury is presented at later stages in Ghana which potentially affects recovery.The study reports high recovery rate among acute kidney injury patients at Korle-bu Teaching Hospital due probably to the young nature of such patients;Normal blood sodium levels and stage III acute kidney injury affects recovery;Fever, peripheral oedema and pulmonary oedema are major clinical features associated with acute kidney injury.The authors declare no competing interest.


Objective: To assess the clinical outcomes of participants of an employee wellness program during four years of service implementation. Methods: A prospective cohort study was conducted at 15 independent community pharmacy chain locations in northwest and central Missouri. A total of 200 participants were enrolled in an employee wellness program, and the program included five monitoring groups—cholesterol, blood pressure, blood glucose, weight, and healthy participant groups. Participants selected a pharmacist wellness coordinator and wellness appointments were conducted, consisting of education, goal-setting, and monitoring through physical assessment and point of care testing. The primary outcome measures were total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), body mass index (BMI), and waist circumference (WC). The secondary outcome measures were the proportion of patients who achieved the clinical value goals at baseline versus 48 months. The primary outcome measures among data collection time points were compared using one-way analysis of variance (ANOVA) tests, and the secondary outcomes were compared between baseline and 48 months by Chi-square or Fisher’s exact tests. One-way ANOVA post hoc tests were also performed using least significant difference, to further identify which time points differed from each other. Results: At baseline, there were 134 patients in the cholesterol monitoring group, 129 in the weight monitoring group, 117 in the blood pressure monitoring group, 46 in the blood glucose monitoring group, and 26 in the healthy participant monitoring group. For patients in the blood pressure monitoring group, compared with baseline, there was a significant decrease in DBP at months 12, 24, 36, and 48, and a significant increase in the proportion of patients achieving blood pressure goals at 48 months. For patients in the blood glucose monitoring group, compared with baseline, there was a significant decrease in FBG at months 12, 24, 36, and 48, and a significant increase in the proportion of patients achieving blood glucose goals at 48 months. Conclusions: Pharmacist-led wellness visits provided to employee wellness patients in a community pharmacy may lead to improvements in BP and FBG values.  According to the Centers for Disease Control and Prevention, sixty percent of adults in the United States (U.S.) are living with a chronic condition. In addition, forty percent of American adults have been diagnosed with two or more chronic conditions . These cIn the U.S., employers cover fifty-eight percent of employee medical costs . EmployeCommunity pharmacists are highly accessible and in an optimal position to provide these services. As the role of the pharmacist shifts from dispensing to service provision, studies have demonstrated the values of pharmacist-provided services ,24. In pDiDonato et al. demonstrated that a one-year employee wellness program (EWP) provided by pharmacists significantly lowered patients’ cardiovascular risk . This EWThe objective of this study was to assess the clinical outcomes of participants during four years of EWP implementation. At the time of the study, the EWP was implemented at fifteen rural independent community pharmacy chain locations in northwest and central Missouri. This family-owned chain pharmacy was self-insured.The study details the full results of the EWP implemented. Of note, the first year’s results of 81 patients were previously reported . The incAt the time of enrollment and annually, participants completed a personal health assessment questionnaire; cardiovascular disease and diabetes risk assessment; and a pharmacist-conducted screening for total cholesterol (TC), serum triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), weight, body mass index (BMI), and waist circumference (WC). 2. In addition, a waist circumference less than 35 inches for females and less than 40 inches for males was considered as the goal [All wellness coordinators in the program were pharmacists. Participants had the option of personally selecting a pharmacist wellness coordinator or, if no preference, a pharmacist coordinator was assigned to them. Patients were placed into one or more of four monitoring groups  if they were identified through screenings to be outside of target ranges or to have a diagnosis of a related chronic condition  . The clithe goal . Individuals could be in more than one patient monitoring group. Otherwise, if none of the above criteria was met, participants were placed into a healthy participant monitoring group. The placement of study subjects into monitoring groups helped guide the education provided by wellness coordinators. Patients in the cholesterol, blood pressure, blood glucose, and weight monitoring groups were encouraged to meet with their wellness coordinator every one to two months, especially for the first year. Participants in the healthy participant monitoring group were encouraged to meet with their wellness coordinator every three months, especially for the first year. A total of 34 pharmacist wellness coordinators were selected on a voluntary basis. The study took place before the National Consortium for Credentialing Health and Wellness Coaches offered a national certification for health and wellness coaches . While nEach wellness visit consisted of discussion, disease-specific education, goal setting, and physical assessment, which lasted up to 60 min. The education was structured and delivered face to face. The progress was assessed by comparing results with the previous visits. The visits occurred in a semi-private counseling area during normal work hours and were free of charge. If needed, following a wellness visit, the patient’s primary care provider was contacted to notify him/her of the screening results and/or make recommendations regarding medication therapy as warranted. p-value of <0.05 was considered statistically significant. To examine the impact of pharmacist wellness and monitoring services, for each group, the primary outcome measures were the clinical values of TC, TG, HDL-C, LDL-C, SBP, DBP, FBG, BMI, and WC at baseline, 12, 24, 36, and 48 months. The secondary outcome measures were the proportion of participants who achieved the clinical value goals at baseline versus 48 months. Data were collected at baseline , 12, 24, 36 and 48 months. Participant recruitment was open during the four-year period, but the study ended in year 4. For example, if an individual was enrolled in year 2 and did not drop out, he/she would have data at baseline, 12, 24, and 36 months. Descriptive statistics were calculated for participants’ demographics. The primary outcome measures among data collection time points were compared using one-way ANOVA tests. In addition, one-way ANOVA post hoc tests were performed using least significant difference, to further identify which time points differed from each other. The secondary outcomes were compared between baseline and 48 months by Chi-square tests, or Fisher’s exact tests if expected values were less than 5. We also performed the same analyses to compare primary and secondary measures after excluding those who withdrew from the program. A The physician communication forms were primarily used to communicate screening results to each patient’s primary care provider. This was done to ensure continuity of care and alert the provider of out-of-range results, but these recommendations were not tracked. In addition, this program’s savings for the employer were requested, but not all information was made available by the pharmacy administration as a result of barriers to compiling the data. Therefore, pharmacists’ recommendations and the program’s savings were not assessed in the study.For the first year, 169 patients were eligible and 90 were enrolled, with a response rate of 53.3% . At the A total of 200 participants regardless of start and end date were included in the analyses. For example, if an individual was enrolled but dropped out 12 months later, he/she would be included in analysis at baseline and 12 months. At baseline, there were 134 patients in the cholesterol monitoring group, 129 in the weight monitoring group, 117 in the blood pressure monitoring group, 46 in the blood glucose monitoring group, and 26 in the healthy participant monitoring group . For theThe two figures reveal two significant findings. First, for patients in the blood pressure monitoring group, compared with baseline, there was a significant decrease in DBP , and a sn = 117) was significantly higher than at 12 months , 24 months , 36 months , and 48 months ; and the comparisons between any other pairs of time points were not significant. For FBG, the value at baseline  was significantly higher than at 12 months , 24 months , 36 months , and 48 months ; and the comparisons between any other pairs of time points were not significant. In one-way ANOVA post hoc tests, for DBP, the value at baseline  for all clinical variables. Regarding potential confounding variables, we assessed smoking (yes/no), alcohol use (yes/no), and exercises  at baseline. Chi-square tests were used to compare these variables for those in each of the five groups versus not. The results were not significant, so the confounding effects of the three variables could be ruled out. Furthermore, we reanalyzed the data after excluding 75 participants who withdrew the program, but at least completed baseline data collection. The results of this study show that community pharmacist-led wellness services improved DBP and FBG values in an EWP. In addition, a 2014 systematic review revealed that patients in EWPs have improved quality of life . For an For both all participants and those who did not withdraw from the program, we found a significant improvement of DBP in the blood pressure monitoring group compared with baseline. However, a significant improvement of SBP was only identified in those who did not drop out. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7), the governing blood pressure guideline at the time of study conduction, states there are higher control rates of DBP than SBP. According to the guideline, many primary care physicians were trained to emphasize DBP control more than SBP . In 2017Although DiDonato et al. found significant improvements in cholesterol levels  for the first year, these improvements were not sustained over the next three years of the program . Similarn = 136) were enrolled in more than one patient monitoring group, and most clinical variables had no significant change over a four-year period, it is implied that the impact of multiple inventions was limited in this study.In this study, FBG rather than HbA1c was evaluated because of four reasons. First of all, when the EWP was developed and implemented, diabetes guidelines recommending HbA1c as a method of diagnosis  were notDespite the encouraged regular meetings between participants and pharmacist wellness coordinators, a study limitation was the decline of participants each year. This could be because of fatigue from regular follow-ups with the coordinators. At each visit, participants were held accountable for the goals set at previous visits. If goals were not being met, this could have led to some patients feeling discouraged or frustrated with the process. As mentioned earlier, another reason could be that participants tended to revert to their previous lifestyles. Recently, Jones et al. reported that there is little evidence to support the positive impact of employee wellness programs, and most existing studies utilize observational comparisons between a study group and a control group . In a raThere were also two other limitations. First, we did not collect information for all potential confounding variables, such as medication adherence and healthy eating. Second, given the observational study design and the fact that the employees might know each other well, we were unable to control for externalities .For future EWPs, the training for pharmacist wellness coordinators should include how to conduct participant follow-ups to ensure participants feel the value of the service. We believe that regular and effective follow-ups could not only have prevented participants from dropping out of the EWP, but also from reverting to unhealthy behaviors. In addition, future EWPs could consider applying additional incentives, as feasible, to encourage participation and motivate participants to reach their goals. To encourage participation in the EWP, participants received a discounted health insurance premium of $50, pedometers, and water bottles. However, incentives directly associated with outcomes, such as a cash reward for meeting goals, may have been more motivating to individuals versus a cost-savings incentive structure. In a study conducted by Schramm et al., a financially incentivized weight loss challenge led to significant weight loss in the study population . InteresPharmacist-led wellness visits provided to employee wellness patients in a community pharmacy may lead to improvements in BP and FBG values. Significant improvements were seen in cholesterol outcome measures after one year of the program, but were not sustained over the next three years, suggesting participants may have reverted to their previous habits.


Adolescents (12–17 years of age) with severe eosinophilic asthma experience frequent exacerbations and reduced lung function leading to poor health-related quality of life. Mepolizumab is approved for add-on maintenance therapy in patients with severe eosinophilic asthma ≥ 6 years of age in the EU and ≥ 12 years of age in other regions (including the USA), based on a Phase II/III program demonstrating reduced exacerbation rates with 4-weekly treatment. A total of 34 adolescent patients were recruited across the Phase III mepolizumab trials. Consistent with outcomes in the overall population, there was a reduction in the annual rate of clinically significant exacerbations, along with a reduction in blood eosinophil counts in response to mepolizumab in adolescent patients. The safety profile in adolescent patients was consistent with that seen in the overall population. Data from the Phase III clinical development program provide evidence for comparable efficacy and safety of mepolizumab between adolescents with severe eosinophilic asthma and the overall population.Clinical trial registration DREAM, NCT01000506 [MEA112997]; MENSA, NCT01691521 [MEA115588]; SIRIUS, NCT01691508 [MEA115575]; MUSCA, NCT02281318 [200862]; COSMOS, NCT01842607 [MEA115661]. Dear editor,Asthma is a substantial health problem among adolescents (12–17 years of age) . In partSeveral biologic therapies are now available for patients with severe asthma who were previously without effective treatment options. Mepolizumab, an anti-interleukin (IL)-5 therapy, was approved in 2015 for add-on maintenance treatment of patients with severe asthma ≥ 12 years of age and with an eosinophilic phenotype; in 2018 the EU license was extended to include patients with severe asthma ≥ 6 years of age. The Phase II/III program for mepolizumab showed that mepolizumab administered once every 4 weeks reduced exacerbation rates and OCS use, and improved quality of life, compared with placebo in patients ≥ 12 years of age with severe eosinophilic asthma –17. HereDue to the low prevalence of severe eosinophilic asthma in adolescents, recruitment of adolescents into the Phase II/III mepolizumab trials was challenging. However, a total of 34 adolescent patients ≥ 12–17 years of age were randomized across 4 studies: the 32-week MENSA study ; the 24-week MUSCA study ; the 52-week DREAM study ; and the 24-week SIRIUS study . In these trials, every 4 weeks, patients with severe eosinophilic asthma received either placebo or 75, 250 or 750 mg intravenous (IV) mepolizumab (DREAM); placebo or 75 mg IV mepolizumab or 100 mg subcutaneous (SC) mepolizumab (MENSA); or placebo or 100 mg mepolizumab (SIRIUS/MUSCA). Full details of the inclusion/exclusion criteria and treatment schedules have been previously published –17.Adolescents in the MENSA study (the study with the largest recruitment of adolescents) displayed similar baseline exacerbation rates, Asthma Control Questionnaire (ACQ) scores and blood eosinophil counts compared with the overall population. However, in the adolescent population, asthma duration was shorter (as expected), a numerically higher proportion of patients were atopic and experienced hospitalizations associated with exacerbations, and a numerically lower proportion of patients were using maintenance OCS at baseline Table .Table 1BEosinophilia has been defined as a key phenotypic characteristic of patients with severe eosinophilic asthma , 18. WhiBlood eosinophil count was also shown to be a predictive biomarker for response to mepolizumab treatment, with reductions in eosinophil counts accompanied by reductions in clinically significant exacerbations , 16, 17.In terms of safety, over the course of the Phase III program, mepolizumab was shown to be well tolerated in the overall population –17, and Given the substantial unmet treatment need in adolescent patients with severe eosinophilic asthma, it is important to determine how biological therapies that have demonstrated efficacy in adult patients with severe eosinophilic asthma perform in the adolescent population. Although the adolescent population was small, data from the Phase III mepolizumab clinical development program provide evidence for comparable efficacy and safety of mepolizumab between adolescents with severe eosinophilic asthma and the overall population.


We aimed to evaluate the relationship between different lifestyle patterns and blood pressure. This study is based on the national survey of the risk factors for non-communicable diseases in Iran in 2012. A total of 8244 people aged 25–70 years old have been enrolled in the survey. Clustering on the individual data of lifestyle factors  were carried out using self-organizing neural network method. Multivariable regression models were used to determine the relationship between blood pressure and the clusters. This study revealed seven lifestyle clusters in the national survey. The first cluster had a healthier lifestyle (15%), and the rest of the clusters had at least one or more lifestyle-related risk factors. Among all the clusters, people in two clusters, i.e. one characterized by consumption of sugar-sweetened beverages, salt, and fast foods, and the other one characterized by physical inactivity, were more exposed to the risk of hypertension . People in another cluster who were 100% smokers and had a very high level of work-related physical activity were about 30% less likely to experience elevated blood pressure. Although a lifestyle with cigarette smoking was associated with a reduction in blood pressure, this might be due to other related factors, such as work-related physical activity, which lower blood pressure. Of course, this hypothesis still needs to be further studied in the future. Various studies have shown that the prevalence of hypertension is increasing in various countries5, however, the highest level of increase has been observed in developing countries, especially in Asia and the East Mediterranean region. According to the Iranian Health Profile Survey, around 22% of the adult population are hypertensive and the problem is more prevalent in the population above 55 years old. The maximum and minimum rate of hypertension within Iran is in Tehran and Qazvin with the prevalence of 47% and 6.9%, respectively. In Iran, the prevalence of hypertension is higher in urban areas6.Elevated blood pressure is one of the most important health problems, which is considered as one of the major risk factors for cardiovascular disease, stroke, and kidney diseases as well10.According to many studies, this increase is due to changes in lifestyle and an increase in behavioral risk factors such as unhealthy nutrition, physical inactivity, and smokingSo far, many different studies have separately examined the relationship between different lifestyle-related factors and blood pressure, but these studies have neglected the fact that lifestyle-related risk factors usually occur together in a person and tend to be clustered.12. A cohort study that was conducted on 20,244 Americans after 11 years of follow-up showed that people with all the four major risk factors to health , compared with those without any of these four risk factors, were four times more prone to death12. Other studies in European and American countries have reported similar patterns on the association between mortality and these risk factors14.The clustering of health-related behavioral risk factors is a major threat to the public health. Recent studies have shown that the coincidence of health-related risk factors in a person can result in synergistic effects that in turn increase the risk of non-communicable diseases and subsequent mortality15. For example, in a study conducted by Thani et al., it was shown that there were three lifestyle patterns in Qatar, and people in clusters characterized by specific characteristics such as smoking, physical inactivity, and fast food consumption, were two times more prone to the risk of developing high blood pressure, as compared with those who had a healthy lifestyle15.Very few studies have been conducted and published on the relationship between different lifestyle clusters and elevated blood pressureTherefore, it seems that blood pressure varies among people in different lifestyle groups. Understanding the characteristics of the various lifestyle subgroups (clusters) and their relationships with blood pressure can help identify different subgroups at a high risk for hypertension and plan appropriate interventions for them.18, so far to the best of our knowledge, no study has examined the relationship between the clustering of lifestyle risk factors and blood pressure at the national level. self-organizing map (SOM) is an artificial neural network clustering technique that can be used for grouping similar individuals that has been introduced since 198220. Although there are several limitations for mapping data points and other data-mining methods are needed to be used in combination with this method to overcome this limitation, SOM provides the great advantage of identifying clusters and their sub-clusters on the maps and makes the complex algorithms easily understandable21. Thus, this study was carried out with SOM technique to achieve the goal.Although many different studies have been conducted in the Iran assessing the association between different individual lifestyle-related variables and blood pressure22. In brief, the mentioned survey was carried out on 12,000 people aged 6 to 70 years old through the guidelines and regulations recommended by the World Health Organization. This study first used stratified sampling  and then utilized cluster sampling (within each strata). Given that people of very high and very low age groups are expected to have different lifestyles and blood pressure, so the study population was limited to people between the ages of 25 and 70. Finally, after cleaning the data, a total of 8244 people were enrolled into the present study.The present study was conducted on data obtained from the national study of major risk factors for non-communicable diseases in 2012. The protocol for the national survey of risk factors of non-communicable disease (SuRFNCD) of Iran was approved by the Iran’s Center for Disease Control (CDC). For all the procedures performed in this study, verbal informed consent was obtained from all individual participants in the study, and for study participants under the age of 18 years verbal informed consent was obtained from their parents and/or a legal guardian. Details of this study have been reported elsewhere23.To collect data, we used a standard questionnaire that was prepared based on the WHO’s guidelines for the stepwise study of non-communicable disease risk factors. The collected data included demographic data  and information about the lifestyle-related behaviors such as nutrition , physical activity , smoking , and alcohol consumption. The methods of measuring variables and reviewing the patterns of health-related behaviors were presented in the previous report24.In order to measure the blood pressure of the subjects, they were asked to sit down calmly for five minutes. Then, blood pressure was measured at the right arm. Blood pressure measurements were repeated in two consecutive rounds, and five minutes of rest between each round was recommended. The mean value of the two measurements was considered as the blood pressure. People with a systolic blood pressure (SBP) ≥140 mmHg or with a diastolic blood pressure (DBP) ≥90 mmHg and those taking blood pressure lowering medications were considered as patients with high blood pressure26. A self-organizing map (SOM), a type of artificial neural network (ANN), was used for clustering of lifestyle risk factors20. Further details about this method have been presented elsewhere20. Details of the lifestyle factors in each of the clusters was described in two tables in appendix that were reported in our previously published paper23.In order to describe the quantitative variables, we reported mean and standard deviations (SD), and to describe qualitative variables the frequency and percentage were reported. Approximately, 3.23% of the data cells had not been recorded. Therefore, the missing (unknown) values were imputed by the single imputation method and regression model in mice package using R softwareIn order to study the relationship between blood pressure and lifestyle patterns, blood pressure was defined in three ways. First, SBP and DBP were evaluated separately in the linear regression model, then high blood pressure was defined as a bivariate variable and their relationship were evaluated in a logistic regression model. When studying the relationship between high blood pressure and lifestyle patterns in the logistic model, age, sex, job, and education were studied as confounding variables. In linear regression model, which was used to study the relationship between systolic and diastolic blood pressure and lifestyle patterns, in addition to the mentioned variables, the use of hypertension drugs was also assessed. It is worth noting that, the standard population of the country was used for weighing in the survey analysis.In the present study we used the known pattern (clusters) of lifestyle risk factors in Iran that was reported in last paper. Last paper was accepted in Caspian internal medicine journal and is in press. We reported it in the 19 references.A total of 8244 people were enrolled into the study, with a mean age of 42.12 years and a SD of 13.60 years. Of all, 3305 subjects were male. Table The mean consumption of fruits, vegetables, and dairy products, respectively, was 1.17, 0.92, and 1.65 units per day. The mean number of days in which the participants consumed fast food and sugar-sweetened beverages was 0.38 and 1.64 days per week, respectively. About 54.5% of the subjects consumed salt with foods and 41.7% used predominant use of unsaturated fat. The studied participants reported 1.49, 0.39, and 0.59 hours of physical activity during work, recreation, and walking, respectively. Of all participants, 14.01% were smokers and 3.39% used hookah at the time of the study.23.The results of clustering showed that in general, the studied population could be categorized into seven subgroups in terms of lifestyle related characteristics. The lifestyle-related features of each group are presented in Table Table Table This study investigated the relationship between different lifestyle patterns and blood pressure. The study assessed the relationship between systolic and diastolic blood pressure, as well as high systolic or diastolic blood pressure with lifestyle patterns, and the results showed that three clusters, including cluster 2, 5, and 7 were associated with developing high blood pressure. In cluster 2, a large number of people consumed salt with their foods, thus the elevated blood pressure was expected in this group. In cluster 5, people reported less added salt and more use of saturated vs. unsaturated fat in cooking, as compared with the other groups, but their physical activity was almost zero. The majority of people in this group this group of people were old and had a higher mean age. The elevated blood pressure in this cluster may be attributed to their age group. However, it is worth noting that, after adjusting the effect of the age, their impact was not removed. For example, concerning SBP, before entering the variable of age in the model, the blood pressure in cluster 5 was about 10.8 mmHg higher than that in cluster 1. Nevertheless, after entering the variable of age into the model, the difference reached 4.84 mmHg. This suggests that part of the risk of blood pressure in the elderly is associated with their lifestyle, which can be corrected through lifestyle modification.But the most important finding in this section was the relationship between cluster 7 and high blood pressure.27. Although this cluster had a significant relationship with blood pressure, we observed a negative (reversed) relationship in all the three analysis models; in other words, this group of people have a lower odds ratio of developing high blood pressure than other groups. Although this finding initially seems strange, after reviewing the related articles, it became clear that there were many articles that reported a negative relationship between cigarette smoking and hypertension and consider it as a paradox33. The important point is that researchers and authors of such articles still find no reason for such a relationship. An explanation for this finding is that obesity is a much more influential factor in elevating blood pressure; since people who smoke are often leaner than other people in the community (smoking can reduce people’s weight), this general fact may justify the negative relationship.Almost all of the individuals in cluster 7 were men with the highest level of work-related physical activity who were all (100%) smokers that is consistent with other studies36 and they have expressed some reasons for this observation. First, they attributed it to the toxic effects of carbon monoxide and other toxic substances in the cigarette on the walls of the veins; second, it might be due to the increase in the number of blood cells and the secondary viscosity of the blood due to exposure to carbon; third, it might be attributed to the adrenergic and sympathetic stimulations caused by nicotine and its metabolites37. As previously mentioned, there are some studies that have reported a reversed relationship and the reasons for these contradictions are still unknown.There are, of course, some studies that have shown that smoking increases the risk of high blood pressureAnother interesting finding of the present study is that smokers were only in two clusters. In cluster 4 about 30% of the subjects were cigarette smokers, and in cluster 7 all the subjects i.e. 100% were smokers. There are two very distinct differences between these two groups: first, the work-related physical activity was very high in cluster 7, while it was lower in cluster 4. On the other hand, in cluster 4 in addition to smoking, the consumption of alcohol and hookah was also high. However, we were limited to assess the quantity of alcohol use. taking into account the body mass index (BMI) of people in these two groups, it can be observed that the BMI in cluster number 5 was about 24, but in cluster number 4 it was about 26. So, it might not be a very acceptable hypothesis to say that cigarette alone causes weight loss and therefore results in a decrease in blood pressure. It seems that cigarette smoking tends to be clustered with two other lifestyle risk factors, including alcohol and hookahs and sugar-sweetened beverages (which is proved in many studies). In such a condition no weight loss is observed and there is no negative relationship with high blood pressure. On the other hand, cigarette smoking also tends to be clustered with the work-related physical activity; in such a condition, not only weight loss occurs, but also there will be a synergistic effect between smoking and work-related physical activity that may reduce the weight and ultimately reduce people’s blood pressure. Another potential explanation is that the regular work-related physical activity plays a stronger role in these individuals or people in this cluster are in a lower socioeconomic status, and some other unmeasured/unreported factor related to lower socioeconomic status is affecting these results.In groups of smokers who do not have a much work-related physical activity, there is no reduction in blood pressure, as they are likely to consume alcohol at the same time. Therefore, it might be the factor resulting in a controversy in the results of various studies that have examined the relationship between hypertension and smoking. It is worth noting that seeing such results will only appear in studies that analyze the factors in clusters; it highlights the need for further cluster analysis studies. On the other hand, as in cluster 4 only 30% of the subjects were smokers, therefore, further studies are needed to prove this hypothesis.To confirm the findings, it is necessary to have two of the following conditions in the study. First, the relationship between cigarette smoking and blood pressure in cluster 4 should be a direct relationship. Second, as in our study the majority of smokers were categorized in cluster 7, this relationship should be negative in the whole population. To evaluate the first condition, the relationship between smoking and hypertension in cluster 4 was analyzed using the logistic regression model after adjusting for age and gender. The results showed that the odds ratio for cigarette smoking was 1.03 (95% CI = 0.61–1.74); although this relationship was not statistically significant, a direct relationship was observed. In order to evaluate the second condition, the relationship between smoking and blood pressure in the whole population was analyzed using the logistic regression model after adjusting all the lifestyle and demographic variables expressed in previous models. The results showed that the odds ratio was 0.61 (95% CI = 0.48–0.77), which indicates that the relation between smoking and blood pressure was negative in all the studied population. Thus, both of the mentioned conditions were met in our study.38.Another point that needs to be considered when interpreting the results is that although many studies report a relationship between work-related physical activity and increased risk of non-communicable diseases, these studies have shown that the elevated blood pressure is the only non-communicable outcome that did not have a significant relationship with increased work-related physical activity. According to these studies, low level of work-related physical activity is associated with an increase in blood pressure14. Moreover, a limited number of studies have examined the relationship between blood pressure and lifestyle patterns. For example, a study conducted in Qatar has examined this relationship in women15. This study used the main component analysis method to determine lifestyle patterns and observed three lifestyle patterns, including healthy lifestyle, unhealthy with fast food consumption and cigarette smoking, and without physical activity. The results of this study showed that the two unhealthy lifestyle patterns showed levels of risk for elevated blood pressure than the healthy one. The group that consumed fast-food and high amounts of salt at the same time showed a nearly two-fold risk of high blood pressure. These results show the mutual effect of smoking and fast food consumption. However, the present study showed that people who consumed more fast food and simultaneously consumed more salt had a higher mean level of blood pressure, but in the group that smoked and had high level of work-related physical activity, the blood pressure was much less than that in the other groups.So far, few studies have been conducted on the relationship between non-communicable diseases and lifestyle patterns in different countries40. Results of the present study are in coherence with this fact. Patients in cluster 5 had reported a higher rate of saturated fat consumption and consequently had higher risk of hypertension.The common point between these two studies is the relationship between fast food consumption and high blood pressure. Many studies have shown that people who consume fast food consume higher amounts of saturated oil and salt than other people in the community, which can affect vascular function and anti-inflammatory mechanisms and ultimately increase their blood pressure42. A meta-analytical study of 13 cohort studies has shown that the risk of developing hypertension has a negative relationship with a person’s physical activity42. Form a biological point of view, however, it has been shown that physical activity can play an important role in better vascular function and flexibility43. Nonetheless, no study has shown a difference between work-related physical activity and recreational physical activity in terms of their effect on the changes in blood pressure.The results of the present study also showed that people who are physically inactive (cluster 5) consumed lower amounts of salt and saturated oil than other groups, however they had higher levels of blood pressure. It is worth noting that the mean age of people in this group was much higher than the mean age of people in other groups. Nevertheless, after adjusting for the effect of age and taking blood pressure medication in the regression model, this relationship was still observed. It indicates that the lifestyle of these people, which is largely associated with physical inactivity, has an independent impact on the increase in their blood pressure. In fact, it shows a synergy between physical inactivity and age. This finding is in line with the results of similar studiesAs one of the most important strengths of the present study, for the first time the data obtained from the national level of the country was used to identify the lifestyle patterns and its relationship with blood pressure. Cluster analysis will probably have more practical application for health policymakers, as compared with the analysis of individual factors.As another strength of this study, we presented different definitions for work-related and recreational physical activities, as they can have a different effect on human health, while so far such a difference has not been considered by other previous studies on lifestyle patterns.44.The data on the amount of consumption of two variables including salt and oil was not available. Thus adding salt to food and the type of oil, were used as substitutes and it is one of the limitations of the present study. Therefore, we only used two variables of salt intake with food and the type of oil used to determine the use of these two food ingredients. However, in most studies conducted to assess the relationship between lifestyle patterns or food patterns with blood pressure, the amount of salt intake is not measuredAs another limitation of the present study, to collect data we relied on self-reports using a questionnaire, and we did not have a better way to measure the variables studied. However, self-reports have always their own constraints. The collected data are largely prone to underestimate the amount of smoking and alcohol consumption, which may affect the results of the present study. However, this bias in answering is observed in all questionnaires and is unavoidable.The results of this study showed a significant relationship between different lifestyle patterns and high blood pressure. People whose lifestyle is associated with salt consumption, high amounts of fast food consumption and physical inactivity are several time more prone to the risk of high blood pressure than people with a healthier lifestyle. In the elderly, although the consumption of saturated oil and salt was lower, physical inactivity regardless of the increase in age was found to be associated with higher levels of blood pressure, as compared with the other groups. This suggests that one of the most important interventions required for this group is to increase physical activity.On the other hand, although a lifestyle with cigarette smoking was associated with a reduction in blood pressure, this might be due to other related factors, such as work-related physical activity or lower socioeconomic status which have an effect on lowering blood pressure. Of course, this hypothesis still needs to be further studied in the future.Relationship between lifestyle pattern and blood pressure - Iranian national survey


To evaluate cardiovascular involvement in children and adolescents with End Stage Renal Disease (ESRD) and to characterize the main risk factors associated with this outcome.Cross-sectional study of 69 children and adolescents at renal transplantation and 33 healthy individuals matched by age and gender. The study outcomes were left ventricular mass z-score (LVMZ) and carotid artery intima-media thickness (CIMT). The potential risk factors considered were age, gender, CKD etiology, use of oral vitamin D and calcium-based phosphate binders, systolic and diastolic blood pressure, body mass index z-score, time since diagnosis, dialysis duration, serum levels of ionic calcium, phosphorus, parathyroid hormone, fibroblast growth factor (FGF 23), uric acid, homocysteine, cholesterol, triglycerides, C-reactive protein (CRP), vitamin D and hemoglobin.In the multivariate analysis, the factors associated with LVMZ were dialysis duration, age, systolic blood pressure, serum hemoglobin and HDL cholesterol levels. Regarding CIMT, in the multivariate analysis, systolic blood pressure was the only factor associated with the outcome.Children exhibited important cardiovascular involvement at the time of the renal transplantation. Both of the studied outcomes were independently associated with systolic blood pressure. For this reason, controlling blood pressure seems to be the main therapy to minimize cardiovascular involvement in children with ESRD. Chronic kidney disease (CKD) is a public health concern for adult and pediatric patients Cardiovascular disease (CVD) is a leading cause of death in pediatric CKD patients Chlamydia pneumoniae) In adults with CKD, CVD results from an interaction of risk factors that are grouped into a) traditional factors, such as hypertension, diabetes, hypercholesterolemia, smoking, sedentary lifestyle, white ethnicity, aging, glucose intolerance, psychosocial stress, family history of heart disease, malnutrition, obesity and male gender; and b) non-traditional factors associated with CKD Considering that infarction and stroke are late events not usually experienced in the pediatric age range, we evaluated cardiovascular changes in children and adolescents with CKD at the time of renal transplantation (RT), considering echocardiography and carotid ultrasound as surrogate endpoints, i.e., substitutes for late clinical events. These changes have already been described in children and adolescents in economically developed countries, but reports are scarce in countries in the southern hemisphere.The present study aimed to evaluate cardiovascular involvement in children and adolescents with ESRD at the time of (RT) using echocardiography and carotid ultrasound. Additionally, we aimed to characterize the main risk factors associated with these outcomes.We performed a cross-sectional study of 69 patients aged 18 years or less who underwent (RT) at Hospital do Rim-UNIFESP. A control group of healthy children paired by sex and age who were treated in the adolescents outpatient service from the same institution was also included. The data were collected from March 2012 to December 2014.The study was approved by the Ethics and Research Committee of the Federal University of São Paulo (Protocol 2031/11). All patients enrolled in the study signed a consent form.The exclusion criteria were: congenital or structural cardiac abnormalities and primary myocardial disease; children with active infectious disease, characterized by fever and bacteremia, or under antimicrobial treatment; diabetes, active inflammatory diseases , or genetic or endocrine diseases with disorders in calcium or phosphorus metabolism; smoking (in adolescents); and the presence of a venous catheter near the carotids.Left ventricular mass z-score (LVMZ) measured by echocardiography and carotid artery intima-media thickness (CIMT) measured by carotid ultrasound in both groups were expressed as a continuous quantitative variable.The following risk factors were considered: age at transplantation, gender, body mass index z-score, time (months) since CKD diagnosis, duration (months) of dialysis before the renal transplantation, etiology of the CKD , systolic blood pressure (SBP), diastolic blood pressure, serum hemoglobin levels, serum albumin levels, serum total cholesterol levels, serum HDL cholesterol levels, serum triglycerides levels, C-reactive protein (CRP), uric acid, homocysteine, serum ionic calcium levels, serum phosphorus levels, serum calcium x phosphorus product levels (CaxP product), serum parathyroid hormone (PTH) levels, serum fibroblast growth factor (FGF23) levels, serum vitamin D levels, vitamin D use and use of calcium-based phosphate binders .To prevent the requirement of invasive and painful procedures in healthy individuals, blood sampling was not performed in the control group.After a median follow-up of 24 days (IQR=16 to 30) following RT transthoracic color Doppler echocardiography was performed by 1 of 2 expert physicians using a standard VIVID 7 dimension device  with a 5-mHz transducer. To calculate the left ventricular mass Z-scores (LVMZ), Parameter Z software was used according to the American Society of Echo's Guidelines and Standards for Performance of a Pediatric Echocardiogram We used American Society of Echocardiography guidelines (iASE version 3.0.4) to evaluate the left ventricular mass index (LVMI), including relative wall thickness and left ventricular geometry. Diastolic dysfunction was evaluated with tissue Doppler and expressed as a binary variable (present or absent diastolic dysfunction) All ultrasound exams were performed by the same examiner using a 3-12-MHz multi-frequency linear transducer device . The patients were maintained in slight neck hyperextension with the chin slightly rotated laterally in the opposite direction to the transducer after at least ten minutes of rest The CIMT measure was defined as the distance between the edges of the lumen-intimal interface and the medial-adventitial interface of the distal wall, measured bilaterally in the common carotid artery 1 cm below the bifurcation For the control group, the echocardiogram and carotid ultrasound were obtained using the same methodology as for the study group.The data were expressed as the mean and standard deviation or median and interquartile range (IQR) according to the distribution of the variables. To compare the two groups, we used Student's t-test for quantitative variables and the chi-squared test or Fisher's exact test for proportions.p<0.10 in the simple linear regression were selected for inclusion in a multivariate linear regression model. In the multivariable models we included up to 5 potential risk variables to respect the proportion of introducing one risk variable for each 10 to 15 individuals in the sample. The covariables that did not exhibit a significant association with the studied outcome were removed one by one . Lastly, the interaction terms between the variables that remained in the final models were investigated.To evaluate a possible association between risk factors and outcomes , a simple linear regression model was used for each outcome. Then, variables with p<0.05 was adopted to reject the null hypothesis, and all calculations were performed using Stata software 14.2® .For all of the tests, a limit of The study was approved by the Ethics and Research Committee of the Federal University of São Paulo (Protocol 2031/11). All patients enrolled in the study signed a consent form.During the data collection, there were 79 pediatric transplants, with all the recipients being candidates for participation in the study. Two refused to participate and eight were excluded, four for infections and four because they did not attend the hospital for the examinations.The demographic, anthropometric and clinical data of the study sample are presented in Regarding the etiology of CKD, there were 26 cases of urinary tract malformations (38%), 16 cases of glomerulopathies (23%), 23 cases of undetermined diseases (33%) and four children with other diagnoses (6%).The median time span since the CKD diagnosis to RT was 35 months (IQR=13–72), and the median duration of RRT was 14 months (IQR=8–23). In 7/69 cases (10%), a preemptive RT was performed. Among the remaining 62 patients, the dialysis methods were exclusive hemodialysis (HD) in 35 patients (51%), exclusive peritoneal dialysis (PD) in 14 cases (20%), and both HD and DP in 13 (19%) cases. Regarding the type of RT, 65 children (94%) received a deceased-donor kidney.The blood pressure values were higher among ESRD children when compared to controls. Among cases, 44 patients (64%) used antihypertensive drugs and 16 had stage 1 hypertension The left ventricular mass z-score (LVMZ) was 0.48 (SD=1.75) in CKD patients and -0.94 (SD=1.00) in patients from the control group, displaying a significant difference between groups . The LVMp<0.001).Among patients with CKD, 42 children (60.9%) exhibited normal left ventricular geometry, whereas concentric hypertrophy was observed in 14 patients (20.3%), eccentric hypertrophy in 11 patients (15.9%) and concentric remodeling in two other (2.9%). Conversely, all individuals from control group had normal left ventricular geometry (p<0.001).The left ventricular systolic function was preserved in all of the patients, except for one case that exhibited moderate dysfunction. All of the controls had normal function. The analysis of the diastolic function was not possible in one case due to tachycardia. Nine patients with CKD (13%) exhibited altered diastolic dysfunction (13%), whereas controls were normal . This result demonstrates arterial involvement in children with ESRD, as illustrated in When comparing the carotid artery intima-medial thickness (CIMT), we found a significant difference between the groups, with a greater thickness in patients with ESRD  and vitamin D use exhibited an association with CIMT and were included in the multivariate linear regression model, after which there was only an association with SBP. According to this analysis, each 10-mmHg increase in SBP was associated with an increase of 0.015 mm in CIMT.The main finding of the present study was that ESRD children and adolescents exhibited cardiovascular involvement at the time of RT presenting increased LVM and CIMT when compared to controls. Such outcomes are substitutes for late clinical events at the pediatric age range. However, these outcomes are relevant because they are recognized risk factors for predictable clinical outcomes, especially in adults Cardiac abnormalities are frequent in adults and children with CKD and contribute to morbidity Left ventricular hypertrophy (LVH) is common in pediatric and adult patients undergoing dialysis The first variable that exhibited an independent association with LVMZ was age at RT, which is biologically plausible. However, because we use the z score to express the LVM, the effect of age on any body size measurement was attenuated. Therefore, this association is likely related to CKD and not simply due to LVM increase with age. In addition to age, we observed the effect of dialysis duration on LVMZ and it is possible that the association between LVM and age is somehow related to dialysis duration. In contrast to our findings, the association between LVM and dialysis duration was not found in another study involving 64 patients undergoing dialysis Another finding was the association between serum hemoglobin and LVM, which is consistent with data from the literature that reports an association between anemia and LVMI Amongst the potential risk factors tested in the present study, only SBP exhibited an association with both of the studied outcomes. This finding agrees with most studies in the literature Low serum HDL is associated with increased coronary disease in adults with CKD, and lower baseline concentrations when compared to the general population have been reported. These lipid abnormalities may produce a 1.2-1.4-fold higher risk for coronary disease Previous studies have reported normal CIMT values in children from the northern hemisphere In a study evaluating 101 children aged between 2 and 18 years of age and healthy controls, dyslipidemia and hypertension were associated with an increase of in the CIMT, The results of the present study must be interpreted considering its limitations. The first is the cross-sectional design of the study, which prevents the establishment of causal relationships between risk factors and the studied outcomes. The development of cardiovascular complications is a process that occurs over time, and cross-sectional studies, only one time point in this progression can be evaluated. Another study feature that prevented us from formulating more in-depth analyses was the lack of data on both dialysis quality and the duration of the medications that the patients were receiving. The fact that patients of the study had been referred for from different regions of the country precluded access to their medical records in the dialysis clinics of origin, rendering it impossible to obtain data on prescription duration, changes in dosages and adherence. This factor limited our analysis of the role of dialysis quality and the use of calcium-based phosphate binders, vitamin D analogs and antihypertensive medications.Nevertheless we believe that our findings indicate that there is significant cardiovascular involvement in at least 1/5 of pediatric ESRD patients at the time of RT. We concluded that children with CKD show cardiac involvement and that the control of modifiable risk factors as hypertension and anemia must be considered therapeutic aims. The independent association between SBP and both markers suggests an opportunity for interventions that aim to prevent cardiovascular complications.Do Val ML was responsible for the preparation of the project, participated in all planning, responsible for selection, recruitment, patient data collection and double database typing, execution and manuscript writing. Menezes FS was responsible for selection, recruitment, patient data collection and double database typing and final approval of the manuscript version to be published. Massaoka HT, student of medical graduation, participated in the study conception and was responsible for the graphical elaboration and tabulation of the database. Scavarda VT, pediatric cardiologist, responsible for performing the echocardiogram examinations of the patients and final approval of the manuscript version to be published. Moisés VA provided substantial contributions to conception and design, and analysis and interpretation of cardiologic data. Czapkowski A, radiologist, responsible for performing the ultrasound examinations to measure the patients’ mean intimal complex of the carotid artery and final approval of the manuscript version to be published. Ajzen SA was responsible for the study conception, design, analysis and interpretation of radiologic data, and final approval of the manuscript version to be published. Pestana JO was responsible for data discussion. Leite HP was responsible for data discussion, project supervision and manuscript drafiting and manuscript revising for critically important intelectuall content. Carvalhaes JT, co-supervisor, was responsible for the project revision and final approval of the manuscript version to be published. Koch-Nogueira P, supervisor, participated in all planning, project manager, data analysis and final approval of the manuscript version to be published.


The evidence concerning how posture influences blood pressure is not consistent. The aim of this cross-sectional study was to consider the clinical and epidemiological implications of blood pressure measured in seated versus supine position, and to investigate the impact of age, sex, body mass index (BMI), and diabetes on these differences.This study included 1298 individuals (mean age 58.6 ± 11.8 years) from the Vara-Skövde cohort at the 10 years’ follow-up visit in 2014. Physical examination included blood pressure measurements in seated and supine position. Self-reported information on diabetes status, hypertension, ongoing medication, leisure time physical activity, and smoking habits were obtained. Linear regression models accounted for differences in age, sex, BMI, and known diabetes.P < .001, 95% confidence interval (95% CI) 0.79–1.54 and 4.2 mm Hg, P < .001, 95% CI 4.08–4.71, respectively]. The prevalence of high blood pressure in seated position was higher (19.9%) than in supine position (13.5%). Linear regression analysis showed that age  and diabetes  were associated with smaller differences in postural diastolic blood pressure and BMI  with greater difference.Both systolic and diastolic blood pressure were significantly higher in the seated position [1.2 mm Hg, This study showed substantial postural differences in blood pressures measured in office. Measuring blood pressure in the supine position shows lower blood pressure readings when compared with the seated position. Clinicians should be aware of how age, BMI, and diabetes influence these differences. There is a general acceptance that posture affects the blood pressure. From supine to seated or standing position, the pressure usually drops. The 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines for the management of arterial hypertension recommend the mean of at least 2 blood pressure measurements in the seated position, spaced 1 to 2 minutes apart. The position of the arm, even in supine position, should be adjusted at heart level to avoid changes in blood pressure. However, there is still uncertainty regarding the importance of the postural differences in blood pressure measurements. In the 2003 ESH recommendations for blood pressure measurement, the authors state that the error made is unlikely to be significant in most people. On the contrary, several authors claim that there is a significant difference in blood pressures measured in seated and supine position,–5 and therefore, they cannot be considered similar. In an overview from 2003, Netea et al point out that different studies have shown contradictory results and list the possible confounders that could explain these differences. Pickering et al state that it is widely accepted, that the diastolic blood pressure (DBP) when measured in a seated position is higher than when measured supine (by 5 mm Hg), although there is less agreement about the systolic blood pressure (SBP). Alternative body positions for measuring the blood pressure have also been proposed. Our review of the available publications on Medline after 2003 showed contradictory results  were stratified by sex and 5-year age groups, from all individuals (no exclusion criteria) 30 to 74 years of age, with intentional oversampling (3-fold) in the age group 30 to <50 as compared with those aged ≥50 years. There were 1811 subjects who fulfilled all requirements for participation from the Vara population (81% participation rate) and 1005 subjects from the Skövde population (70% participation rate). During 2012 to 2014, a 10-years’ follow-up survey was completed. Within the Vara–Skövde cohort, 1954 subjects were consecutively invited to participate; of those, 85 died during the follow-up, and 35 subjects could not be reached because they had moved. The remaining 1834 subjects were invited to participate in the study. Of these, 490 individuals declined to participate, and 17 participants could not fulfil the study and were consequently excluded. In total, 1327 individuals (73% participation rate) were examined according to the study protocol. In 29 cases, complete data on blood pressure measurements were lacking, and these subjects were also excluded from further analyses. The final sample consisted of 1298 (men N = 638) subjects who had complete data including filling out the questionnaires, undergoing a physical examination, and having blood samples stored  was conducted on all subjects without known diabetes and type 2 diabetes was defined according to the WHO criteria. All ongoing medications were documented, and physical examinations included waist circumference, body weight , body height (nearest cm), and heart rate. Blood pressures were measured in 2 positions, supine and seated, on the right arm, which was supported at the heart level using pillow or arm chair. All blood pressure measurements were done in accordance to ESH/ESC 2013 guidelines using Tricuff for automatic adjustment of cuff size to arm circumference. First, the patients took supine position, and after 5 minutes’ rest, 2 blood pressure measurements were taken with a 1-minute interval. Following that, noninvasive pulse wave measurements were conducted. Patients then took seated position and rested for 5 minutes before the 2 blood pressure measurements with 1-minute interval. On average, the time between the positions was 15 minutes. Mean values from 2 measurements were used in the study. Hypertension was diagnosed in accordance with national and international guidelines. The definition of hypertension was based on 3 consecutive high readings with 4-week intervals (≥140 systolic and/or ≥ 90 mm Hg diastolic in sitting position), or the participant had a known doctor's diagnosis with ongoing treatment. High blood pressure was defined as a 1-time measurement of SBP ≥140 mm Hg and/or DBP ≥ 90 mm Hg. BMI was estimated using the formula body weight (kg) divided by the square of body height in meters (m2). Obesity was defined as body mass index (BMI) more or equal 30 kg/m2 and overweight if BMI ≥ 25 but < 30 kg/m2. The positional differences in SBP and DBP (ΔSBP and ΔDBP) were calculated by subtracting supine blood pressure from the seated blood pressures, systolic and diastolic, respectively . Three categories were defined depending on the difference in blood pressures that the subjects had in different positions. The first category included subjects with considerably (≥ 2 mm Hg) higher blood pressures in supine position, the second category included subjects with small differences in blood pressure (< 2 mm Hg between positions), and the third category included subjects who had considerably (≥ 2 mm Hg) higher blood pressure in seated position . Standard methods were used for descriptive statistics. The paired Student 33.1No significant differences in age or BMI were observed when comparing men and women; however, women had significantly lower SBP and DBP in both supine and seated positions and higher heart rate than men. The difference in ΔSBP and ΔDBP  between sexes was small and not statistically significant. All comparisons between sexes were age adjusted Table . Regardi3.2P < .001). However, a gradual decrease in DBP with age was noted after 60 years of age (P < .001). The mean SBP was higher in the seated position in all age groups except for the age group 70 to 74 years. The greatest difference between positions was in the age group 55 to 59 years, where the average seated SBP was 2.0 mm Hg higher (P < .001). DBPs were significantly higher in the seated position in all age groups, and the biggest difference was in the age group < 45 years, wherein the mean seated diastolic pressure was 6.5 mm Hg higher. ΔSBP ranged from −23 to 33 mm Hg and ΔDBP ranged from −15 to 24 mm Hg. There was a significant difference in the mean ΔDBP between all the age groups (P < .001). A trend of gradual decrease in ΔDBP with age . The difference in mean ΔSBP between age groups was not statistically significant.As summarized in Table 3.3P < .001, Chi-square = 20.3)  and diabetes mellitus  were inversely associated with mean ΔDBP, whereas BMI was positively associated with ΔDBP . Sex did not show any significant association. In a second model, the ΔSBP was used as a dependent variable and the same variables as previously were used as the independent variables. In this model, none of the above variables were significantly associated with ΔSBP . Others, such as Sala et al and Lu et al have also reported higher supine blood pressure readings, with their study cohorts consisting entirely of hypertensive patients. Our findings support the study from Krzesinski et al, who, on average, also found higher blood pressure readings in the seated position . Lacruz et al presented similar results in a paper from 2017, showing higher seated DBP in both sexes, while men also had higher seated SBP. In our study, the same results were found for both sexes. One possible explanation for the differences in the results across studies could be selection of the study population. However, a different study population structure might not play a crucial role. Studies that used cohorts of only young healthy subjects or only elderly with hypertension,8 did not show a significant impact of the selected study population on reported results. Next, the sequence of blood pressure measurements could potentially contribute to the divergence in results. It has been shown that the sequence of blood pressure measurements can have a significant effect on the blood pressure, with a higher seated SBP and DBP when the sequence seated-supine is used. In our study as in other with results similar to ours, the seated measurement was first done, followed by the supine. In a contrast, both studies that showed different results compared with ours,8 measured blood pressure first in supine position, followed by a seated position. No detail on the sequence were described in the work of Krzesinski et al. Although it was reported, that the sequence of measurements does not cause any significant carry-over effect on the postural difference, a randomized sequence of measurements would be the optimal choice to investigate the role of the posture. The number of measurements could also have an important effect; a low number of blood pressure readings leads to a higher error, whereas high number of readings extends the time the patient spends relaxing, which has shown to produce lower blood pressure results. The diagnostic value of supine blood pressure is unclear. We noted a much lower prevalence of high blood pressure in supine position, which means that measuring blood pressure only in supine position misses a significant number of actual hypertensive patients. However, Krzesinski et al demonstrated that the cut-off value of supine blood pressure ≥130/80 mm Hg was more precise than seated blood pressure ≥140/90 mm Hg in the diagnosis of hypertension, as it identified patients with increased night-time blood pressure better. Still, they concluded that the in-office seated blood pressure value ≥140/90 mm Hg remains more accurate with elevated daytime blood pressure. Trend analyses revealed a significant negative association between increasing age and positional difference in DBP, but not in SBP. To further explain the association and reveal possible confounding, we used several different multiple linear regression models. We observed that age, BMI, and diabetes mellitus shared a strong association with difference in DBP between the 2 positions. In fact, age was inversely associated with postural difference in DBP, while BMI was positively associated with postural differences. Subjects with diabetes had significantly lower postural differences than subjects without diabetes regardless of age. In contrast to other studies, sex did not show any significant association. Several factors might explain these associations. In fact, aging and diabetes are strongly correlated with cardiovascular medication that influences the autonomic nervous system. This could cause the loss of the adaptation of the circulation during the postural change and thus lower postural differences. To explore the possible confounding effect of cardiovascular medication, we adjusted our analysis using known hypertension as a proxy variable, as these patients usually have prescribed cardiovascular medication. However, the adjustment had no significant effect on the regression models and trend analysis. Similarly, Lu et al reported that neither monotherapy or combination drug therapy predicted posture-related changes in SBP and DBP. The influence on autonomic regulation of blood pressure can also be directly exerted by the age and diabetes and linked to obesity as well.,24 However, with BMI being associated with higher postural difference, this might suggest a different type of autonomic dysregulation in obese people or another underlying mechanism. Such an alternative mechanism could be the difference in arterial stiffness. The relationship between age and increased arterial stiffness is well documented, while its relation with BMI is ambiguous. An increased cardiac output and hypervolemia have been described in patient with obesity. Combined with a stiffer arterial bed, this could explain the increase in postural change with increasing BMI. Finally, in concordance with previous observations, women had significantly lower both SBP and DBP, regardless of the body posture; however, the position-related differences in blood pressure were similar to those in men.This population-based study showed that both men and women had significantly higher seated SBP and DBP. Moreover, the study showed that these postural differences were larger in the measurement of DBP and declined significantly by age. These differences resulted in a notably higher occurrence of high blood pressure if measured in the seated position. Comparing these results to previous work in this area, some major differences were found. Most of the studies after 2003 show higher blood pressure in the supine position. T-M et al4.2This study had a well-characterized large sample size with a high participation rate and was representative for a Caucasian population. The inclusion of a large range of ages permitted the investigation of the age differences in the postural changes of blood pressure measurements. One of the weaknesses of our study is the nonrandomized order of blood pressure measurements. In addition, the number of blood pressure measurements for each position was low (only 2); however, on average, the variation between the 2 measurements was relatively small. The time between the positions, during which the pulse wave measurements were conducted, was not standardized, but the impact in our results should be minimal.4.3In conclusion, this study confirms and expands existing evidence that there is a significant difference in blood pressure between seated and supine position. Measuring blood pressure in the supine position shows lower blood pressure readings when compared with the seated position. The results reinforce the importance of following the international hypertension guidelines – blood pressure must be measured in the seated position to ensure a correct diagnosis. As supine blood pressure measurement was a standard practice 10 years ago with most Swedish primary care doctors, and the DBP in seated position is higher, the change in routines may have resulted in an increase in the prevalence of hypertension. Clinicians should be aware of how age, BMI, and diabetes influence these differences. Future research to elucidate the mechanisms behind these differences is warranted.We are very thankful to every participant from Vara and Skövde whose contribution made our study possible.Conceptualization: Ernest Privšek, Margareta Hellgren, Lennart Råstam, Ulf Lindblad, Bledar Daka.Data curation: Ulf Lindblad, Bledar Daka, Ernest PrivšekFormal analysis: Ernest Privšek, Bledar Daka, Ulf LindbladMethodology: Margareta Hellgren, Lennart Råstam, Ulf Lindblad, Bledar Daka.Resources: Lennart Råstam, Ulf Lindblad, Bledar Daka, Margareta HellgrenSupervision: Bledar Daka, Ulf LindbladValidation: Bledar Daka, Ulf LindbladVisualization: Ernest Privšek.Writing – original draft: Ernest Privšek, Ulf Lindblad, Bledar Daka.Writing – review & editing: Ernest Privšek, Bledar Daka, Ulf Lindblad, Margareta Hellgren, Lennart Råstam