Decreased residual urine volume (RUV) is associated with higher mortality in hemodialysis (HD). However, few studies have examined RUV in patients on HD in Sub-Saharan Africa. The aim of this study was to identify predictors of RUV among incident hemodialysis patients in Kinshasa.p < 0.05 was considered the threshold of statistical significance.This historical cohort study enrolled 250 patients with ESRD undergoing hemodialysis between January 2007 and July 2013 in two hemodialysis centers in Kinshasa. RUV were collected over 24 h at the initiation of HD and 6 and 12 months later during the interdialytic period. We compared the baseline characteristics of the patients according to their initial RUV (≤ 500 ml/day vs >  500 ml/day) using Student’s t, Mann-Whitney U and Chi2 tests. Linear mixed-effects models were used to search for predictors of decreased RUV by adding potentially predictive baseline covariates of the evolution of RUV to the effect of time: age, sex, diabetes mellitus, hypertension, diastolic blood pressure, diuretics, angiotensin conversion enzyme inhibitors (ACEI), angiotensin receptor blockers, hypovolemia, chronic tubulointerstitial nephropathy, left ventricular hypertrophy and initial hemodialysis characteristic. A value of p < 0.001) and the presence of chronic tubulointerstitial nephropathy  were significantly associated with RUV preservation over time. In contrast, the presence of left ventricular hypertrophy at the initiation of HD was significantly associated with decreased RUV over time .The majority of hemodialysis patients were male , with a mean age of 52.5 ± 12.3 years. The population’s RUV decreased with time, but with a slight deceleration. The mean RUV values were 680 ± 537 ml/day, 558 ± 442 ml/day and 499 ± 475 ml/day, respectively, at the initiation of HD and at 6 and 12 months later. The use of ACEI at the initiation of HD (beta coefficient 219.5, Among incident hemodialysis patients, the use of ACEI, the presence of chronic tubulointerstitial nephropathy and reduced left ventricular hypertrophy are associated with greater RUV preservation in the first year of dialysis. In Kinshasa, the capital City of the Democratic Republic of the Congo, the overall prevalence of chronic kidney disease (CKD) in the general population is estimated to be 12.4%, with 0.2% of individuals with end-stage renal disease (ESRD) , female This historical cohort study enrolled 250 patients with ESRD undergoing HD in two HD centers in Kinshasa  between January 2007 and July 2013. These facilities own Fresenius 4008B, 4008 s and, since 2010, 5008 s machines and a water treatment unit with double-pass reverse osmosis, which ensures the production of ultrapure water. Patients were alternately treated with hemodialysis (HD) or hemodiafiltration (HDF). The dialyzers used were made of polysulfone or high-flux membranes such as Helixone® Plus High-flux.All patients with ESRD admitted for HD who received at least 4 weeks of renal replacement therapy were included in this study. Socio-demographic and anthropometric parameters of interest were age, gender, weight and height. For clinical parameters, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured before the first session of HD using an electronic sphygmomanometer. Pulse pressure (PP) was calculated as the difference between SBP and DBP. The current medical treatment and complications at the initiation of HD were recorded on the appropriate form. Twenty-four-hour urine collection was used to measure RUV before beginning HD, and a similar urine collection protocol was used on days between dialysis 6 and 12 months later. The definition of volemia combined measurements of venous pressure, blood pressure and weight gain. For the evaluation of central venous pressure, we first performed a clinical assessment by placing the patient lying at 45° from the bed plane and appreciating the visibility of the jugular vein for a clinical estimation of 5–7 cm H2O. Patients with a value greater than 7 cm H2O benefited from the measure of central venous pressure. Hypervolemia was defined as a central venous pressure ≥ 13 cm H2O . If the The continuous variables are presented as an average with the standard deviation or median values and interquartile range (IQR), and the categorical variables are presented in the form of absolute frequency (percentage).We compared the baseline characteristics of the patients according to their initial RUVs (≤ 500 ml/day vs >  500 ml/day) using Student’s t, Mann-Whitney U and Chi2 tests, as appropriated.We described the average populational and individual evolution of RUV repeated-measurements by graphical analysis. The RUV medians (IQR) at each assessment time are presented based on baseline categorical covariates. For the continuous covariates, the Pearson correlation coefficient r was presented.For modelization, we first chose a linear mixed-effects model to analyze the effect of time alone on the decline in RUV (model 1). As the course of RUV mainly showed a non-linear pattern in the repeated-measurements analyses, this model allows a random intercept, a random slope and the quadratic term of time in fixed effects, with an unstructured variance-covariance matrix. Next, we constructed model 2 based on model 1 by adding baseline covariates as potential predictors of the evolution of RUV: age (years), sex , diabetes mellitus (yes vs no), hypertension (yes vs no), diastolic blood pressure (mm Hg), the use of diuretics (yes vs no), ACE inhibitors (yes vs no) and angiotensin receptor blockers , hypovolemia (yes vs no), Chronic tubulointerstitial nephropathy (yes vs no), left ventricular hypertrophy (yes vs no) and initial hemodialysis characteristic (≥ 3 vs ≤ 2 times weekly). Congestive heart failure was not chosen because of its correlation with left ventricular hypertrophy. Proteinuria was not tested because of the importance of missing data. In addition, using model 2 (main model), we tested other models, each time adding a term of time interactions with each of the baseline covariates tested in model 2, with the exception of age. For each of these models, only the variables that were significantly associated with the evolution of RUV were included in the final models. We conducted the residuals analysis to ensure the validity of the model assumptions, and plotted the predicted marginal means of RUV over time. Finally, we performed a sensitivity analysis based on the final model 2 by fitting a model allowing the quadratic term of time as a random effect  and those with the exchangeable and autoregressive residual AR(1) covariance structures instead of the unstructured covariance matrix. We used the Akaike information criterion (AIC) to compare these models.p < 0.05 was considered the threshold of statistical significance.SPSS software version 24 and Stata/IC version 14.2  were used to carry out all statistical analyses. A value of The Ethics Committee of the Faculty of Medicine, University of Kinshasa approved the implementation of this study.2, 12.0 (8.2–17.8) mg/dl and 197 (147–288) mg/dl, respectively. The median values (IQR) of eGFR, serum creatinine and plasma urea of HD patients with and without preserved IUV  were 6.0 (4.0–8.0) vs 4.0 (3.0–8.0) ml/min/1.73 m2 (p = 0.023), 11.0 (8.0–16.0) vs 13.0 (8.4–20.0) mg/dl (p = 0.036) and 187 (139–261) vs 223 (168–331) mg/dl (p = 0.004), respectively.The majority of dialysis patients were male , with a mean age of 52.5 ± 12.3 years (Table p = 0.032) and ACE inhibitors . They had less hypervolemia , hyperkalemia  and anemia . In addition, their serum albumin level was higher .Patients with preserved initial RUV, compared to those with an initial RUV of less than 500 ml/day, were often on diuretics  at the initiation of HD, 127 (50.8%) at 6 months and 77 (30.8%) at 12 months from the start of HD. The RUV varied between 0 and 2740 ml/day, with a median value (IQR) of 500 ml/day (200–1000 ml/day).Figure r = 0.004) or diastolic blood pressure .Urine volume (median) decreased over time in all patients, except in non-hypertensive patients, whose urine volume tended to increase over time Table . Roughly2) shows that there was a deceleration of this decline (the decline slowed down with time). The use of ACE inhibitors at the initiation of HD  and the presence of interstitial initial nephropathy  were the baseline characteristics significantly associated with the preservation of RUV over time. In contrast, the presence of left ventricular hypertrophy at the initiation of HD was significantly associated with decreased RUV over time . There were no significant interactions between the time variable and the baseline characteristics of patients.As the Table For the sensitivity analysis, the model in which the quadratic term of time was allowed as a random effect failed to converge. However, the model 2 containing an unstructured covariance matrix (AIC = 6410.8.) provided a better fit than those with the exchangeable (AIC = 6427.3) and the AR(1) (AIC = 6420.4) covariance structures.Figure This study assessed predictors of RUV preservation in HD patients. The mean RUV at the initiation of HD was as high as 680 ml. This is significantly elevated compared to the data reported in the CHOICE study . RUV wasIndeed, one year after the initiation of HD, 60% of patients in this study still yielded > 250 ml/day as opposed to 23.2% in the CHOICE study . NumerouWhen we analyze the effect of time alone, we note that the speed of the decline in RUV slowed down with time. This effect remained present even after adjustments for ACE inhibitors use, chronic tubulointerstitial nephropathy and LVH in model 2. This slowing of the decline in urine volume with time could be attributed to an improvement in the technique of dialysis with the introduction of the HDF technique in the two study centers since 2010. HDF is characterized by a small decrease in RUV, similar to peritoneal dialysis.The present study did not show an association between urine volume and age or sex. These results are contrary to those of the literature –7. HowevIn the present study, independent predictors of urine volume were the use of ACE inhibitors, chronic tubulointerstitial nephropathy and LVH.β, IL-6, TNFα, reactive oxygen species (ROS), and nitrogen monoxide, and the release of proteins from the acute phase of inflammation, such as C reactive protein [The beneficial role of ACE inhibitors on RKF and RUV in HD has been demonstrated in the analysis of the U.S. Renal Data System data, a study of 2211 incident dialysis patients with RKF defined by UV > 200 ml/day. This study found that the use of an ACE inhibitor was independently associated with a decreased risk of UV loss . Several protein . The use protein , resulti protein .The principal manifestations of TIN are those of tubular dysfunction. The tubulointerstitial lesions are localized either to the cortex or medulla. The extent of damage determines the severity of tubular dysfunction. Disruption of these structures, therefore, results in different degrees of nephrogenic diabetes insipidus and clinically manifests as polyuria and nocturia , 34. A cLVH is an important predictor of cardiovascular mortality and morbidity in dialysis patients. Hypertension, diabetes, increased body mass index, gender, age, anemia, and hyperparathyroidism have been described as risk factors for LVH in HD patients . LVH is Given the influence of the time spent in HD on RUV, it is necessary to make efforts to improve the practice of HD. The quality of the water treatment (ultrapure water) , the useThe interpretation of the results of the present study should consider some limitations. First, the retrospective characteristic of the study design precludes the establishment of an all cause-effect relationship. Second, the small sample size did not confer much power to the statistical tests to identify additional associations. Without urine creatinine available, the accuracy of 24-h urine output in the present study could not be certified. However, despite these limitations, the present study is the first to evaluate independent predictors of RUV in Sub-Saharan Africa.In the present study, the use of ACE inhibitors, chronic tubulointerstitial nephropathy and LVH reduction emerged as the main independent predictors of RUV preservation over time. The use of ACE inhibitors and HDF should be preferred for the optimal management of HD patients.


P-values < 0.05) with reductions of 32% for ACQ5, 31% for ACQ6, 22% for ACQ7-FEV1, and 21% for ACQ7-PEF with high Pearson’s correlation coefficients of all scores (r between 0.96 and 0.99). ACQ7-FEV1 scores were significantly higher than others. Separated courses of lung function parameters showed nearly no change, but ACQ5 and ACQ6 as scores for symptoms and reliever medication improved constantly. ACQ5 and ACQ6 revealed higher percentages of patients classified as “controlled” than ACQ7-scores. In conclusion, with only a few missing data points, our results suggest feasibility of FEV1-self-measurements. Courses of symptom-related and lung function-related ACQ items differ clearly. Our results support the GINA recommendations to consider symptoms and lung function separately. FEV1-self-measurements for research purposes may be included with the ACQ, but in clinical practice seem to measure a different domain to symptomatic asthma control.The “Asthma Control Questionnaire” (ACQ) is a very common questionnaire for assessing asthma control. This study compares different ACQ versions in a self-monitoring program over a 12-week period combining them with patients' self-measurements of peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1). The objective was to test the feasibility of FEV1-self-measurements and to compare ACQ versions regarding possible additional information given by lung function. In this prospective multicenter observational study 100 adult asthma patients, recruited at six family practices and two pulmologists' private practices in Germany, completed the ACQ weekly, performing self-measurements of PEF and FEV1. Seventy-six patients were included into final analysis with only 3% missing values. Scores for all ACQ versions improved significantly , which describes symptom severity and medication use. Looking at data from 76 participants, the researchers found that people did well measuring forced expiratory volume in one second, but they could not say whether this test was superior to another metric of lung function that considers peak expiratory flow. The results also showed that symptom scores and lung function assays seem to capture different aspects of the disease, meaning they’re worth considering separately rather than lumping together in a single test. Since then it is in use in a large number of countries being translated in 115 languages so far.11 This questionnaire is available in several versions. The original version includes not only questions about symptoms and reliever medication, but also an item on lung function. The authors of the ACQ recommend preferring measurements of FEV1 to measurements of peak expiratory flow (PEF) in usage with the ACQ, as the questionnaire has been validated with FEV1, but for practical reasons in daily disease management, they also accept PEF.11 Due to technical reasons, in the past it has not been possible for patients to perform self-measurements of FEV1 themselves at home. Still only a few but expensive portable devices are available. For all ACQ versions – whether including an item on lung function or not – an overall summary score is calculated. Previous studies, one of them done by Juniper et al. themselves, compared different ACQ versions and found extremely high correlation coefficients suggesting that adding or leaving out lung function makes little difference.16Therefore, in clinical routine assessing asthma control means to measure the patients' clinical symptoms and lung function parameters. To assess symptoms, there are several questionnaires in use, which ask about the frequency of typical asthma symptoms and use of reliever medications.7 In its 2017 update, GINA recommends long-term lung function-monitoring (PEF) for severe asthma cases and patients with poor perception of air flow limitation only.17In the 2015 update of its strategy for asthma management and prevention the “Global Initiative for Asthma” (GINA) advises to consider symptoms and lung function parameters separately, with lung function being no longer included among symptom measures numerically, but being mainly used for further risk assessment.In the study described below, we aimed to investigate, if weekly FEV1-measurements performed by patients at home over a 12 weeks period are feasible. Furthermore, we compared different versions of the ACQ to investigate whether inclusion of lung function provides additional relevant information, and whether it makes a difference if FEV1 is used instead of PEF.Of the 100 patients, who gave consent and were provided with asthma questionnaires and measurement devices at the beginning, 80 sets of records were returned. Three sets of records had been handed out to under-aged persons by mistake. Two patients quit the study prematurely because they spontaneously were free of symptoms. Six participants did not return their questionnaires and could not be contacted. Nine sets of records got lost by practices or patients. Furthermore, four more patients were excluded from the study: one patient had been given questionnaires because of his medical history only, but indeed had not been diagnosed securely, by neither a pulmologist nor a GP. For three patients no baseline values for ACQ7-FEV1 could be calculated. Finally, 76 patients were included into analysis. Overall, questionnaires were filled in very carefully by patients with only 3% missings of a total of 9880 item values. However, in 27 patients one or more ACQ items were missing for at least 1 week. 49 patients (64%) had filled in their sets of records without any missing data. The online 2. Fourteen persons (18%) were smokers. Eighteen patients (24%) had been diagnosed with asthma by a GP and 58 patients (76%) by a pulmologist. Fifty-two (68%) had undergone an asthma training program prior to the study with 92% of those participants being current non-smokers. 36 patients (47%) were recruited at general practitioners' practices, 40 (53%) at pulmologists' practices. The mean ACQ6 value at baseline was 1.3 with 34 (45%) of participants presenting with controlled asthma, mean FEV1 %-predicted in week 1 was 80.5%. In all, 92% were using a controller medication with 83% taking an inhalative corticosteroid, some in combination with other controllers. 59% took a reliever medication, one patient did not take any medication. Qualitative review of medication at baseline revealed an exceptional variety of treatment strategies. Some strategies seemed inconsistent with seven participants' treatment being incompatible with any guidelines.Characteristics of study participants are shown in Table p-values < 0.05; Fig. Over the 12-week period summary scores for all four versions of the ACQ improved significantly, both in complete cases and when replacing missing values  higher than for all other ACQ scores. ACQ–PEF summary scores tended to be higher than ACQ5 and ACQ6 scores but differences were not always significant. Yet, Pearson’s correlation coefficients of the four ACQ summary scores were very high . Findings for the other ACQ versions were similar. Correlations between puffs and lung function were low to moderate (r between 0.22 and 0.35 for week 2). Results were similar if evening measurements were analyzed instead of morning measurements.This led to an increasing difference in the courses of ACQ scores and isolated courses of FEV1 and PEF (biggest difference to ACQ seen in FEV1)  are likely to have increased adherence. Finally, we assessed feasibility only by counting missing. It could also be discussed, if improvement in asthma of some of the participants was derived from changes in their medication made at baseline visit. But as every patient diagnosed with asthma earlier on was offered to participate in the study, not only if consulting the doctor for problems with their asthma but for whatever reason, we think our study population represents a realistic sample of typical asthma patients with typical courses of their disease. Also, because of the broad selection criteria it is likely that patients represent typical asthma outpatients in the German health care system, although our sample of patients is not very large. Another argument against a medication derived change during the study is the persisting difference of lung function and symptom scores with lung function getting even slightly worse over a period of 12 weeks, which clearly stands against the improving symptom score only being caused by an effective change in medication. Within our study, it was not possible to investigate the validity of lung function self-measurements, e.g. by comparing these to regular spirometry in physicians' practices, but another study showed no significant difference between FEV1 at home and FEV1 using official spirometry at a physicians' offices .16 At the same time scores for symptoms and need for reliever medication improved significantly in contrast to both absolute values and the course over time of ACQ items for lung function, in particular for FEV1, which showed constant courses with even non-significant worsening (FEV1 showed 10% worse results than PEF). A recent study reporting a factorial analysis of ACQ6 and ACQ7 (with FEV1) found that the FEV1 item showed no relation to the latent factor derived from all other items and concluded that the factor structure of the ACQ7 remains unclear.19 It is likely that the very high correlations between different ACQ versions are mainly owing to the fact, that the majority of items (symptoms) is the same in all versions, with FEV1/PEF being only one of seven items. Lung function items do correlate with the other items but only moderately or weakly. They only have a little impact on ACQ7-scores, which rather mainly are influenced by patients' subjective concerns about their symptoms and by their reactions using their emergency devices according to emergency/self-management plans. The question is therefore, why put in this effort doing lung function measurements at all. So to us, it seems likely that symptomatic and lung function items could measure different dimensions of asthma control or disease status: on the one hand the subjective perceived present clinical control presented by symptoms and need of reliever medication, on the other hand the more objective unadulterated aspect of control, measured by lung function which may be an indicator of future risk regarding patients' prognosis for the disease.The very high correlation in scores of all ACQ versions meets the results of previous studies, which also presented usability of ACQ versions with and without lung function without loss of validity or change in interpretation.21 It could be considered to weight lung function items as such of overriding importance, so they would have more impact on ACQ7.Previous reviews showed equal benefits for patients using self-management programs with PEF-measurements or with symptom scores.20 But even as there is a lack of studies for FEV1, this is very questionable for both parameters if following the results of another review, which showed improving health outcomes for patients using action plans based on personal best PEF, in contrast to patients using plans based on PEF %-predicted.22Currently, the same coding rules are used for transforming raw values of FEV1 %-predicted and PEF %-predicted into an ACQ item. Maybe this should be changed, because in repeated observations FEV1 %-predicted on average was about 10% worse than PEF %-predicted if coded in the same way.A third alternative would be to present the ACQ6 summary score and lung function separately: the difference in courses of symptom scores and lung function items could be caused by on the one hand patients' individual and subjective perception of symptoms and deterioration. It is likely that improving scores of ACQ5 and ACQ6 express the effect of patients getting used to the procedure, e.g., as a learning effect in responding questions in a diary repeatedly. This can result in understanding the questions better and subsequently assigning better scores. Improving scores for symptoms and reliever medication can also be caused by patients getting used to stable asthma control and so being confirmed in their efforts positively. For lung function, this effect is not possible because you have to write down a value, which is not subjective.23 Implying this into interpretation of our study's results gives additional support to consider symptom scores and lung function separately.On the other hand, the stable courses of lung function parameters could be interpreted as a sign of these items being a helpful because objective and so unadulterated parameters in assessing asthma control. A previous study showed a discordance in patients' perception of asthma control and their actual asthma control comparing their personal impressions and perceptions with the results of another questionnaire to measure asthma control, the “Asthma Control Test”, with a high percentage of patients feeling controlled despite their test results showing an uncontrolled asthma.If this would be true, it would have potential consequences for the use of the ACQ. The very strong correlation between all four ACQ versions is raising the question, why lung function measurements should be done at all, if being integrated in summary scores according to current rules:Following this argumentation, we think symptoms and lung function both should be measured in clinical studies using the ACQ, for example, when investigating whether an intervention or treatment modifies only one or both of these aspects.24 it seems to be appropriate measuring both in clinical studies using the ACQ and rectifies additional costs by an expectable gain of knowledge. In self-management plans for patients ACQ so far has been used with PEF, although it was developed with FEV1, just because of regular FEV1-measurements being too expensive. More than this, there seems to be no additional benefit for patients from self-management plans with PEF-self-measurements than those involving symptoms only.21 Unless randomized trials could prove that interventions involving self-measurement of FEV1 lead to better patient-relevant outcomes, there is little argument for advocating their use.It could be questioned if in these cases there should be PEF- or FEV1-measurements or both. Because FEV1%-predicted and PEF %-predicted have been shown to differ systematically,In conclusion, we cannot give any recommendation to prefer FEV1 to PEF in use with the ACQ in clinical studies, but we think in connection with the ACQ lung function is more suitable for use in studies, where you can use a device measuring both, than for daily routine.The results of this study show the feasibility of regular FEV1-self-measurements performed by patients themselves at home monitoring their asthma control. However, following our data no recommendation can be given for preferring FEV1- to PEF-measurements. More than this, our results lend further support to the GINA recommendation to look at symptom scores and lung function separately. Further studies should investigate whether the ACQ7 including a lung function item should be considered a two-dimensional instrument. Self-monitoring of FEV1 is feasible, and for research purposes may be included with the ACQ questions, but in clinical practice measures a different domain to symptomatic asthma control.The study was approved by the Ethics Committee of the Medical Faculty of the Technical University Munich. It was run according to all relevant guidelines and procedures, especially in accordance to the professional code of medical doctors, the Declaration of Helsinki in its 2008 version and to the German Federal Data Protection Act. All patients gave written consent to their participation.This was a 12-week prospective multicenter observational study conducted by the Institute of General Practice of the Technical University Munich, Germany in 2011. Patients were recruited at six family practices and two pulmologists' private practices. All consecutive patients with a diagnosis of asthma consulting study practices for whatever reason who met inclusion criteria were informed about the study and offered to participate. Inclusion criteria were age ≥ 18 years, asthma diagnosis confirmed by spirometry in family practice or by a pulmologists via spirometry or bronchial provocation, signed declaration of informed consent and sufficient knowledge of German language. Patients were offered an incentive of €20 each for completing their asthma questionnaires. In addition, they could keep the used digital FEV1- and Peak-Flow-Meter (worth €70) after the study was finished.25 This questionnaire consists of five questions regarding the most frequent asthma symptoms in the previous week , one question regarding puffs of reliever medication and one question regarding lung function parameters before use of a bronchodilator.8 For every question, a score from zero to six is set up. For lung function parameters, measurements of FEV1 or PEF are transferred into percentage of nominal value and then into the same score from zero  to six (<50%). By adding all scores for single items and dividing the result by the number of items, summary scores are calculated to define the degree of asthma control. In our study, scores were calculated for four different versions of the ACQ: the ACQ5, consisting of five questions about symptoms only, the ACQ6, consisting of ACQ5 and one question about use of reliever medication, ACQ7-PEF, consisting of ACQ6 and PEF-self-measurements and ACQ7-FEV1, same as ACQ7-PEF, but conducted with FEV1-self-measurements instead. Cutoff points for asthma control are ≤ 0.75 for controlled asthma, 0.76–1.49 for partly controlled asthma and ≥ 1.5 for uncontrolled asthma and can be used the same for all four versions.26For assessment of asthma control the German version of the ACQ was used.Both, FEV1- and PEF-measurements were done by the patients themselves with the digital peak-flow-meter Vitalograph asma-1-monitor, which is a high quality and very reliable device saving up to 600 measurements. In the first week, patients measured FEV1 and PEF twice a day, mornings and evenings, by taking the best results out of three measurements at each time. This procedure was done to get reliable baseline values and to get patients used to the electronic device and possible differences to the readings by their usual mechanical devices. At the end of week one they answered the ACQ and made optional comments.28From week 2–12, patients did their measurements of FEV1 and PEF in the mornings and evenings once a week only, again taking the best of three results, completing the ACQ again once a week. The ACQ7-scores for week one were set up using the means of FEV1- und PEF-measurements in the morning. In weeks 2–12, the weekly gathered measurements in the morning were used. Besides, patients reported their medication use per week and important events like hospitalization. In addition, participants received an individual self-management-plan for adjusting their medication etc. in case of a worsening of their asthma including an individual emergency action plan. There was no further planned intervention such as control appointments or phone calls, except in case of exacerbations, when patients consulted the doctors. Severe exacerbations were defined by the need for oral glucocorticoids or even hospitalization.t-test was used to explore whether the different ACQ summary scores differed between each other for single weeks. A formal sample size calculation was not performed. Methods were performed in accordance with relevant regulations and guidelines.Data were entered into and processed with SPSS using all available data. Descriptive analysis was done on data using means (standard deviations) or absolute frequencies (percentages). Changes in ACQ scores over the 12-week period were analyzed using repeated measures analysis of variance. As about a quarter of the patients at some point had a missing value, we used multiple imputation (five runs) to investigate the influence of missing data. Pearson coefficients were used to quantify correlations. Consistency of the four ACQ scores was tested with Crohnbach’s α. The paired Prior to the performing of the study, we guaranteed to our patients that their data would not be transmitted outside, even not anonymously. Therefore, our medical ethics committee considers data sharing in this case as problematic.Supplementary tables


Despite strong evidence for beta-blockers and angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in chronic heart failure (CHF), they have been under-utilised especially in general medical units. We aim to evaluate the effectiveness and feasibility of a physician-targeted quality improvement intervention with education and feedback on the prescription of beta-blockers and ACEI/ARB for CHF management in an inpatient setting.We conducted an interrupted time series study between January 2009 and February 2012. A two-stage intervention was implemented. Between November 2009 and January 2011, a structured physician-oriented education program was undertaken. From February 2011, quarterly performance feedback was provided to each medical unit by a senior clinician. Medical notes of patients admitted with CHF under general medical units before and during the intervention were prospectively audited. Main outcomes were beta-blockers and ACEI/ARB prescription rates, and 180-day readmission rates for CHF.p = 0.003), but a non-sustained rise in ACEI/ARB prescription. Regular performance feedback resulted in a further sustained increase in ACEI/ARB prescription rates from 62 to 93% (p = 0.028) and a positive trend for beta-blockers with rates maintained at 89%. There was a reduction in 180-day readmission rates that correlated with the improvements in beta-blocker (p = 0.030) and ACEI/ARB (p = 0.035) prescription.Four hundred and sixty-eight patients were included in this study. Structured education program was associated with a significant rise in beta-blockers prescription rates from a baseline of 60 to 92% (Implementation of a structured education program with regular performance feedback was durable and was associated with improvements in appropriate prescribing and an observed decrease in CHF-related readmissions. Exacerbation of chronic heart failure (CHF) is a leading cause of hospitalisation worldwide. CHF is estimated to cost more than $1 billion per year in Australia and more than $34 billion per year in the United States of America (USA), with hospitalisation accounting for two-thirds of the total expenditure [There is compelling evidence that the use of certain beta-blockers and an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) can alleviate symptoms, reduce hospitalisations and extend the survival of patients with CHF , 6. InteMultiple studies have observed underutilisation of these medications in patients hospitalised for exacerbation of CHF, especially among general medical units. Prescription rates for ACEI or ARB have been reported to be between 58.7 to 89.2%, and beta-blockers between 10.4 and 80.1% for hospitalised patients with CHF . In-hospTranslating clinical guidelines to clinical practice is challenging. Multiple methods have been used to change physicians’ practices: audit and feedback, reminders, education, local consensus processes, financial incentives and financial penalties . SystemaThis study aims to report the effectiveness of structured education, audit and feedback as a quality improvement initiative targeted at physicians on the prescription of evidence-based medications in CHF management in general medical units of an outer metropolitan teaching hospital.This was an interrupted time series study conducted between January 2009 and February 2012 at The Northern Hospital, a 320 bed outer metropolitan public teaching hospital catering to a community of approximately 728,000 people in North of Melbourne, Victoria, Australia. There were six general medical units during our study period.A two-stage intervention targeting all physicians and junior medical doctors in general medical units was implemented.Stage one focused on structured education program and dissemination of CHF management guidelines involving physicians and junior doctors at all levels of training. A hospital-based CHF management guideline was developed with emphasis on two key performance measures: 1) prescribing evidence-based beta-blockers, 2) prescribing ACEI or ARB. A senior physician presented the guideline regularly during medical grand rounds and doctors’ education sessions in the allocated period. Printed materials such as posters and policies were distributed around the hospital.Rates of prescription of beta-blockers and ACEI/ARB for patients under each general medical unit was audited and fed back to each unit. Feedback of audit results was provided quarterly to doctors of each general medical unit by a senior physician in both written and verbal format. The audit results were also made available to all medical units, with results presented regularly in the broader general medical unit meetings. The average beta-blocker and ACEI/ARB prescription rates across all medical units were provided for benchmarking.There was no specific intervention by researchers in the management of individual patients and individual patient level data was not routinely made available to doctors.Patients were eligible for auditing if they were discharged alive from a general medical unit with a primary diagnosis of heart failure. This was defined as a International classification of diseases 10th Revision (ICD-10) diagnostic-related group (DRG) code of F62A (heart failure with catastrophic complications) or F62B (heart failure without catastrophic complications). The term ‘catastrophic complications’ relate to the amount of resources used during that episode as determined by a nationwide standardised case complexity matrix. The use of ICD-10 codes for case identification was a reliable method as it was compulsory for every patient to have a discharge summary that was coded with ICD-10 codes to ensure appropriate assignment of DRG, which impacted on funding allocation to the hospital. Patients were excluded from the audit if they were under 18 years of age, did not require an inpatient admission, managed by another specialty medical team within the health service or died during that admission. The health service administrative dataset was used prospectively to identify all potential eligible cases. We audited every second eligible patient with a minimum target of five patients per general medical unit per month. If less than five patients were discharged from a general medical unit in a particular month, all eligible patients from that unit were audited.Researchers reviewed the discharge prescriptions and recorded the use of evidence-based beta-blockers, ACEI or ARB. The beta-blockers deemed appropriate for use were metoprolol succinate, carvedilol and bisoprolol. Patients on nebivolol were not included in this study as the evidence for nebivolol and its routine use was not available at the time of establishing the project protocol and for the first half of the study period. The proportion of patients prescribed each of the medication classes was calculated as the percentage of potential eligible patients for that treatment modality. If patients met exclusion criteria for the use of beta-blockers  or ACE/ARB , hyperkalaemia (exceeding 5.5 mmol/L) or bilateral renal artery stenosis), they were excluded from the denominator for their respective treatment modalities. Of note, the presence of an echocardiogram result and documentation of left ventricular dysfunction was not collected to use for feedback in order to avoid pressure on hospital costs and access to this limited resource.Baseline data on prescription rates was collected from January 2009 to October 2009. Stage one intervention occurred between November 2009 and January 2011. Stage two commenced in February 2011 and continued through to February 2012.The primary outcomes for this study were the proportion of patients with a primary diagnosis of CHF who received an evidence-based beta-blocker where there was no contraindication, and the proportion of patients who received an ACEI/ARB where there was no contraindication.Secondary outcome measure was the 180-day hospital readmission rates for exacerbation of CHF for all patients in the dataset. Outcomes were collected on a monthly basis from January 2009 to February 2012.The trends of medication prescriptions were analysed using interrupted time series analysis procedures. The possibility of both an instantaneous shift and progressive increasing or decreasing change in the medication prescription rates per month following the introduction of each stage of the interventions were assessed.p-value of less than 0.05 considered to indicate statistical significance.Using the Durbin-Watson statistic and by examining auto-correlation it was determined that there was little evidence of auto-correlation in the beta-blocker and ACE/ARB data series. The trends in prescription rates were generally stationary when taking into account shifts after each intervention and seasonal components of the series, thus only Auto-Regressive and Moving Average (ARMA) processes were explored. Statistical analyses were performed with Stata, version 12 , with a two-sided This project was registered with the Quality and Patient Safety Unit at Northern Health as a quality improvement (audit and feedback) activity and approved for publication by the Northern Health Low-Risk Research Ethics committee.Between January 2009 and February 2012, a total of 847 patients were discharged from the general medical units of The Northern Hospital with a primary diagnosis of CHF exacerbation. Of which, we audited the medical records of 468 (55%) patients. The mean age of audited patients was 78 (±10.4) years, with 52% of total patients being female. Baseline characteristics of patients were similar between the audited and non-audited groups  over the 15-month period. The prescription rate for beta-blockers increased from 60% before the intervention, to 92% at the conclusion of stage one. Throughout stage two of our intervention, there was no significant shift (p = 0.791) or change to the underlying trend (p = 0.415) in the prescription of beta-blockers with the rates stabilising to a range of 87 to 89% over the remainder of the study period.The use of beta-blockers rose significantly during stage one of our intervention, with an average increase of 3.3% per month  from 53 to 94.6% at the start of stage one of the intervention, although the impact was lagged by 1 month. Over the remainder of stage one, the prescription rates for ACEI/ARB reduced steadily to a level of 62%. In stage two, we observed a significant sustained upward trend for ACEI/ARB prescription rates at an average rate of 3.6% increase per month , also lagged by 1 month, with values reaching 93% by the conclusion of stage two.ACEI/ARB prescription rates had a significant initial rise of 41.6%  and ACEI/ARB (p = 0.035), with the 180-day readmission rate for CHF reducing in the month following increases in the prescription rates of beta-blockers and ACEI/ARB.As shown in Fig. This study examined the feasibility and durability of implementing a structured education, audit and feedback program on physicians’ prescribing behaviours in the inpatient management of CHF in a real-world public hospital. Our intervention was carried out over a 27-month period to provide a realistic reflection of its applicability. Overall, we have demonstrated that this combination of quality improvement strategies was associated with significant improvements in evidence-based medication use, and may have lead to the observed reduction in the readmission rates for patients hospitalised for exacerbation of CHF.Studies have evaluated the use of CHF disease management programs or registries to improve the quality of care in CHF patients –23. MostWe observed that our first intervention with a structured education program resulted in significant increases in prescriptions for beta-blockers and ACEI/ARB that was sustained for beta-blockers but not ACEI/ARB. The reason for this discrepancy is not immediately clear, but possible explanations include concerns with medication side effects such as hypotension or renal impairment. The baseline ACEI/ARB prescription rates were also observed to be higher than beta-blockers, which may have accounted for the reduced impact of our first intervention It may also reflect the inconsistent performance of education and guideline dissemination as an intervention in altering physician behaviour as shown in previous studies –27. NeveIn theory, physicians perform better when their performance is monitored regularly and feedback provided with minimal delay to allow appropriate modification of clinical practice . This efFollowing the implementation of our quality improvement intervention, particularly in Stage 2, there is a notable reduction in the 180-day readmission rates for CHF at our hospital that coincided with the increased prescription of ACEI/ARB and beta-blockers. This is in line with existing strong evidence demonstrating improvements in this outcome , 32. ThiIn order to reduce the impact on limited resources, we did not mandate the demonstration of left ventricular dysfunction of patients for entry in to this study by echocardiography or other methods. This is important as the evidence of benefit from the assessed medications for patients with heart failure with preserved ejection fraction (HFPEF) is less clear , 34. PatThis study was conducted in a single hospital and the impact of our intervention may not be generalised to other hospitals due to the difference in processes of care and organisational factors. We did not have a control group, thus the improvements in care observed may reflect secular trends in care rather than direct effects of our intervention. A control group was not established as the Australian hospital system was such that junior doctors frequently rotate through different general medical units within the same hospital and may confound the results. Nonethless, utilising interrupted time-series analysis as a statistical technique overcomes many of the limitations of the lack of control group if using historical control. Moreover, to our knowledge, there was no concurrent local or regional intervention implemented for CHF management during the study period to account for our findings. The use of interrupted time-series analysis also allowed us to adjust for random and seasonal variations in medication prescription rates, and confirm that the demonstrated improvements were not merely seasonal fluctuations. Although there is potential for sample bias, inclusion of approximately 68% of discharges each quarter over a period of 3 years and the conservative statistical analysis techniques used should be sufficient to overcome the issue of random sampling error.General medicine has traditionally had few clinical indicators to support quality practice. The prescription rates of beta-blockers and ACEI/ARB for patients admitted with CHF is a prime candidate given CHF is a common cause of hospitalisation, has high mortality and morbidity, with clear evidence for improved outcomes with these medications. The Australian Council on Healthcare Standards (ACHS) has recently recommended this indicator as a potential measure of the quality use of medications, however widespread reporting has been limited and it is unclear to what extent it is being monitored within individual health services . The finIn this study, implementation of a structured education program and regular performance feedback was feasible, and associated with durable improvements in appropriate prescribing for CHF with a corresponding decrease in CHF related readmissions. These findings support the more widespread use of these interventions to improve the management of patients admitted with CHF.


Upon comparing the mean difference in both systolic and diastolic blood pressure with BMI, we found significant differences in both systolic (p < 0.001) and diastolic (p = 0.002) blood pressure. We also found that smokers have significantly (p = 0.025) higher systolic blood pressure , but no significant difference for diastolic blood pressure (p = 0.386), compared to nonsmokers. First-degree family history of both hypertension and cardiovascular diseases affected systolic but not diastolic blood pressure. Taking into account the adverse short- and long-term effect of hypertension, we recommend adopting an awareness program highlighting the importance of screening blood pressure in young adolescent populations, keeping in mind that both high BMI and smoking are important modifiable factors.Hypertension is one of the major risk factors associated with cardiovascular diseases. In this study, we will assess the frequency of hypertension among healthy university students and its association with gender, body mass index, smoking, and family history of both hypertension and cardiovascular diseases. We screened healthy university students ranging from 18 to 26 years of age. For each participant, we performed blood pressure measurements using a previously validated device and obtained demographic data, body mass index (BMI), smoking status, and family history of both hypertension and cardiovascular diseases. Out of the total number of 505 participants included in this study, 35.2% have blood pressure between 130/80 and 139/89, and 13.5% have blood pressure of more than 140/90. We found significant gender differences in both systolic pressure ( The Middle East is known to have a significantly higher percentage of younger populations compared to the west, with the prevalence of disabling cardiovascular diseases in those younger populations significantly higher compared to western populations . MoreoveHypertension is one of the major risk factors associated with cardiovascular diseases, and it is also a component of the metabolic syndrome . RecentlThis study was approved by our ethical committee and was conducted in concordance with the Declaration of Helsinki's latest report.We recruited university students studying at the University of Jordan in healthcare faculties, including faculty of medicine, pharmacy, and nursing. We only included healthy students . Each participant involved in this study had a previous detailed checkup upon admission to the university; the checkup included a complete history and physical examination, in addition to complete blood count and urine analysis. We recruited participants via an announcement published in relevant social media websites. Each eligible participant was instructed not to take any stimulant before blood pressure measurement  for at least one hour. We measured each participant's height, weight, and both systolic and diastolic blood pressure at the nephrology clinics. Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared (kg/m2).We used an upper arm automated blood pressure device (an Omron 705IT (HEM-759-E)) for blood pressure measurement, a validated blood pressure device [We obtained both family history of either hypertension or cardiovascular diseases  and smoking history (measured in pack-year).We used SPSS version 21.0 . We described our included sample using frequency (% proportion) for gender and mean (± standard deviation) for weight, height, systolic pressure, diastolic pressure, and BMI. We categorized BMI into the following groups: 18.5–24.9, 25–29.9, and 30–34.9, as shown in Z-test for proportions to analyze the relation between hypertension status  and both gender and BMI category. We used independent sample t-test to analyze the mean difference in both systolic and diastolic blood pressure between each gender and between smoking statuses. We used one-way ANOVA to analyze the mean differences in both systolic and diastolic blood pressure for BMI and family history of both hypertension and cardiovascular diseases. We reported our data using mean difference and 95% confidence interval (CI), and we used a p value threshold of 0.05.We used Chi-square test followed by A total of 505 participants were included in this study with a mean age of 21.2 years . They were 188 (37.2%) men and 317 (62.8%) women. Mean, standard deviation, minimum, and maximum for the included sample's weight, height, systolic BP, diastolic BP, and BMI are shown in For smoking, only 111 (22%) participants were smokers with a mean of 1.04 pack-years (±2.08). Family history of hypertension is present in 126 (25%), as 77 (15.3%) have a first-degree history and 49 (9.7%) have a second-degree family history of hypertension. Family history of cardiovascular diseases is present in 46 (9.1%), as 15 (3%) have a first-degree history and 31 (6.1%) have a second-degree family history of cardiovascular diseases.Detailed frequencies for each hypertensive category are shown in p < 0.001) regarding hypertension, as 25.1% of males do not have hypertension (<130/80) compared to 74.9% of females. Moreover, we found significant difference (p < 0.001) between each BMI category and hypertension status. Details regarding both gender differences and the difference in each BMI category with hypertension status are found in We found significant gender difference (p = 0.003) with mean difference = 18.08 mmHg (CI: 16.13 to 19.9) and diastolic BP (p = 0.011) with mean difference = 3.6 mmHg (CI: 2.06 to 5.14). Upon comparing the mean differences in both systolic and diastolic blood pressure with BMI, we found significant differences in both systolic (p < 0.001) and diastolic (p = 0.002) blood pressure. Details regarding these differences are shown in p = 0.025) high systolic blood pressure , but no significant difference for diastolic blood pressure (p = 0.386). Upon comparing the mean differences in both systolic and diastolic blood pressure among participants with (first or second degree) and without family history of hypertension, we only observed significant difference in mean systolic blood pressure (but not diastolic) in participants with first-degree family history of hypertension (but not in second degree), as systolic blood pressure for those with first-degree family history compared to those without is higher by a mean of 4.4 mmHg (CI: 0.4 mmHg to 8.3 mmHg). Family history of cardiovascular diseases has a similar effect as found in hypertension, as a difference in blood pressure is only found in systolic blood pressure upon comparing participants with first-degree history of cardiovascular diseases and those without .We found significant gender differences in both systolic BP  will further clarify the relation between blood pressure and BMI. Future studies should investigate the long-term effects of having high blood pressure early during adolescent life.We conclude with the existence of a high frequency of high blood pressure among university students, especially if we adopt the new limits for hypertension diagnosis. We also found a significant association between BMI and smoking with blood pressure, both of which are associated with higher blood pressure (only higher systolic BP for smokers), and both can be modified. Moreover, gender differences also should be considered, as boys have higher mean blood pressure compared to girls. Finally, having first-degree family history of hypertension or cardiovascular diseases has been shown to be associated with higher systolic blood pressure.


This study aimed to describe the pulmonary hemodynamic changes during the course of pregnancy and to observe any significant effects on symptomatology and outcome of pregnancy due to these changes.A total of 75 patients were recruited for the study, 60 pregnant women from first trimester to third trimester and 6 weeks of puerperium for the study group and 15 non-pregnant patients. All the subjects were interrogated about their complaints like excessive cough, exertional dyspnea, palpitations, orthopnea, syncope, exertional chest pain and lower extremity edema along with their duration. Baseline investigations, echocardiography (ECG) and Doppler echo were done.The commonest symptoms were palpitations (40%), exertional dyspnea (35%) and lower extremity edema (47%). Palpitations and dyspnea were also present in control group. Right axis deviation was the next most common abnormality in study group (12.3% patients). Pulmonary blood flow was decreased by more than 50% of predelivery value at the end of puerperium. Fall in pulmonary vascular resistance returned to base line values. Increased pulmonary artery pressure was seen during the pregnancy, which was not statistically significant.During pregnancy, though the pulmonary blood flow increases significantly, the pulmonary artery pressure remains unchanged due to substantial fall in pulmonary vascular resistance in early gestation. Pregnancy induces a multitude of anatomic, physiologic, biochemical and psychological changes in the gravid female. It imposes a functional load on the heart and circulation which includes increases in stroke volume, heart rate, plasma volume, red blood cell mass, and certain coagulation factors, and decreases in peripheral vascular resistance, colloid osmotic pressure, and blood pressure.The pulmonary circulation is a low-pressure, low-resistance, high-capacitance circuit that can accommodate large increases in blood flow without significant increase in pressure. During the first trimester, the right ventricle and pulmonary vasculature must rapidly adapt to marked increase in circulating blood volume and cardiac output. There are several periods in gestation when the risk of cardiac decompensation is especially great. Increased pulmonary blood flow is a recognized precipitant of pulmonary vascular disease. Pulmonary vascular pathology though is not often encountered in pregnant women, but when pulmonary vascular disease and pregnancy coincide, there is a very high risk of maternal complications. Pulmonary hypertension, in contrast to majority of other cardiovascular disorders, is poorly compatible with the cardiovascular burden of pregnancy and postpartum and moderate to severe degree of pulmonary hypertension may result in high maternal mortality, regardless of its cause. Maternal mortality exceeds 50% when pulmonary artery pressures approach 60% of systemic pressures.At present, there is a library of literature about changes in left ventricular function and systemic hemodynamics during pregnancy but a paucity of contemporary reports regarding maternal pulmonary hemodynamic effects of gestation. Current literature does not strongly link development of pulmonary arterial hypertension (PAH) with pregnancy and whether or not pregnancy actually induces the onset of PAH is yet to be determined. This study aimed to describe the pulmonary hemodynamic changes during the course of pregnancy and to observe any significant effects on symptomatology and outcome of pregnancy due to these changes.1) To assess the effect of pregnancy on pulmonary hemodynamics especially on pulmonary arterial pressures in all three trimesters including puerperium.2) To assess the clinical symptomatology and effect of elevated pulmonary arterial pressures in pregnant women.3) To observe effect of change in pulmonary hemodynamics on outcome of pregnancy.The present study was a prospective case-control study conducted over a period of 1 year from May 2011 to 2012 in a tertiary hospital. A total of 75 patients were recruited for the study, 60 pregnant women from first trimester to third trimester and 6 weeks of puerperium for the study group and 15 non-pregnant patients of same age group and corresponding height and weight for the control group. The pregnant women were divided according to number of pregnancies . These pregnancies were further subdivided according to single or multiple gestations .1) Pregnancy was confirmed by urine pregnancy test and/or ultrasonography.2) All pregnant women were of age group between 18 and 40 years.3) Mentally and physically fit to participate in the study.4) All pregnant women who have written informed consent for completing the entire study.Pregnant women with history of smoking, rheumatic heart diseases, congenital heart disease and other co-morbidities known to cause increase in pulmonary hemodynamics like hypoxic lung diseases, hepatic cirrhosis, scleroderma, sarcoidosis, pulmonary veno-occlusive diseases, and glycogen storage diseases were not included in the study.All the subjects were interrogated about their complaints like excessive cough, exertional dyspnea, palpitations, orthopnea, syncope, exertional chest pain and lower extremity edema along with their duration. A complete physical examination including measurement of height, weight, body surface area, with special emphasis pertaining to cardiovascular system, i.e. pulse rate, blood pressure (standing and supine), jugular venous pressure, apex beat, parasternal heave and auscultation of heart was performed.Hemogram, random blood sugar, blood urea, kidney function test, liver function test and complete urine examination were carried out in all three trimesters.A standard 12-lead electrocardiogram (Vega 12-lead electrocardiograph) was done in all subjects serially in all three trimesters and puerperium. The 2D, M-mode and pulsed Doppler echocardiography (ECG) was done (Philips HD11 echocardiograph) with high frequency phased array transducer in left lateral decubitus position using parasternal long axis and parasternal short axis and apical four chambers view in quiet respiration for the assessment of pulmonary hemodynamics specifically to calculate pulmonary velocities and mean pulmonary artery pressure. Pulmonary flow was measured by Doppler and cross-sectional ECG. These two measurements were used to determine pulmonary vascular resistance with the help of method recommended by Abbas et al in 2003 [An assessment of pulmonary artery pressures and pulmonary vascular resistance was made by using non-invasive transthoracic Doppler ECG. This technique depends on the presence of an identifiable regurgitant jet across the tricuspid valve. The speed of this jet is measured and the ventricular pressure necessary to produce it is calculated using a modification of the Bernoulli equation:max)2 + RAPSystolic PAP = RV systolic pressure = 4 equal to the area enclosed by the Doppler velocity profile during one ejection period was calculated by integrating the area under the velocity curve of right ventricular outflow tract.RVOT × TVIRVOT) × HRPulmonary blood flow =  to the TVIRVOT (in cm) obtained by Doppler ECG was used to determine pulmonary vascular resistance ).The ratio of tricuspid regurgitant velocity (TRVECHO = (TRVmax/TVIRVOT × 10) + 0.16PVRmax is peak regurgitate flow velocity across tricuspid valve, and TVIRVOT is time-velocity integral of right ventricular outflow tract.Where TRVAll these patients were given a helpline number for any undue complaint or to contact round-the-clock for follow-up and suggestions.Prior ethical clearance was obtained from Institutional Ethical Committee - Human Research of our institution.Fifty percent of the cases were from group A (18 - 25 years), 27% from group B (26 - 32 years) and 23.3% from group C (33 - 40 years). There was no statistically significant difference among different age groups of study and control groups .Bigravida women (43.3%) outnumbered the primigravida (36.66%) and multigravida (20%) .The commonest symptoms were palpitations (40%), exertional dyspnea (35%) and lower extremity edema (47%). These symptoms were attributed to increase in body weight and hemodynamic overloading of cardiovascular system. Palpitations and dyspnea were also present in control group .The commonest signs were pedal edema (6.7%), loud P2 (6.7%) and tachycardia (40%) .We found significantly lower mean Hb and PCV levels in study group as compared to controls especially in study group B and group C.3, respectively). This clearly suggests dilutional fall in Hb levels during gestation (There was significant difference in mean platelet count in study group as compared to control group (1.84 and 2.2 lakh/mmestation .Mild proteinuria (1+) was seen amongst 30% of the cases, and 23.3% cases had hematuria. The mean specific gravity remained within normal limits throughout gestation .We observed no significant alterations in hepatic enzyme levels, bilirubin levels and albumin levels within study and control groups .Sinus tachycardia was the most common ECG abnormality observed within the study group (40% patients), most commonly found in group A (28.3% patients).Right axis deviation was the next commonest abnormality in study group (12.3% patients) .In the ECG assessment of 75 women in the first trimester, the baseline values of pulmonary hemodynamic parameters were found to be within normal limits. The minor intergroup differences in pulmonary artery systolic pressure, pulmonary artery diastolic pressure and pulmonary vascular resistance were not found to be statistically significant (P > 0.05) .In the second trimester, no significant changes were observed in pulmonary artery pressures compared to first trimester. Pulmonary blood flow was increased by 29% and pulmonary vascular resistance was decreased by 15% in the study group compared to first trimester. There were no significant changes found in the control group .Of 60 cases in the study group, four cases could not be studied in the last trimester and puerperium because they were lost to follow-up. Last trimester assessment showed no significant changes in pulmonary artery pressures compared to first and second trimester, probably due to hemodilution of pregnancy, sinus tachycardia and high capacitance of pulmonary circulation during pregnancy. Pulmonary blood flow increased by 40.75% over first trimester values and 12.7% over second trimester. Pulmonary vascular resistance was decreased by 16.8% compared to first trimester values and by 1.8% compared to second trimester values. There were no significant changes observed in the control group .No significant changes were observed in pulmonary artery pressures during puerperium compared to gestation. Pulmonary blood flow was decreased by more than 50% of predelivery value at the end of puerperium. Fall in pulmonary vascular resistance returned to baseline values. There were no significant changes observed in control group parameters .There was a trend of increasing pulmonary artery pressures within the study group during the pregnancy, but it was not found to reach the statistical significance. The estimated pulmonary blood flow was increased by 28-30% in second trimester and 44-46% in third trimester . This flow returned to normal at the end of puerperium.The decrease in pulmonary vascular resistance by 13-16% in second trimester and 17.5% in third trimester (largest reduction in group B and least in group C) also returned to baseline value at the end of puerperium.The control group did not show any significant changes in pulmonary hemodynamics throughout the study.The present study was undertaken to assess the serial pulmonary hemodynamic changes during course of pregnancy. On contrary to popular belief, the changes in pulmonary artery pressures and thus the occurrence of pulmonary hypertension during pregnancy were found insignificant.Twenty-two percent cases remained asymptomatic throughout gestation. The commonest symptom in other cases was pedal edema (46.6%). Dyspnea on exertion was a common complaint in 35% cases. Palpitation was another important symptom noticed by 40% cases. The occurrence of these symptoms is consistent with observation made by Madden . AccordiOut of 60 cases, 34 (56.6%) cases showed significant change in their Hb and PCV levels. This finding is consistent with hemodilution in pregnancy as observed by Clapp et al [Electrocardiographic assessment revealed that sinus tachycardia was the most frequent manifestation (40%) followed by right axis deviation 12.3%). RBBB was also seen in 1.6% cases especially in elderly para. This was consistent with earlier findings of maternal cardiovascular changes during pregnancy by Clapp et al [%. RBBB wThe pulmonary hemodynamic assessment through 2D and Doppler ECG revealed a trend of increasing pulmonary artery pressures with advancement of pregnancy, but it was not found to reach statistical significance. The estimated pulmonary blood flow was increased by 28-30% in second trimester and up to 44-46% in third trimester attributable to hemodilution of pregnancy, sinus tachycardia, and probably higher capacitance of pulmonary circulation during pregnancy , 6. The To conclude, during pregnancy, though the pulmonary blood flow increases significantly, the pulmonary artery pressure remains unchanged due to substantial fall in pulmonary vascular resistance in early gestation. By the end of puerperium, pulmonary hemodynamics showed a strong trend of returning towards baseline levels in all the cases. Outcomes of pregnancies were favorable and normal, irrespective of degree in increment in pulmonary flow. However, large-scale studies are required for the assessment of true incidence and prevalence of pulmonary hypertension in pregnancy.


To determine the predictors of hypertension among nonpregnant females attending a health promotion clinic. A cross-sectional study was conducted during March to June 2016, at the National Institute of Cancer Prevention and Research, India. The study included 319 nonpregnant females of age 20–70 years. Demographics such as age, literacy, and income were noted. History regarding use, frequency, and quantity of smokeless tobacco was taken. Height, weight, and blood pressure were measured and body mass index was calculated. Pearson's product-moment correlation coefficient was calculated between each of the variables of age, smokeless tobacco consumption, and body mass index versus systolic and diastolic blood pressure, respectively. The linear as well as multiple linear regression analysis was employed to identify the risk factors for hypertension.P value < 0.001 for each). For diastolic blood pressure, high body mass index was a predictor. Multiple linear regression analysis showed that both systolic and diastolic hypertension were associated with high body mass index and low level of education. Moreover, the systolic hypertension was associated with higher age and smokeless tobacco use. A univariate linear regression analysis showed that age, smokeless tobacco consumption, and body mass index were associated with systolic blood pressure ( Health promotion requires control of body mass index and smokeless tobacco cessation for preventing hypertension and its complications. Hypertension (HTN) is an extremely common disease cutting across the territorial boundaries of the countries. HTN has been labeled as a “silent killer” due to the associated risk of ischemic heart disease and cerebrovascular accidents . To curbn = 511) were screened for cervical cancer and breast cancer , oral cancer, diabetes mellitus, hypertension, and obesity. Of these, 319 nonpregnant females in the age range of 20–70 years who had blood pressure measurement and gave informed consent to participate in the study were included. Pregnant females and women using smoked forms of tobacco  were excluded from the study. These patients were excluded due to their low numbers, the possible confounding by pregnancy-associated hypertension and changes in body mass index (BMI) during pregnancy. The small numbers of males screened in the clinic could possibly result in bias of the results of the study and hence were excluded. The sample size was calculated by assuming the sample correlation of 0.35 which has come from the population with a correlation of 0.50, α (type 1 error) of 5%, and power of the study to be 90%. A total of 314 participants were required to be enrolled in the study. The quantity of smokeless tobacco was derived by taking the product of packets per day and years of consumption of SLT. For all the participants, demographic parameters including age, education, and family income were noted. Height and weight were recorded and the BMI was measured using Omron HBF-212-IN . Blood pressure was measured in sitting position after 5 minutes of rest, in the left arm by using Omron JPN 1 . Participants were labeled as hypertensive as per the definition of Joint National Commission-8. The JNC-8 defines hypertension as the systolic blood pressure more than or equal to 140 mm of Hg and diastolic blood pressure as more than or equal to 90 mm of Hg on two or more properly measured blood pressure readings from two or more clinical visits, among adults 18 years and older. The blood pressure goals for adults more than sixty years old are <150/90 [All adults visiting our health promotion clinic during the four-month period from March till June 2016 . Two-sided The age range of participants was 20–72 years with mean ± SD being 38.62 ± 10.04. Approximately half (45%) of the study participants were illiterate, 9.7% had a primary education (grades I–V), 12.7% had an upper primary education (grades VI–VIII), 23.2% had a secondary education (grades IX–XII), 7.2% had a graduate degree, and only 1.6% had a postgraduate degree. The majority (67.4%) of the study participants had a monthly income between 5,000 and 10,000 INR per month while 13.8% had a monthly income below 5000 INR per month, 16% had a monthly income between 10,000 and 30,000 INR per month, and only 2.8% had a monthly income above 30,000 INR per month.2 with the mean ± SD of 23.41 ± 4.33.The systolic blood pressure ranged from 92 to 206 mm Hg with the mean ± SD being 127.13 ± 19.72. The diastolic blood pressure ranged from 55 to 165 mm Hg, mean ± SD being 80.39 ± 12.08. BMI of the participants varied from 12 to 36 kg/cm gutka, khaini, pan masala with tobacco, or tooth powder containing tobacco was elicited in 14.4% of the participants.Regular SLT product use in the form ofP < 0.001) except the correlation between diastolic blood pressure and quantity of SLT consumed  is one of the most important noncommunicable disease attaining epidemic proportions across the world as reported by WHO in 2013. HTN is one of the most important contributors to coronary artery disease, cerebrovascular diseases, premature deaths, and disability [P < 0.001) as well as diastolic blood pressure (P < 0.001). This association assumes significance since weight is a modifiable risk factor for HTN and its complications.Overweight and obesity have been identified as a significant and independent risk factor for HTN and its associated cardiovascular complications . The SEEP < 0.001) as well diastolic (P = 0.019) blood pressure.Age has been documented as a vital nonmodifiable risk factor for HTN and cardiovascular diseases in numerous studies , 15. OurTobacco consumption, both as smoking and in smokeless form, has been associated with adverse cardiovascular effects. Smoking has been shown to be a risk factor for coronary heart disease and ischemic stroke . NicotinP = 0.003) but not with diastolic blood pressure (P = 0.16). A contributing factor, apart from nicotine, may be the high content of sodium as part of alkaline buffer required to facilitate nicotine absorption and the quantity of licorice in the flavor [Tobacco consumption in smokeless forms is very common in India, especially among females . Associae flavor . Of noteOne of the limitations of the present study was the inability to confirm SLT usage with biochemical analysis. The history of SLT use, as well as the amount consumed, was based on self-assessment. However, an attempt was undertaken to avoid reporting bias on these aspects by eliciting a detailed history of the type of SLT used, the packaging along with weight, and the average number of packs consumed per day.The association of smoking with hypertension is well established in literature. However, the same is not true for smokeless tobacco where conflicting results have been reported in various studies. Hence, the present study was undertaken to lend some clarification to this controversy. In conclusion, the present study reaffirms the association of increasing age and body mass index with a higher prevalence of hypertension in female subjects. More importantly, long-term consumption of smokeless tobacco was seen to be associated with systolic hypertension. These results underscore the importance of educating hypertensive patients and their family regarding beneficial effects of cessation of smokeless tobacco in addition to diet and lifestyle modifications to control body mass index. A number of price and nonprice tobacco control measures have been undertaken by the government to tackle the tobacco menace. Price of smokeless tobacco products has gone up significantly due to increase in taxes. However, the effectiveness of this price increase in reducing the affordability of these products is still not amply clear. Direct and indirect advertising of smokeless tobacco products have been banned under the COTPA (Cigarettes and Other Tobacco Products Act) of 2003. Depiction of use of smokeless tobacco products has been prohibited in the content on television and movies. If such depiction is deemed necessary, a “Statutory Warning” has to be displayed during such scenes for clearance by the requisite censor board . The man


The pathogenesis of albuminuria in SCD remains incompletely understood. We evaluated the association of albuminuria with measures of endothelial function, and explored associations of both albuminuria and measures of endothelial function with selected biological variables .Spot urine measurements for albumin-creatinine ratio (UACR) and 24-hour urine protein were obtained. Endothelial function was assessed using brachial artery ultrasound with measurements of flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NTMD) and hyperemic velocity.Twenty three subjects with varying degrees of albuminuria were evaluated. UACR was significantly correlated with FMD . In univariate analysis, UACR was correlated with VEGF , plasma hemoglobin  and ET-1 . Multivariable analysis showed significant associations of ET-1 , VEGF  and sFLT-1  with UACR. Only ET-1  was significantly associated with FMD in multivariable analyses. Finally, UACR was correlated with both 24-hour urine protein  and urine aliquots for albumin-creatinine ratio obtained from the 24-hour urine collection .This study provides more definitive evidence for the association of albuminuria with endothelial dysfunction in SCD. Elevated circulating levels of ET-1 may contribute to SCD-related glomerulopathy by mediating endothelial dysfunction. The survival of patients with sickle cell disease (SCD) into adulthood is associated with an increased incidence of organ dysfunction. It is well recognized that SCD is characterized by a vasculopathy which is thought to result in multiple clinical complications including ischemic stroke, pulmonary hypertension, autosplenectomy, priapism, and chronic kidney disease  2009;9:2The term “sickle vasculopathy” has been used to describe a generalized form of endothelial dysfunction . SimilarOur primary hypothesis is that endothelial dysfunction is an important contributor to the pathophysiology of albuminuria in SCD. The present study evaluates the association of measures of endothelial function, assessed non-invasively by ultrasound imaging of the brachial artery, with albuminuria in patients with SCD. In addition, we explored the association of multiple biological variables with albuminuria, as well as the association of these variables with measures of endothelial function.0 thalassemia and varying degrees of albuminuria, normal albuminuria , moderately increased albuminuria  and severely increased albuminuria , were recruited from the Sickle Cell Clinic at the University of North Carolina (UNC) at Chapel Hill. Spot urine samples were obtained for albumin-creatinine ratio over 2–3 visits in a three to six month period during the non-crisis “steady state.” The UACR obtained in the final spot urine collection was used to ascertain the degree of albuminuria. A 24-hour urine collection to assess protein and creatinine clearance was obtained at the final visit. Study subjects were evaluated in the non-crisis, “steady state” with no acute pain episodes requiring medical contact during the preceding 4 weeks; had normal baseline prothrombin and activated partial thromboplastin times; had acceptable hematologic, hepatic, neurologic, cardiovascular and endocrine function; were able to understand the study requirements and willing to give informed consent; and individuals receiving hydroxyurea or renin-angiotensin-aldosterone system blocking agents (such as angiotensin converting enzyme inhibitors or angiotensin receptor blockers) were required to be on stable doses for at least 3 months. Patients were excluded if they were pregnant; had a history of poorly controlled hypertension; had a history of diabetes mellitus; had a history of hypercholesterolemia; were on treatment with a statin; had chronic daily use of non-steroidal anti-inflammatory drugs; were breastfeeding; were on a chronic transfusion program; had conditions that increase the risk associated with or complicate interpretation of FMD and nitroglycerin-mediated dilation (NTMD) measurements ; or had ingested any investigational drugs within the preceding 4 weeks. The study was approved by the Institutional Review Board at UNC, Chapel Hill and all subjects gave written informed consent to participate in accordance with the Declaration of Helsinki.Patients with HbSS or HbSβVascular endothelial function was assessed by measuring endothelium-dependent (flow-mediated) and endothelium-independent (nitroglycerin-mediated) dilation of the brachial artery as described previously ,12. In aBlood samples were obtained via venipuncture and drawn into citrate- and heparin-containing tubes. The plasma samples were aliquoted and frozen immediately at -80°C for subsequent analysis. Quantification of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble fms-like tyrosine kinase-1  and human soluble vascular cell adhesion molecule-1 (soluble VCAM-1) were accomplished using commercially available ELISA kits . Samples were assayed in duplicate and according to manufacturer's instructions. The quantification of free plasma hemoglobin was accomplished using a laboratory developed test  adapted to the Vitros 5600 chemistry platform . The absorbance at 600 nm was subtracted from the absorbance at 575 nm and multiplied by a fixed calibration factor that took into account any performed dilutions. Routine laboratory studies, including complete blood counts, chemistries to assess renal function, liver function and measures of hemolysis, spot urine for albumin-creatinine ratio and 24-hour urine for protein were performed by the McClendon Clinical Laboratory at UNC Hospitals. Glomerular filtration rate (GFR) was estimated by an equation developed by the Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration . HemogloDescriptive statistics were computed for the primary outcome variables and other covariates. Medians and the corresponding interquartile ranges are presented. Albuminuria was analyzed as both continuous and categorical variables for testing the primary hypothesis. For the primary hypothesis, the correlations between FMD, NTMD or hyperemic velocity and albuminuria were examined using Spearman’s rank correlation coefficient. The correlations between endothelial function measures and biological variables were also examined using Spearman’s rank correlation coefficient. Univariate and multivariable regression analyses were conducted to investigate the association of selected biological variables with albuminuria and FMD. Because the distribution of albuminuria and FMD were skewed, the bootstrap method was used with 10,000 replications to obtain the p value and 95% confidence interval . A backwTwenty three patients with HbSS , and with a median age of 42 years (range: 25–67 years), were enrolled. Normal albuminuria was present in 7 subjects, moderately increased albuminuria in 9 subjects, and severely increased albuminuria in 7 subjects. Consistent with their definitions, patients with severely increased albuminuria had higher median UACR than those with moderately increased albuminuria and normal albuminuria. Patients with severely increased albuminuria appeared to be older, and had significantly higher systolic and diastolic blood pressures than those patients with moderately increased or normal albuminuria . In addiUACR was negatively correlated with FMD  . In addiThe levels of evaluated biological variables based on the albuminuria categories are shown in There were modest correlations between FMD and ET-1 , FMD and VEGF , and FMD and soluble VCAM-1 , although these were not statistically significant. No significant correlations were observed between FMD and either sFLT-1 , or plasma hemoglobin  in univariate analyses. In addition, there were no significant correlations between FMD and hemoglobin, fetal hemoglobin, lactate dehydrogenase, indirect bilirubin, triglyceride, LDL-cholesterol, HDL-cholesterol or non-HDL-cholesterol .Multivariable analysis was conducted to investigate selected biological factors that could be associated with UACR in the study subjects. A backward variable selection procedure was used for variable selection. The initial model included ET-1, VEGF, sFLT-1, soluble VCAM-1, log(plasma hemoglobin), lactate dehydrogenase, indirect bilirubin, hemoglobin, and fetal hemoglobin. In the final model, using only significant covariates after the model selection, ET-1 , VEGF  and sFLT-1 , were significantly associated with UACR. This means, for example, that we expect an increase in UACR by 455.1 mcg/mg for every 1 pg/mL increase in plasma ET-1, given the same levels of VEGF and sFLT-1.Similarly, multivariable analysis was conducted to investigate selected biological factors that could be associated with FMD in the study patients. The initial model included ET-1, VEGF, sFLT-1, soluble VCAM, log(plasma hemoglobin), lactate dehydrogenase, indirect bilirubin, hemoglobin, fetal hemoglobin, triglyceride, LDL-cholesterol, HDL-cholesterol, and non-HDL-cholesterol. In the final model, using only significant covariates after the model selection, only ET-1  was significantly associated with FMD. This means that we expect a decrease in FMD by approximately 8% for every 1 pg/mL increase in plasma ET-1.As UACR, assessed by spot urine collections, was the primary variable of interest in this study, we evaluated the correlation between this variable and 24-hour urine protein collection, the gold standard for assessment of proteinuria. UACR was strongly correlated with total urinary protein assessed by 24-hour urine collection  . In addiAlbuminuria, the most common clinical manifestation of glomerular damage, is highly prevalent in patients with SCD. The prevalence of albuminuria increases with age, with estimates of between 4.5 and 26% in patients up to 21 years, and between 26 and 68% in older patients . The patA receptor [A receptor antagonist, ambrisentan, to evaluate its safety and effect on albuminuria in patients with SCD is ongoing .The significant association of plasma ET-1 with UACR in the multivariable analysis suggests a role for ET-1 in the pathogenesis of albuminuria in SCD. ET-1, an endothelium-derived peptide, is a potent vasoconstrictor which is released in response to hypoxia, hemin, angiotensin II, sheer stress, thrombin activation and inflammatory cytokines . It has receptor ,21. Withreceptor , and thereceptor –25. WithA significant negative association was observed between UACR and VEGF. This is consistent with a previous report which showed that higher VEGF concentrations are associated with decreased odds of elevated TRV in children and young adults with SCD . PodocytWe observed a significant correlation between UACR and plasma hemoglobin in univariate analysis, but not in the multivariable analysis. Although the published data on the association of albuminuria with markers of hemolysis in patients with SCD are conflicting , recent Potential contributors to the pathobiology of the chronic vasculopathy and endothelial dysfunction of SCD include RBC sickling following hemoglobin S polymerization, systemic inflammation, upregulation of endothelial adhesion molecules, coagulation activation, decreased NO bioavailability, vascular instability with up-regulation of non-NO vasoregulators, disruption of normal endothelial signaling function, increased oxidative stress, vascular stasis and recurrent ischemia-reperfusion . We now Although the gold standard for quantitative assessment of albuminuria is a 24-hour urine collection, many studies assessing albuminuria in SCD have been based on spot urine assessments of UACR. Urine albumin-creatinine ratio has not been validated in SCD. In the present study, we find a strong correlation between UACR and 24-hour urine protein collection, with an even stronger correlation between UACR and urine aliquots for albumin-creatinine ratio obtained from the 24-hour urine collection. Although proteinuria in SCD is mainly due to glomerular injury with subsequent albuminuria, patients are also known to have renal tubular dysfunction, with increased urinary concentrations of tubular proteins, such as beta-2-microglobulin and retinol-binding protein . The preOur study is limited by the small number of subjects in the albuminuria categories. As with all cross-sectional studies, this analysis demonstrates associations, but cannot prove causation. As most of the study subjects were on hydroxyurea, we did not evaluate the association of hydroxyurea use with endothelial function. Hydroxyurea has been reported to reduce albuminuria in patients with SCD ,43, an eIn summary, the present study, confirms the association of albuminuria with endothelial dysfunction in SCD. We also show that elevated plasma ET-1 levels may contribute to SCD-related glomerulopathy by mediating endothelial dysfunction. Studies to determine whether interventions that improve endothelial function can attenuate albuminuria in SCD are warranted.S1 File(XLTX)Click here for additional data file.