The presence of chronic kidney disease (CKD) is an indicator of a worse long-term prognosis in patients with ischemic stroke (IS). Unfortunately, not much is known about renal function in the population of post-IS subjects. The aim of our study was to assess the prevalence of renal damage and impaired renal function (IRF) in the population of post-IS subjects.This prospective analysis concerned 352 consecutive post-IS survivors hospitalized in Pomeranian stroke centers (Poland) in 2009. In this group estimated glomerular filtration rate (eGFR) according to MDRD  and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formulas and urine albumin/creatinine ratio (ACR) were determined.2 according to MDRD or CKD-EPI) or ACR≥30mg/g were detected in 40.38% . The highest prevalence of IRF was noted in post-IS subjects with atheromatic and lacunar IS. In multivariate analysis the ACR≥30mg/g was predicted by older age, diabetes mellitus (DM) and physical disability . The association with reduced eGFR was proved for sex , DM and physical disability.Among survivors decreased eGFR (<60 mL/min./1.73mCKD is a frequently occurring problem in the group of post-IS subjects, especially after lacunar and atheromatic IS. Post-IS patients, mainly the elderly women, with physical disability and diabetes mellitus, should be regularly screened for CKD. This could reduce the risk of further cardiovascular events and delay the progression of IRF. Worldwide, stroke is the second most common cause of mortality and the third most common cause of disability .Moreover, the incidence of stroke is increasing in Eastern Europe while, in contrast, in the US and Western Europe the incidence of stroke is decreasing .The prevalence of Chronic Kidney Disease (CKD) worldwide is continuously increasing . However, a credible assessment of the occurrence of CKD is limited, apart from stage 5, where data is quite precise due to the need for renal replacement therapy –5.2 has been well described, but there is now clear evidence that mild to moderate renal dysfunction is also associated with a substantial increase in CVD risk [Patients with CKD have an increased risk of cardiovascular diseases (CVD). The increased CVD risk in patients with end-stage renal disease (ESRD) with eGFR below 15 mL/min/1.73 mCVD risk .Practice guidelines from the National Kidney Foundation in 2002 recommended that CKD should be considered as CVD risk equivalent .Both decreased glomerular filtration rate and the presence of albuminuria/proteinuria, increase the risk of CVD. These associations have been shown in community-based populations , and in populations of patients at high cardiovascular risk  ,9Impaired renal function is an independent risk factor of IS. Furthermore, the presence of CKD is an indicator of a worse long-term prognosis in post-IS patients.Unfortunately, not much is known about renal function in the population of post-IS subjects. The data concerning the prevalence of CKD in this group is very limited. Earlier studies were conducted among different populations (eg. Caucasian or not Caucasian) and stroke subtypes . Furthermore, in those surveys the way of renal impairment estimation was not the same –15. The The aim of the study was to assess the prevalence of renal damage and impaired renal function in the population of post-IS subjects beyond the acute phase of stroke. An additional aim was to estimate the need for professional nephrologic care in this group of patients.All post-IS subjects were recruited to the study after written or verbal (in case of dominant hand dysfunction) informed consent.The study was ethically approved by bioethical committee of Medical University of Gdańsk (Poland).Diagnosis of IS was based on the WHO’s definition and stroke etiology according to the TOAST classification , 17.Patients' medical and demographic records were obtained from the Pomeranian Stroke Register (PRUM). This is an open, multi-center, Internet-based, consecutive stroke register established in 2006 at the Neurology Department of the Medical University of Gdańsk, in Gdańsk, Poland). Detailed characteristics of PRUM were already presented in an earlier publication .The study concerned post-IS patients > = 18 years old who had been hospitalized during the period of January-March 2009 in randomly selected 3 out of 15 stroke centers in Pomerania. The study was conducted beyond acute phase of stroke to ensure the reliability of measurements .The survey fieldwork was carried out in the period of 3 to 6 months after IS by nurses working at neurological wards, who were familiar with IS-subjects and who were experienced in performing such tests in the elderly (over 60 years old). The nurses had been trained by the authors of the project to assess the functional and mental status of the patients. The training also concerned interpersonal techniques, aimed at reducing the percentage of potential refusals to participate in the study.A nurse visited the patient in their house two to three times.During the first visit she collected the medical history of the patient and completed a questionnaire. She also performed a functional assessment, anthropometric and blood pressure measurements.The second visit was to repeat blood pressure measurements and to collect blood and urine samples. Patients with increased fasting glucose (without previously diagnosed diabetes mellitus) had an additional glucose level measurement during the third visit.To compare surviving and non-surviving subjects the data from hospital records was used. Laboratory results were derived from last in-hospital sampling.A detailed questionnaire was used to evaluate several aspects, namely: comorbidity, treatment methods, lifestyle and knowledge of cardiovascular prevention among the subjects as well as their socio-demographic status.The questionnaire was completed on the basis of medical history collected from either the patient or their guardian.Functional status (FS) was rated during the first visit. Modified Rankin score (mRs) and Barthel Index (BI) were used to assess FS . PotentiAnthropometric measurements were performed during the study: height, body weight, waist, hip and arm size, blood pressure (BP) and pulse. The blood pressure was measured twice on the operational or on the right arm  with the automatic Omron M5I apparatus .Arterial hypertension (AH) diagnostics was performed on the basis of two measurements during two independent visits, in accordance with JNC VII guidelines .Blood and urine sampling was completed in the respondents’ homes during the second visit. All analyses were performed in the Central Laboratory of Medical University of Gdansk. The Laboratory of Gdansk’ Medical University is encompassed in the international Common External Quality Assessment System LabQuality. The measurements were taken with the help of the Architect c8000 chemistry analyser . Creatinine was measured using the Jaffe method. The concentration of albumin in the urine was expressed as for every 1g of excreted creatinine. The albumin/creatinine urinary ratio was calculated. Renal function was estimated by eGFR with MDRD and CKD-EPI formulas. The concentrations of total cholesterol, triglycerides and HDL cholesterol were measured using enzymatic methods. The fasting glucose in venous blood was measured with the enzymatic/hexokinase and glucose-6-phosphate dehydrogenase reaction.P ≤ 0.25 for any ratio calculation from univariate analysis, and the variable retention criterion to P < 0.05.Statistical analyses were performed using the SAS System v. 9.4 software . Continuous variables are expressed as mean and standard deviation (SD) or median. Categorical variables are expressed as a percentage. Simple associations were performed using t-test or appropriate non-parametric tests for continuous variables, and chi-square tests for categorical variables. The stepwise logistic regression models were used to identify the variables from univariate analyses predicting renal dysfunction or death among post-IS subjects. In this case, odds ratios (OR), and 95% confidence intervals (CIs) were generated. The variable entry criterion to models was set to a significance level of Originally, the survey was to include 597 patients who survived hospitalization due to IS. Overall, 352 subjects participated in the project (66.42% of survivors), including 191 men (M) and 161 women (W). Blood and urine tests were performed in 306 people. Median time from IS to the first assessment was 4.0 months . The baseline characteristics of the examined population , based on data from hospitalization period, are shown in The average age of survivors was nearly 5 years lower than that of the deceased patients (p<0.05). In both groups women were definitely older than men. There was a high prevalence of CVD risk factors especially AH and HCH.Initial severity of stroke measured with NIHSS at admission was higher among the non-surviving group. A significant degree of physical disability (mRS 3 to 5 pts.—incapable of independent existence) was noted in over 50% of the surviving and 90% of the non-surviving subjects (p<0.05). In the non-surviving group there was much higher proportion of cardiogenic stroke .2) was found in 18.0% of the surviving patients when MDRD formula was used, and in 20,9% according to the CKD-EPI formula. Corresponding numbers for non-surviving subjects were 35,62% (MDRD) and 43,84% (CKD-EPI).Impaired renal function , 25.51% were diagnosed with a small-vessel occlusion (lacunar infarcts), and 23.48% of the patients suffered from cardiac thromboembolism. In 14.49% of the remaining subjects the etiology was other or undetermined. More than 1/3 of survivors showed a substantial cognitive impairment (MMSE<24).2) was diagnosed in 18.63% of the surviving patients  when MDRD formula was used, and in 23.86% according to the CKD-EPI formula . These results didn’t significantly differ from those obtained (from)/during hospitalization period. The incidence of the eGFR of stage 3 to 5 is shown in Impaired renal function (eGFR<60mL/min/1.73mP = 0.03). Albuminuria≥30 mg/l was detected in 27.12% of post-IS subjects.Urine albumin/creatinine ratio (ACR)≥30 mg/g was noted in 27.62%. It was significantly more frequent in women than in men  was present in 40.38% of the surviving subjects .Impaired renal function (eGFR<60 mL/min./1.73m2 for both—MDRD and CKD-EPI formulas).The incidence of ACR≥30 mg/g in patients with lacunar or atheromatic stroke was significantly higher than in the group of cardioembolic IS . A similUnivariate analysis of potential risk factors for albuminuria (ACR)/impaired filtration is shown in Among women, statistical links to ACR≥30 mg/g were found for: age ≥65, functional dependency (mRs 3–5 pts.), presence of cognitive impairment (MMSE<24 points), diabetes mellitus, the lack of ACEI/ARBs drugs in the therapeutic regimen. For men major factor was only age ≥65 years.Impaired glomerular filtration in women was related to age ≥ 65 years, mRs 3–5 points, no smoking and obesity (BMI> = 30 kg/m2). Among men impaired renal function was not influenced by modifiable CVD risk factors (including AH). However, it was related to age ≥65 years and mRs 3–5 points.To better characterize independent risk factors for renal impairment a multivariate logistic regression analysis was performed. The multivariate analysis predicted respectively:2);the occurrence of reduced eGFR .<0.05 was proved for older age, diabetes mellitus and mRs 3–5 points , atrial fibrillation and ranges of NIHSS value (every 4 points). In this model of a stepwise logistic regression the reduced eGFR wasn’t a statistically significant risk factor of post-IS mortality , but the model was strongly influenced by higher NIHSS  and older age  in non-survivors.In order to analyze the impact of renal dysfunction on mortality during the period from IS to the first visit, a multivariate model was built based on The results of our study support the hypothesis that CKD is a frequently occurring problem in the group of post-IS subjects.Both CKD and IS are issues of increasing importance not only in Poland, but also in Eastern Europe. This is due to a high incidence rate and a slow decrease in mortality rate, comparing to the countries of the so-called old EU.Our study shows a significantly higher prevalence of renal dysfunction in the post-IS population as compared to the general population. The biggest difference concerns a higher incidence of albuminuria: 27.1% in our study vs. 11.9% in the general population  .According to our study the frequency of renal dysfunction among post-IS patients definitely increases with age. Similar results come from PolSenior survey  and from NHANES 1999–2006  , 24.In the PolSenior study the incidence of ACR≥30 mg/g was lower than in the post-IS population (12.5% vs 27.6%) However, the average age in the PolSenior study was about six years higher (76 vs 70 years) . CompareIn our study, urine albumin concentration was compared/likened to urine creatinine concentration, which made the albuminuria result unaffected by the amount of excreted urine . Ultimately, however, in our study, ACR ≥ 30 mg/g and albuminuria ≥ 30 mg/L occurred with the same frequency.2 (MDRD formula) occurred in 18.6% of post-IS patients vs. 8.8% in the general population (PolNef Study) [2—from 4.3 to 16.7%) [Similarly to albuminuria, also reduced filtration occurred more frequently in post-IS patients. The filtration <60 mL/min/1.73mf Study) . A propoo 16.7%) . It shou2) was 0.33%, and does not differ much from the general population of Poland [On the basis of the Report of Renal Replacement Therapy in Poland it is known that renal replacement therapy in Pomeranian Region in 2008 was implemented among 40/100 thousand patients. In our study the occurrence of end-stage renal disease  , 29.Our results show a statistical link between certain factors and renal impairment in post-IS population. In multivariate analysis albuminuria was predicted by older age, DM and worse functional status (mRs 3–5). The reduced eGFR was influenced by older age, sex  and DM. These results are partially consistent with other surveys like PolSenior and Framingham Heart Study , 30. The2 according to MDRD formula) but they concerned both ischemic and hemorrhagic stroke [Our study shows the prevalence of renal dysfunction among post-IS survivors in Pomeranian Region (Poland). This is the only such analysis on the prevalence of CKD in the post-IS population. Other existing analyses were generally observational (eg. HOPE—Canada) or included hemorrhagic stroke. They were also commonly based on renal assessment in acute phase of stroke, when the value of GFR formulas may be limited. In comparison with our results, studies of Tsagalis et al. (Grece) or Yahalom et al. (Israel) conducted in acute phase of stroke showed slightly greater proportion of reduced eGFR (respectively 28% and 22% of patients with eGFR<60 mL/min/1.73mc stroke –13. In tc stroke .2). There was also no analysis based on the etiology of IS. Significantly fewer patients from the Chinese study were in the eGFR range of 15–59 mL/min/1.73m2 (<10% vs. 17.6% in our study). This difference may be also due to a lower average age of patients (by nearly 8 years) in the Y. Bao et al. study [A retrospective study of Y. Bao (China) on IS patients (data from acute phase) analyzed a slightly larger group than ours. However, albuminuria or ACR were not specified there, CKD-EPI formula was not used, and the prevalence of end-stage renal disease was not estimated  is closely associated with kidney function in patients with stroke ,34.Our data do not show clear evidence of a higher incidence of arterial hypertension in CKD group compared with the group without CKD. The incompatibility of our results with the previous publications may result from:high prevalence of AH (81%) in the examined population—the group without AH was small, which probably made it difficult to detect statistical significance.a considerable number of patients taking ACEI/ARBs drugs; 58% of the examined patients took these drugs, which decreased albuminuria.In conclusion, CKD is a common disorder in the post-IS patients, especially after lacunar and atheromatic IS. Subjects after IS, mainly the elderly (>65 years old), in a worse functional status (mRs>2), with diabetes mellitus, should be regularly screened for CKD. In the presence of abnormalities they should be professionally treated. This would reduce the risk of subsequent cardiovascular events and delay the progression of renal dysfunction.


Arterial compliance is an independent predictor of cardiovascular events. It decreases with age and this decrease is accelerated by hypertension. The objectives were to determine the arterial compliance in a group of normotensive and untreated hypertensive stage 1, 2 and 3 Cameroonian subjects.® device was used to determine cfPWV  and central Augmentation Index % (AIx). Other measurements obtained were: blood pressure (BP), body mass index (BMI), fasting glycaemia, lipid profile and serum creatinine.A cross-sectional study was conducted from August 2012 to February 2013 in Yaoundé. Our sample size was 88 participants. The PulsePenOur sample's mean age was 35.48 years and ranged from 20 to 60 years. The means of: cfPWV, SBP, DBP, Pulse Pressure (PP) and Heart Rate (HR) showed a statistically significant increase  across the groups from normotensive to severely hypertensive patients. cfPWV was significantly correlated  to: Age, Central SBP, Central DBP, Central PP, HR, BMI and central Augmentation index (AIx). Furthermore, cfPWV was significantly dependent on LVH .This study suggests that arterial compliance decreases with increase severity of hypertension, indicating a higher risk of developing cardiovascular events in severely hypertensive patients. Arterial compliance decreases with age and this decrease is accelerated by hypertension. Carotid-femoral pulse wave velocity (PWV), the current 'gold-standard' measure of arterial compliance, has emerged as an important independent predictor of cardiovascular events in hypertensive patients . ArteriaIn a cross-sectional study, we recruited 103 Cameroonians subjects through free hypertension screening campaigns organized in public places. Participants were also recruited amongst patients consulting at the cardiology outpatient clinic of the Yaoundé General and Central Hospitals from August 2012 to February 2013. Included in our study were consenting Normotensive and untreated hypertensive subjects aged from 20 to 60 years. We excluded: patients with Diabetes, subjects with a renal disease, pregnant women, subjects in an active infectious state and patients with incomplete data. During clinical clerking, blood pressure, temperature, weight and height were recorded. We also did a fasting glycaemia and a urine Beta Human Chorionic Gonadotropin pregnancy test was done in women suspected to be pregnant. Blood samples were later collected in test tubes and taken to the laboratory to analyze serum creatinine and lipid profile. Of the 103 recruited subjects, 15 were excluded as follows: 05 participants had a positive pregnancy test  , 03 had ® device , a non-invasive validated, easy to use and high-fidelity tonometer. Briefly, the PulsePen is comprised of one tonometer and an integrated ECG unit. Both pressure and electrocardiographic signals are transmitted to a computer by means of an optical fiber. Central artery pressure waveforms were evaluated noninvasively using applanation tonometry [®705, Omron Corporation, Tokyo Japan). The subject's identification, age, height, weight and blood pressure were entered into the pulsepen software. After placing the ECG electrodes, the common carotid artery pulse was palpated and the waveform recorded by gently placing the tonometer at a right angle to the artery. ECG was recorded simultaneously. Then the femoral artery was palpated followed by waveform recording. ECG was also recorded simultaneously. The blood pressure was measured before and after waveform recordings. A measuring tape was used to get the distance from: the supra-sternal notch to the carotid point of tonometer application (d1), the supra-sternal notch to the femoral point of tonometer application (d2). The difference between these distances (d2-d1) was then entered manually into the Pulsepen software. The pulsepen software automatically determined the pulse wave delay time by calculating the time elapsed from the peak of the R wave to the 'foot' of the pressure pulse contour. The device automatically measured the pulse wave delay time from the: R wave of the ECG qRs complex to the 'foot' of the carotid pressure pulse contour (t1), R wave of the ECG qRs complex to the 'foot' of the femoral pressure pulse contour (t2). Carotid-femoral PWV was defined as, the difference in distance (Δd) of the pulse wave transit which represents the difference between the distance from the supra-sternal notch to the femoral point of tonometer application (d2) and the distance from the supra-sternal notch to the carotid point of tonometer application (d1) divided by the time difference (Δt) between the time delay from the R wave of the ECG qRs complex to the 'foot' of the femoral pressure pulse contour (t2) and the delay time from the R wave of the ECG qRs complex to the 'foot' of the carotid pressure pulse contour (t1). This is shown on .PWV is the 'gold-standard' measurement of arterial stiffness. It was determined by means of a PulsePenonometry , 8. All ® quality control criteria were accepted.Augmentation index(AIx) is an important arterial stiffness parameter. It was measured by automatic identification of the “first shoulder” (inflection point) on the average carotid pulse signal by the pulsepen software. AIx= 100 x (Augmentation pressure / pulse pressure). To assure that alterations in blood pressure and heart rate did not bias the results of stiffness assessment, the Pulsepen software automatically rejected measurements in which blood pressure or heart rate changed by more than 5% during the time between the sequential carotid and femoral pulse wave recordings. For reliable results, only high-quality recordings were included in our analysis defined as an in-device quality index of >80%. Carotid-femoral or aortic PWV (cfPWV), Central SBP mmHg, Central DBP mmHg, Central PP mmHg, Heart rate beats/min, MAP and central Augmentation index % (AIx) are arterial stiffness parameters whose values were given automatically by the device. Only measurements meeting PulsepenData was analyzed using the R-software and Microsoft Excel. Univariate Analysis was used to determine the mean, SD and range of quantitative variables. Pearson's chi square test was used to show the independence of qualitative variables and Student's t-test for equality of means in the case where the distribution of the variables were normal. Otherwise the Mann-Whitney test was used. The Kruskal-Wallis rank sum test was used to test for independence between qualitative and quantitative variables. We used the Kendall's tau rank test to test for correlation between quantitative variables in the case where the distribution was not normal. Jonckheere's trend test was used to test for the trend of means of quantitative variables across the groups. Statistical significance was set at the 5% interval.Of the 88 participants studied, 51.1% were females and 48.9% were males. The mean age of the study population was 35.48 years and ranged from 20 to 60 years. The mean of hemodynamic parameters  ) showed a statistically significant increase  as we moved across the groups from normotensive to severely hypertensive patients as seen on The main objective of this study was to determine the arterial compliance in a group of normotensive and untreated hypertensive stage 1, 2 and 3 subjects in a sub-Saharan African setting. Untreated patients were studied in order to avoid the effect of some anti-hypertensive drugs like calcium channel blockers and ACE inhibitors which may ameliorate arterial compliance .CfPWV was positively correlated to BP parameter . Ngim et al  in 1999,In our study, PWV was positively correlated to age. Avolio et al  showed tIn this study we found a statistically significant link between increased rigidity of central arteries and an elevated heart rate, a major risk factor of cardiovascular diseases. In an observational study, Sa Cunha et al  in 1997,In our study, cfPWV was positively correlated to central Augmentation. Yasmin and Brown  in 1999 cfPWV was significantly dependent on LVH. Darne et al in 1989  and GireLooking at the means in the normotensive, hypertension stage 1, 2 and 3 groups, There was a statistically significant increase in the mean Age and mean of all hemodynamic parameters  across the groups with increase severity of hypertension. The decrease in arterial compliance across the groups with increasing hypertension stage may be due to the fact that, increase in blood pressure causes endothelial injury leading to impaired nitric oxide availability which has a vital role in vasodilation thereby favouring increase arterial stiffness. On the other hand; BMI, FBS, HDL-C, TC and TG showed no statistically significant increase in their means across the different groups.cfPWV was not significantly related to total cholesterol, triglycerides and HDL-C. Our results were similar to those of EJ Kim et al  who in 2This study suggests that arterial compliance decreases with increase severity of hypertension, indicating a higher risk of developing cardiovascular events in severely hypertensive patients.Arterial compliance decreases with age and this decrease is accelerated by hypertension;Arterial Compliance is an independent predictor of cardiovascular Events;Arterial stiffness is associated with an increase in Systolic Blood Pressure and Pulse Pressure, raising left ventricular afterload and myocardial work, leading to hypertrophy with reduced coronary perfusion, which may result in sub-endocardial ischemia.Arterial Compliance in hypertensive patients in a typical Sub-Saharan African setting;Arterial compliance in different stages of hypertension;Arterial compliance in Sub-Saharan African patients with left ventricular hypertrophy.


The 8-item Morisky Medication Adherence Scale (MMAS-8) is reliable and valid in patients with hypertension, but to our knowledge validity has not been established for patients with asthma. The aim of the study was to determine the criterion validity of the MMAS-8 in patients with asthma. In the cross-sectional study patients older than 12 year were recruited when dispensed asthma medications in community pharmacies. Criterion validity of the scale was assessed through associations with asthma control and quality of life. Asthma control was assessed by the Asthma Control Test (ACT) and quality of life was evaluated by the Saint George Respiratory Questionnaire (SGRQ). A total of 208 patients  were included in the study. Almost all patients were prescribed inhaled corticosteroids (96%). Asthma was not controlled in 37% of the patients and 22% experienced at least one exacerbation requiring emergency room visit, hospitalization or treatment with oral corticosteroid therapy in the previous year. The 8-item MMAS was significantly associated with asthma control and quality of life. Patients who scored 8 points, <8 to >6 points and ≤6 points on the scale were considered to have high, medium and low adherence, respectively. High, medium and low adherence was found in 53%, 23% and 24% of the patients, respectively. As adherence improved from low to medium or from medium to high, the odds of asthma control increased by 1.7 times . Patients with high and medium adherence had SGRQ scores that were 6.1 and 5.3 points lower, respectively, compared with patients with low adherence. The MMAS-8 was found to be valid for assessing medication adherence and predicting health outcomes in patients with asthma. Poor adherence to long-term therapies significantly undermines the effectiveness of treatment and represents an important issue in disease control in terms of both the patients’ quality of life and health economics . For patTackling medication nonadherence is a difficult task, starting with the first step, which is detecting nonadherence in clinical practice. Several different ways exist for measuring adherence to medication regimens. Each approach has advantages and disadvantages, and no method is considered the gold standard. Direct approaches, such as observed therapy or measurement of concentrations of a drug or its metabolite in blood, are expensive and burdensome to the patient and the health care provider. Consequently, indirect methods such as pill count or use of validated questionnaires are more suitable for use in clinical practice . One of The study sample comprised patients who met the following inclusion criteria: (I) had been prescribed at least one controller medication to treat asthma, including inhaled glucocorticoid (IGC), fixed combination of IGC and long-acting β agonist (IGC/LABA), leukotriene modifiers or systemic glucocorticoids; (II) were undergoing regular asthma therapy and had received ≥ 2 prescriptions; (III) stated they have asthma; (IV) were aged 12 years or older; and (V) were able to understand and communicate in the Slovenian language.The sample size was calculated based on the assumption of 59% adherence, which comes from a systematic review of the literature. A total of 119 patients were required for the study, taking a 15% relative margin of error for the adherence estimation into account.We performed a cross-sectional study in 16 community pharmacies across Slovenia in September 2014 and February 2015. Eligible patients were invited to participate by community pharmacists when asthma medication was being dispensed. Those who agreed to participate were directed to a researcher who provided information about the study and obtained written consent from each patient. During the introductory interview the researcher collected patients’ demographic characteristics as well as information about asthma treatment and exacerbations in the past year. After the introductory interview, patients self-completed questionnaires to evaluate medication adherence, asthma control and quality of life. Patients were included in the analysis based on the self-reported diagnosis of asthma. Information about asthma medication and other medications that had been dispensed was also obtained from the pharmacy claims data. Moreover, to validate the data from patients regarding diagnosis, asthma treatment and exacerbations in the past year, information was obtained from participants’ GPs.Medication adherence was assessed using the MMAS-8. The scale consists of eight questions, first seven items having a dichotomous answer (yes/no) that indicates adherent or non-adherent behaviour. For item 8, a patient can choose an answer on a 5-point Likert scale, expressing how often happens that a patient does not take his medications. MMAS-8 scores can range from 0 to 8 points. Cut-off values for categorizing patients as having a high, medium or low adherence rate were chosen based upon association with asthma control and quality of life. The original MMAS-8 was translated to Slovenian language through forward/backward translation and tested for content validity in a pilot study.Health outcomes included asthma control, quality of life and asthma exacerbations in the past year. Asthma control was evaluated by patients’ self-completion of the Asthma Control Test (ACT). The ACT is a reliable, valid tool that helps physicians identify patients with uncontrolled asthma in a clinical setting . The queQuality of life was assessed using the Saint George Respiratory Questionnaire (SGRQ), which specifically measures health-related quality of life in patients with asthma and other airway obstruction diseases. The questionnaire has been shown to be reliable and valid . It contAsthma exacerbation was defined as the patient having had at least 1 event that indicated significant worsening of asthma control, namely, emergency room visit, hospitalization or therapy with oral glucocorticoids. Data about exacerbations in the 12 months prior to study participation was obtained during the introductory interviews. Information about the exacerbation was also obtained from GPs, but patient-provided data were used for analyses because of possibly incomplete data in the medical records.Criterion validity of the scale was assessed through associations with asthma control and quality of life. The association between medication adherence and asthma control was estimated using a logistic regression model with two categories of asthma control according to ACT score (controlled and uncontrolled). Additionally, the logistic regression model was adjusted for potential confounders including gender, age, living alone or sharing a household, education, smoking status, the number of concomitant medications for other diseases, possession of an asthma self-management plan, exacerbation in the past year and medication adherence . The association between medication adherence and health-related quality of life was estimated using linear regression modelling with quality of life  as the dependent variable. The same independent variables as in the logistic regression model were included. The association between occurrence of asthma exacerbation and asthma control or quality of life was evaluated by Mann-Whitney test. All statistical analyses were performed using the statistical package IBM SPSS v 23.0. A p<0.05 was considered statistically significant.Written informed consent was obtained from all participants. For patients under 18 years old, written consent was also given by their parents. The study was approved by the National Medical Ethics Committee of the Republic of Slovenia.A total of 208 participants met the inclusion criteria. The mean (SD) age of the patients was 56 (19.6) years, and the majority were female (59%). The patient characteristics are presented in Asthma was partially controlled and completely controlled in 21% and 43% of the patients, respectively. More than a third (37%) of patients had uncontrolled asthma. The ACT score ranged between 6 and 25, with a mean (SD) of 19.7 (5.1). The SGRQ total score ranged between 0 and 87.9, with a mean (SD) of 33.3 (21.8). The highest scores were obtained in the domain of symptoms , followed by activity  and impacts . Exacerbation that required emergency room visit, hospitalization and treatment with oral corticosteroid therapy was experienced in 9%, 9% and 14% of the patients, respectively. At least one of these events was experienced by 22% of the patients in the past year. Patients with at least one exacerbation in the past year had significantly worse asthma control  and quality of life .MMAS-8 scores ranged between 0.75 and 8 points, with a median of 8. Patients’ responses showed that the most common reason for non-adherence was forgetfulness, followed by skipping doses when feeling better and other reasons besides forgetfulness.Cut-off values for categorizing patients as having low, medium or high adherence were chosen based on the relation to asthma control and quality of life . LOESS c2 was 0.039. Based on these results, a linear relationship between categorized medication adherence and the occurrence of controlled asthma was assumed in subsequent analysis.The relationship between medication adherence and asthma control was evaluated using univariable logistic regression. Patients with high adherence had 2.3 times higher odds  for having controlled asthma compared to those with low adherence (reference), while patients with medium adherence had 1.3 times higher odds  compared to the reference. Nagelkerke R2.The multiple logistic regression model showed a statistically significant relationship between medication adherence and asthma control . As adheThe linear regression model showed medication adherence to be significantly associated with quality of life . PatientTo our knowledge this study is the first to determine criterion validity of the MMAS-8 in patients with asthma. The relationship between medication adherence and health outcomes might differ for asthma compared with hypertension or other chronic health conditions because of the specifics of the disease and the required therapy. Only if a tool for measuring adherence is validated can it be regarded as useful in clinical practice for specific patient populations. The cut-off values for defining high, medium and low adherence rates in this study differed from previous studies. In contrast to previous studies, the cut-off values in the current study were based on the association between adherence and asthma control as well as quality of life in patients with asthma. In contrast with Morisky’s cut-off values, a score of 6 points was assigned to the low adherence rate category because these participants were more similar to those with low, rather than medium adherence rates in terms of ACT and SGRQ scores.A majority of patients (76%) were found to have a high or medium adherence rate, while a quarter did not adhere to their asthma therapy. Data on medication adherence in asthma patients as assessed by MMAS-8 is scarce in the international literature. Moreover, in studies conducted so far, cut-off values that were previously established for patients with hypertension were used. The proportion of adherent patients found in the present study is comparable to a study from Turkey (74%) . HoweverThe quality of life of asthma patients in this study was comparable to that reported by other studies . As in sThe study showed that more than a third of the patients (37%) do not have asthma control. In a large cross-sectional survey in five European countries and the United States, a greater proportion of patients (43%) without asthma control was found . In anotBetter asthma control is associated with fewer exacerbations that may require emergency room visits and hospitalisations . Twenty-Few patients with a very low MMAS-8 score were found to have a high ACT and a low SGRQ score. In some cases this pattern might be explained by “reverse” medication adherence. After achieving good disease control and quality of life, a patient may decide to adjust therapeutic regimen according to their own judgment, leading to poor medication adherence. Boland et al. found an indication of reversed causality in patients with chronic obstructive pulmonary disease (COPD) . ImproveThis study should be interpreted in light of its limitations. First, the study sample consisted of individuals with self-reported asthma. Data about diagnosis was also provided by patients’ GPs. We found a great agreement between patient-obtained and GP-obtained information regarding an asthma diagnosis. In 90% of the cases, patients’ self-reported asthma was confirmed by their medical records. The remaining patients had asthma-COPD overlap syndrome (5%), COPD (3%) or other respiratory condition (2%). We obtained data for 42% of the patients. Information from medical records was not available for the other participants because they did not approve access to their records or because of a lack of their GPs’ cooperation. All enrolled patients were included in the analysis. However, the relation between medication adherence and health outcomes might differ if patients have other diagnoses. Second, adherence can be overestimated when evaluated by self-report. Therefore, the result might overestimate the true medication adherence among asthma patients in Slovenia. We tried to minimize social desirability bias by administering the questionnaire to the patient in the presence of a researcher and not the pharmacist or a patient’s doctor. Data about symptoms and medication use were based on patient recall over a period of 1 month or 1 year, which could potentially introduce recall bias.The study shows that medication adherence is associated with asthma control as well as with quality of life in patients with asthma. The 8-item MMAS is valid for assessing medication adherence in patients with asthma. Adherence as assessed by the scale can predict health outcomes in patients with asthma.


Raised intracranial pressure is a common problem in a variety of neurosurgical conditions including traumatic brain injury, hydrocephalus and intracranial haemorrhage. The clinical management of these patients is guided by a variety of haemodynamic, biochemical and clinical factors. However to date there is no single parameter that is used to guide clinical management of patients with raised intracranial pressure (ICP). However, the role of ICP indices, specifically the mean pulse amplitude (AMP) and RAP index , as an indicator of true ICP has been investigated. Whilst the RAP index has been used both as a descriptor of neurological deterioration in TBI patients and as a way of characterising the compensatory reserve in hydrocephalus, more recent studies have highlighted the limitation of the RAP index due to the influence that baseline effect errors have on the mean ICP, which is used in the calculation of the RAP index. These studies have suggested that the ICP mean pulse amplitude may be a more accurate marker of true intracranial pressure due to the fact that it is uninfluenced by the mean ICP and, therefore, the AMP may be a more reliable marker than the RAP index for guiding the clinical management of patients with raised ICP. Although further investigation needs to be undertaken in order to fully assess the role of ICP indices in guiding the clinical management of patients with raised ICP, the studies undertaken to date provide an insight into the potential role of ICP indices to treat raised ICP proactively rather than reactively and therefore help prevent or minimise secondary brain injury. The accurate measurement of dynamic intracranial pressure is complex. Although the measurement of ICP is an important factor in determining both the clinical management and outcome of patients with several neurosurgical conditions, recent studies have looked at the use of measuring the compensatory reserve as a possible predictor of clinical outcome and how it could be used to guide clinical management. Czosnyka et al. designed a coefficient between the mean intracranial pressure and the ICP mean pulse amplitude, the RAP index, as a potential descriptor of neurological deterioration in traumatic brain injury (TBI) patients . Since tThis review will give an overview of intracranial pressure including its monitoring and examine the evidence from previous studies regarding the potential role of both the RAP index and the AMP as a marker to guide clinical management.Intracranial pressure (ICP) is derived from the circulatory dynamics of the CSF and cerebral blood flow that occur within the rigid intracranial compartment . This reUnder normal circumstances ICP is kept within a certain range primarily with cerebral auto-regulation, which is itself dependent on cerebrovascular reactivity. The fact that true ICP is influenced by many factors and has both inter- and intra-patient variability makes accurate measurement of true ICP difficult. For example, the value of ICP is affected by age, body posture, time of day as well as the clinical condition of the patient. However a normal range of ICP has been established in order to address the multi-variant nature of ICP, as well as general interventional thresholds for ICP in different neurosurgical conditions.Intracranial factors that can affect ICP can be broadly categorised into three main intracranial areas: disturbances in the dynamics of CSF; the expansion of intracranial tissue itself; the expansion of blood volume Fig. . Disturb2 in patients with TBI . This was first introduced as a potential descriptor for neurological deterioration in TBI patients. It was subsequently used to characterise the pressure-volume compensatory reserve in patients with hydrocephalus. The RAP index has been shown to be a reliable measure of the compensatory reserve; however in more chronic states the cerebrospinal elasticity coefficient (E1) and AMP have been shown to express the compensatory reserve better –16. ThisThe numerical value of the RAP index can range from +1 to -1 Fig. . An RAP When the RAP index rises to +1, there is synchronisation between the rise in AMP and the rise in ICP. In terms of the pressure-volume relationship, a small rise in intracranial volume results in a larger rise in ICP.If the ICP continues to rise, the RAP index value becomes -1. At this point the AMP has an inverse relationship to ICP—the AMP decreases as the ICP continues to rise. At this stage the compensatory reserve is exhausted and cerebral auto-regulation collapses. It is at this point that cerebral ischaemia- induced irreversible brain damage will likely occur and, ultimately, brain herniation. Note however that cerebral ischaemia will rise in a gradient fashion as the ICP continues to rise.More recent studies have researched the potential role of the RAP index as a marker to guide clinical management , 19, 20.The ICP mean pulse amplitude relates to the pressure fluctuations of the ICP during the cardiac cycle. The AMP increases as the ICP rises; however once the critical ICP has been reached there will be subsequent derangement of cerebrovascular reactivity and AMP will decrease.More studies are beginning to research the use of AMP both as a more accurate marker of the true ICP, in place of the mean ICP, as well as a tool to help guide the clinical management of patients , 22. TheAlthough it has been demonstrated that AMP is refractory to baseline effect errors, further study into what other factors could potentially affect AMP, and therefore its usefulness in clinical management, must be investigated. This includes investigating the extent to which any factor influences AMP across the different pathological conditions. For example, studies have shown that AMP is more dependent on pulse changes in arterial blood volume in patients with TBI than in those with normal pressure hydrocephalus .Further studies have assessed the AMP in relation to clinical outcome and have shown that a lower AMP is associated with a better outcome following TBI  and surgOne proposed advantage of using AMP instead of the RAP index is its ability to reflect the dynamic nature of true ICP without influences from static values, which have the potential to be affected by other dynamic factors such as baseline effect errors. However one limitation of using the AMP is the ability of researchers to accurately analyse the multi-variant and dynamic nature of the ICP waveform in an objective way. Studies have looked at more sophisticated algorithms of objectively analysing ICP wave parameters, including AMP, with a degree of success.For example, it has been shown that the time domain method is superior to the frequency domain method for ICP waveform analysis since the frequency domain method can underestimate the AMP in the presence of heart rate variability or if the waveform has a high harmonic distortion . Holm etMore recent studies have used more sophisticated algorithms to analyse the individual ICP waveform peaks  with a high degree of accuracy.However the successful clinical use of such algorithms for accurate, objective analysis of Lundberg waves, in particular B waves, has still to be proven , 29. TheBaseline effect errors (BEEs) are spontaneous shifts in baseline pressure that occur during continuous ICP monitoring. They were first described by Eide in 2006  when monBaseline effect errors can be caused by a variety of factors ranging from all components of the ICP monitoring system, including the sensor, cable, display and transducer, to imperfect fluid connection caused by debris or air bubbles.In relation to ICP indices, this is very important since any ICP index that includes mean ICP in its component will be affected, including the RAP index. However since the AMP is included in the RAP index, the effect of BEE is less pronounced in the RAP index than in the mean ICP. Therefore, any ICP index that is solely based on static pressure measurements can expect to be affected by BEE.The ability of baseline effect errors to influence the value of the RAP index, and therefore the true nature of the patients underlying intracranial compensatory reserve, has the potential to affect clinical management. It has been shown that significant differences in the RAP index correspond to the occurence of BEEs and that the differences are of a magnitude that could affect patient management . For exaBaseline effect errors also have the potential to affect cerebral perfusion pressure, through the effect it has on intracranial pressure . For example, if BEEs are caused by an imperfect fluid connection as a result of debris or air bubbles, this could result in a fall in CPP if the ICP rises beyond the limits of cerebral auto-regulation.Raised ICP is defined as a sustained ICP of greater than 20 mmHg. However the thresholds for management depend, in part, on the underlying cause. At present there is no single parameter that has been proven to be the best marker to guide the clinical management of raised ICP. Due to the multi-variant nature of ICP between conditions and between patients it is doubtful whether it is possible to have one single parameter that can successfully guide the clinical management. The current treatment options for raised ICP range from initial medical management involving general physiological homeostasis to management, which involves more radical interventions including endotracheal intubation, barbiturate coma, and surgical evacuation or decompression. The ultimate goal of treating raised ICP is to prevent or minimise secondary brain injury by restoring intracranial homeostasis in order to reach optimum cerebral function.General physiological homeostasis involves controlling several parameters, which include blood pressure, serum osmolarity, temperature and blood glucose, as well as maintaining adequate partial arterial pressures of oxygen.Blood pressure control has an important role in the treatment of raised ICP; however the exact treatment thresholds required to achieve optimum cerebral function in the setting of raised ICP remains ambiguous. This is in part due to the fact that patients with raised ICP often have several contributing factors. An important consideration in the control of a patient’s blood pressure within the context of raised ICP is the fine balance required between under-treatment of hypertension, and therefore increasing the possibility of haemorrhage or mass effect, and over-treatment of hypertension, and thus increasing the risk of ischaemia-induced damage to cerebral function. One therapy that aims to reduced the risk of ischaemia-induced cerebral damage is cerebral perfusion pressure (CPP)-guided therapy. This therapy aims to maintain CPP greater than 70 mmHg in order to minimise ischaemia, which is induced by compensatory cerebral vasodilation –36. HoweAnother approach used to control blood pressure is the “Lund Protocol” in which a disruption of the blood-brain barrier is assumed. This places emphasis on reducing the hydrostatic forces whilst increasing the osmotic forces to maintain fluid within the intravascular compartment and thus prevent vasogenic oedema .In addition to ensuring adequate CPP, oxygen levels must be adequately maintained, particularly in patients who have suffered TBI or intracerebral haemorrhage (ICH) in which the presence of pericapillary oedema may reduce the diffusion ability of oxygen to cross the blood-brain barrier.Another important therapeutic target in raised ICP is glycaemic control. It has been shown in several studies that hyperglycaemia increases both the morbidity and mortality in patients with several neurological conditions including ICH and traumatic brain injury (TBI) , 43, 44.Minimising pyrexic episodes in patients with raised ICP is very important as an increase in temperature results in a rise in the cerebral metabolic rate, which can precipitate ischaemia directly, or indirectly through oedema. This is evident by studies that have shown, through experimental models of brain injury, the detrimental effect fever has on clinical outcome , 47. FurElevation of the head to 30° improves jugular venous outflow and reduces ICP. However caution must be used in patients who are hypovolemic as elevation in these patients could result in a fall in CPP, which could have significant effects on cerebral function, depending on the volume and duration of the drop in CPP.Analgesia is important in order to minimise the potential harmful effect on ICP. Sedation may be used in order to appropriately ventilate patients who are unable to achieve adequate ventilation on their own. However this must be titrated with care in order to minimise the detrimental effect it may have on the clinician’s ability to clinically evaluate the patient.Patients who fail to respond to analgesia and sedation, and who still have intracranial hypertension, may benefit from neuromuscular blockade as seizure activity causes a rise in intra-thoracic pressure, which can obstruct cerebral venous outflow resulting in an increase in ICP. One of the drawbacks of this therapy is the masking of seizure activity.One of the most important physiological properties that must be carefully balanced in patients with raised ICP is serum osmolarity. Both mannitol and hypertonic sodium chloride are the most common agents used.Mannitol acts through two mechanisms. First, it increases intravascular volume and results in a reduction in blood viscosity. The intravascular volume expansion results in an increase in cardiac pre-load and thus an increase in CPP. Through cerebral auto-regulation, compensatory cerebral vasoconstriction occurs, which reduces the ICP. Second, mannitol draws water from the extracellular cerebral tissue into the plasma, thereby reducing cerebral oedema. However if the blood-brain barrier is disrupted, care must be taken to avoid worsening any cerebral oedema.Hypertonic saline (HTS) can be used because of its osmotic effects as a result of its hypertonicity compared to extracellular cerebral tissue. However hypertonic saline also has haemodynamic, vaso-regulatory, immunological and neurochemical effects . One recThe use of steroids in raised ICP is limited to treat vasogenic oedema where the underlying cause is primary and metastatic tumours. Steroids have shown no benefit in TBI or spontaneous intracerebral haemorrhage , 51.In some studies they have been shown to have a detrimental effect , 53.Steroids can also be used in CNS infection; however care should be taken in intracerebral abscesses as they can retard the encapsulation process, worsen necrosis and reduce the permeability of antibiotics.2 influence on cerebral auto-regulation provides one of the most effective methods for rapidly lowering ICP. This is achieved through ventilation, which allows the clinician to lower CO2 levels and induce compensatory cerebral vasoconstriction and thus reduce the ICP. One caveat to using this property of CO2 is the ability of the extracellular space of the brain to accommodate the associated changes in pH, and thus once CO2 levels begin to normalise a compensatory increase in ICP can occur. Therefore the main limitation of hyperventilation is its short therapeutic duration.The use of COCSF drainage is an effective method of lowering ICP in patients who have an intraventricular catheter to monitor ICP . This isThe use of barbiturates to induce a coma state is only suitable for refractory raised ICP. Barbiturates work by reducing the cerebral metabolic activity and thus reduce cerebral blood flow. However there are several potential side effects of this therapy including hypotension , 58. TheThe role of decompressive craniotomy in the presence of a compressive pathology  is well documented. However its role in the absence of a compressive pathology is less well documented.A number of studies, including the International Surgical Trial in Intracerebral Haemorrhage (STICH) trial, showed no real benefit in treating supra-tentorial ICH with craniotomy. Of those who were treated, a higher Glasgow Coma Scale (≥9) and a clot within 1 cm of the surface were associated with a 29 % relative benefit in functional outcome when compared with medical management –61. FurtHowever these studies did not include patients where the haemorrhage was located in the cerebellum. Further studies that did look at cerebellar ICH provided the conclusion that large cerebellar haemorrhages that either compress the brain stem or obstruct the fourth ventricle should be surgically removed as soon as possible , 64–69.With regards to the timings of when surgery should be performed, there is no clear guidance on this . The mosFurthermore, bifrontal decompressive craniectomy in post-traumatic intracranial hypertension has been associated with significant reductions in AMP and has increased the compensatory reserve and therefore led to an improvement in the patient’s RAP index.  AlthoughICP indices were introduced to help improve the diagnostic value of ICP. One of the main reasons for using ICP indices in patients with raised ICP is to allow clinicians to treat raised ICP proactively rather than reactively. The RAP index has already been used as a descriptor of neurological deterioration in TBI patients. However it has yet to be used to guide clinical management. One of the main reasons the RAP index may not be a suitable marker to guide clinical management is its susceptibility to baseline effect errors. Given the dynamic nature of ICP in conjunction with the varying causes responsible for baseline pressure effects, it is little surprise that the use of a static value of ICP (the mean ICP) may not provide the most accurate measure of true, global ICP. One appeal of using AMP instead of the RAP index as a marker for guiding clinical management in patients with raised ICP is the fact that the AMP has been shown to be uninfluenced by baseline effect errors. However one limitation of using AMP, and other parameters of the ICP waveform, as a marker to guide clinical management is the lack of appropriate tools to accurately analyse the ICP waveform objectively. However more sophisticated algorithms are making this less of a problem, such as the MOCAIP  method , which hIt is clear from the literature to date that the use of either the RAP index or the AMP as a marker to guide clinical management has its limitations.However given the complexity of ICP, and the heterogeneity of the intracranial conditions that it is affected by, it is difficult to imagine that the RAP index or AMP alone will allow the clinician to make an informed decision that will optimise patient outcome, without other factors being involved including patient history, examination findings, basic neuro-imaging, haemodynamic and biochemical markers.The interval between the onset of raised ICP and just prior to the onset of cerebral damage is where ICP indices could prove most beneficial Fig. .Fig. 5TRaised ICP is in essence the result of cumulative molecular interactions, which establish three-dimensional multi-variant vectors within the intracranial cavity. This in turn generates pressure gradients that are exacerbated by the rigidity of the encompassing skull.A sound understanding of this complexity of ICP and how it is affected by intracranial conditions is essential to achieve successful clinical outcome. In addition, as the intracranial cavity is essentially a highly dynamic and organised collection of cells and molecules, the use of mathematical and statistical modelling as a tool to accurately quantify and interpret intracranial dynamics is important.The important role of minimising disturbances in ICP on a patient’s clinical outcome is evident and several studies have improved the ability to use certain ICP parameters to help achieve this. However it remains unclear which of these parameters, specifically, is best in predicting clinical outcome. Both the RAP index and AMP are currently used as markers for certain intracranial physiological parameters; however neither have yet been used as a marker to guide clinical management. Further studies into this potential role of the RAP index and AMP, including current barriers, are warranted.


Background. No study has assessed the possible involvement of GGC androgen receptor (AR) polymorphism in sexual function. Our aim is to evaluate the association between CAG and GGC AR polymorphisms in this function. Methods. We retrospectively examined eighty-five outpatients. Clinical, biochemical, and genetic parameters were considered. Sexual assessment was performed using the International Index of Erectile Function (IIEF) which evaluates erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), and overall satisfaction (OS). Results. In the whole sample, CAG repeats were inversely correlated with EF, OF, and total IIEF-15 score, whereas GGC tracts did not show any significant correlation with sexual function. CAG relationship with IIEF items retained significance only in the eugonadal but not in the hypogonadal cohort. On the other hand, GGC tracts were not found to be significantly correlated with IIEF variables in either eugonadal or hypogonadal subjects. In eugonadal subjects, logistic regression pointed out that a higher number of CAG triplets were associated with lower values of EF, OF, SD, OS, and total IIEF independently from other confounders. Conclusions. GGC polymorphism seems not to exert any influence on sexual function, whereas CAG polymorphism appears to affect sexual parameters only in eugonadal subjects. Testosterone, along with its metabolite dihydrotestosterone, exerts its effects by binding to the androgen receptor (AR) –3. CAG aMany works have assessed the relationship between androgen receptor CAG and GGC polymorphisms and clinical parameters related to testosterone activity  , 12–14. Therefore, the aim of the present study is to perform an evaluation of the possible association between the two AR polymorphisms and sexual function in a cohort of patients consulting for sexual dysfunction.This retrospective study evaluated outpatients consulting at our andrological unit between 2010 and 2016 for sexual dysfunctions. Selection of subjects was made on the basis of patient characteristics present at the moment of their first evaluation. Inclusion criteria were (1) absence of important systemic diseases, both previous and ongoing, apart from late-onset hypogonadism or type 2 diabetes mellitus; (2) availability of all the considered clinical, biochemical, and genetic parameters; (3) sexual relationship since at least 1 year before the visit; and (4) absence of previous investigation or treatment for sexual dysfunction. Exclusion criteria were (1) ongoing pharmacological treatment for hypogonadism; (2) presence of endocrinological disorders other than late-onset hypogonadism or type 2 diabetes mellitus; (3) alcohol or drug dependence; and (4) psychiatric diseases.Late-onset hypogonadism was defined according to previous accepted biochemical criteria  together with signs and symptoms consistent with hypogonadism , 21.Eighty-five patients were finally eligible for this retrospective study.In order to determine hypogonadism or eugonadism, at least two measurements of testosterone were performed.All the clinical and biochemical parameters were performed in the context of the clinical work-up. On the contrary, genetic analyses were carried out in the context of previous research protocols. Proper communication of this retrospective analysis was given to our institutional review board, which approved it.The following clinical parameters were considered: age and body mass index (BMI). BMI was calculated according to standard methods previously described . PresencThe following biochemical parameters were considered: follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, calculated free testosterone, sexual hormone-binding globulin (SHBG), and estradiol. Blood samples for FSH, LH, total testosterone, SHBG, and estradiol were taken in the morning after overnight fast, and their assay was carried out as previously specified .The normal reference ranges for the biochemical parameters studied were the following: FSH, 1.7–6.9 IU/L; LH, 1.6–10.0 IU/L; total testosterone, 3–8.5 ng/mL; SHBG, 20–60 nmol/L; and estradiol, 11–47 pg/mL.http://www.issam.ch/freetesto.htm) [Free testosterone was calculated according to Vermeulen's formula (at sto.htm) .Sexual assessment was evaluated using the International Index of Erectile Function-15 (IIEF-15) which provides a score for erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), and overall satisfaction (OS) , 27. TheGenetic parameters were evaluated as previously described . BrieflyU test because of the skewed distribution of data. Fisher's exact test was adopted for comparisons between the frequencies of the two groups. Spearman correlation was performed to analyze the relationships of clinical, hormonal, and genetic variables with sexual parameters. Continuous variables which were significantly correlated with sexual parameters at bivariate correlations or categorical clinical variables  which differed in sexual profile were entered into logistic regression models in order to assess their independent association with sexual parameters. In order to fit with logistic regression, sexual parameters (dependent variables) were dichotomized according to their median value. Dependent variables are categorized as 0  and 1 .Shapiro-Wilk's test was applied to verify the normal distribution of the continuous variables. Continuous variables are presented as mean and standard deviation if normally distributed or as median and interquartile range if not normally distributed. Comparisons between the two groups were performed with Mann–Whitney's p < 0.05. Statistical analyses were performed using SPSS 16 package .Significance was set at Table In the whole sample, age was negatively correlated with all sexual function variables, whereas total testosterone and estradiol levels showed positive correlations with all sexual parameters Table . Of noteWe subsequently evaluated the same correlations categorizing the cohort according to gonadal status Table . In hypoAmong the considered clinical comorbidities, in the whole sample, only diabetes mellitus influenced sexual function as diabetic subjects showed a worse sexual function than nondiabetic ones Table . On the In eugonadal subjects, logistic regression models were performed in order to establish the independent contribution of CAG repeat polymorphism on sexual function Table . After aIn hypogonadal subjects, logistic regression was not performed since, at bivariate correlations, the genetic parameters were not found to be significantly correlated with any of the sexual parameters.This study confirms the view  that, inOn the other hand, we found that longer CAG polymorphism was significantly associated with worse sexual parameters, although this finding was evident only in eugonadal subjects. Our results are in line with those reported by Liu et al.  who recen = 15) with hypogonadotropic hypogonadism, a very rare form of male hypogonadism [Only two reports have evaluated the effects of CAG polymorphism on conditioning sexual function recovery after testosterone therapy in hypogonadal male patients. They both found that shorter CAG length is associated with a greater improvement of several aspects of the IIEF questionnaire , 30. Howgonadism . Moreovegonadism .The findings of the present work support the model of androgen effects conceived by Zitzmann . In factBefore concluding, it should be acknowledged that because the study population is retrospectively enrolled from an outpatient clinic and the patient number is relatively small, a selection bias could exist and the results may not be extended to the general population. This is a study limitation and further large epidemiologic studies will be needed to confirm our preliminary findings.In conclusion, our work has ruled out the influence of GGC androgen receptor polymorphism on sexual function regulation in both hypogonadal and eugonadal subjects. On the other hand, we confirmed the role of CAG polymorphism in influencing sexual parameters in eugonadal subjects but not in hypogonadal ones. However, future research should explore the hypothesized possible influence of cofactors , 32 on t


To analyze the relationship between dietary glycemic index (GI) and retinal microvasculature in adults.This was a cross-sectional study of 300 subjects from the EVIDENT II study. Dietary GI was calculated using a validated, semi-quantitative food frequency questionnaire. Retinal photographs were digitized, temporal vessels were measured in an area 0.5–1 disc diameter from the optic disc and arteriolar-venular index (AVI) was estimated with semi-automated software.p = 0.014).AVI showed a significant difference between the tertiles of GI, after adjusting for potential confounders. The lowest AVI values were observed among subjects in the highest tertile of GI, whereas the greatest were found among those in the lowest tertile (estimated marginal mean of 0.738 vs. 0.768, In adults, high dietary GI implies lowering AVI values regardless of age, gender and other confounding variables.NCT02016014. Registered 9 December 2013.Clinical Trials.gov Identifier:  The glycemic index (GI) represents the relative rate at which blood glucose levels rise after consuming 1 g of a carbohydrate-containing food as compared to pure glucose .Accumulating evidence suggests that the development of CVD such as stroke could be predicted by retinal microvascular changes . RetinalThe purpose of this study was to analyze the relationship of dietary GI with retinal microvasculature in a sample of adults.A cross-sectional study was conducted with 300 subjects, as a sub-analysis of the EVIDENT II trial . The recProcedures for collecting sociodemographic and clinical data, obtaining analytical parameters and performing office blood pressure and anthropometric measurements have been reported in a prior publication .A food frequency questionnaire (FFQ) validated for Spain  was usedRetinography was performed using a Topcon TRC NW 200 non-mydriatic retinal camera , obtaining nasal and temporal images centered on the disc. The nasal image with the centered disc was loaded into an arteriolar-venular index (AVI) calculator developed for us , whose validation has been published elsewhere . We usedp < 0.05 was considered statistically significant.Continuous variables were expressed as the mean ± standard deviation, and qualitative variables as frequency distributions. We used a multivariate analysis based on the analysis of covariance (ANCOVA) method, to compare the retinal microvasculature variables between tertiles of GI. The model was adjusted for age, gender, total energy intake, body mass index (BMI), systolic blood pressure (SBP) and medical treatment . IBM SPSS Statistics for Windows version 23.0  was used. A value of 2 and 83 (27.7 %) were smokers. The proportion of patients treated with antihypertensive, antidiabetic and lipid-lowering agents was 20.7 %, 4.3 % and 14 %, respectively. The mean blood pressure (BP) was 121/74 mmHg, with a mean BMI of 27.3 Kg/m2 and a waist circumference of 92.9 cm. The median values of total cholesterol, triglycerides, serum glucose and HbA1c were 200.5 mg/dl, 99.7 mg/dl, 85.3 mg/dl and 5.4 %, respectively. The average total energy intake was 2547.9 ± 757.0 Kcal/day with a mean carbohydrates consumption of 274.7 ± 97.7 g/day and an overall GI of 47.8 ± 5.5. The mean AVI, calculated from a retinal arteriolar caliber of 100.8 ± 11.4 μm and a venular caliber of 134.6 ± 14.5 μm, was 0.76 ± 0.08. Table The mean age of the sample group was 51.6 years , of whom 77 (25.7 %) were hypertensives, 13 (4.3 %) were type 2 diabetics, 84 (28 %) had dyslipidemia, 73 (24.3 %) had a BMI higher than 30 kg/mp = 0.014). Furthermore, a tendency towards reduction of the arteriolar caliber among subjects of the highest tertiles of GI was revealed. A subanalysis was performed in hypertensive (n = 77) and dyslipidemic individuals (n = 84), using the same model adjustment than in the overall sample. We found the lowest AVI in the third tertile of GI (the highest) in dyslipidemic subjects. However the differences did not reach statistical significance (p = 0.085). Also, we have not found significant differences in hypertensive subjects (p = 0.500).In the multivariate analysis, AVI showed a significant difference between tertiles of GI, after adjusting for potential confounders. There were no differences in the case of the retinal arteriolar or venular caliber. As illustrated by Fig. The results of our study show that a higher dietary GI implies lower AVI values in a sample of adults, after multivariable adjustment. This suggests that the protective effect from low GI food consumption against vascular disease could partly explain the changes in retinal microvasculature. To our knowledge, high GI diets had never been linked to lower AVI values in the adult population. It has been postulated that a smaller AVI reflects generalized arteriolar narrowing and predicts the risk of CVD . These dWe conducted an analysis of covariance (ANCOVA) to control the effect of certain confounding variables that was not possible to control due to the type of the experimental design. Therefore, we believe that the results are consistent and independent of the influence of age, gender and other variables used in the model. Our findings indicate that dietary GI has a greater influence on retinal arteriolar-venular ratio than on arteriole or venule caliber separately. These data are similar to those collected by Lim et al. , who repThe limitations of our study include the fact that the cross-sectional design prevents the establishment of causal relationships between dietary GI and retinal microvasculature, GI was estimated using a self-administered questionnaire that had not been specifically developed to elucidate it and retinal microvasculature was assessed from two vessels (an arteriole and a venule) as described above.In conclusion, a high dietary GI implies lowering AVI values in adults regardless of age, gender and other confounding variables. Further longitudinal studies would be needed to confirm the observed relationship.


SBF), total blood volume of the finger (TBVF), pulse pressure (PP), heart rate (HR), systolic, and diastolic blood pressure (BP) were analyzed in 10 healthy young subjects in supine and upright positions. By lowering the arm in supine position, SBF decreased compared to its basal measurement, PR increased, and PP contracted, indicating arterial vasoconstriction that rise BP. TBVF increased, demonstrating an increment in venous volume. HR did not change, reflecting no action of the baroreceptor reflex. In upright position with lowered arm, there was an additional increase in BP variables, demonstrating vasoconstriction. Moreover, BP and HR showed oscillations at 0.1 Hz reflecting the entrance of the baroreceptor reflex. The action of gravity in a dependent limb in supine position induces a regional vasoconstriction and an increase of BP due to activation of the myogenic response, while the baroreceptor reflex or other neural factors do not appear to operate. In the upright position with the arm dependent, there is a further increase in regional vasoconstriction and BP with reciprocal changes in HR, indicating the entrance of the baroreceptor superimposed to the myogenic response. This study demonstrates that the myogenic and baroreceptor vasoconstriction can be separated in vivo.Myogenic vascular response is a form of systemic and regional vasoconstriction produced increasing the intra‐arterial pressure by gravity. Here, the vasoconstriction due to the myogenic response, induced by the gravitational action in a dependent limb, is separated from that caused by the baroreceptor reflex. Regional changes of skin blood flow ( It is widely accepted that when a normal subject assumes the upright posture there is a redistribution of the blood volume; from 600 to 800 mL are displaced to the abdomen and the lower extremities due to the action of gravity. As a consequence of the volume displacement, there is an abrupt fall in the blood pressure (BP) of about 40 mmHg (5.33 kPa) that is rapidly compensated, in about 20 to 25 sec, by the vasoconstriction of the arteries below the heart. Concomitantly, there is an increase in the heart rate (HR) of about 15 beats per minute, which is induced by the withdrawal of the vagal action and subsequently maintained by sympathetic discharges to the sinus node, thus increasing the cardiac output. There is a simultaneous increase from 80 to 100 mmHg (10.66–13.33 kPa) in venous pressure in the veins below the heart. This change is directly proportional to the distance from the veins of the lower limbs and the abdomen to the heart, specifically to the right atrium. The venous return to the right side of the heart is aided by the changes induced by the negative intrathoracic pressure , produced by inspiration and by the muscle contraction of the abdomen and muscles of the lower extremities (Wieling and van Lieshout The vasoconstriction of the arteries has been attributed to an activation of the baroreceptor reflex (BRR) that induces, as a consequence of the fall of BP at the carotid sinus and aortic receptors, a sympathetic discharge to the sinus node (cardiosympathetic BRR) and to the arterial and arteriolar vessels by the BRR (vasosympathetic reflex) Rowell . The comHowever, this classical model does not take into consideration the increase in BP induced by the pressure of gravity on the walls of the arteries and arterioles . Subjects underwent a complete physical examination by a medical doctor. They were healthy control subjects without a history of hypertension, diabetes mellitus, cardiovascular or peripheral vascular disease, peripheral, or central neurological disorders. They did not take antihypertensive, antidiabetic, sympathetic, anticholinergic, or adrenergic medications. They all had blood glucose levels below 92 mg/dL and normal muscle stretch reflexes.All the subjects provided written informed consent after the procedure was explained to them, emphasizing its noninvasive nature. The study was performed according to the Helsinki and Tokyo recommendations for human investigations and was approved by our institutional review board.°C. The skin temperature on the arm was kept between 34 to 36°C measured with an infrared thermometer .The room temperature was kept at 23Pulsatile arteriolar skin blood flow (SBF) and nonpulsatile total blood volume of the index finger (TBVF) were recorded with a red‐infrared photoplethysmograph. Red‐infrared photopletismography has been used in several studies for a long time Burton . Pulsati® sphygmomanometer model CE0297, México City, Mexico).Basal BP of each subject was assessed by routine sphygmomanometry after a 5‐minute rest both in a supine and in an upright position  to monitor multiple hemodynamic parameters, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean average blood pressure (MBP), pulse pressure (PP), heart rate (HR), interbeat interval (IBI), and total peripheral resistance (TPR). The signals were obtained with the probe positioned on the middle finger. The height sensor was disconnected from the device and the distance from the hand to the heart was measured manually with a measuring tape.Noninvasive short‐term measurements of BP were taken at each heartbeat using a PortapresIn humans, in the supine position, BP is the same at feet, head, and heart levels , and h is the distance from the heart  below the heart level and supported by a lever. Subjects were asked to make no muscle effort with the dependent arm.Supine position with one arm dependent. One arm was passively lowered by the researcher 45Standing position with one arm dependent. Subjects were asked to stand up as rapidly as possible, keeping the arm in the dependent position and with the same inclination as in the supine position.Standing position with the hand at heart level. Subjects were asked to return the previously dependent limb to the heart level.Supine position with the hand at heart level .sk), and the kurtosis (κ) , standard deviation (SD), skewness  region from 0.04 to 0.15 Hz, and in the high‐frequency (HF) region from 0.15 to 0.4 Hz. We calculated the slope of the power spectral density (PSD) by using a linear minimum squares approximation and the associated parameters LF/HF, P < 0.05.Differences occurring between maneuvers were assessed by ANOVA with the subsequent Sidak's multiple comparisons test. Statistical significance changes were defined as ® are shown in Figure Typical records of the noninvasive short‐term time series measurements of the PortapresThe photopletysmographic noninvasive temporal records of nonpulsatile TBVF and PP of a typical young subject during the five maneuvers are plotted in Figure Numerical results for the parameters of HR variability for the different maneuvers are summarized in Table P = 0.05 level  of the lowered arm from the heart. Even when in supine position, the PSD slope of SBP at a P = 0.05 level, statistically is not significantly different from the basal conditions . The pulse pressure widened from 40 ± 3 to 70 ± 4 mmHg , and in all the BP variables, in particular SBP increases 60 mmHg with respect to basal values. SBP becomes less correlated, as can be seen in the PSD Fig. , 6 and 7All the variables indicating vasoconstriction  returned in 3–4 beats to the previous value (before lowering the arm) and the TBVF also returned to its previous value of basal oscillation. When the subject is upright with his arm at the heart level, the amplitude of the pulsatile skin blood flow immediately increases, whereas the nonpulsatile blood volume decreases Fig. , going tWhen reassuming the supine position with the hand at the heart level, the pulsatile skin blood flow has some rebound increase in amplitude and the venous volume return to basal values making the return of all the variables to their basal values, including those reflecting vasoconstriction and those reflecting changes of BP and HR.h of the dependent arm to the heart level considered as the hydrostatic neutral point;the increase of BP was directly proportional to the distance the increase of BP was not associated with changes of HR and therefore not likely to be secondary to BRR activation or central command;there were no oscillations of BP at 0.1 Hz (characteristic of BRR activation). The peripheral resistance increased, the amplitude of the pulsatile SBF decreased, and the PP widened, indicating vasoconstriction. It was unlikely that an adrenergic stimulation could induce the arterial vasoconstriction because intensive study of this response has shown that it persists in the lower extremities with epidural blockade , the isolated regional changes of BP and the SBF induced by the gravity stress in the dependent arm. Assuming the upright position with the arm down (third maneuver), we analyzed the generalized vasoconstrictive changes of BP and SBF induced by the BRR superimposed to the gravity‐induced myogenic vasoconstriction, as the arm was kept lowered during the upright position. In all subjects, lowering the arm in the supine position induced a vasoconstriction response with an increase in SBP, DBP, and an important rise of regional peripheral resistances, and an increase of the PP. We also demonstrated that there was a decrease in the amplitude of the arterial pulsatile SBF due to vasoconstriction and an increase in the total volume of blood in the cutaneous vessels of the finger. In the second position, all these changes were regional as the BRR was not activated. This is suggested by the fact that the subjects remained in the supine position, and the changes of BP were not associated with reciprocal changes of the HR. The central command was not activated because the arm was lowered passively and the HR did not increase. Therefore, vasoconstriction was likely to be due to a local myogenic response induced by the pressure of gravity. The facts that militate for a myogenic response induced by gravity are:there is a further increase of BP that occurs when the subject stands up. It is known that in assuming the upright position, there is a generalized redistribution of the blood volume below the heart and a sudden fall of BP followed by BRR activation and generalized vasoconstriction Berne ,there are oscillations at 0.1 Hz that are characteristic of BRR activation, the BP fluctuates in a characteristic fashion on visual inspection (Mayer waves), and there is more variability of BP typical of reflex control, andthe HR increases in a reciprocal way to the increment of BP. There was an additional increase in peripheral resistances and a decrease in the amplitude of the pulsatile SBF indicating an increment of vasoconstriction.When the subject is upright with the arm dependent, there is a further increment of BP that is related to BRR activation. This response is superimposed to the already existing gravity‐induced myogenic vasoconstriction. The facts that support that there is BRR activation and sympathetic vasoconstriction when standing with the arm dependent are:All these changes were readily observed in our subjects. This is also supported by the last phase of the experiment: when the subject, while still standing, elevates his arm to the heart level, the BP in the arm abruptly descends due to the withdrawal of the gravity‐induced myogenic local response, whereas the BRR maintains the BP slightly above the basal level. The HR continues to increase with respect to its basal levels and the low‐frequency oscillations at 0.1 Hz persists. The regional peripheral resistance decreases and the amplitude of the SBF increases, demonstrating a reduction in arterial and arteriolar vasoconstriction. Lastly, when the subject lies down, with his arm at the heart level, the BP, HR, peripheral resistances return to basal values, as the BRR is not active and there is no gravity stress on the arm and finger at the heart level. The increase in venous pressure, arterial vasoconstriction, and in BP seems to be due, at least in part, to the action of gravity, as both, venous and arterial pressure are increased by gravity. The venous pressure at the feet has been shown to increase from 5 mmHg in supine position to 100 mmHg (13.33 kPa) in the upright position, whereas the SBP increases from 120 mmHg (15.99 kPa) in the supine position to 200 to 220 mmHg (26.66 to 29.33 kPa) in the upright position. Meanwhile, supine BP is approximately the same at the heart level, the head, and the feet because the gravitational vector does not act upon the arterial and venous system either below or above the heart Berne ., in healthy young humans. MVR was discovered by Bayliss The important finding of our experiment is the demonstration that it is possible to separate or segregate the myogenic vascular response (MVR) induced by gravity and the vascular response induced by the BRR, in vivoLimitation of the study: Although the generalized BRR was assessed by HR variability, we also used the changes on the SBP and the spectral analysis that relates the sympathetic activity with baroreflex activation at 0.1 Hz (Mayer waves). One limitation of this study is that, as a noninvasive approach was taken, we could not record the muscle sympathetic nerve activity. This can be done in a future study, in order to characterize with some other method, the entrance of the BRR.We are bipeds, with our heads above our heart that have to live two‐thirds of our lives with our circulatory system counteracting the action of gravity. In fact, it is likely that the BP, in microgravity conditions, is the same in all regions of the body, no matter the position of the body, as the BP under this condition, is a function only of the cardiac output as all the vessels are vasodilated (Norsk et al. The vascular myogenic response is thought to be present in the kidney, the brain, and the coronary arteries (Davis and Hill The authors have no conflict of interest to report.