The worldwide epidemic of diabetes and obesity has resulted in a rapid upsurge in the prevalence of metabolic syndrome (MetS). MetS makes the individual liable to endothelial dysfunction which can initiate sexual dysfunction (SD). This study assessed the association between MetS and SD among clinically diagnosed diabetic subjects in Tema, Greater Accra Region of Ghana.Sexual functioning was assessed using Golombok Rust Inventory of Sexual Satisfaction in 300 consecutive diabetic men visiting the diabetic clinic of Tema General Hospital between November, 2010 and March, 2011. Anthropometric data including waist and hip circumference as well as blood pressure were measured. The levels of fasting blood glucose and serum lipid profile were assessed. All the men had a steady heterosexual relationship for at least 2 years before enrolment in the study.The response rate was 91.3% out of the 300 subjects recruited for the study. Those with SD were significantly older and had diabetes for a longer period as compared to those without SD. The prevalence of MetS as defined by the various criteria was 78.8%, 43.4% and 51.8% for WHO, NCEP ATP III and IDF respectively. Central obesity (p = 0.0482) and raised blood pressure (p = 0.0309) are the significant MetS components when the studied population was stratified according to sexual functioning. Generally, SD as well as its sub-scales correlate positively with age, blood pressure, duration of diabetes and MetS score. Whereas TC and LDL-c correlated positively with non-communication, TG correlates positively with avoidance and infrequency.SD and its sub-scales have a direct relationship with duration of diabetes, blood pressure and MetS score from this study. Central obesity and raised blood pressure seem to be the link between MetS and SD among this clinically diagnosed diabetic subjects. Reduced sexual function, defined as the inability to participate in a sexual relationship as one would wish has multifactorial causes with medical and psychological complications of diabetes being implicated -3. By 20MetS is defined as a constellation of conditions involving at least three out of five risk factors including abdominal obesity, elevated blood pressure, elevated fasting blood glucose, high triglyceride as well as low HDL-cholesterol. The prevalence of MetS and SD would vary depending on the defining criteria, age, genetic make-up, diet, occupation, cultural background, socioeconomic status, medical condition as well as the population involved. Depending on the criteria used among Ghanaians, the prevalence of MetS varies between 11.5 - 15.5% among psychiatric patients , 1.6 – 1The prevalence of SD among the Ghanaian community has been reported to vary between 59.8 to 70% depending on the population ,12, mediEven though some studies support the existence of an association between CVD and MetS which is a risk factor for endothelial dysfunction as well as vascular damage, a link between SD and MetS also appear to exist. However, the nature of the association using Golombok Rust Inventory of Sexual Satisfactory as an assessment of sexual function with MetS is limited among diabetic subjects. These are interconnected conditions in terms of their cause and require an integrated approach. This study attempts to define the association between SD and MetS among clinically diagnosed diabetic subjects using Golombok Rust Inventory of Sexual Satisfactory. To our knowledge, this is the first study seeking to determine the association between MetS and SD among this population in Ghana.This cross-sectional study was conducted among 300 clinically diagnosed diabetic patients visiting Tema General Hospital in the Greater Accra region of Ghana. Sexually active individuals who are at least 18 years and engaged in or maintained heterosexual relationship for at least 2 years regardless of their marital status were recruited in a consecutive procedure from November 2010 to March 2011. Participation of the respondents was voluntary and informed consent was obtained from each participant. The study was approved by the Committee on Human Research, Publication and Ethics of the School of Medical Science and the Komfo Anokye Teaching Hospital, Kumasi.Information on age and duration of diabetes were collected using a semi-structured questionnaire. Waist circumference (to the nearest centimetre) was measured with a Gulick II spring-loaded measuring tape  midway between the inferior angle of the ribs and the suprailiac crest. Hip circumference was measured as the maximal circumference over the buttocks in centimetres and the waist-to-hip ratio (WHR) calculated by dividing the waist circumference (cm) by the hip circumference (cm). Blood pressure was measured by qualified nurses using a mercury sphygmomanometer and stethoscope. Measurements were taken from the upper left arm after subjects had been sitting for >5 minutes in accordance with the recommendation of the American Heart Association . Duplicaalways”, through “usually”, “sometimes”, and “hardly ever”, to “never”. It provides overall scores of the quality of sexual functioning within a relationship. In addition, subscale scores of impotence, premature ejaculation, infrequency, non-communication, dissatisfaction, non-sensuality and avoidance can be obtained and represented as a profile. Responses are summed up to give a total raw score (range 28–140). The total score and subscale scores are transformed using a standard nine point scale, with high scores indicating greater problems. Scores of five or more are considered to indicate SD. The GRISS was chosen because it is standardized, easy to administer and score, relatively unobtrusive and substantially inexpensive. The reliability of the overall scales has been found to be 0.94 for men, and that of the subscales on average 0.74 (ranging between 0.61 and 0.83). Validity has been demonstrated under a variety of circumstances [Sexual function was assessed using GRISS questionnaire. The GRISS has 28 items on a single sheet and is used for assessing the existence and severity of sexual problems in heterosexual couples or individuals who have a current heterosexual relationship. All the 28 questions are answered on a five-point (Likert type) scale from “mstances -19.g for 15 minutes within 30 minutes of sample collection and separated into plasma and serum respectively. The plasma sample was used for fasting blood glucose measurement using BT 3000® Random Access Chemistry Analyzer . Serum derived from the evacuated gel tubes were stored in cryovials at −80°C until time for lipid profile measurement using BT 3000® Random Access Chemistry Analyzer . The methods adopted by the automated instruments for the determination of biochemical parameters were according to the reagent manufacturers’ instructions .After observing an overnight fast, 6 ml of venous blood sample was collected from each participant in the morning between 07:00 to 09:00 GMT into fluoride oxalate and evacuated gel tubes . Blood samples in the fluoride oxalate and evacuated gel tubes were centrifuged at 500 MetS was defined according to the criteria of the National Cholesterol Education Program, Adult Treatment Panel III (NCEP ATP III) to include individuals with three or more of the following five components: (1) abdominal obesity (waist circumference > 102 cm); (2) high TG ≥ 1.7 mmol/L (150 mg/dl); (3) low HDL-C : < 0.9 mmol/L (< 40 mg/dl); and (4) High BP (systolic BP ≥ 130 mm Hg or diastolic BP ≥ 85 mm Hg or treatment of hypertension) and (5) high fasting glucose ≥ 6.1 mmol/l .According to the new definition by the International Diabetes Federation (IDF) , MetS caWHO criteria  requiredt-tests whilst categorical variables were analyzed using Fischer’s exact test. In all statistical tests, a value of p < 0.05 was considered significant. All analyses were performed using SigmaPlot for Windows, Version 11.0,  www.systat.com.The data were presented as mean ± standard deviation or percentages. Continuous data were analyzed using unpaired This study indicated 91.3% response rate out of the 300 subjects that were recruited for the study. Twenty subjects found the subject matter too sensitive and hence refused to partake in the study and 6 of the respondents returned incomplete data leaving 274 evaluable data. As shown in Table The prevalence of MetS as defined by the various criteria was 78.8%, 43.4% and 51.8% for WHO, NCEP ATP III and IDF respectively. Even though the prevalence of MetS was found to be higher among those with SD irrespective of the criteria used, the differences were not significant Table . About 8Using the WHO criteria, the highest prevalence of components of MetS was central obesity as measured by WHR (76.6%), followed by hypertension (59.5%) and hyperlipidemia (47.8%). From the NCEP ATP III criteria, the highest prevalence of components of MetS was raised BP 73.0%) followed by raised TG (32.1%), reduced HDL-C(i.e. 28.5%) and abdominal obesity as measured by WC (19.3%). Raised BP had the highest prevalence rate (73.0%), followed by abdominal obesity (65.0%), raised TG (32.1%) and reduced HDL-C (28.5%) using the IDF criteria  that deactivates nitric oxide ,27. IncrMetS, diabetes, CVD including hypertension, obesity and SD were previously thought to be independent factors for aging men. However, MetS and SD have received a great deal of attention over the past decades due to their association with CVD and diabetes in the face of a growing worldwide epidemic of obesity. The complex relationship between MetS and SD among these diabetic subjects could be explained by the prevailing central obesity and raised blood pressure. Obesity is not only a major component of MetS, but also a key factor for MetS progression. Increased central obesity normally leads to increased leptin that could be responsible for the decrease in testosterone level previously reported among this population  via funcThe mediating effect of raised blood pressure between MetS and SD is in conformity with previous studies ,35. IncrThe prevalence of MetS as defined by the various criteria was 78.8%, 43.4% and 51.8% for WHO, NCEP ATP III and IDF respectively. The prevalence of MetS amongst subjects with SD was 80.0%, 44.2% and 52.1% using WHO, NCEP ATP III and IDF criteria respectively. There was a strong positive correlation of SD and its sub-scales with MetS scores, blood pressure, and the duration of diabetes which implies the worsening of SD once a subject had MetS. Central obesity and raised blood pressure are the link between MetS and SD among this cohort of diabetic patients.The authors declare that they have no competing interests.NA and WKBAO developed the concept and designed the study. NA, WKBAO, HA, CS, LQ and CKG-S administered the questionnaire, measured anthropometric parameters and assay for FBS, Lipid profile and testosterone, analysed and interpreted the data. NA, HA, CS, LQ and CKG-S drafted the manuscript. NA, WKBAO, HA, CS, LQ and CKG-S revised the manuscript for intellectual content. All authors read and approved the final manuscript.


The males were significantly older and heavier than the females while the females had higher mean values of BMI and WC. The prevalence of hypertension is becoming alarmingly high in the rural communities of sub-Saharan Africa.Cardiovascular diseases (CVDs) are the main causes of death in industrialized countries, and are significant causes of morbidity and mortality in sub-Saharan Africa. Hypertension is the most common cardiovascular disease in Nigerians, and the risk of CVD associated with hypertension is independent of other risk factors. Despite the high level of awareness of its presence in the developed countries, the level of control is still poor. CVDs tend to be commoner in urban settlements, and it has been hypothesized that rural sub-Saharan Africa is at an early stage of epidemiological transition from communicable to non-communicable diseases (NCD) because of the gradual adoption of unhealthy lifestyles. This study aimed at describing the pattern of blood pressure indices among the hypertensive residents of a rural community in South East Nigeria. A total of 858 individuals comprising 247 males and 611 females took part in the study. 46.4% of the subjects had hypertension. Hypertension was commoner in the males (50.2% vs. 44.8%) ( Cardiovascular disease (CVD) is the main cause of death in industrialized countries and is increasingly recognized as a significant cause of morbidity and mortality in sub-Saharan Africa including Nigeria , 2. GlobThough the current emphasis now is on both systolic blood pressure (SBP) and diastolic blood pressure (DBP) based on current weight of evidence, it does appear that the risk associated with them is still more with SBP. Before now, DBP had been the attention of the medical community until facts on the risk associated with SBP began to emerge, one of which was that from Framingham Heart Study in 1971 –13.Several studies have compared rural and urban populations or attempted to describe cardiovascular risk factors in rural communities –16. For This study was carried out in a rural Igbo community in Ezeagu local government area of Enugu state. The community—Imezi Owa—is located about 20 km from Enugu, the capital city of Enugu State in south east Nigeria. Its inhabitants are mainly elderly men and women, their children, and some young and middle-aged women. The population is estimated to be about 28,808 people based on 2005 population census figures. The community is predominantly dominated by children and their young/middle-aged mothers as well as the elderly men and women, most of who have retired from active work. The young and middle-aged men live in the cities where they are more gainfully employed and visit their families at the rural areas periodically. The few young and middle-aged men who reside in these rural areas are mostly subsistent farmers and work in the farms from the early hours of the morning till late in the evening, and they are usually not available for these community-based studies.All the adults aged 40–70 years from randomly selected households totaling eight hundred were invited for the study. Out of about 1,219 subjects invited, 858 people reported at the health centres for data collection giving a response rate of 70.4%. Informed consent was duly obtained from all the participants using the information sheet and consent forms. The research protocol was approved by the Ethics Committee of the University of Nigeria Teaching Hospital Ituku Ozalla, Enugu.All measurements were conducted by two trained physicians and one nurse between 8 AM and 10 AM at designated health centres. Questionnaires were administered by the physicians and data obtained included age, gender, and occupation.Systemic blood pressure was measured using a standard mercury sphygmomanometer on the left arm after 5-minute rest using the appropriate size with the subject in the sitting position. The first and fifth phases of Korotkoff sounds were used for systolic (SBP) and diastolic blood pressures (DBP) respectively. Two independent measurements were obtained with a minimum interval of one minute . The mea Anthropometric measurements including height, weight, waist, and hip circumferences were done by the nurse. Height was measured without shoes to the nearest centimeter using a ruler attached to the wall, while weight was measured to the nearest 0.1 kg on an electronic scale with the subject wearing light outdoor clothing and no shoes. Waist circumference was measured at the highest point of the iliac crest with the subject in light clothing.Fasting blood samples for dry chemistry were collected under aseptic procedures from a finger puncture. The participants had been earlier instructed during the selection of households to observe a minimum of eight-hour overnight fast to be eligible to participate in the study. Compliance with this instruction was ascertained from each participant before samples were collected. Dry chemistry tests were used to measure total cholesterol (TC) and fasting blood glucose (FBG) level using the Accutrend GC System . Measuring ranges of the device were 1.1–33.3 mmol/L and 3.88–7.76 mmol/L for glucose and total cholesterol, respectively. The Accutrend GC System does not measure LDL cholesterol, HDL cholesterol or VLDL cholesterol; hence these lipid parameters were not assessed. Precision for glucose was <3% and for cholesterol <5%. Accuracy of the Accutrend GC system for glucose test was ±5% compared to a hexokinase protein-free precipitate method and for cholesterol was ±5% compared with cholesterol oxidase/P-aminophenazone (CHOP-PAP) method. Results for the glucose were obtained within 12 seconds and 180 seconds for cholesterol test. Measuring principle of the device was reflectance photometry.Sample volumes needed for the device were one drop of blood for cholesterol and one drop of blood for glucose applied directly from the fingertip. The Accu-chek softclix prolancing device was used in the study for the finger prick.Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg  or being2, respectively. Abdominal obesity was defined as waist circumference of ≥102 cm in men and ≥88 cm in women [Participants were diagnosed to have diabetes mellitus (DM) if they had fasting blood glucose level (FBG) ≥7 mmol/L or reported a history of diabetes or use of glucose-lowering drugs . Subjectin women . High chin women .t test for continuous variables or chi-square analysis for categorical variables. Pearson's correlation was done to determine the degree of relationship between some quantitative variables while multiple stepwise linear regression analysis was used to determine the significant predictors of SBP and DBP. The level of significance level was set at P ≤ 0.05.Statistical analysis was done using the Personal Computer (PC) analytical software Statistical Package for Social Sciences  version 17. Results were expressed as either mean values (standard deviation) or proportions, and comparison for statistical significance was by A total of 858 individuals made up of 247 (28.8%) males and 611 (71.2%) females took part in the study with 398 (46.4%) subjects defined as having hypertension. The characteristics of all the subjects are shown in As shown in Among these hypertensive subjects, hypercholesterolaemia was seen in 13 (3.3%) subjects while elevated fasting blood glucose profile was observed in 19 (4.8%) subjects made up of 11 subjects with impaired fasting glycaemia and eight subjects with diabetes mellitus. Central obesity was present in 141 (35.4%) subjects. Mean SBP and DBP varied between the age groups but these did not maintain a linear increase or decrease across the age groups, respectively . Finding Over half of the 398 subjects were defined as having hypertension using systolic-diastolic hypertension (SDH) while the rest were defined using either isolated systolic (ISH) or diastolic (IDH) hypertension . Mild hypertension was the most common grade of hypertension among the hypertensive patients . Mild, mχ2(4) = 79.0; P < 0.0001). Evaluation of the most common pattern of blood pressure elevation among the different grades of hypertension showed that elevation of SBP was the most common pattern in those with mild hypertension (112 (56.9%) whereas elevation of both SBP and DBP was the most common pattern in those with moderate  and severe  hypertension . This is higher than that found in Gambia (6.8%) %. This i and UlasSimilar to the study by Banegas et al. , SBP conFew variables were found to significantly predict hypertension among our subjects. Each of the indices, however, was also found to be a significant predictor of the other. Ageing was common as a predictor of both SBP and DBP in this study. Age is known to significantly influence the pattern of blood pressure; hence SBP tends to increase with advancing age as a result of loss of arterial compliance while DBP tends to flatten out or decrease after 50 years of age as was observed in this study . The decCentral obesity represented by waist circumference was the other predictor of DBP. Obesity is a common CVD risk factor in Nigerian hypertensive patients . These pThe prevalence of hypertension is becoming alarmingly high in the rural communities contrary to the existing trend of rarity noted many years ago despite the traditional way of life of these inhabitants. It was also observed that systolic-diastolic as well as isolated systolic hypertension is dominant in these subjects and they are therefore likely to be exposed to high risks of hypertension-related morbidity and mortality. Ageing and obesity are also significant predictors of hypertension among rural dwellers.We recommend that in view of the increasing trend in prevalence, there is the need to institute educational programmes to guard against possible epidemiologic transition among these rural dwellers. It is to be noted that of all the predictors of hypertension observed in this study, while obesity is modifiable, age is not.Though this is a population-based study, the cross-sectional design of this study requires that the findings be interpreted cautiously. The use of two blood pressure readings taken at one sitting may also have influenced the blood pressure readings obtained and used to classify the subjects.


P < 0.05 for all). The patients with DK had higher levels of plasma glucose and HbA1c but lower levels of glutamyl transpeptidase and protein compared with the non-DK and control groups (P < 0.05). Prealbumin levels were significantly reduced in the severe DKA patients compared with the mild/moderate DKA patients. Serum prealbumin levels were correlated with albumin levels , HCO3 , and arterial pH  in the DKA patients. A diagnostic analysis showed that lower prealbumin levels significantly reflected the presence of hyperglycemic emergencies (P < 0.001). Liver and kidney function parameters deteriorated, especially in DKA. Prealbumin levels can be of value in detecting the presence of hyperglycemic crisis. This clinical trial is registered with ChiCTR-OCH-12003077.Studies on the alterations of liver and kidney function parameters in patients with diabetic ketoacidosis (DKA) and diabetic ketosis (DK) were limited. Participants with DKA, DK, non-DK, and healthy controls were enrolled in the current study. Parameters of liver and kidney function were measured and evaluated. The patients with DKA had higher levels of plasma glucose, hemoglobin A1c (HbA1c), uric acid, and creatinine but lower levels of transferases and protein compared with the other three groups ( Diabetic ketoacidosis (DKA) and diabetic ketosis (DK) are common and serious complications of diabetes mellitus. DKA most often occurs in patients with type 1 diabetes (T1D). However, increasing evidence indicates that DKA and DK are also common features of ketosis-prone type 2 diabetes (T2D) .γ-glutamyl transferase (GGT) are associated with T2D incidence [Previous studies in the field of DKA have paid much attention to proinflammatory cytokines, whereas clinical parameters of liver and kidney function have not been well characterized , 5. Testncidence , 7. Few ncidence , 9. The Prealbumin, a marker for protein malnutrition, has been advocated as a useful marker for predicting gastric surgery complications, cardiovascular outcome, and mortality in diabetic hemodialysis patients , 11. To This study was performed in the endocrinology and emergency departments of two medical college-affiliated hospitals from October 2012 to March 2013 in accordance with the principles of the Declaration of Helsinki (2001). Ethical approval was obtained from the Ethical Committees of Xuzhou Medical College and Nanchang University. Written informed consent was obtained from all of the participants.A total of 40 consecutive patients with DKA (DKA group), 40 patients with DK (DK group), 40 diabetic patients in stable condition (non-DK group), and 40 normal control subjects (control group) participated in the study . The DKAThe participants underwent a routine medical examination. None of the subjects had heart failure, hematologic disease, or liver or kidney dysfunction. Their previous liver or kidney dysfunctions were within normal range, and none of the patients were taking steroids. The non-DK and control subjects did not have fatty livers. The DKA, DK, and non-DK patients received medical treatment in the form of nutrition, oral hypoglycemic agents, and insulin therapy. Patients with DKA and DK were monitored until their ketosis and/or acidosis resolved.Blood samples from the control and non-DK groups were collected into Vacutainer tubes by venipuncture after an overnight fast. In the DKA and DK groups, the blood samples were drawn both at admission, before the initial therapy, and at the time of discharge from the hospital.Laboratory tests, including routine biochemistry tests, were performed using routine laboratory methods for such serum parameters as albumin, ALT, AST, bilirubin, creatinine, prealbumin, and uric acid levels. Blood samples were collected into tubes for kidney-liver function tests and immediately processed using an Olympus AU 2700 autoanalyzer . Arterial gas analyses were performed using commercial kits and a GEM Premier 3000 . Glycated hemoglobin A1c (HbA1c) levels were measured using an HbA1c meter from Bio-Rad Laboratories, Ltd. . The estimated Glomerular Filtration Rate (eGFR) was calculated by using the estimating equation from Chinese patients with CKD .P value < 0.05 was considered statistically significant.The results are expressed as the mean ± SD for quantitative variables with normal distributions. Skewed parameters are presented as the median and range (min–max). Pairwise comparisons of the four groups were performed using the Tukey and Kruskal-Wallis nonparametric ANOVA tests. A Mann-Whitney U analysis was used as the nonparametric test for the two subgroups. Chi-squared tests were utilized for the comparison of other clinical features. Correlations between the observed variables were analyzed by Pearson's correlation test. The risk markers for the diagnosis of DKA and DK were assessed by multiple logistic regression analyses. Receiver operating characteristic (ROC) curve analyses were performed to determine the diagnostic performance of each variable. Statistical analyses were conducted with the SPSS 18.0 software  and MedCalc version 12.1.4.0. A two-tailed P < 0.001). The glycemic variables had higher values in the DKA and DK groups than in the non-DK group (P < 0.05). The difference in the duration of diabetes reached statistical significance (P < 0.05).The baseline demographic and clinical characteristics of the subjects are shown in P < 0.05). This study demonstrated that most of the liver function-related concentrations were significantly lower in DKA patients compared with the other three groups (P < 0.001 or P < 0.05). Serum creatinine and uric acid levels were significantly elevated in the DKA patients (P < 0.05). Accordingly, the eGFR levels were significantly elevated in the DKA patients (P < 0.05). However, the levels of AST and bilirubin were not different among the four groups. Of all of the liver function parameters in DK patients, the levels of GGT, total protein, albumin, globulin, and prealbumin were significantly lower than in patients with stable diabetes and control subjects . These results are shown in The differences in the kidney-liver function values among the four groups were statistically significant (P = 0.035). In addition, the patients with T2D were older than the patients with T1D . The levels of prealbumin were similar between the T1D and the T2D cases (P = 0.775). No significant differences were observed regarding the other parameters.As shown in P < 0.05). Among DK patients, the infection subgroup had significantly lower levels of albumin and ALT . However, among DKA patients, protein levels related to kidney-liver function were similar in both subgroups. Furthermore, there was no difference in the prealbumin levels of the two subgroups.As in 3, and prealbumin were significantly lower in the severe DKA patients compared with the mild/moderate DKA patients (P < 0.05). For the rest of the variables, there were no significant differences between the mild/moderate and severe DKA cases.As shown in 3, arterial pH, and plasma glucose returned to normal. Accordingly, the kidney function parameters declined to the normal range, but liver function-related levels were higher than at admission , HCO3 levels , and arterial pH . In DK patients, there was no clinical correlation. Accordingly, pH was the most significant factor influencing the prealbumin levels  but the levels of albumin  and HCO3  were not. Multiple logistic regression analyses with significant clinical variables  were performed for the DKA and DK groups. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. There were no clinically significant differences in the DKA and the DK groups. The results are not shown.Bivariate correlation analyses were performed to assess the relationships at baseline in DKA and DK patients . In DKA P < 0.0001).The ROC curve for the comparison of prealbumin levels in DKA and DK patients is shown in The present study demonstrates that kidney-liver function is significantly altered in patients with DK and DKA. To our knowledge, there have been very few clinical studies on this topic. The data in the current study showed that in patients with ketoacidosis, the values of glycemic and renal variables were significantly increased, but the levels of protein biomarkers and eGFR were markedly reduced. The prealbumin levels were significantly reduced in hyperglycemic crisis. Although the exact mechanism behind this phenomenon is unclear, it can be concluded that the most significant factor influencing prealbumin levels might be metabolic acidosis status. Metabolic acidosis and ketone bodies induced an alteration in protein degradation and synthesis . It is o+ levels may significantly reduce the liver's production and release of enzymes and proteins [Hyperketonemia with or without acidosis is considered to be an acute complication of poorly controlled or newly diagnosed diabetes mellitus. The degree of hyperketonemia severity is significantly associated with the arterial pH level. Higher Hproteins . In the proteins . We deduIn contrast to the levels observed at admission, the kidney function parameters recovered to the normal range, whereas the levels of proteins related to liver function increased after insulin treatment. A mild increase in AST and ALT levels is occasionally observed among patients with DK or DKA after insulin treatment, although the exact mechanism is still undefined . It has The identification of prerenal deterioration has important clinical significance. Both ketosis and ketoacidosis are characterized by varying degrees of water and electrolyte depletion. A certain degree of prerenal azotemia can be associated with hyperglycemic emergencies. Dehydration leads to hypotension and a hyperosmolar state. Upon presentation of the symptoms, the magnitude of specific deficits in an individual patient varies, depending on the duration and severity of T1D or DKA , 21. The3 and arterial pH. However, prealbumin levels cannot be used to distinguish between infected and noninfected patients. Therefore, we can conclude that ketoacidosis induces changes in acute-phase response protein. Assessment of prealbumin levels will be helpful not only in early diagnosis but also in determining the prognosis of T2D patients. One limitation of this cross-sectional study is that the results represent preliminary evidence from a small study of patients with hyperglycemic emergencies. The clinical significance and the potential role of the alterations of prealbumin levels remain to be explored, particularly in diabetic patients with acute or chronic complications.Biomarker discovery is known to be a valuable field of study and has become one of the most attractive subdisciplines in clinical proteomics for human diseases. Prealbumin, a visceral protein, is sensitive to protein malnutrition, and this biomarker has been detected in urine . In the In summary, DK and DKA deteriorate liver and kidney function parameters, especially in patients with ketoacidosis. After considering the values of glycemic variables, the diagnosis of a hyperglycemic crisis should be cautious when based on lower prealbumin levels in overt hyperglycemia.


Due to lack of efficacy in recent trials, current guidelines for the treatment of neurally-mediated  syncope do not promote cardiac pacemaker implantation. However, the finding of asystole during head-up tilt –induced (pre)syncope may lead to excessive cardioinhibitory syncope diagnosis and treatment with cardiac pacemakers as blood pressure is often discontinuously measured. Furthermore, physicians may be more inclined to implant cardiac pacemakers in older patients. We hypothesized that true cardioinhibitory syncope in which the decrease in heart rate precedes the fall in blood pressure is a very rare finding which might explain the lack of efficacy of pacemakers in neurally-mediated syncope.We studied 173 consecutive patients referred for unexplained syncope . All had experienced (pre)syncope during head-up tilt testing followed by additional lower body negative suction. We classified hemodynamic responses according to the modified Vasovagal Syncope International Study (VASIS) classification as mixed response (VASIS I), cardioinhibitory without (VASIS IIa) or with asystole (VASIS IIb), and vasodepressor (VASIS III). Then, we defined the exact temporal relationship between hypotension and bradycardia to identify patients with true cardioinhibitory syncope.Of the (pre)syncopal events during tilt testing, 63% were classified as VASIS I, 6% as VASIS IIb, 2% as VASIS IIa, and 29% as VASIS III. Cardioinhibitory responses (VASIS class II) progressively decreased from the youngest to the oldest age quartile. With more detailed temporal analysis, blood pressure reduction preceded the heart-rate decrease in all but six individuals (97%) overall and in 10 out of 11 patients with asystole (VASIS IIb).Hypotension precedes bradycardia onset during head-up tilt-induced (pre)syncope in the vast majority of patients, even in those classified as cardioinhibitory syncope according to the modified VASIS classification. Furthermore, cardioinhibitory syncope becomes less frequent with increasing age. Neurally-mediated  syncope is common in all age groups We conducted a retrospective analysis of data acquired during routine diagnostic work-up in patients with unexplained syncope. Thus, patients did not undergo experimental diagnostic tests or treatments, which would require obtaining a separate informed consent. The analysis of data is covered by the general contract governing medical treatment of the Medical University Charité which all patients signed and agreed on. The institutional ethics committee of the Medical University Charité approved the study analysis and publication of anonymous data.We retrospectively analyzed data of 173 consecutive patients  who were referred to the Autonomic Dysfunction Laboratory of the Medical University Charité for head-up tilt testing as part of the routine diagnostic work-up for unexplained syncope. Only patients who experienced neurally-mediated (pre)syncope during head-up tilt were included in the analysis. Patients (n = 132) either received no current medications or their medications were discontinued at least 5 half-lives before testing. In 41 patients, medication had not been fully discontinued.Head-up tilt testing began in the morning in the majority of patients . For baseline recordings, patients rested supine in a quiet laboratory at an ambient temperature of 22–23°C. After a stable baseline was achieved, patients were passively tilted to 60° head-up tilt. After 20 min and while still at 60° head-up tilt, lower body negative pressure of −20 mmHg was applied for 10 min, followed by another 10 min at −40 mmHg . RR intervals (time between subsequent R waves in the EKG) and blood pressure were defined off-line using a program written by André Diedrich based on PV-wave software . The onset of the decrease in blood pressure and – if present – heart rate was identified manually from beat-to-beat recordings see . FurtherAll data is expressed as mean±SEM. We compared variances between the groups by using the F test. Differences in parametric data were compared by unpaired t test. Nonparametric data was analyzed by Mann-Whitney U test. For multiple comparisons of continuous data between age quartiles, one-way ANOVA and Bonferroni post-test were applied. Distribution of VASIS classes between groups was analyzed by chi square test. A value for p<.05 was considered significant. All calculations were done with Prism 5.01 .Mean age was similar in male and female syncope patients . Women reported more syncopal episodes , indicating an earlier onset of syncope in women. However, the frequency of syncopal spells was similar in women and in men. Cardiovagal tone assessed by heart rate variability was not different between sexes, but women had lower blood pressure and higher heart rates than men, both in the supine position and throughout head-up tilt. However, orthostatic tolerance did not differ between sexes  nor between age quartiles .The most common hemodynamic pattern upon tilt-induced (pre)syncope was a mixed response , followed by the vasodepressor type . Cardioinhibitory with  or without asystole  were much rarer. Interestingly, the onset of hypotension (116±6 sec before (pre)syncope) preceded the onset of bradycardia (47±5 sec) in all but six individuals 97%, , irrespeClinical data of age quartiles is summarized in With head-up tilt, the increase in heart rate was blunted with age , while vThe main finding of our study is that hypotension precedes bradycardia onset during head-up tilt-induced (pre)syncope in the vast majority of patients. The finding is in accordance with earlier studies We applied head-up tilt testing combined with lower body negative pressure to induce neurally-mediated (pre)syncope under laboratory conditions. Compared with standard head-up tilt testing, the methodology may provide a more reproducible measure of orthostatic tolerance Occurrence of asystole is disquieting. However, asystole in the setting of neurally-mediated syncope occurs in 1.3–5.1% of adult patients Whether or not cardiac pacing may have utility in the treatment of neurally-mediated syncope is still debated. While Sir Thomas Lewis was convinced that vasodilatation and the resulting decrease in peripheral resistance were the prevailing mechanisms In our study, hypotension preceded bradycardia onset in the vast majority of patients including those who presented a cardioinhibitory response with asystole for more than 3 sec. The finding challenges the modified VASIS classification which postulates that in cardioinhibitory syncope with asystole of more than 3 sec the fall in heart rate “coincides with or precedes” the fall in blood pressure Traditionally, neurally-mediated syncope was considered to primarily affect young people. Recently The heart rate increase with upright posture decreases with age We observed that the decrease in blood pressure preceded the decrease in heart rate during (pre)syncope in the vast majority of patients, even in those with cardioinhibitory syncope according to the modified VASIS classification. Furthermore, our findings challenge utility of the modified VASIS classification which is ambivalent in that it requires asystole of more than 3 sec duration and heart rate reduction coinciding or preceding the fall in blood pressure to account for a cardioinhibitory type IIb. As suggested by Sir Thomas Lewis, a decrease in blood pressure rather than a decrease in heart rate initiates the hemodynamic reaction ultimately leading to neurally mediated syncope


Data of the German population-based cohort SHIP  were analysed to examine treatment rates, antihypertensive substances prescribed, and the proportion of hypertensive study participants reaching target values for blood pressure as well as determinants.The study population was defined using baseline data of the cohort (collected between 1997 and 2001). Participants with blood pressure values ≥140/90 mmHg and/or antihypertensive medication with known hypertension and participants with risk-comorbidity  and blood pressure values ≥130/80 mmHg were included. The analysis of treatment and target values was based on the 5-year follow-up of the cohort (collected between 2002 and 2006). Logistic regression was used to identify determinants for a normotensive blood pressure.3278 SHIP-participants with hypertensive blood pressure values were included . The raw hypertension prevalence was 50.9% (N = 1761). 58.7% (N = 1074) of all hypertensive patients reported some form of antihypertensive treatment. Thereof 65.1% (N = 728) received combination therapy. Of the patients without risk-comorbidity, 42.1% (N = 489) reached their target blood pressure values at the time of the 5-year follow-up of the cohort. Of the patients with any risk-comorbidity this proportion was only 21.7% (N = 131). Significant determinants for reaching the target values were being female and having antihypertensive combination therapy. Increasing age, having risk-comorbidities, and obesity were negatively associated with reaching the target values.Both the proportion of participants receiving therapy and the number of participants reaching their target blood pressure values are very low. Combination therapy is associated with better blood pressure control as compared to mono therapy. However, even in the subgroup of hypertensive patients under combination therapy only 36% (both patients with and without comorbidity) reach target values. In Germany, about half of all adults have high blood pressure values ≥140/90 mmHg), with increasing prevalence in the higher age groups and higher rates in the male population. Compare0/90 mmHgAlthough patients with hypertension have various treatment options, there are large discrepancies between the numbers of patients with known, treated and controlled hypertension,2.The population representative German Health Survey from 1998 showed, that 23.1% of the population had a known hypertension. Population prevalence of treated hypertension was 18.6%. In only 23.8% of all patients with treated hypertension blood pressure was sufficiently controlled . The proMost important goal of the treatment of hypertension patients is to reach normotensive blood pressure values to decrease the risk for secondary disorders. Reaching normotensive blood pressure values can therefore be considered as an indicator of the effectiveness of antihypertensive therapy. According to major guidelines targeted values are below 140/90 mmHg,7. AlthoPharmacotherapy of hypertension adopts a stepwise approach. Medical treatment can start with a single antihypertensive drug (monotherapy), usually an inhibitor of the angiotensin converting enzyme (ACE). If the target blood pressure values are not reached, the dosage should be increased. If this doesn’t show effect, an alternative drug should be prescribed. If the target blood pressure values cannot be reached under monotherapy, a combination of drugs can be prescribed . In many cases, a combination therapy is needed for patients with more severe hypertension,7,10. AlIn this paper, we analysed:1. The proportion of hypertensive study participants reaching their target blood pressure values in the population-representative German SHIP-cohort. Target blood pressure values are <140/90 mmHg, for patients with risk comorbidities < 130/80 mmHg.2. The proportions of hypertensive study participants reaching their target blood pressure values, separate for study participants without antihypertensive drugs, with mono, and with combination therapy.3. Possible determinants of reaching target blood pressure values.Data from the Study of Health in Pomerania (SHIP) were included in the analysis. SHIP is an observational population based cohort study of adult German residents conducted in the region of Western Pomerania in northeast Germany. The main goal of SHIP is the provision of population-based data for the epidemiological analysis of a broad range of diseases, risk factors, and health indicators. SHIP was planned and accompanied with support and advice from an external Data safety and Monitoring Committee (DSMC). All participants gave written informed consent. The study conforms to the principles of the Declaration of Helsinki, as reflected by an a priori approval of the Ethics Committee of the Board of Physicians Mecklenburg-Pomerania at the University of Greifswald.6267 persons (age 20–79 years) with German citizenship were drawn from population registries in the region of Western Pomerania, selected persons received up to three written invitations, followed by a telephone call or home visit in the case of non-response. At the end, the response was 68.7% (N = 4308),12.For this analysis we used data from the baseline  to define the study population of participants with hypertension (concrete inclusion criteria: see further below) and the 5-year-follow up  to examine treatment rates and determinants for controlled hypertension. Lifetime prevalence was used to define risk-comorbidity at the time of SHIP-1,12.From the 3300 persons that participated both in the baseline study (SHIP-0) and in the 5-year-follow up of the SHIP-study (SHIP-1), 22 participants were excluded because of missing information about the possible presence of hypertension. The analyses were based on the data of 3278 participants, thereof 51.9% (N = 1700) were female.Sociodemographic data as well as the presence of diagnoses and risk factors were assessed in standardized, computer-assisted interviews and questionnaires. Blood pressure measurements in SHIP-0 and SHIP-1 were carried out with an automated oscillometric device . The measurements were conducted on the right arm after a rest period of five minutes in a sitting position. Blood pressure was measured three times at an interval of three minutes by trained and certified personnel. The mean value of the second and third measurement was used in the analysis. To assess medication, the participants were asked to bring all medication, taken during the last seven days, with them to the examination. All drugs were classified according to the Anatomical Therapeutic Chemical (ATC) classification. CombineWe included SHIP-0-participants with blood pressure values in need of treatment:study participants with blood pressure values ≥140/90 mmHg and/or antihypertensive medication with known hypertension;study participants with risk-comorbidity  and blood pressure values ≥130/80 mmHg. Risk-comorbidities were assessed by asking the patients for physician-confirmed diagnoses and the assessment of medication.The participants were allocated to the different categories of the WHO/ISH-classification. This classification has seven categories: optimal blood pressure (syst: <120 mmHg/diast: <80 mmHg), normal (syst: 120–129 mmHg/diast:80–84 mmHg), high-normal (syst: 130–139 mmHg/diast: 85–89 mmHg), mild hypertension (syst: 140–159 mmHg/diast: 90–99 mmHg), moderate hypertension (syst: 160–179 mmHg/diast: 100–109 mmHg), severe hypertension (syst: ≥180 mmHg/diast: ≥110 mmHg), and isolated systolic hypertension (syst: ≥140 mmHg/diast: <90 mmHg)[Descriptive statistics were applied to calculate prevalences and treatment rates. To identify possible determinants for normotensive blood pressure values, two multivariate logistic regression models were applied. Subjects with missing values on any of the analytical variables (n = 12) were excluded. Independent variables were sex, age, risk-comorbidity, obesity, smoking status, household size, and antihypertensive drug therapy. The first model includes active substances with the indication hypertension. The second model includes the kind of therapy (no therapy against mono or combination therapy).All calculations were conducted using sample-design-weights to adjust for different selection probabilities within the sample by usingThe patients included in the different analyses are described in the flowchart in Figure Applying the criteria described in the methods section, in SHIP-0, 1761 of 3278 included study participants had hypertension or blood pressure values in need of treatment (raw rate: 50.9%). The age-standardized hypertension prevalence in SHIP-0 was 39.4% . This prevalence can be considered as representative for the region Western Pomerania in which the SHIP cohort was recruited.The mean age of the study participants with hypertension in SHIP-0 was 55.5 years . The female study participants (N = 734) had a mean age of 56.7 years , the male study participants (N = 1027) 54.6 years .The hypertension prevalences increase with higher age from 27.3% in the age group 25–34 years to 83.5% in the oldest age group.Table 58.7% (N = 1074) of all hypertensive patients received some antihypertensive drug treatment. Gender differences are apparent: 67.5% of the female patients were treated, but only 51.8% of the males (p < 0.001). The proportion of treated hypertension patients increased with higher age.Of all antihypertensive active substances, beta blockers were the most frequently prescribed substance class , ACE-inhibitors were taken by 52.4% (N = 586) of the treated hypertension patients. The next most prevalent substances were diuretics , and calcium channel blockers . Again there are differences between male and female patients: males take less beta blockers and more ACE-inhibitors as female patients (Table 34.9% (N = 346) of the treated study participants received mono therapy, 65.1% combination therapy. Gender differences are small. The proportion of study participants with mono therapy decreased with increasing age from 81.8% (N = 10) in the youngest age group (25–34 years) to 20.1% (N = 50) in the oldest age group (≥ 75 years).Most combinations comprised two substances , the most frequent combinations in females were ACE-inhibitors with diuretics and ACE-inhibitors with beta-blocker . Male participants received most frequently combinations of ACE-inhibitor with beta-blocker  and ACE-inhibitor with diuretics . Also combinations of three substances were frequent .Table 42.1% (N = 489) of the study participants without risk-comorbidity reached their target blood pressure values. The proportions of the female study participants show only slight differences between study participants with mono and with combination therapy (respectively 46.5% and 49.0%). Regarding male patients, there are larger differences between the patients with mono and combination therapy, 31.4% and 42.3%, respectively.Lower target blood pressure values for patients with risk-comorbidities are reflected in lower proportions of normotensive patients (21.7%) in this subgroup. Regarding the patients with combination therapy, only small differences between males and females are apparent. Regarding the patients with mono therapy, only 5.8% of the male patients with risk-comorbidities reach normotensive blood pressure values .Table The analysis of the SHIP cohort provides detailed information about prevalences of hypertension, treatment characteristics and success of treatment of the population in the region Western Pomerania.The results of the analyses show high prevalences of hypertension, both in the raw and age standardized rates.Regarding medical treatment, differences between males and females were obvious, which is similar to the results of the German MONICA/KORA-studies. RegardiAlthough the proportion of patients treated for hypertension is relatively high, only a small part of the patients reached their target blood pressure values. Positive determinants for reaching the target values were being female, receiving combination therapy and taking beta blockers. Negative determinants were increasing age, having risk-comorbidity  and being obese.The results of the analyses show that the management of hypertension is still a challenge, especially for patients with risk-comorbidity. A different result is shown in the Canadian Heart Health Surveys. Here, hypertension patients with cardiovascular or cerebrovascular diseases were more likely to reach their target values than patients without one of these diseases. The authors of the study suggest that this unusual result depends on a more intensive therapy to patients with a high risk or a better compliance of these patients. Erkens Nevertheless, non-adherence to antihypertensive medication may be a reason for not reaching the target blood pressure values. The results of a study on elderly patients of Turner et al. show that non-adherence leads to poorer blood pressure control in this patient group.At the same time, non-adherence is a modifiable, patient-related factor which beStrenghts and limitations:Strength of this analysis is the population based data base with highly standardized blood pressure measurement and structured assessment of antihypertensive medication.We only documented drugs which were brought along by the patient to the study center. This increases data quality but may lead to some underreporting of drugs that were left at home. Several other drug-related-problems as the occurrence of drug-drug interaction may affect blood pressure level, too.Another limitation is the absence of data to adherence, so the theory that treated hypertension patients with poor blood pressure values are less adherent can not be examined for the SHIP-participants.A high prevalence of hypertension and low rates of patients reaching target values of blood pressure values according to pertinent guidelines were shown in the German population based SHIP-cohort. These results support observations from other countries. Combination therapy is associated with better blood pressure control as compared to mono therapy. However, even in the subgroup of hypertensive patients under combination therapy only 36% (both patients with and without comorbidity) reach target values. Our data clearly show that patient- and provider-related intervention strategies need to be further developed, consequently implemented and prospectively evaluated.The authors declare that they have no competing interests.NB, CM, TF, and WH participated in the design of the study. CM and SB performed statistical analysis. All authors participated in the interpretation of the results. NB drafted the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/13/594/prepub


Maintaining blood pressure (BP) and heart rate (HR) after laryngoscopy and tracheal intubation has always been a concern in injured patients. Opioids can attenuate or stop an increase in these two parameters if administered with proper doses or targets in target-controlled infusion (TCI). Remifentanil and sufentanil are widely used for this purpose because their cardiac side effects are low and, especially in traumatic patients, they are tolerated well. A comparison of the benefits and limitations of these two opioids in TCI is much needed. A literature review in electronic data bases revealed few results. 40 normotensive patients were enrolled to this randomized clinical trial study. After BIS guided anesthesia with a target-controlled propofol infusion and muscle relaxation with cisatracurium, remifentanil and sufentanil were infused using TCI with 2 and 0.2 ng.ml-1 targets respectively. BP and HR were recorded for five data points and compared with Fischer's exact test. Systolic, mean and diastolic arterial pressure and HR in different points of the study remained below baseline values but were out of control in some cases, however the out-of-control values showed significant difference between the two groups only for heart rate changes. The relative risk for producing out-of-control changes with remifentanil compared to sufentanil is significantly more than 1 for HR decrease. Sufentanil produced more common pre-intubation hypotension than remifentanil in propofol anesthetized patients but this hypotension disappeared sooner than remifentanil after tracheal intubation. Both opioids prevent an increase in BP and HR after tracheal intubation but the side effects (hypotension and bradycardia) may be a cause for concern (IRCT138710011361N3). Various drugs and techniques have been investigated for the blunting of these stimuli and the bringing about of catecholamine release. 4 Opioids are always among the drugs of choice for this purpose. 5 Many opioids such as fentanil, alfentanil, sufentanil and remifentanil have an important role in controlling changes in hemodynamic variables in response to tracheal intubation. 7 Remifentanil on the other hand is one of the newest synthetic opioids with unique characteristics which makes it ideal for the per-induction period in anesthesia mainly a short onset and the fastest offset among anilidopiperidine family,9 however conventional administration of these opioids should be timed so their maximum effects are predictably matched with the stimuli. In this regard sufentanil and fentanil may have slower effect site equilibration times than alfentanil 3 and remifentanil but when a target-controlled infusion technique is used for administration it is the physician's decision which determines the rapidity of equilibration. Blood pressure and heart rate are among the most widely used hemodynamic parameters during anesthesia and surgery to evaluate cardiovascular status and in traumatic injured patients to preserve these hemodynamic parameters in physiological ranges are particularly important. Although there are also other parameters such as stroke volume, cardiac index and systemic vascular resistance which are more important for this evaluation, they have more limited use in daily clinical anesthesia practice; hence BP and HR are the clues for further cardiovascular assessment during anesthesia. Tracheal intubation under light anesthesia often causes a hemodynamic response probably generated by direct laryngoscopy which may be even more intense than skin incision. 13 however comparison of target-controlled infusion (TCI) of remifentanil and sufentanil which are technically available in commercial TCI pumps is also necessary because of the frequent use of these two opioids in daily anesthesia practice. Hence we believe our study is novel and constitutes the first comparison of these two drugs for this goal.Several authors have compared the blunting of the hemodynamic response to tracheal intubation when using manual administration of different opioids 14 three compartment model and an effect site concentration target of propofol (CeP) as 3μg.ml-1, with induction time set as 120 seconds and maximum plasmatic concentration of propofol limited to 6μg.ml-1. The goal of slow induction was the modest reduction in blood pressure produced with propofol.Participants enrolled in the study from January 2008 until July 2010. After approval from the institute’s ethical committee and written informed consent from each patient we enrolled 40 normotensive patients to this randomized double-blinded clinical trial study. Inclusion criteria were ASA class I-II patients, aged from 18 to 60 years old who were candidates for general orotracheal anesthesia to perform non -emergent abdominal surgeries in traumatic patients. Exclusion criteria were: age below 18 and above 60 years; treated or untreated hypertension; gross upper airway anomaly; previous sensitivity to propofol, egg or soya bean; chronic use of alcohol, sedatives or opioid abuse; and predicted difficult intubation according to preoperative assessment clinic sheet. Also, every patient with a laryngoscopy duration of more than 15 seconds or several previous laryngoscopies was then excluded from the study. All patients were premedicated with oral diazepam 5 mg the night before the operation. In the preoperative period the patients were visited again by the anesthesia resident and after review of their medical history and brief examination, the height and weight of patients were measured and recorded in the checklist. In the operating room a 20-gauge intravenous catheter was inserted in a large antecubital vein and 10ml.kg-1. Ringer solution was infused slowly during a 30 minute period. The Ethical Committee did not allow the use of any invasive monitoring such as intra-arterial catheter in the absence of other clinical indications; hence standard monitoring such as 3-lead electrocardiogram, noninvasive blood pressure and pulse oximetrey were applied. The monitoring unit used for study was DATASCOPE  and the same unit was used for all measurements in this study. The module of NIBP of the monitoring unit was calibrated by the medical engineering department of the hospital before the first case enrollment. One patient in R group was excluded from the study because of propofol induced hypotension after 14 minutes of steady propofol infusion (more than 15% decrease in systolic and mean blood pressure) and one patient in S group was also excluded because of a laryngoscopy duration of more than 15 seconds. The next patients on the list were substituted in each group. In 5 patients interval recalibration was done and if there were more than 5 mmHg differences with standard pressure all previous 5 cases were excluded. Baseline (pre-induction) blood pressure and heart rate of the patients were measured and recorded after the Ringer serum infusion was ended; this was the To point which was assumed as the baseline to compare the consecutive changes of BP and HR. The skin of the patient’s forehead was scrubbed, cleaned and prepared with alcohol and gauze, and then a four electrode BIS sensor was attached to the forehead according to instructions. On connecting the sensor to the converter of the BIS monitor  a measurement of level of consciousness was started. The inside of the electrodes was applied with gel only if the recorded impedance showed more than 10kΩ. The smoothening time of the BIS monitor was set as 15 seconds. Propofol, sufentanil and remifentanil were administered with a Frenesius Modular DPS infusion pump connected to Base Prima with integrated Orchestra TCI system . The patients and physician responsible for data collection were blind to study groups. Propofol  infusion was started first with the Schnider15 we tried to maintain the patients in a physiologically steady state before performing the experimental intervention; hence we allowed the patients to stay in steady effect site concentration after stable BIS value for 14 minutes to reach physiologic stability. In this period the patients were ventilated with a mask and pure oxygen. According to a randomized numbers sequence, patients were assigned to one of two groups; sufentanil(S) or remifentanil(R) group.After equilibration of predicted and set target concentrations, if the BIS value was above 60, CeP was increased 0.5μg.ml-1 and if the BIS value was below 45 the CeP was reduced 0.5μg.ml-1 until the BIS value was located between 45 and 60. As new concerns are emerging about prolonged depression of the cardiovascular system after induction of general anesthesia with propofol16 three compartments model in group R or sufentanil  with effect site concentration (CeS) of 0.2 ng.ml-1 with Gepts 17 three compartments model in group S were infused by the other modules of the same TCI pump performing propofol infusion. The selected targets for remifentanil and sufentanil are equipotent targets and suitable for suppressing major surgical stimulus. 20 After 2 minutes and following confirmation of one single twitch on train-of-four stimulation (diagnosed by neuromuscular monitoring) and equilibration of predicted and set target concentration of opioids in each group, BP and HR were measured, recorded and noticed as T1 (pre-intubation) point. Laryngoscopy and tracheal intubation were performed using standard Macintosh blade laryngoscope size 3 or 4  and then a cuffed tracheal tube size 7.0 or 7.5  was placed in the trachea. The laryngoscopist was the same for all patients. Variables of the study were measured and recorded immediately (T2 point), 1 minute, 3 minutes and 5 minutes  after tracheal intubation. After recording of the variables of the study, anesthesia continued according to the patient’s status and with decision taking by the anesthesiologist. Independent t-test was used to compare mean BIS values and CeP in T1 points between R and S groups.After reaching the hypnotic steady state, BP was measured and if it differed more than 15% from the T0 value, the appropriate treatment was done and the patient was excluded because the propofol induced hypotension might confound the result of our intervention, if not the study was continued and cis-atracurium bromide  was administered bolus i.v. with a dose of 0.15 mg.kg-1 of body weight and remifentanil  with effect site concentration (CeR) of 2 ng.ml-1 with Minto A relevant change in the BP was assessed as a 15% change in systolic, diastolic and mean arterial pressure and 10% for heart rate with a 90% chance to detect a difference, a confidence interval of 95% and type 1 error (α) = 0.05. Hence the sample size was assessed as 33 cases which we enrolled 40 cases in the study. Every missed or excluded patient was substituted with the next patient (intention to treat). If the changes of variables in T2, T3, T4 and T5 points compared to T0 point (baseline) were in the range of 15% and 10% for blood pressure and heart rate respectively, they were assumed as being in control and if the changes were more than these ranges they were assumed as out of control. Fisher’s exact test was used to compare the changes in different data points in each group. The relative risk for out-of-control values of blood pressure and heart rate for remifentanil compared to sufentanil in different data points was assessed and a risk of more than 1 was confirmed as significant if the p value was lower than 0.05. This study was primarily registered in UMIN (Japan) with number UMIN000001564 in 2008/12/30 (www.umin.ac.jp) and also in IRCT with number IRCT138710011361N3 in 2008/12/12 (www.irct.ir).Forty patients completed the study without need for treatment with vasodilators, vasopressors or atropine hence variables were measured and gathered in 240 data points totally. Characteristics of the patients in the two groups are shown in Systolic, mean and diastolic arterial pressure and heart rate in different points of the study remained below baseline values but were out of control in some cases which are shown in 2 As we didn’t find any target controlled comparison of these two opioids for tracheal intubation responses in the literature review we chose sufentanill and remifentanil targets which were high enough to be effective for preventing blood pressure increase. Indeed opioids can attenuate or stop increase or may decrease blood pressure when administered in a dose- dependent fashion.18 In our study when remifentanil or sufentanil were administered a decrease in systolic blood pressure was more common than the mean and as was the case with diastolic blood pressure but the time of hypotension differed in the two groups: when sufentanil was administered hypotension was more common in the pre-intubation period and when remifentanil was administered it was more common in the three minutes after intubation. In this study both sufentanil and remifentanil controlled blood pressure increase after laryngoscopy with TCI but they decreased systolic, diastolic and mean arterial pressure in some cases. Opioids are the most useful and widely accepted drugs which are administered as an adjuvant by anesthesiologists before laryngoscopy and tracheal intubation to prevent blood pressure increase but they may decrease blood pressure if the dose or concentration is chosen inappropriately, the condition which is synergistically intensified with hypnotic agents. 19 we measured blood pressure and heart rate from commencement until 5 minutes after completion of tracheal intubation for more confidence but didn't find a specific time point for maximum responses, indeed we didn’t find any exaggerated responses because they were suppressed well by effect-site opioid concentration. We think this may be due to the difference between TCI and other conventional administration methods. Time to peak effect of intravenous analgesics should be spent when they are administered in conventional bolus form: this time is 5.6 min and 1.6 min for sufentanil and remifentanil respectively. 20 It's only after this period that appropriate effect site concentration is guaranteed and if tracheal intubation is performed sooner the goal of opioid administration is not achieved. However when TCI is used the pharmacokinetic driven model predicts the target in the effect site precisely and even the operator can determine the time of target equilibration in the effect site.As several studies have discovered that maximum heamodynamic responses occur about 1-5 minutes after tracheal intubation, 21 and coworkers found that in normotensive patients administration of small doses of either remifentanil (0.1μg.kg-1.min-1) or sufentanil (0.01μg.kg-1.min-1) after target-controlled induction with propofol (3 μg.ml-1 effect site) was an effective strategy to blunt the cardiovascular response to intubation, but the sufentanil group showed more stable systolic and diastolic blood pressure vs. transient systolic and diastolic pressure variations in the remifentanil group. Also Safavi and coworkers22 in their study compared sufentanil with another opioid, pethidin. They found no significant difference in systolic, mean and diastolic blood pressure change after laryngoscopy and tracheal intubation where sufentanil (1.5μg.kg-1) was administered intravenously vs. pethidin (1.5mg.kg-1) 3 minutes before laryngoscopy and tachycardia. A difference of more than 20% of basal value was not found between the two groups in this study. Indeed sufentanil didn’t perform better than pethidin in this manner. These authors focused on the time to peak effect to explain the blood pressure control with these two different opioids. As we found hypotension and bradycardia in some cases in our study with selected targets it's better to avoid higher target concentrations for blood pressure control after tracheal intubation specially when opioids would be coadministered with hypnotic agents such as propofol. As we administered targets recommended in the majority of the literature it is unwise to recommend lower target concentrations because of the inability to control blood pressure and heart rate rise. It would be better to reduce the induction speed and limit plasmatic target concentration in the TCI pump setup. These maneuvers could decrease cardiovascular system depression due to a high target concentrations of opioids. With these considerations, sufentanil and remifentanil by means of TCI both could prevent blood pressure rise after tracheal intubation however the more common and sustained bradycardia occurring with remifentanil remains a concern.In a study similar to our own, but not in target-controlled manner, IannuzziSufentanil produced more common preintubation hypotension than remifentanil in propofol anesthetized patients but this hypotension disappeared sooner than remifentanil after tracheal intubation. On the other hand, remifentanil produced more profound preintubation bradycardia and more sustained bradycardia than sufentanil after tracheal intubation. Target concentration adjustment according to administered hypnotic and increasing the induction time when the TCI technique is used could be recommended to decrease the side effects of opioids during induction. In this manner an increase in blood pressure and heart rate will be prevented when sufentanil or remifentanil are administered with the fewest side effects.


Patients with type 2 diabetes have 2–4 times greater risk for cardiovascular morbidity and mortality than those without, and this is even further aggravated if they also suffer from hypertension. Unfortunately, less than one third of hypertensive diabetic patients meet blood pressure targets, and more than half fail to achieve target HbA1c values. Thus, appropriate blood pressure and glucose control are of utmost importance. Since treatment sometimes fails in clinical practice while clinical trials generally suggest good efficacy, data from daily clinical practice, especially with regard to the use of newly developed anti-diabetic and anti-hypertensive compounds in unselected patient populations, are essential. The DIALOGUE registry aims to close this important gap by evaluating different treatment approaches in hypertensive type 2 diabetic patients with respect to their effectiveness and tolerability and their impact on outcomes. In addition, DIALOGUE is the first registry to determine treatment success based on the new individualized treatment targets recommended by the ADA and the EASD.DIALOGUE is a prospective observational German multicentre registry and will enrol 10,000 patients with both diabetes and hypertension in up to 700 sites. After a baseline visit, further documentations are scheduled at 6, 12 and 24 months. There are two co-primary objectives referring to the most recent guidelines for the treatment of diabetes and hypertension: 1) individual HbA1c goal achievement with respect to anti-diabetic pharmacotherapy and 2) individual blood pressure goal achievement with different antihypertensive treatments. Among the secondary objectives the rate of major cardio-vascular and cerebro-vascular events (MACCE) and the rate of hospitalizations are the most important.The registry will be able to gain insights into the reasons for the obvious gap between the demonstrated efficacy and safety of anti-diabetic and anti-hypertensive drugs in clinical trials and their real world balance of effectiveness and safety. There is an increasing prevalence of type-2 diabetes, which is attributable to a growing population, an increase in life expectancy, increased diagnostic efforts, and a reduced diabetes attributable risk due to recent advances in diabetes treatment . HyperteA number of studies have shown improved glycaemic control to be able to delay the onset and also to halt the progression of micro-vascular complications such as diabetic retinopathy and nephropathy. This has also been shown for neuropathic secondary disorders ,6. For mAn exploratory analysis of the United Kingdom Prospective Diabetes Study (UKPDS) data showed that the risk of both micro- and macro-vascular complications of type 2 diabetes (T2D) was strongly associated with the mean systolic blood pressure and that blood pressure lowering by 10 mmHg led to a 15 % reduction in the risk for death related to diabetes .In the Steno-2 study, intensified therapy of the modifiable risk factors in patients with T2D and microalbuminuria was compared to standard treatment. In addition to lifestyle changes and diet modifications, all patients in this group received ACE-inhibitors (ACEI) or angiotensin receptor blockers (ARB) irrespective of baseline BP values and a vitamin-mineral supplement. The target limits for HbA1c, fasting cholesterol and triglycerides and blood pressure were much stricter than in the control group. This multi-factorial approach led to significant reductions in both micro- and macro-vascular event rates ,10.Thus, in diabetic patients with hypertension, appropriate blood pressure control as well as glucose control is important. Current guidelines ,12 recomDuring recent years new medications and fixed dose combinations have been developed for the treatment of T2D and hypertension. For achieving glycaemic control, a number of oral therapeutic options are available, using different approaches. There are agents that increase insulin secretion, such that improve insulin action and also substances delaying carbohydrate absorption. Unfortunately, most of them – with the exception of metformin – are associated with weight gain. Hypoglycaemia and in some cases gastrointestinal side effects and oedema are other possible disadvantages. Another issue is the failure to achieve adequate control of postprandial blood glucose and also long term glycaemic control . In receTo achieve adequate blood pressure control, an even larger number of therapy options exist. As diabetic patients frequently also have impaired renal function associated with microalbuminuria, substances affecting the renin-angiotensin system, which are known to display renal benefits independent of blood pressure reduction, appear to be particularly beneficial -23. ACEITreatment recommendations by current guidelines are mainly based on evidence from randomised controlled trials. However, these trials reflect only selected patient populations defined by detailed in- and exclusion criteria of these trials. Patients in daily practice are usually older and suffer from more co-morbidities as compared to those in clinical trials ,27. AvaiThe purpose of the registry is to evaluate various therapy regimes of anti-diabetic (including incretin-based and exclusively non-incretin-based therapies) and anti-hypertensive treatments (including RAAS-inhibitors and exclusively non-RAAS-inhibitors) as well as their combinations, patient reported outcomes and treatment success in hypertensive T2D patients. It is the first prospective registry to determine treatment success based on the new individualized treatment targets of the ADA and the EASD .DIALOGUE is a prospective observational national multicentre registry with a follow-up of 24 months and will enrol 10,000 patients with both T2D and hypertension from up to 700 sites in Germany. Data are recorded at baseline and will be prospectively documented during follow up visits at 6, 12 and 24 months.Verband forschender Arzneimittelhersteller (VFA).This registry is conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and adhere to the principles of Good Epidemiology Practice (GEP), and applicable regulatory requirements. The protocol of this registry was approved by the ethics committee of the Ruhr University Bochum, Germany. Patients that being enrolled into this registry will provide written informed consent. DIALOGUE has further been registered in the database of the The two co-primary objectives are: 1) documentation of individual HbA1c goal achievement with respect to anti-diabetic pharmacotherapy and 2) documentation of individual blood pressure goal achievement with different anti-hypertensive treatments.Secondary objectives are (1) to document major cardio-vascular and cerebro-vascular events (MACCE) during 2 year follow-up; (2) to document hospitalizations during 2 year follow-up; (3) to assess the proportion of patients reaching blood glucose target values without experiencing the following adverse effects: peripheral oedema or proven hypoglycaemic events or discontinuation due to gastrointestinal events or significant weight gain (>5 %); (4) to describe patient characteristics in patients with diabetes mellitus and hypertension in clinical practice in the overall registry population; (5) to document anti-diabetic and anti-hypertensive therapy and its impact on treatment target achievements in diverse subject populations, which have to be pre-specified by the scientific committee ; (6) to verify the applicability of and the adherence to the current guidelines for the treatment of diabetes and hypertension in clinical practice; (7) to document utilisation patterns of drugs used for the treatment of diabetes as well as hypertension in clinical practice; (8) To evaluate adverse cardio-vascular events as well as diabetes-related micro-vascular and macro-vascular events; (9) to evaluate the glycaemic profiles of the participants with regards to differences in anti-diabetic treatment patterns; (10) to evaluate the blood pressure profiles; (11) To evaluate co-morbid disease conditions; (12) to evaluate the change in BMI over the course of the study; (13) to evaluate the proportion of patients with hypoglycaemic events over the course of the follow-up; (14) to evaluate cardio-vascular risk by using validated cardio-vascular risk scores such as the EURO Score; (15) to evaluate health status (EQ-5D); (16) to determine costs associated with the treatment and disease related complications; (17) to document treatment persistence over time, change in treatments / dosing during a follow-up of two years ; (18) to document patient reported outcome (PRO).Institut für Herzinfarktforschung to be representative for the ambulatory treatment of diabetes and hypertension in Germany. For this purpose, a representative cross-section of different types of centres including diabetologists and primary care physicians will be built. The sampling strategy will thus provide a representative dataset for the description of oral anti-diabetic treatment patterns in Germany.The registry will be performed in primary care and diabetes centres in Germany, with a planned participation of up to 700 sites. Centres will be selected from a database maintained at the Inclusion criteria are as follows: 1) Age: ≥18 years 2) Diagnosed type 2 diabetes mellitus and manifest hypertension (comorbidity) 3) Antidiabetic therapy presently on oral mono- or dual combination therapy  4) The treating physician considers blood glucose lowering medication to be not adequate and/or not safe/tolerable 5) The physician adds another oral drug / switches drug treatment to achieve glycaemic control 6) Written informed consent for participation obtained from the subject.exclusion criteria apply: 1.) Current participation in any randomised controlled trial. 2) Patients not under regular supervision of the treating physician for the duration of the study 3) Use of GLP-1-analogues or insulin before enrolment 4) Patients treated with aliskiren in a dual renin angiotensin aldosterone (RAAS) blockade 5) Pregnancy 6) Diabetes secondary to malnutrition, infection or surgery 7) Maturity onset diabetes of the young 8) Known cancer.Patients will not be eligible for inclusion if any of the following Patients will be enrolled according to a pre-specified ratio based on their treatment, which is not pre-determined by the study protocol but based on the physician’s decision Figure . “IncretPatient enrolment has started in July 2012. It is estimated that the first visit of the last patient enrolled will take place in early 2013, the last visit of the last patient is planned for early 2015. The Clinical Study Report will then be published in April of the following year. Figure Table There are three strategies for data quality checks: validations that occur at the time of data entry , a second, more sophisticated quality control program that runs as a prelude to the creation of the analysis data set and on-site data monitoring.Front-end data checks are advantageous because mistakes are caught and corrected at the time of entry – a system that is efficient for data collectors. Certain data elements can be required, while other variables may allow for missing values. Additionally, parameters will be defined to allow entry of only those records that meet inclusion criteria.Prior to the creation of the analytic dataset, more extensive quality control processes are performed. These checks, programmed in SAS, include parent–child edits, consistency edits, and data transformations that will facilitate analyses.Source documentation and data accuracy will be verified by site visits in randomly selected 2% of the sites.All variables collected in the eCRF as well as the data obtained from the quality of life assessments and all derived parameters will be used in the statistical analysis. Binary, categorical, and ordinal parameters will be summarised by means of absolute and percentage numbers within the various categories . Numerical data will be summarised by means of standard statistics . In addition, adequate graphs  may be presented to summarise the results for some parameters. Time-to-event variables will be analysed via a Cox proportional hazard regression model presenting hazard ratios and the corresponding 95% confidence intervals. In addition Kaplan-Meier curves will be presented for these variables. Two-sided 95%-CI will be presented for important parameters, but should be interpreted in an exploratory descriptive way. Further multivariable analyses will be performed according to the statistical analysis plan (SAP). Formal statistical tests will not be performed within the statistical analysis. A report including descriptive statistics of all documented parameters will be generated for the overall patient population. Depending on the variable(s) of interest, additional selection criteria for patients  considered in specific analyses may be used, if considered useful during the statistical analysis. Details on the selection criteria used will be given in the SAP and in the statistical section of the report. The statistical analysis will be performed using SAS .There are a number of epidemiological studies, which documented (among other aspects) the treatment of type-2 diabetes in Germany. Table and hypertension and the effect of two matching treatment approaches on target goal achievement as to the more recent guidelines which suggest more individualized treatment targets [Most of these studies however either had a detailed look on the prevalence of type-2 diabetes in primary care practice (HYDRA and DETECT), the co-morbidity burden (DETECT), the costs , or on self-monitoring of blood glucose (ROSSO). Some were also retrospective in design . Similar to DIALOGUE the effect of a tailored intervention on target achievement was investigated in DUTY and DIG. The added value of DIALOGUE is, that it will enrol almost 10,000 patients exclusively with the co-morbid disease constellation diabetes targets ,42,43 batargets ,45.DIALOGUE is the first registry that focuses at the evaluation of T2D patients who also suffer from hypertension, addressing both achievement of glycaemic and anti-hypertensive goals considering the individualized treatment targets as recommended by recent guidelines. As the combination of both diseases is a major factor in the development of vascular complications, data obtained will help to explain the gap between the inadequate glycaemic and blood pressure control in the “real world setting” despite the demonstrated efficacy and safety of anti-diabetic and anti-hypertensive drugs in clinical trials.MACCE: Major Cardiovascular and Cerebrovascular Events; MAGE: Mean Amplitude of Glycaemic Excursions; T2D: Type-2 Diabetes Mellitus; UKPDS: United Kingdom Prospective Diabetes Study; ACEI: ACE-inhibitor; ARB: Antiotensin Receptor Blocker; RAAS: Renin Angiotensin Aldosterone System.Anselm K Gitt (AKG), Roland E. Schmieder (RES), Peter Bramlage (PB), and Diethelm Tschöpe (DT) have received research support and honoraria for lectures from a number of pharmaceutical companies producing anti-diabetic drugs including Novartis the sponsor of this study. Eve Duetting (ED) is employee of the sponsor. Steffen Schneider (StS) has no potential conflict of interest to disclose.AKG, ED, RES and DT designed the registry. StS is responsible for the analysis of data. PB drafted the manuscript based on the protocol and all other authors revised the article for important intellectual content. All authors have finally approved the version to be published.DIALOGUE study group: Sibel Avsar (Ludwigshafen), Peter Bramlage (Mahlow), Eva Duetting (Nürnberg), Anselm K. Gitt (Ludwigshafen), Alexander Neumer (Ludwigshafen), Taoufik Ouarrak (Ludwigshafen), Roland E. Schmieder (Erlangen), Steffen Schneider (Ludwigshafen), Diethelm Tschöpe (Bad Oeynhausen).


The insertion of Ventricular Assist Devices is a common strategy for cardiovascular support in patients with refractory cardiogenic shock. This study sought to determine the impact of ventricular assist devices on the dynamic relationship between arterial blood pressure and cerebral blood flow velocity.A sample of 5 patients supported with a pulsatile ventricular assist device was compared with 5 control patients. Controls were matched for age, co-morbidities, current diagnosis and cardiac output state, to cases. Beat-to-beat recordings of mean arterial pressure and cerebral blood flow velocity, using transcranial Doppler were obtained. Transfer function analysis was performed on the lowpass filtered pressure and flow signals, to assess gain, phase and coherence of the relationship between mean arterial blood pressure and cerebral blood flow velocity. These parameters were derived from the very low frequency (0.02-0.07 Hz), low frequency (0.07-0.2 Hz) and high frequency (0.2-0.35 Hz).P = 0.04). The two cases with highest coherence (~0.8) also had much higher spectral power in mean arterial blood pressure.No significant difference was found in gain and phase values between the two groups, but the low frequency coherence was significantly higher in cases compared with controls (mean ± SD: 0.65 ± 0.16 vs 0.38 ± 0.19, Pulsatile ventricular assist devices affect the coherence but not the gain or phase of the cerebral pressure-flow relationship in the low frequency range; thus whether there was any significant disruption of cerebral autoregulation mechanism was not exactly clear. The augmentation of input pressure fluctuations might contribute in part to the higher coherence observed. Ventricular assist devices (VAD) are mechanical pumps that replace or augment left and/or right ventricular function in cases of refractory cardiogenic shock. A number of approaches are currently taken related to the indications of these devices: VAD can be used as a bridge to heart transplantation, as a bridge to myocardial recovery leading in some cases to their prolonged use with meaningful survival and improved quality of life . RecentlFundamental differences regarding cardiac output and systemic circulation distinguish two main types of VAD: pulsatile and continuous-flow VAD. The main advantages of continuous-flow VAD being the self-contained nature, not requiring a pneumatic driver, longevity, lack of bearing contacting with blood and absence of artificial valves with theoretically smaller thrombogenic surface . HoweverDespite the use of pulsatile VADs, non-homogeneous output is often generated as pulsatile VADs eject once the pre-established filling volume (stroke volume) has been reached. Therefore, the VAD ejection rate varies depending on preload and systemic resistance. Frequently there is a variable degree of persistent native cardiac contractibility, leading to asynchrony, and irregularities in arterial blood pressure waveform Figure . In suchCerebral autoregulation is the mechanism by which cerebral blood flow (CBF) is maintained despite changes in cerebral perfusion pressure (CPP). Cerebral autoregulation mediates states of hyperemia and ischemia to avoid vasogenic edema or infarction respectively . ImpaireRider and coworkers assessed cerebral autoregulation in patients supported with non-pulsatile VADs, by exposing them to dynamic maneuvers such as head-up tilting and measuring the change in CBFV. They found that cerebral autoregulation was impaired, suggesting that circulatory pulsatility is crucial for the maintenance of cerebral autoregulation . HoweverInstitutional Ethics Committee approval for the performance of the study was granted. All patients or their next of kin gave informed consent prior to enrolment in the study.A convenience sample of five patients supported with a pulsatile Thoratec VAD  was compared with five control patients, matched for age, comorbidities, current diagnosis and cardiac output state Table . All cas2 . CBFV of middle cerebral arteries (MCAs) were measured using TCD following referenced criteria at the temporal acoustic window [2) during measurements.We recorded at least 5 minutes of data under resting conditions in all subjects. Simultaneous beat-to-beat recordings of BP and cerebral blood flow velocity (CBFV) waveforms were sampled using a data acquisition unit . The BP waveform was acquired from an intra-arterial catheter; CBFV of middle cerebral artery (MCA) was measured using a transcranial Doppler device with a 2 MHz probe and a power of 100 mW/cmc window . Both MCc window . StabiliTherapeutic and clinical variables were recorded at the moment of data acquisition. This study was merely observational and did not interfere with the treating physician's management plan.For the assessment of cerebral autoregulation, this study used TFA based on frequency domain cross-spectral analysis. TFA assesses the relationship between two signals in the frequency domain and yields three interpretable parameters . Gain is the indicator of the magnitude with which the change of output signal (i.e. CBFV) is caused by the change of input signal (i.e. BP). In the context of cerebral autoregulation analysis, a small gain indicates that cerebral blood flow does not change significantly when blood pressure changes, indicating that the cerebral autoregulatory mechanisms are intact. Phase shift relates to the temporal lag between BP and CBFV at each frequency. Zero phase lag signifies synchronous fluctuations, whilst positive phase suggests CBFV leading BP, and negative phase suggests BP leading CBFV.The gain and phase metrics, however, need to be interpreted in the context of the cross-spectral coherence, which is an estimation of the linear correlation between the input and output signals at particular frequencies. Coherence varies between 0 and 1; where 0 indicates no linear relationship and 1 indicates perfect linear relationship. It has been suggested that an increase in coherence may be indicative of a blunted cerebral autoregulation . A low cSxx(f) and Syy(f) (with f denoting frequency), the cross-spectrum of BP and CBFV, Sxy(f), was computed as the product of Sxx*(f) and Syy(f) (asterisk denotes the complex conjugate). The transfer function from BP to CBFV was computed as H(f) = Sxy(f)/Sxx(f), and the gain magnitude and phase angle of the transfer function was obtained accordingly. The magnitude-squared coherence function was computed as γ2(f) = |Sxy(f)|2/Sxx(f)Syy(f), for detecting linear correlation between the spectral components in the two signals. Coherence ranged from 0 (lack of linear correlation) to 1 (perfect linear relationship).In this study, spectral analysis was performed on 5 min artifact-free segments of continuous CBFV and BP signals. Signals were downsampled to 1 Hz after appropriate anti-aliasing lowpass filtering, with any slow trend removed by cubic spline detrending. The frequency spectra and transfer function were obtained using the Welch method . This inP < 0.05 was considered statistically significant.The spectral powers of BP and CBFV and the mean values of the transfer function gain, phase and coherence were calculated in the very low frequency , low frequency  and high frequency  ranges as previously defined . Unpaire2 and LVEF was found between the VAD and the control groups. The levels of pCO2 were maintained within normal ranges and stable throughout the study, thus the effect of CO2 on cerebral vessel was minimised. LVEF was generally lower for the VAD cases, whichwas expected as these were patients with baseline refractory cardiogenic shock who required a VAD for life support. However the difference did not reached statistical significance.The patient characteristics are presented in table P = 0.04).The results from spectral and cross-spectral transfer function analysis of MAP and CBFV were presented in table In this study, the cross-spectral transfer function analysis technique was applied to study the dynamic relationship between systemic BP and CBFV in patients using pulsatile VAD. The rationale was to describe any potential alteration of cerebral autoregulation function associated with the use of VAD, as the long term use of VAD may lead to impaired cerebral autoregulation and worse neurological outcomes.The key finding of the study was the higher coherence between MAP and CBFV in the VAD patients compared with the controls, at the LF range. A low coherence between MAP and CBFV (<0.5)indicates a lack of linear relationship between pressure and flow at the particular frequency range, and can be attributed to the presence of an intact cerebral autoregulation that introduces nonlinearity relationship ,22. It hThe lack of differences in TFA gain and phase between the VAD and the control group also raised questions whether there was significant disruption of cerebral autoregulation by the use of pulsatile VAD. Alterations in cerebral autoregulation function by pathological conditions  are 2 is directly related with vessel diameter and was maintained stable and within normal values, during patient recruitment.In this study, direct assessment of CBF was not feasible as the use of non-imaging TCD does not facilitate the measurement of the cerebral vessel cross-sectional area. Instead, there is a global consensus supporting the use of CBFV as a surrogate for CBF, provided the vessel diameter remains stable during the study . Among aFor TCD recordings, only the MCA with better acoustic properties was recorded and analyzed. Although spatial heterogeneity of cerebral perfusion as well as interhemispheric differences has been described ; the endNo significant change in gain and phase was found between the two groups in this study, but the small population recruited could have contributed to the lack of statistical significance, thus further studies with larger sample size would be desirable.The use of pulsatile VAD affected the coherence but not the gain or phase of the cerebral pressure-flow relationship in the low frequency range, thus whether there was any significant disruption of cerebral autoregulation mechanism was not clear. The augmentation of input pressure fluctuations might contribute in part to the higher coherence observed. Given the absence of all conditions that define autoregulation, these results should be regarded as preliminary data, and further studies, employing bigger samples, are warranted.The authors declare that they have no competing interests.JB and JFF conceived and designed the study; JB undertook patient screen and data acquisition; JB drafted the manuscript which was reviewed and amended by all other authors. GC and Y-C T undertook data analysis and contributed to its interpretation. AGB undertook statistical analysis. KRD conceived and designed the technical components of the study, also reviewed revised the manuscript. RB and PA reviewed and amended the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2253/11/4/prepub