Logistic regression analysis revealed a complex of informative factors, including female gender, previous myocardial infarction, age greater than 75 years, and clinical course of abdominal aortic aneurysm as important indicators for lethal outcome. A  Care of patients with abdominal aortic aneurysm (AAA) has been a benchmark of progress in vascular surgery for more than 50 years. By the early 1990s, elective repair of AAA was regularly carried out with a mortality rate of less than 5% .The aim of this study was threefold: (1) to evaluate and compare risk factors that influence the outcome of treatment in patients undergoing surgery for non-ruptured AAA, (2) to identify a complex of informative factors for lethal outcome, and (3) to define various risk groups.From January 1999 to August 2003 100 patients with a diagnosis of AAA were treated surgically at the Department of Vascular Surgery at the Kaunas University of Medicine. Thirty-one patients (31%) had surgery for a ruptured AAA and were excluded from our study. The 69 remaining patients (69%) underwent surgery for a non-ruptured AAA; these cases were analyzed in our study. There were 56 bifurcated  and 13 (18.8%) straight grafts. All patients analyzed in this study had a midline laparotomy incision, and during AAA resection, the abdominal aorta was clamped below the renal arteries. Sixty-one patients survived while eight patients (11.6%) died within 30 days after surgery. Variables recorded for each patient were categorized as preoperative, intraoperative or postoperative.All patients had consultations with an internist and a cardiologist. Cardiac ultrasonography was performed, and left ventricular ejection fraction (LVEF) was estimated. Patients without coronary artery disease (CAD) or with minor CAD included asymptomatic patients, patients with normal electrocardiogram (ECG) results, and patients in whom myocardial infarction (MI) was diagnosed with electrocardiography more than 6 months earlier.Patients were considered as having normal or only minor renal dysfunction when the serum creatinine level was less than 110 μmol/L.Patients with normal pulmonary function included asymptomatic patients with normal results on chest radiographs and normal results on respiratory function assessments.AAA diameter was measured during examination of the patient with computerized tomography (CT) and ultrasonography. Forty-two patients (61%) were examined with aortography.Operative risk was assessed according to the American Society of Anesthesiologists (ASA) classification. The following variables were recorded: type of operation, abdominal aorta "cross-clamping" time, declamping hypotension, blood loss during operation, urine output during operation (ml per hour) and total operation time.We recorded the following variables: durability of artificial pulmonary ventilation, length of stay in intensive care, length of hospital stay after operation, and total length of hospital stay. Complications during the postoperative period were not analyzed in this study.2) and Wald statistics. When using the multidimensional logistic model coefficients, we developed a risk score model for the evaluation of complexes of risk factors. The accuracy of significant variables for prediction of LO was estimated by means of Receiver Operating Characteristic (ROC) curves. Variables that were statistically significant (p < 0.05) between groups of survivors and deceased were entered into a maximum probability logistic regression program. For each significant variable in the logistic regression analysis, the odds ratio (OR) was calculated . In order to determine low-, medium-, and high risk groups, we used LO probability estimation in the multinomial regression model, or logit function of the probability estimation log (p/(1-p)).All variables defined above were subjected to univariate analysis using Microsoft Excel 2000 to test their influence on the mortality. Fisher's exact test was performed with SPSS 10.0 for Windows and Statistics v.5 for Windows. The complex influence of several predictors on the probability of lethal outcome (LO) was evaluated using the multidimensional logistic regression model . The sigSixty-nine patients underwent surgery for non-ruptured AAA. For each patient a set of variables were compared between the surviving group of patients and the group of deceased. The variables that differed significantly between the groups of survivors and deceased were age, blood loss, days of hospitalization, days of hospitalization after operation and LVEF as given in Table Table The ability of significant variables to predict LO was estimated by means of ROC curves. The area under the ROC curve is a measure of how well the groups are separated. The ROC curve's position above the mean line demonstrates the capability of the method to predict lethal outcome with some degree of precision. An area of 1 represents a perfect test. In our study, the area under the age curve was 0.778; CI ; p = 0.011; the area under the sex distribution curve was 0.714; CI ; p = 0.050; and the area under previous MI was 0.716; CI ; p = 0.048 (not shown). Other variables were not found to be significant as estimated by the ROC curve.To evaluate the informative parameters for LO, we used logistic regression. Age, previous MI, insufficiency of respiratory function, blood loss, LVEF and clinical course of AAA were confirmed as informative factors for LO Table . Previou2. The logistic regression model included the variables as long as the p-value was significantly decreasing. Two models turned out to be able to predict LO. One model included the variables patient gender, previous MI and age above 75 years:A logistic model for LO was established by using an informative parameter method, taking into consideration the strong correlation between some of the variables. For this model, the optimal criterion was a p-value that was adequate for the logistical model criterion Gp(LO) = 1/1+exp{1.83 × gender + 2 × previous MI + 1.44 × (age>75 years) - 6.5}2 = 14.5 p = 0.023χA second model included the variables patient gender, previous MI and clinical course of AAA:p(LO) = 1/1+exp{1.8 × gender + 2.3 × previous MI + 1.12 ×  - 7.2}2 = 15.1 p = 0.0017χβ. The value of female gender (β = 1.83) was 6 (6.21); the value of previous MI (β = 2) was 7 (7.4); and the value of age greater than 75 years (β = 1.44) was 4 (4.23). The maximum sum of risk scores was 17. In 54 patients (78%), the score was less than 10, and mortality in this group was 3.7% (two patients). In 15 patients (22%), the score was higher than 10, and mortality in this group was 40% (six patients).The risk score model allows evaluation of the groups for risk stratification. Score evaluation was performed by eUsing the second logistic model, the value of female gender β = 1.8) was 6 (6.1), the value of previous MI (β = 2.3) was 10 9.94), and the value of clinical course of AAA (β = 1.12) was 3 (3.06). The maximal sum of scores was 19. In 35 patients (51%), the sum was less than 13, and mortality in this group was 2.9% (1 patient). Twenty-five patients (36%) had scores of 13 to 16, and two patients (8.0%) in this group died postoperatively. Nine patients (13%) had scores higher than 16; four patients (44.4%) from this group died postoperatively. These findings were used for establishing low-, moderate-, and high-risk groups (Table , and the.8 was 6 The 30-day postoperative mortality rate reported in the literature ranges from 0 to 10.5%. In our material it is slightly higher, 11.6%, probably due to the small number of patients. In a previous report based on a large number of patients collected from studies published between 1985 and 1997, the mortality rate was 5.8% .In the elective situation, advanced age and cardiac, pulmonary, and renal disease increase the risk of postoperative mortality . As in pBlood loss during the operation was a statistically significant factor for increased mortality. Other investigators have also concluded that blood loss during surgery is an informative factor for lethal outcome .All postoperative complications increase length of stay in intensive care. However, postoperative complications were not analyzed in our study.risk score model allows identification of groups of patients running a high risk for postoperative death. Mortality was 2.9% in the low-risk group, 8.0% in the moderate-risk group, and 44.4% in the high-risk group.Logistic regression analysis revealed a combination of informative factors for mortality after surgical repair of non-ruptured AAA. In one model these factors were female gender, previous MI, and age greater than 75 years. In a second model female gender, previous MI, and clinical course of AAA were important predictors of lethal outcome. The latter


Skeletal muscle depletion is an important complication of chronic obstructive pulmonary disease (COPD) but little prospective data exists about the rate at which it occurs and the factors that promote its development. We therefore prospectively investigated the impact of disease severity, exacerbation frequency and treatment with corticosteroids on change in body composition and maximum isometric quadriceps strength (QMVC) over one year.1 mean (SD) 35.8(18.4) %predicted) were recruited from clinic and studied on two occasions one year apart. Fat free mass was determined using bioelectrical impedance analysis and a disease specific regression equation.64 patients with stable COPD (FEVQMVC fell from 34.8(1.5) kg to 33.3(1.5) kg (p = 0.04). The decline in quadriceps strength was greatest in those with the highest strength at baseline (R -0.28 p = 0.02) and was not correlated with lung function, exacerbation frequency or steroid treatment. Decline in fat free mass was similarly higher in those with largest FFM at baseline (R = -0.31 p = 0.01) but was more strongly correlated with greater gas trapping (R = -0.4 p = 0.001). Patients with frequent exacerbations (>1 per year) (n = 36) experienced a greater decline in fat free mass compared to infrequent exacerbators (n = 28) -1.3(3.7)kg vs. +1.2(3.1)kg (p = 0.005), as did patients on maintenance oral steroids (n = 8) -2.8(3.3) kg vs. +0.2(3.5) kg (p = 0.024) whereas in those who stopped smoking (n = 7) fat free mass increased; +2.7(3.1) kg vs. -0.51(3.5) kg (p = 0.026).Decline in fat free mass in COPD is associated with worse lung function, continued cigarette consumption and frequent exacerbations. Factors predicting progression of quadriceps weakness could not be identified from the present cohort. It is well established that chronic obstructive pulmonary disease (COPD) has systemic consequences, one of which is fat free mass depletion , which iHowever no prospective data are available regarding the rate of decline of strength in COPD and the factors that are responsible for it. Short term studies have shown that exacerbations of COPD are associated with increased inflammatory mediators and acute and partially reversible reductions in both quadriceps  and handa priori determined factors to determine their utility in predicting decline in fat free mass and quadriceps strength. The factors to be evaluated were indices of lung function, oral corticosteroid exposure and having frequent exacerbationsBased on this interpretation of the literature, this study evaluated various Patients were recruited from clinics at The Royal Brompton Hospital if they had COPD, defined according to the GOLD guidelines , withoutSpirometry was obtained using a pneumotachograph with flow integration, lung volumes by whole body plethysmography and gas transfer with a single breath technique . Blood gas tensions were measured in arterialised earlobe capillary samples. Fat free mass (FFM) was determined using bioelectrical impedance analysis  and a disease specific regression equation .Maximum isometric quadriceps strength (QMVC) was measured with subjects seated, trying to extend their dominant leg as hard as possible against an inextensible strap connecting their ankle to a strain gauge  . The sigTo assess respiratory muscle strength, maximum sniff nasal (SNiP) and static expiratory (PEmax) mouth pressures were also determined ,23.CO), forced expiratory volume in one second (FEV1), and functional residual capacity (FRC). Frequent exacerbators were defined a priori as those having two or more exacerbations per year consistent with international guidelines [The main outcome measures were change in FFM and QMVC. Analysis was performed using StatView 5.0  and focused on the effect of exacerbation rate, oral steroid exposure and disease severity  were actively excluded from analysis because they developed significant co morbidity during the year  and nine (8.3%) patients died during the follow up period. We did not seek to follow up two patients who had moved to a distant part of the country and were no longer patients of the hospital. Thirteen (11.9%) declined to come back for further testing. Of these, two felt too unwell to come, two declined to travel and nine gave no specific reason. For 16 of the remaining 80 patients, clinical data, lung function and weight were available but not measures of strength or fat free mass. This was primarily for logistical reasons, for example difficulty coordinating visits to the lab with patients' clinic appointments. The group that was not followed up did not differ significantly from those who were, in terms of baseline lung function, GOLD stage, strength, body composition, or ADD steroids and exacerbation rate in the year prior to the start of the study (Table The results given henceforth in this paper are for the 64 patients in whom both baseline and follow up measurements of FFM were performed. 22 (34 %) were female, mean cigarette exposure was 47 (28) pack years and 16 (25%) were continued smokers. At baseline, 43 (67%) were using inhaled steroids, seven (10%) were taking regular oral steroids (≤ 10 mg prednisone per day), 19 (30%) had a nebuliser and 12 (19%) were on long term home oxygen therapy. 1,13,15,35 patients were in GOLD stages 1 to 4 respectively. Other baseline characteristics are given in Table -2 for women or < 16 kg.m-2 for men). The FFM deplete group also had significantly worse gas transfer; %predicted TLCO 30.9 (16.8) vs. 44.5 (19.4) (p = 0.008), but did not differ significantly in other lung function parameters or in terms of oral steroid exposure or reported exacerbation rate in the year prior to the start of the study.At baseline 23 (36%) of the patients studied had fat free mass depletion (defined as a fat free mass index (FFMI) < 15 kg.m2O vs. 109.7 (46.4) cmH2O (p = 0.016) but SNiP did not differ significantly 64.6 (20.0) cmH2O vs. 68.3 (19.5) cmH2O (p = 0.5).Patients with FFM depletion had significantly weaker quadriceps QMVC 27.5 (9.3) kg vs. 38.7 (11.3) kg (p = 0.0002) and expiratory muscle strength MEP 79.1(31.2) cmH2 0.35 p < 0.0001) and %predicted TLCO (r2 0.1 p = 0.04), but not with lung volume or airflow obstruction, nor with having frequent exacerbations, ADD prednisone in the preceding year and smoking history. Only FFM was retained as an independent variable in stepwise regression analysis.Quadriceps strength at baseline was significantly correlated with FFM (rOver the course of a year mean (SD) QMVC fell significantly from 34.8 1.5) kg 66.3 (17.9) % predicted, to 33.3 (1.5) kg 62.3 (17.7) %predicted (p = 0.04 and 0.009 respectively) (Table .5 kg 66.2 0.1 p = 0.025) with the greatest decline in the patients who were strongest at baseline. 36 (56%) of the patients were defined as frequent exacerbators. Decline in QMVC in this cohort was not associated with disease severity, having frequent exacerbations or corticosteroid treatment.Decline in QMVC was only correlated with baseline QMVC , worse lung function, being on maintenance prednisone and having frequent exacerbations Table  Figure .-1. Changes in FFM did not differ significantly between those who had (n = 32) or had not received any prednisone during the year, being -0.86 (3.2) kg vs. +0.54 (3.8) kg (p = 0.12) respectively. In addition, to look for evidence of a dose response effect, ADD prednisone was log transformed to normalize it . There was no correlation between log transformed ADD prednisone and change in FFM. Patients on maintenance oral prednisone were more likely to be frequent exacerbators (Chi2 12.4 p < 0.001).The 8 patients on long term maintenance prednisone at the one year follow up visit had a significantly greater decline in FFM compared to the rest of the group; -2.8(3.3) kg vs. +0.2(3.5) kg (p = 0.024). The ADD prednisone received during follow up was median (range) 0 (0–26.1) mg.daySeven patients stopped smoking during the follow up period and experienced a significant increase in FFM compared to the rest of the patients studied; +2.7 (3.1)kg vs. -0.51(3.5)kg (p = 0.026). Comparing quitters to continued smokers (n = 9) the change in FFM was +2.7(3.1)kg vs +0.6(1.0)kg (p = 0.08).By stepwise regression analysis, percent predicted FRC, being on maintenance prednisone, smoking cessation and baseline FFM were retained, with the equation ΔFFM = -0.165 × (FFM) – 0.037 × (%predicted FRC) + 6.5 × (smoking cessation = 1) - 3.3 × (maintenance prednisone = 1) explaining 46% of the variance (p < 0.0001).Measures of respiratory muscle strength are given in Table This study investigated changes in fat free mass and skeletal muscle strength in a cohort of patients with COPD over one year's follow up. Skeletal muscle depletion was common at baseline and was associated with a more severe impairment in gas transfer. During follow up, decline in fat free mass was independently associated with more marked gas trapping, a higher FFM at baseline and use of maintenance oral corticosteroids, whereas FFM increased in patients who stopped smoking. An association between frequent exacerbations and decline in FFM was not retained as an independent correlate.At baseline, quadriceps weakness was most marked in those with reduced fat free mass and declined further over the course of a year. The only parameter predicting decline in QMVC during follow up was QMVC at baseline. Of note the mean decline in QMVC was 4.3% which is significantly more than the 1–2% per annum anticipated in a healthy aging population -27. ThisFollow up data was not available for all of the patients studied at baseline which could be a source of bias. Even in shorter term studies of muscle strength in COPD follow up has been problematic . A numbeWe chose to define exacerbations as episodes of worsening of disease sufficient to cause patients to seek medical assistance and receive a prescription for antibiotics. This definition can therefore to some extent be criticized as dependent on behaviour. On the other hand it has the merit of incorporating an element of 'clinical significance'. Other definitions and techniques such as diary cards have been used and this remains an area of controversy, but to date no consensus exists in the literature as to which is the 'gold standard'. It seems unlikely that a different definition would have caused any systematic difference in the results obtained. In addition it was possible in most patients to correlate their reports of exacerbations with the medical notes relating to clinic attendances in the intervening year to increase accuracy. As part of their routine clinical care at clinic visits during the year patients had been asked to recall exacerbations treated at home. Thus at the end of the year a 'contemporary' record of events was available to correlate with patients' recollection.Bioelectrical impedance analysis has been shown to be highly repeatable on consecutive days in patients with COPD . In healActivity levels might also be expected to impact on changes in strength and body composition but these data were not collected in this study.To our knowledge this is the first prospective study looking at skeletal muscle impairment in patients with COPD over a significant period of follow up. Other studies have been short term ,34, or w1, SGRQ and in particular FRC.Exacerbations of COPD are known to be associated with negative nitrogen balance and elevated levels of cytokines  and an aOral corticosteroids have been proposed as a significant cause of skeletal muscle impairment in COPD  althoughThe benefits of smoking cessation on decline in lung function are well established . Our datSniff nasal inspiratory pressure did not decline during the course of this study. The diaphragm in COPD experiences an increase in loading in contrast to the lower limb muscles where disuse is an important feature. Our findings are consistent with the view that systemic factors such as inflammation are relatively unimportant in the aetiology of muscle weakness or else that they have a synergistic effect with disuse which spares the inspiratory muscles but impacts on muscles of locomotion.It should be noted that by the time patients were enrolled in this study they had already developed significant weakness with mean QMVC only 66 percent predicted. In addition more than a third of them had significant nutritional depletion. Given that baseline FFM was strongly correlated with quadriceps strength at baseline, these two factors are clearly linked even if change over the period of follow up appeared to be dependent on different factors.A further question will be to investigate the interaction between COPD and other co morbidities that occur frequently in these patients and also impact on skeletal muscle such as heart failure and vascular disease.This study demonstrates a reduction in quadriceps strength over one year of follow up greater than would be anticipated in a healthy population. We do not know if there is early rapid loss of strength which then slows or if the decline is steady or if it is stepwise, perhaps in the context of exacerbations. The pattern of decline may well differ in different disease phenotypes. Our model explained only 46% of the decline in fat free mass over one year. Because our patients were recruited from hospital rather than primary care the population was inevitably weighted towards patients with more severe disease and it is clear that in order fully to understand the aetiology of muscle weakness and fat free mass depletion, future studies will need to enrol patients at an earlier point in the disease process and for longer periods of follow up. This should make it possible to understand better the role of factors such as systemic inflammation or hormonal depletion.ADD average daily dose of prednisoneBMI body mass indexCOPD chronic obstructive pulmonary disease1 forced expiratory volume in one second,FEVFFM fat free massFFMI fat free mass indexFRC functional residual capacityPEmax maximum expiratory pressure,QMVC quadriceps maximum voluntary contractionSGRQ St George's respiratory questionnaireSNiP sniff nasal pressureCO carbon monoxide transfer factorTLThe author(s) declare that they have no competing interests.NSH, MIP, JM and TTH conceived the study, NSH drafted the original manuscript. NSH, RCT, MJD, EBS took part in data collection. All authors have been involved in interpretation of the data and have seen and approved the final version of the manuscript.


The efficacy and safety of three different doses of granisetron  were compared in a randomised, double-blind study of 157 patients due to receive high-dose cisplatin therapy (mean dose > 97 mg m-2). In each group, up to two 3 mg rescue doses of granisetron were allowed if more than mild nausea or vomiting occurred. In group A 30.8%, in group B 61.5% and in group C 67.9% of patients were complete responders (i.e. no vomiting or nothing worse than mild nausea) during the first 24 h. These differences are significant between groups A and B, and A and C. There were no statistically significant differences in any efficacy variable between the 10 micrograms kg-1 and 40 micrograms kg-1 groups, although in each case the trend favoured the higher dose. Additional rescue doses resulted in resolved or improved symptoms in 95.3% for the first rescue dose and 93.3% for the second. Over the 7 days of the study, 82.7%, 82.7% and 86.8% of patients in groups A, B and C respectively were treated with granisetron alone. Headache was the most common side-effect, reported by 9.6% of patients; the majority of headaches were mild. There was no difference between the treatment groups regarding the adverse event rate. We concluded that prophylactic doses of 10 or 40 micrograms kg-1 lead to a safe and satisfactory degree of control of nausea and vomiting induced by high-dose cisplatin.


Hyperhomocysteinemia is known as an independent risk factor of atherosclerosis, but the probable role of hyperhomocysteinemia in premature Coronary Artery Disease (CAD) is not well studied. The aim of this study was to assess the role of hyperhomocysteinemia, folate and Vitamin B12 deficiency in the development of premature CAD.We performed an analytical case-control study on 294 individuals under 45 years  who were admitted for selective coronary angiography to two centers in Tehran.After considering the exclusion criteria, a total number of 225 individuals were enrolled of which 43.1% had CAD. The mean age of participants was 39.9 +/- 4.3 years . Compared to the control group, the level of homocysteine measured in the plasma of the male participants was significantly high . However there was no significant difference in homocysteine level of females with and without CAD . Mean plasma level of folic acid and vitamin B12 in the study group were 6.3 +/- 0.2 and 282.5 +/- 9.1 respectively. Based on these findings, 10.7% of the study group had folate deficiency while 26.6% had Vitamin B12 deficiency. Logistic regression analysis for evaluating independent CAD risk factors showed hyperhomocysteinemia as an independent risk factor for premature CAD in males . Study for the underlying causes of hyperhomocysteinemia showed that male gender and Vitamin B12 deficiency had significant influence on incidence of hyperhomocysteinemia.We may conclude that hyperhomocysteinemia is an independent risk factor for CAD in young patients (bellow 45 years old) – especially in men -and vitamin B12 deficiency is a preventable cause of hyperhomocysteinemia. Homocysteine is a sulfhydryl containing amino acid produced by demethylation of an essential amino acid (methionine) . MethylaExcept in cases of severe hyperhomocysteinemia  > 100 μmol/lit), usually due to metabolic disorders of methyonine metabolism, mild or moderate cases of hyperhomocysteinemia tHcy > 15 μmol/lit), prevalent in the general population, can be the result of dietary deficiency of factors such as vitamin B12 and folic acid  μmol/lit. Other cMeanwhile, we do not have sufficient data regarding the role of hyperhomocysteinemia in development of premature CAD and this question needs further investigations ,14. HereIn addition to CAD development, high plasma levels of homocysteine have a relation with the incidence of several neurologic disorders such as congenital neural tube defect, Alzheimer's disease and suspicious carcinogenic potentials -19.This study was performed to assess the role of homocysteine, folic acid and vitamin B12 (as probable causes of hyperhomocysteinemia) in the occurrence of premature CAD while considering other known risk factors of CAD.This case-control analytical study was performed in a group of 294 participants  including consecutive patients aged less than 45 years old, who underwent selective coronary angiography into two medical and educational centers in Tehran. From the 294 patients included in this study: 144 were referring angina (56 stable angina and 88 unstable angina); 41 had a previous myocardial infarction; 65 had a positive ergometric test and 44 had a positive scintigraphy test. The sample population was stratified in patients with CAD (127) and normal (167) groups. There were two sources for data collection. Some data were gathered by interview and filling a questionnaire covering all personal data and medical history. This questionnaire was designed based on standard Rose questionnaire for anginal pain, known CAD risk factors and confounding factors.The second source of data was lab exams  and the results of selective coronary angiography. We excluded patients with myocardial infarction in the last 6 weeks, those who had taken any medication containing vitamin B12 or folic acid and N-Acetyl Cysteine (NAC) within 6 weeks of enrollment, those suffering from hypothyroidism ,anemia (hemoglobin<12 g/dl) and creatinine levels equal or greater than 1.5 mg/dl plus any features of chronic renal failure. By applying these criteria, 69 participants  were excluded from the study.Blood samples were withdrawn from patients after an overnight fast, and the plasma were put in a cooled container and immediately carried to the "Massoud" laboratory, where the plasma was separated within 1 hour of sampling by centrifugation  and aliquots were stored at -70°C until analysis. Plasma level of homocysteine was determined by high performance liquid chromatography (HPLC) method, coupled with fluorescence detector and plasma level of folic acid and vitamin B12 by Radio immunoassay (RIA). The serum level of lipids and lipoproteins were determined by calorimetric method. Folic acid levels less than 2.2 ng/ml and vitamin B12 levels less than 175 pg/ml were classified as folate and B12 deficiency, respectively.The traditional or classical coronary risk factors include: (1) diabetes mellitus ; (2) hypertension ; (3) Hyperlipidemia ; (4) smoking (Regularly using tobacco for the last 6 months); and (5) family history of CAD .After collection of crude necessary data, these data were statistically analyzed by statistical analysis system (SAS) software for windows 9.1. We used chi-square and t-test to compare qualitative variables and quantitative variables, respectively. Logistic regression analysis was used for detecting independent variables. The differences were considered significant if P value was less than 0.05.The committee for medical ethics of the Tehran Heart Center approved the study. Each participant signed an informed consent form before completing the questionnaire.A total number of 225 participants were enrolled from which 179 (79.6%) were male and 46 (20.4%) were female. All participants were under 45 years old.Considering results of coronary angiogram, 97 participants (43.1%) had premature coronary artery disease of which 86 patients (88.7%) were male and 11 (11.3%) were female ;128 participants (56.9%) were free of significant CAD of which 93 (72.7%) were male and 35 (27.3%) were female that stratified in control group. In patients with significant CAD; 32 (33%) had single vessel disease, 37 (38.2%) two vessel disease and 28 (28.8%) had three vessel disease.The mean age of the study group was 40.1 ± 4.2) years in males and (39.4 ± 4.8) in females. No significant difference was noted between the patient and control group in this regard. Major CAD risk factors are compared between controls and patients in Table  ± 4.2 yeThe mean serum level of homocysteine was (16.6 ± 1.01 μmol/lit) in the study group and was significantly higher in males 17.9 ± 1.2 μmol/lit) compared to females (11.5 ± 0.9 μmol/lit) (P < 0.01). The mean plasma level of homocysteine in patients (19.3 ± 1.7 μmol/lit) was significantly higher than the control group (13.9 ± 0.9 μmol/lit) (P < 0.005). Considering the sex factor, a similar relationship was present in male participants (P < 0.01) but not in females (P = 0.87)  Table .Logistic regression test in males with and without hyperhomocysteinemia compared to total subjects showed similar results in effect of hyperhomocysteinemia on development of CAD  while in females there was no increased chance for premature CAD in individuals with hyperhomocysteinemia. However, prevalence of premature CAD was higher in females with hyperhomocysteinemia (above 15 μmol/lit) than who did not have hyperhomocysteinemia (42.9% versus 20.5%). The role of other known risk factors of CAD in increasing the risk of premature CAD is also demonstrated in Table We studied the relation between hyperhomocysteinemia and plasma level of folic acid, vitamin B12, male gender, increasing age, cigarette smoking, diabetes mellitus and hypertension. Mean plasma level of folic acid in the study group was 6.33 ± 0.29 ng/ml . Mean plasma level of vitamin B12 was 282.5 ± 9.1 pg/ml . Therefore, 10.7% of the study group (24 participants) had folic acid deficiency . Also 24.3% (55 participants) had vitamin B12 deficiency .Although generally speaking there is a reverse relationship between plasma level of homocysteine and folic acid level  or vitamin B12 , the logistic regression test for the study group showed that male sex  and vitamin B12 deficiency  were two factors that caused significant increase in homocysteine levels.Other factors such as cigarette smoking, increasing age, diabetes mellitus and hypertension did not have any statistically significant role in hyperhomocysteinemia (tHcy>15 μmol/lit). Although the mean plasma level of homocysteine in cigarette smokers (17.5 ± 1.4 μmol/lit) was higher than non-smokers (14.9 ± 1.2 μmol/lit), this was not statistically significant (P = 0.16). Mean plasma level of homocysteine in hypertensive individuals was not significantly different from normotensives . The differences in diabetic and non diabetic individuals were also non significant . No significant difference in plasma homocysteine level was observed in either of age groups (above and bellow 35 years) (P = 0.1).In the present study, the prevalence of hyperhomocysteinemia in patients with premature CAD was 47.4%. American Heart Association (AHA) reported a prevalence of 12 to 47% in 1999 for patients with CAD . The resPinto et al in Bellvitge hospital (Spain) also found a correlation between high plasma level of homocysteine and premature CAD . In their study hyperhomocysteinemia was presented as a risk factor for premature CAD .Lolin et al (China) showed that in patients with premature CAD, plasma levels of homocysteine was significantly higher than normal participants  . Clarke Although, in none of the above mentioned studies was there any difference between males and females in this regard, Foody et al (Cleveland – USA) showed that despite the presence of a correlation between hyperhomocysteinemia and premature CAD in males  no such correlation was noted in females  which resembles our findings .Based on the results of our study and other previous studies it seems that hyperhomocysteinemia is a risk factor for premature CAD in men, but not proven so in women. A Correlation between plasma levels of homocysteine, severity of CAD and number of involved vessels was studied and no significant correlation was found. Brilakis et al have also studied the correlation between plasma level of homocysteine and angiographic findings in patients with CAD and found no significant correlation .Plasma level of homocysteine in male participants was significantly higher than females . Logistic regression analysis yeilded the same results, meaning male sex was an effective factor in plasma level of homocysteine in our study group . Like wise, Jucques et al(Boston- USA) showed that the mean plasma level of homocysteine in men was 11% more than women (P < 0.001). This difference could be having several explanations . First; In our study, the prevalence of hyperhomocysteinemia was higher than other populations. It could be due to geographical variations, racial and ethnic differences , geneticBased on results of the present study, the prevalence of folic acid deficiency was 10.7% (13.1% in men and 2% in women) while vitamin B12 deficiency had a rate of 24.4% (26.6% in men and 16.7% in women). This deficiency  is considerable. Logistic regression tests demonstrate that vitamin B12 deficiency was an effective factor in hyperhomocysteinemia in our study group  which resembles Jucques et al findings . DespiteThe present study is one of the few studies in which the control group is chosen precisely and based on angiographic results, while in most of studies, lack of CAD symptoms and signs have been the inclusion criteria for the control group ,37.We may conclude that hyperhomocysteinemia is an independent risk factor for CAD in young patients (bellow 45 years old)  and vitamin B12 deficiency is a preventable cause of hyperhomocysteinemia.AHA: American Heart Association, CAD: Coronary Artery Disease, CBS: cystathionine-β-synthase, HDL: high density lipoprotein, HPLC: High performance liquid chromatography, LDL: low density lipoprotein, MTHFR: methylene tetrahydrofolate reductase, NAC: N-Acetyl Cysteine, OR: odds ratio, RIA: Radio immunoassay, SAS: statistical analysis system, tHcy: plasma total homocysteineThe author(s) declare that they have no competing interests.1) SS: principle investigator, has made substantial contributions to conception and design of the study2) FF: performed angiography3) MS: performed angiography4) GD: performed angiography and has been involved in drafting5) MM: has made substantial contributions to data acquisition and has been involved in drafting and interpretation of data6) NF: data analysis and substantial contribution7) SD: has been involved in drafting and interpretation of data8) AK: has given final approval of the version to be published and revising it critically for important intellectual contentDeclaration: All authors read and approved the final manuscriptThe pre-publication history for this paper can be accessed here:


Taxol, a unique tubulin active agent, was found to demonstrate a marked schedule-dependent synergistic interaction with cisplatin (DDP) in the killing of human ovarian carcinoma 2008 cells in vitro as determined by median effect analysis. The interaction was highly synergistic when 19 h taxol exposure was followed by 1 h concurrent exposure to taxol and DDP. The combination indices (CIs) on this schedule were 0.11 +/- 0.1, 0.25 +/- 0.15 and 0.39 +/- 0.14 at 20%, 50% and 80% cell kill respectively. However, the interaction was antagonistic when 1 h exposure to DDP was followed by 20 h exposure to taxol, or when cells were exposed to DDP and taxol for 1 h concurrently. When taxol preceded DDP, synergy was also observed with the 11-fold DDP-resistant 2008/C13*5.25 subline, which yielded CI values of 0.21 +/- 0.02, 0.30 +/- 0.11 and 0.31 +/- 0.17 at 20%, 50% and 80% cell kill respectively. At an IC50 concentration, taxol had no effect on [3H]cis-dichloro(ethylenediamine) platinum uptake, on the permeability of the plasma membrane or on glutathione or metallothionein levels in 2008 or 2008/C13*5.25 cells. Mitotic arrest in these cells was observed only at taxol concentrations well above those required for synergy with DDP, suggesting that the mechanism underlying the synergistic interaction was not a taxol-induced alteration in cell cycle kinetics. Of additional interest was the fact that the 2008/C13*5.25 cells were hypersensitive to taxol, and that this was partially explained by an alteration in the biochemical pharmacology of taxol. Although cellular taxol accumulation reached steady state within 2 h in both cell lines, taxol efflux was slower and the taxol was more extensively bound in 2008/C13*5.25 cells than in 2008 cells. In addition, the 2008/C13*5.25 cells had only 55% of the parental levels of beta-tubulin content. However, in another pair of DDP-sensitive and -resistant ovarian cell lines no taxol hypersensitivity and no change in beta-tubulin content was observed, indicating that the DDP-resistant and taxol-hypersensitive phenotypes do not segregate together. We conclude that taxol interacts synergistically with DDP in a manner that is highly schedule dependent, and that the hypersensitivity of 2008/C13*5.25 cells no taxol is unrelated to the mechanism of synergy. These in vitro observations suggest that drug schedule will be an important determinant of the activity and toxicity of the DDP and taxol drug combination in clinical studies.


To determine the association of human papillomavirus infection (HPV) and transitional cell carcinoma (TCC).Using polymerase chain reaction, fifty-nine bladder tissue specimens of patients with transitional cell carcinoma of bladder compared with 20 bladder samples of cases with non-neoplastic disorders.P = 0.62). Mean age was 67 ± 10.8 years and 52 ± 20.3 years in the case and control groups, respectively (P = 0.6). Of the 59 tissue specimens with diagnosis of transitional cell carcinoma, HPV DNA was detected in 21 (35.6%) samples, while it was present in only one sample (5%) in the control group (P = 0.008). HPV18 was the most common type of virus with the incidence rate of 17/21(81%).Male to female ratio was similar in the two groups (50/9 vs. 16/4, HPV might play a causative role in transitional cell carcinoma of bladder in our geographic area. The etiology of transitional cell carcinoma (TCC), which represents 90 percent of bladder malignancies, is not quite clear, while squamous cell carcinoma 5%) of the bladder is well associated with some factors like urinary stones and prolonged infections. Some genital malignancies like vulvar or cervical neoplasms are associated with previous infection with human papillomavirus (HPV). Recently, conflicting findings have been reported on association of HPV infection and TCC -5.% of the Using PCR, the overall prevalence of human papillomavirus (HPV) DNA in penile carcinoma is about 40–45%, which is similar to the detection rate of HPV-DNA in vulvar carcinoma . Males mWhile Kamel et al found HPV DNA in 57% of cases of TCC , Tekin'sThe medical records and bladder tissue specimens of 59 consecutive patients with transitional cell carcinoma of bladder who underwent transurethral resection of bladder tissue from October1999 to May 2002 were reviewed and compared with those of 20 consecutive patients with non-neoplastic disorders who were served as controls. So, a total of 79 biopsy tissues of urinary bladder were re-evaluated and analyzed by polymerase chain reaction (PCR). The designing and conducting of this study was in accordance with the ethical standards of UNRC ethics committee. Table Specimens were taken from paraffin-embeded bladder tissues stored in laboratory of our hospital- Tajrish Shohada medical center. All specimens were collected and transported to molecular biology research center of shaheed Beheshti University of Medical Sciences under a well-controlled condition. Biopsy specimens were digested in lyses buffer  at 37°C for 4 hours. Phenol-chloroform extraction and ethanol precipitation were performed. The precipitated DNA was suspended in distilled water and used for amplification.2, 0.1 mM of each dNTP, 20 pico mol of each primer, 0.1 μg DNA, 1.25 unit of Taq DAN polymerase and 1× PCR buffer. PCR conditions are: 30 cycles of denaturing at 94°C for 30 sec., annealing temperature at 45°C for 30 sec. and extension at 72°C for 30 sec. PCR reaction was performed using automated thermal cycler machine .Two primer pairs were designed of HPV L1 gene (encodes the major capsid protein): one primer pair amplify a 269-bp fragment of HPV 6, 11, 31 and 33, and another primer pair amplify a 564-bp fragment of HPV 16, 18 and 35; and HPV types were defined by PCR products restriction analysis. PCR: Amplifications were carried out in 50-μl volumes. The reaction mixture contained 1.5 mM MgClPCR products were electrophoresis on 2% agarose gel. Gels were stained by ethidium bromide and photographed by UV transilluminator at 254 nm.P < 0.05.Statistical analysis was performed using Mann-Whitney, chi-square and fisher's exact tests as appropriate with significance considered at P = 0.62). Mean age was 67 ± 10.8 (range 38 to 85) years and 52 ± 20.3 (range18 to 81) years in the case and control groups, respectively (P = 0.6).The study population comprised 59 cases and 20 controls whose demographic and clinical characteristics are given in table P = 0.008) that was histolologically diagnosed as severe chronic cystitis with some degrees of atypical hyperplasia, that might be considered as a pre-malignant condition.Of the 59 tissue specimens with diagnosis of transitional cell carcinoma, HPV DNA was detected in 21 (35.6%) samples. Human papillomavirus DNA was positive in only one sample (5%) in the control group , one male and 1 female; HPV 18 was found in 14/21 patients (66.7%),13 males and 1 female ; and HPV 33 sequences were detected in2/21(9.5%), 1 male and 1 female. In 3 HPV-positive male cases (14.3%) more than one type was found; 2 patients with HPV6/HPV18, and 1 witht HPV18/HPV33. Thus, HPV18 was the most common type of virus with the incidence rate of 17/21(81%). HPV18 was also found in one male patient in the control group. HPV types 11, 16, 31 were present in no tissue specimens. Table P = 0.59).The histopathological stages and grades of tissue samples with diagnosis of transitional cell carcinoma considering infection with HPV are given in Table P = 0.00). In the case group, 12 out of 21 (57%) infected patients and 20 out of 38 (52.6%) non-infected were cigarette smokers, respectively (P = 0.7). Ten cases (16.9%) but no patient in the control group were addicted to opium (P = 0.05). On the other hand, four infected (18.2%) and 6 non-infected (10.5%) subjects were addicted to opium (P = 0.36).Smoking rate in the case group was significantly higher than control group  oncoprotein E7 is a mechanism by which HPV promotes cell growth . Human pHPV may have a great role in progression of TCCs toward higher stages and/or grades by inactivation of the tumor suppressors or other unknown mechanisms.Larue et al. reported that sensitivity of detection of HPV is largely dependent on a series of technical factors such as tissue fixation, DNA preparation and amplification conditions. In their study, presence of HPV correlated with grade but not stage of the tumors. . Our speHigh rate of HPV positivity in present study suggests that other sexually transmissible viruses may play some roles in development and progression of transitional cell carcinoma of the bladder. As Gazzaniga et al demonstrated, there may be a high synergism between Human Papillomaviruses type 16 and 18 , Epstein-Barr virus (EBV), cytomegalovirus (CMV) and herpes simplex virus type 2 (HSV-2) and bladder carcinogenesis. In thisOn the basis of high rate of HPV positivity in TCC cases (35.6%), comparing with control group(5%), the present report supports an etiologic role of HPV in bladder carcinogenesis.This quasi-experimental study is the first report from Iran on HPV infection and transitional cell carcinoma. Our findings, in spite of some previous reports, suggest that HPV may play a causative role in transitional cell carcinoma of bladder in our geographic area. Public education regarding HPV transmission and high-risk behavior may be helpful for decreasing the incidence of urogenital malignancies.HPV: Human Papilloma VirusThe author(s) declare that they have no competing interest.M.R.B. and A.H. introduced the cases and performed surgical operations. S.M.M.H.M. designed the study and performed statistical analyses. B. K. performed laboratory examinations and PCR. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Basal TSH levels reflect the metabolic status of thyroid function, however the definition and interpretation of the basal levels of TSH is a matter of controversial debate. The aim of this study was to evaluate basal TSH levels in relation to the physiological response to i.v. TRH stimulation.A series of 2570 women attending a specialized endocrine unit were evaluated. A standardized i.v. TRH stimulation test was carried out by applying 200 μg of TRH. TSH levels were measured both in the basal and the 30 minute blood sample. The normal response to TRH stimulation had been previously determined to be an absolute value lying between 2.5 and 20 mIU/l. Both TSH values were analyzed by cross tabulation. In addition the results were compared to reference values taken from the literature.Basal TSH values were within the normal range (0.3 to 3.5 mIU/l) in 91,5% of cases, diminished in 3,8% and elevated in 4.7%. Based on the response to TRH, 82.4% were considered euthyroid, 3.3% were latent hyperthyroid, and 14.3% were latent hypothyroid. Combining the data on basal and stimulated TSH levels, latent hypothyroidism was found in the following proportions for different TSH levels: 5.4% for TSH < 2.0 mIU/l, 30.2% for TSH between 2.0 and 3.0 mIU/l, 65,5% for TSH between 3.0 and 3.50 mIU/l, 87.5% for TSH between 3.5 and 4.0 mIU/l, and 88.2% for TSH between 4 and 5 mIU/l. The use of an upper normal range for TSH of 2.5 mIU/l, as recommended in the literature, misclassified 7.7% of euthyroid cases.Our analysis strategy allows us to delineate the predictive value of basal TSH levels in relation to latent hypothyroidism. A grey area can be identified for values between 3.0 and 3.5 mIU/l. Elevated levels of TSH are the hallmark of decreased thyroid function. In order to correctly identify these patients it is imperative to have a clear definition of the upper reference range for basal TSH. Patients whose TSH lies in the upper reference range might appear to have minimal thyroid deficiency. Although this might appear to be an easy task, the definition of the upper reference range for TSH has been matter of controversial debate -5. ReporWithin the setting of a fertility unit, the exclusion or identification of causes of infertility requires a broad diagnostic approach. In a recent review by Poppe, Velkeniers, and Glinoer, special emphasis was put on the evaluation of thyroid function . ReferriThe laboratory methods used have been described elsewhere . A totalThe reference ranges from the literature were taken from Zöphel  and BaloThe laboratory results were classified according to the criteria presented by Dayan . StatistStratification of data according to age groups did not reveal any age-dependency of thyroid function parameters . The classification of cases according to the levels of the free thyroid hormone showed 86,65% of cases to lie within the normal range, 2.3% lied above and 11.05% below. The proportion of patients having a normal basal TSH according to the 3 evaluation criteria was: 91.52% for I-TSH, 90.66 for Z-TSH and 83.77 for B-TSH, respectively. The lower number of euthyroid cases using the B-TSH criteria was accompanied by a 7.76% increase in the proportion of cases classified as having elevated TSH levels  declare that they have no competing interests.OD and HE carried out the clinical work with the patients. RM created the data based and carried out the statistical analyses.The pre-publication history for this paper can be accessed here:


There is strong evidence that breast cancer risk is influenced by environmental factors, and animal experiments and human ecological data suggest that increased dietary fat intake increases the incidence of the disease. Epidemiological evidence on the relationship of dietary fat to breast cancer from cohort and case control studies has however been inconsistent. To examine the available evidence we have carried out a meta-analysis to summarise quantitatively the large published literature on dietary fat in the aetiology of breast cancer. After assembling all of the published case control and cohort studies, we extracted the relative risk in each study that compared the highest to the lowest level of intake. We then calculated a summary relative risk for all studies. The summary relative risk for the 23 studies that examined fat as a nutrient was 1.12 (95% CI 1.04-1.21). Cohort studies had a summary relative risk of 1.01 (95% CI 0.90-1.13) and case control studies a relative risk of 1.21 (95% CI 1.10-1.34). Summary estimates of risk for specific types of fat excluded unity for only saturated fat. For the 19 studies that examined food intake, the summary relative risks were 1.18 (95% CI 1.06-1.32) for meat, 1.17 (95% CI 1.04-1.31) for milk, and 1.17 (95% CI 1.02-1.36) for cheese. Summary relative risks for total fat intake were examined for several potential modifying factors. Regression analysis showed that European studies were more likely than studies done in other countries to show an increased relative risk associated with dietary fat and breast cancer, after taking into account potential modifying factors that included study design and quality.


Dental surgery can be carried out on patients under oral anticoagulation therapy by using haemostyptic measures. The aim of the study was a comparative analysis of coagulation by laboratory methods and immediate patient diagnosis on the day of the planned procedure.On the planned day of treatment, diagnoses were carried out on 298 patients for Prothrombin Time (PT), the International Normalised Ratio (INR), and Partial Thromboplastin Time (PTT). The decision to proceed with treatment was made with an INR < 4.0 according to laboratory results.Planned treatment did not go ahead in 2.7% of cases. Postoperatively, 14.8% resulted in secondary bleeding, but were able to be treated as out-patients. 1.7% had to be treated as in-patients. The average error between the immediate diagnosis and the laboratory method: 95% confidence interval was -5.8 ± 15.2% for PT, -2.7 ± 17.9 s for PTT and 0.23 ± 0.80 for INR. The limits for concordance were 9.4 and -21.1% for PT, 15.2 and -20.5 s for PTT, and 1.03 and -0.57 for INR.This study showed a clinically acceptable concordance between laboratory and immediate diagnosis for INR. Concordance for PT and PTT did not meet clinical requirements. For patients under oral anticoagulation therapy, patient INR diagnosis enabled optimisation of the treatment procedure when planning dental surgery. To prevent thrombosis and embolism, patients are treated increasingly as out-patients and are sometimes given anticoagulant therapy for many years. The anticoagulant with coumarin derivatives is widely distributed. As vitamin K antagonists, these derivatives inhibit the g-carboxylation of glutamic acids in the synthesis of coagulation factors II, VII, IX and X in the liver. With regards to comparability and standardisation of test results for oral anticoagulation therapy, the International Normalised Ratio (INR) is recommended by WHO for monitoring of patients' coagulation physiology. INR values between 2.0 and 3.0 are recommended for thromboembolic illnesses, atrial fibrillation, heart valve diseases and myocardial infarct. For mechanical heart valves and recurring embolism, an INR value between 2.5 and 3.5 is set.Haemorrhages, which can occur after teeth extractions, for example, only present a significant risk for patients under anticoagulation therapy in exceptional cases . In contA total of 298 patients who received dental treatment under anticoagulation therapy were included in this study. The period of acquisition reached from 10.10.2002 to 16.04.2004. The group tested consisted of 106 women and 192 men with an age range of 11–91 years and an average age of 60.1 years. Anticoagulation treatment was carried out after thromboembolic illnesses (30.5%), atrial fibrillation (27.4%), myocardial infarct (15.1%) and heart valve replacement (34.0%). Coumarin therapy was carried out for 92.4% of patients. 6.6% were treated under general anaesthesia and oral anticoagulation was administered by intravenous heparin. Additional inhibition of thrombocyte aggregation by acetylsalicylic acid or ticlopidine occurred for 2.7%. The decision to proceed with treatment was made with an INR < 4.0 according to laboratory results [Local haemostyptic measures consisted of sealing the thick wound in a collagen dressing (66.0%), a fibrin adhesive (27.4%), and the use of a protective plate (18.9%). A local flap coverage was used in 15.1% of cases.Patients' intra- and postoperative trends were recorded and complications were documented. Before treatment, capillary blood was extracted. The diagnosis for Prothrombin Time (PT), International Normalised Ration (INR) and Partial Thromboplastin Time (PTT) was carried out with a CoaguChek Pro device . CoaguChek Pro PT cassettes contain thromboplastin from rabbit brains (ISI 2.04). As a PTT reagent, cow brain sulphatide was used as an activator, and soya phosphatide as a platelet substitute. The measuring principle of the machine is based on laser-photometric detection of erythrocyte movement, which is suspended when coagulation begins to set in. Measurement and quality control were carried out, in accordance with the manufacturer's instructions, by 3 experienced assistant medical technicians. At the same time, blood tests were taken in the coagulation tubes  and analysed in the clinic's main laboratory. Both the PT and PTT diagnoses were carried out with a BCS coagulation analyser . Thromborel S  and Pathromtin SL  were used as reagents.Bland and Altman [The test results were analysed by a thorough data analysis with determination of average values and standard deviations. As a cohesive measurement between the parameters, the correlation coefficient r with the corresponding test (HO: r = 0) was used. With p values < 0.01 the correlation was accepted. Selected parameter combinations were depicted in range diagrams with the corresponding regression line. The concordance between measurement methods was analysed in accordance with d Altman . Averaged Altman .Planned treatment did not go ahead in 2.7% of cases. 2.3% also had an INR value > 4.0 in immediate diagnosis. 2.3% of immediate diagnoses were in the same measurement range; laboratory diagnoses gave an INR value > 4.0. Intra-operatively, there was the complication of one major haemorrhage. Postoperatively, 14.8% resulted in secondary bleeding, but were able to be treated as out-patients. 1.7% had to be treated as in-patients.No significant difference was determined in coagulation values for patients who did and did not suffer secondary bleeding Fig. . On analFig. The relative error between the laboratory and immediate determination method ± 95% confidence interval was -5.8 ± 15.2% for PT Fig. , -2.7 ± The relative error between the laboratory methods and immediate diagnosis was 21.3% with an average PT of 34.5%, 6.3% with an average PTT of 47.2 s, and 7.6% with an average INR of 2.77. The relative limit for concordance between laboratory methods and immediate diagnosis was 48.6% for PT, 35.7% for PTT and 24.3% for INR.The proportion of patients with postoperative secondary bleeding is comparable with the literature ,6,16 as Concordance for PTT diagnoses are also the subject of controversial discussion. There are also studies on good concordance , as wellIn conclusion, patient INR diagnosis with the CoaguChek Pro device allows for clinically acceptable optimisation of the treatment procedure when planning dental surgery for patients under oral anticoagulation therapy.The author(s) declare that they have no competing interests.BKL set up the design of the study, performed the surgical part, and helped to draft the manuscript. MK carried out the statistical analysis. JK performed the statistical analysis and participated in the design of the study, the coordination of the patients and helped to draft the manuscript. All authors read and approved the final version of the manuscript.


A retrospective review of 30 patients with eso/exodeviations less than 20 prism diopters (PD) who underwent one injection of BPX into their medial/lateral rectus was carried out. Preoperative deviations were recorded in PD, using the alternate prism cover test. Postoperative angles at 1 and 3 months were measured in the same manner. 11 out of 30 patients achieved an acceptable outcome and required no further intervention.The mean angle of deviation for near in all patients reduced significantly by 3.1 PD and 2.1 PD at 1 and 3 months. The mean angle of deviation for distance in all patients also decreased significantly by 2.3 PD and 1.9 PD at 1 and 3 months. In conclusion, single injection of BPX in a heterogeneous group of patients with horizontal strabismus caused a mild improvement and a qualitative success rate of 37%. Bupivacaine hydrochloride (BPX) is a sodium channel blocker local anesthetic that also displaces calcium from membrane binding sites and increases cytoplasmic Ca2+ level. This results in a particular myotoxixcity that leaves the basal lamina, satellite cells, nerve fibers and vessels intact allowing regeneration of muscle fibers , 2.Unintentional injection of BPX into the extraocular muscles during the local anesthesia for cataract surgery can cause strabismus due to muscle hypertrophy and increased stiffness -5.Scott et al showed for the first time that the injection of BPX into the lateral rectus corrected esotropia in 4 of 6 patients. The average improvement in alignment for all patients was 8 PD, with associated 6.2% increase in muscle volume measured from MRI images. Later they reported an average improvement of 19.7 PD in alignment when treated the affected muscle with BPX and its antagonist with botulinum type A toxin . We report the outcome of a single injection of BPX for correction of small angle (<20 PD) horizontal strabismus in a heterogeneous group of patients.This is a retrospective review of all patients injected with BPX at a referral center in Liverpool, UK, from March 2008 to February 2013. Eventually, this study included thirty  patients with horizontal strabismus. Four additional patients also received BPX injection but were lost to follow- up after injection and therefore not included in this report. BPX was injected into their lateral (LR) or medial rectus (MR) muscle, depending on diagnosis. This method has been part of the standard management of patients with small angle deviation (≤ 20 PD) and in those with multiple previous surgeries who preferred a non-surgical alternative for small residual deviations.Institutional audit approval was obtained. Marcaine  - bupivacaine hydrochloride injection containing 0.5 g/dl bupivacaine, in individual dose of 4.5 to 5 ml was injected into the LR or MR under topical anesthesia  using a special needle insulated apart from the bevel and electromyography from the bevel. Maximal electrical signal indicated the area of greatest density of neuromuscular junctions and at that point the BPX was injected. A single surgeon (I.B.M) carried out all injections.Preoperative measurements of the horizontal deviations of all patients were recorded in PD, using the alternate prism cover test at both 1/3 meter and 6 meters for all patients. Postoperative deviations were measured in the same manner at 1 and 3 months.The following information were recorded as much as possible; age at presentation, best corrected visual acuity, diagnosis, detail of previous surgery and chemodenervation, sensory status, angle of deviation before and at 1 and 3 months after injection, outcome and complications. Patients with thyroid eye disease were excluded.Values of angle of deviation are given as mean+/- standard deviation . Repeated Measures ANOVA and Wilcoxon paired test were employed to assess the comparison of the angle of deviation before or 1 and 3 months after the injection. P values less than 0.05 are considered significant. Graphpad prism 6  was used for statistical analysis.The age distribution of our patients was between 20 and 81 years with a mean of 43.4 (median = 40). The average visual acuity was 0.1 (range: 0.2 to 1.0) LogMAR. Five patients had visual acuity worse than 0.8 LogMAR in the deviating eye.Sixteen patients  with esotropia underwent one injection of BPX into their LR, . Their average age was 44 (range: 24–81) years. Eight patients had previous surgery on their LR and were left with small angle residual esotropia, two had residual esotropia following recovery from abducens nerve palsy. None had chemodenervation of LR but three had previous MR chemodenervation.The average preoperative distance angle in LR group was 9.6 +/- 5.0 . At 1 and 3 month after injection, it reduced significantly to 7.1+/-4.7, and to 7.5+/- 4.9  respectively, P=0.0086. The difference between the mean angle at 1 and 3 months after injection did not reach statistical significance Table 1). The average preoperative near angle in LR group was 9.9+/- 5.2 . At 1 month after injection, it reduced to 7.6+/- 4.7,  and to 8.3+/- 5.1,  at 3 months. These reductions did not reach statistical significance  injection into their LR for esodeviation; 5 improved to the extent that patients were content and discharged, while 11 required surgery. Among these 11 patients, five were better initially but not completely cured and therefore needed surgery while the other six did not change significantly. At 3 months, the angle of deviation improved to ≤10 PD for distance in 13 of 16(81%) and for near in 11 of 16(69%) compared to 8 of 16(50%) at pre-op for distance and near.ed and discharged, 4 had successful surgery, 2 were lost to follow-up, 1 is managed with prism and one did not want further intervention. At 3 months, the angle of deviation improved to ≤10 PD for distance in 11 of 14(74%) compared to 10 of 14 (71%) preoperatively and for near in 8 of 14(57%) compared to 6of 14 (43%) before the injection.Fourteen patients  with exotropia had one injection of BPX into their MR muscle, . Their average age was 43 (range: 20–60) years. 10/14 patients had previous surgery on their MR and were left with small angle residual exotropia. None had chemodenervation. The average preoperative distance angle in MR group was 7.9 +/- 5.1. At 1 and 3 months after injection, it reduced to 5.9+/-4.0 , and to 6.2+/- 4.7 , p>0.05(Table 1). The average preoperative near angle in MR group was 11.3+/- 4.9, . At 1 and 3 months after injection, it was reduced to 7.1+/- 5.5  and 8.6+/- 6.8, respectively , P=0.06 (Table 1). Out of 14 patients who had LA injection into their MR, 6 were improved to the extent that patients were contentThe overall pre-op angle of deviation for distance was 8.8+/- 5.1 , reduced to 6.5+/- 4.4  at 1 month and to 6.9+/-4.3 at 3 month, p=0.02Table 1). The overall pre-op angle of deviation for near was 10.5+/- 5.1  and reduced to 7.4+/- 4.9 , or 8.4+/-5.8 at 1 and 3 months, respectively . All their measurements were at 3 meters and therefore are not directly comparable with our results.Earlier Scott et al showed an average reduction of 8 PD with BPX alone and 19.7 PD reduction when combined with botulinum type A toxin into the antagonist –8. WutthOur results support others’ findings as over one-third of our patients achieved satisfactory outcome after one injection. However, the success rate and the overall improvement are more modest than in the other groups. This may be due to the selection of patients with deviations less than 20PD or due to the difference the angle of deviations were measured and reported. Namely, these measurements in our study were performed at both 1/3 and 6 meters fixation targets. Scott et al also used a higher concentration of BPX 0.75% -3%) and higher volume compared to us , although they had limited number of patients with 8, 6 and 3 patients after 1, 2 and 3 years .Increase in the mean angle of deviation at 3 months compared to 1 month, did not reach statistical significance. On the other hand, none of our 11 patients that were discharged with satisfactory outcome at 3 month have come back with a recurrence after a minimum of 8 months following injection. There is of course the slim possibility that they have sought treatment elsewhere.Since BPX is, apparently, not effective in chronically denervated muscles, Miller et al excluded paralytic strabismus from their analysis . We alsoAs any other retrospective study, ours is burdened with some classical limitations, such as: relatively small number of cases, which may explain the lack of statistical significance. Despite this, we believe that these results are helpful to the individual cases in clinical practice. Therefore, we believe we should continue to inform our patients of the 37% success rate when counseling.


Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high worldwide prevalence, which is increasing, particularly in developing countries , 2; moreCOPD is characterized by chronic diffuse irreversible airflow obstruction involving mainly small airways. This condition is a growing cause of morbidity, disability, and mortality in both developed and developing countries that can be related to environmental exposures, smoking and respiratory infectious diseases . AlthougPreviously published studies evaluating the prevalence of COPD have provided a range of estimates across different countries. The prevalence of previously diagnosed COPD (when diagnosis was made in the past and reported by a respondent) ranged from 18 per 1000 (Sweden) to 222 per 1000 (Russia); and the prevalence of COPD diagnosed by spirometry ranged from 37 per 1000 (United Arab Emirates) to 240 per 1000 (The Netherlands). In the multinational BOLD study the overall prevalence of COPD diagnosed by spirometry using a standardized approach was 193 per 1000 [More than half of those with chronic respiratory diseases live in low and middle income countries, including some Commonwealth of Independent States (CIS) countries , where tThe CORE study is a multi-national, cross-sectional population-based epidemiological study conducted across major cities in Ukraine, Kazakhstan and Azerbaijan  from the first half of 2013 until the end of 2015. The study enrolled subjects who were ≥18 years old, had lived in the selected city for ≥10 years and provided written informed consent to participate in the study.Subjects for whom spirometry could not be performed, and subjects who were not able to answer the study questionnaires (American Thoracic Society (ATS) Respiratory Symptoms Questionnaire, COPD Assessment Test (CAT™), Alcohol Intake, Tobacco Smoking Questions) or had any contraindication for spirometry or hypersensitivity to bronchodilator  were excluded from the study. Contraindications for spirometry were established based on the judgment of the investigator and defined according to Cooper BG, 2011  includin1 (forced expiratory volume in one second) and FVC  were estimated during the spirometry using a standardized approach defined by Miller MR et al., 2005 [Diagnosis of COPD was established based on the study questionnaire and/or spirometry conducted without bronchodilator (pre-dose) and with bronchodilator . Consequently, FEVl., 2005 . SpiromePreviously diagnosed: When self-reported by the respondent while completing the study questionnaire. Respondents were asked to answer the following question to identify “previously diagnosed COPD”:COPD was identified through three definitions:Has a doctor ever told you that you have chronic obstructive pulmonary disease (COPD)?If YES, please, indicate number of exacerbations during the last year.2.1/FVC <  0.70). Spirometry was conducted as part of the study  guideline 2011)  was used for the sampling strategy. Districts and streets for household visits were selected by the Study Executive Committee. The interviewers visited households sequentially, starting with the first apartment of the first house in the selected street, and continuing in ascending order. At every household the interviewers assessed the eligibility of all inhabitants. Participants who provided their consent and were eligible to participate in the study provided their socio-demographic information and medical history, underwent weight/height measurement and spirometry with bronchodilator and completed the study questionnaires, as described previously .Socio-demographic data were collected to describe the characteristics of the overall study population, including gender, age and ethnicity distribution, body mass index (BMI), smoking status and alcohol intake. COPD prevalence data were collected using the case definition described above and the impact of age, gender and severity were assessed. Additionally, the type and frequency of co-morbidities and any potential association between COPD and its related risk factors  were investigated.The COPD Assessment Test (CAT™) and the modified Medical Research Council (mMRC) Dyspnoea Scale were used to assess additional characteristics of COPD in this study. All respondents answered the CAT™ and were assessed by the mMRC Dyspnoea Scale at the interview. The CAT™ is a validated short questionnaire for measurement of the impact of COPD on a patient’s health status . It compp˂0.05) of associations between risk factors and COPD. Statistical analysis was performed using IBM SPSS Statistics software  version 21.0 and R software version 3.1.2 .The point prevalence of COPD, , is defined as the number of COPD individuals divided by total number of subjects included in the study, and is expressed as a number per 1000 for each country. Prevalence was calculated in the subject population with valid data. 95% confidence intervals (CI) were calculated for each frequency using the Clopper-Pearson method . Odds ra2), and in Kazakhstan, (25.7 (5.1) kg/m2), while it was slightly higher in Azerbaijan (26.4 (5.3) kg/m2). Approximately one-third of participants were either current or past smokers . Heavy alcohol consumption was reported by 53.4% of respondents in Ukraine, 44.8% in Kazakhstan and 22.7% in Azerbaijan. See Table A total of 2842 adult subjects were included in the CORE study . The majority of study population were women across the three countries: 58.2% in Ukraine; 63.2% in Kazakhstan and 58.3% in Azerbaijan. The mean age was slightly above 40 years old in all participating countries. As expected, the majority of participants were Caucasian in Ukraine (99.7%) and Azerbaijan (100%), and almost two-thirds of participants in Kazakhstan were Asian (62.8%). The mean BMI was at the boundary of overweight in Ukraine, (25.0 (5.1) kg/mSubjects who fulfilled the definitions used in this study for COPD are shown in Table A similar picture was obtained for the prevalence of COPD among respondents ≥40 years old Fig. . The est1/FVC <  0.70, FEV1 ≥ 80% normal) and II . In all three participating countries, more patients were found in stage II (18.1 (95% CI 10.6–28.8) per 1000 in Ukraine; 48.7 (95% CI 35.9–64.4) per 1000 in Kazakhstan and 21.4 (95% CI 13.1–32.9) per 1000 in Azerbaijan)   was used7 95% CI 5.9–64.4 A higher prevalence of previously diagnosed COPD was observed in the age group ≥65 years old compared to the younger age groups in Kazakhstan and Azerbaijan: 73.5 95% CI 24.3–163.3) and 38.5 (95% CI 4.7–132.1) per 1000 respectively. However, in Ukraine, the highest prevalence was observed in the 40–64 years old age group: 14.8 (95% CI 5.4–31.9) per 1000  per 1000 in men vs 7.2 (95% CI 2.0–18.3) per 1000 in women in Ukraine; 17.2 95% CI 6.4–37.2) per 1000 in men vs 11.7 (95% CI 4.7–24.0) per 1000 in women in Kazakhstan and 10.3 (95% CI 2.8–26.1) per 1000 in men vs 0.0 (95% CI 0.0–6.8) in women in Azerbaijan. The prevalence of COPD diagnosed by spirometry was 45.6 (95% CI 27.2–71.1) per 1000 in men vs 22.1 (95% CI 11.4–38.2) per 1000 in women in Ukraine; 120.7 (95% CI 88.4–159.6) per 1000 in men vs 35.2 (95% CI 21.9–53.3) per 1000 in women in Kazakhstan and 54.0 (95% CI 33.7–81.3) per 1000 in men vs 25.7 (95% CI 14.1–42.8) per 1000 in women in Azerbaijan  per 1000 in Caucasians vs 11.8 (95% CI 4.8–24.2) per 1000 in Asians), and for COPD diagnosed by spirometry (68.8 (95% CI 44.6–100.6) per 1000 in Caucasians vs 64.1 (95% CI 45.7–86.9) per 1000 in Asians).2), tuberculosis (ever diagnosed), dusty work, and open fire cooking was investigated and statistical significance was found between COPD and smoking in Kazakhstan (OR 3.756 (CI 2.156–6.543) p < 0.001) and Azerbaijan (OR 2.808 (CI 1.423–5.542) p = 0.002). Tuberculosis was a significant risk factor associated with COPD in Ukraine (OR 32.393 (CI 4.403–238.330) p < 0.001). Dusty work might increase the appearance of COPD in Kazakhstan (OR 2.306 (CI 1.328–4.002) p = 0.002)The relationship between the presence of COPD and smoking status (current/past smoker), alcohol intake , BMI  and those without COPD (non-COPD population). As seen in Table While completing the study questionnaire the respondents were asked to report the presence of other chronic medical conditions except for respiratory diseases. Co-morbidities were reported by 44.2% of respondents in Ukraine, 23.5% respondents in Kazakhstan and 54.6% respondents in Azerbaijan. The respondents with COPD diagnosed by spirometry (COPD population) were compared to the rest of the respondents (non-COPD population) by the rate of co-morbidities. In all participating countries, the number of subjects that reported suffering from a chronic health condition was higher in the COPD population compared to the non-COPD population: 57% vs 43% in Ukraine, 51% vs 27% in Kazakhstan, and 74% vs 54% in Azerbaijan, respectively . The same results were obtained for a previous cardiovascular disease . Additionally, hypertension occurred significantly more often in the COPD population compared to the non-COPD population in Ukraine  and Azerbaijan . In Kazakhstan, hypertension was also more frequently observed in the COPD population (36.5%) compared to the non-COPD population (25.5%) but the difference was not shown to be significant (p = 0.074)  were recorded during the study period. Non-serious adverse events were not collected, as there was no investigational drug administration in this study.The CORE study is, to our knowledge, the first epidemiological study conducted to evaluate the prevalence and burden of COPD in CIS countries using a standardized methodology. The study showed that COPD prevalence reported by respondents ‘previously diagnosed’ with COPD was 10.4, 13.8 and 4.3 per 1000 in Ukraine, Kazakhstan, and Azerbaijan, respectively, but the prevalence of COPD diagnosed by spirometry was much higher, 31.9, 66.7 and 37.5 per 1000 respectively. This can be explained by under diagnosis of the disease in CIS countries. Therefore, the majority of respondents with COPD were diagnosed for the first time in this study. As highlighted by Pasko (2002), COPD is often under-reported which could explain why official data on COPD prevalence are up to 10-fold lower than actual population data . The preA statistically significant relationship was shown between smoking and COPD in Kazakhstan and Azerbaijan; tuberculosis and COPD in Ukraine; and dusty work and COPD in Kazakhstan. Co-morbidities were significantly more frequent in the COPD population compared to the non-COPD population.In all countries studied, the frequency of COPD diagnosed by spirometry had a tendency to increase with age . This trend has been observed in many studies –17 and cIn all three countries, COPD was more prevalent in men (both diagnosed by spirometry and previously diagnosed), in line with numerous other studies , 15. ThiEthnicity-related differences were assessed in Kazakhstan only and revealed a higher prevalence of COPD (both diagnosed by spirometry and previously diagnosed by a physician) in Caucasians compared to Asians, together with more prominent symptoms and spirometry changes. Other studies have mentioned that genetic factors are probably involved in the decreased COPD risk observed in Asian .The prevalence of previously diagnosed COPD shown in the present study is low compared to estimates provided by previous studies . It is well established, that COPD is a precursor to cardiovascular disease development and/or its aggravation , 31. TheThis study has several strengths. It is a multi-national, cross-sectional, population-based study with a large sample size using consistent methodology across all countries, providing a standardized measure of prevalence in the CIS countries. In addition, the case definition of COPD used is based on both (i) self-reported diagnosis and (ii) diagnosis confirmed by spirometry. Furthermore, severity of COPD has been assessed based on the validated international GOLD guidelines. As it is the first time such an epidemiological study has been conducted in CIS countries, this study could facilitate increased recognition of COPD in CIS countries and allow preparation of educational interventions to optimize management of patients with COPD. Whereas many previously published studies on COPD concern patients only over 40 years of age, this study evaluates COPD prevalence in the overall adult population.1/FVC was used as the diagnostic criteria for COPD in this study.We acknowledge that the current study has several limitations. The method of district and street sampling may not ensure completely random selection of streets and participants. The relatively small number of COPD patients limits the analysis of risk factors associated with COPD and can limit the power for specific types of within-city analysis, such as detailed subgroup analyses. The subjectivity of the diagnostic criteria based on symptoms can lead to over or under diagnosis. Spirometry was the only objective diagnostic measure in the present study and its results were reviewed centrally, but difficulties encountered when conducting spirometry can affect the results of this procedure. Additionally, the physiological decrease in lung function in the elderly may influence the estimation of COPD prevalence stratified by age, taking into account that fixed ratio FEVThe city population may not be representative of each country in general, because risk factors and healthcare provision  may vary widely across the country. In particular, the results may only reflect the situation in urban areas and not represent the whole country, since rural areas could have different levels of healthcare provision and accessibility to medical care and different living and working conditions for the people who live in these areas. Finally, some data are missing due to a lack of relevant information from participants, as a lot of study data were collected from respondents’ interview.In conclusion, in Ukraine, Kazakhstan and Azerbaijan the prevalence of COPD diagnosed by spirometry is significantly higher than the prevalence self-reported by respondents and/or based on anamnesis, demonstrating that COPD is under-reported in these countries. Compared to other countries, the COPD prevalence estimates in these CIS countries were relatively low. Factors such as limited funding from the government, lack of COPD knowledge, attitude within the population and of primary care physicians, and low access to high-quality spirometry may play a role in the under-reporting of COPD in these countries. A higher rate of COPD prevalence was observed in Kazakhstan (Almaty) compared to Ukraine (Kiev) and Azerbaijan (Baku) likely due to poor ecological conditions, but this assumption needs further investigation. The information provided in this paper will be helpful for healthcare policy makers in CIS countries to instruct COPD disease management and prevention strategies and allocate healthcare resources accordingly.


Sexual dysfunction may affect 80% of women in hemodialysis. However the specific patterns and clinical correlates of sexual functioning remain poorly described. The aim of this study was to assess prevalence and correlates of the individual domains of sexual functioning in women treated with hemodialysis. We recruited, into this multinational cross-sectional study, women treated with long-term hemodialysis . Self-reported domains of sexual functioning were assessed by the Female Sexual Function Index, which is routinely administered within the network of dialysis patients followed by the working group. Lower scores represented lower sexual functioning. Socio-demographic and clinical correlates of each domain of sexual functioning were identified by stepwise multivariable linear regression. Sensitivity analyses were restricted to women who reported being sexually active. We found that of 1309 enrolled women, 659 (50.3%) provided complete responses to FSFI survey questions and 232 (35%) reported being sexually active. Overall, most respondents reported either no sexual activity or low sexual functioning in all measured domains . Respondents who were waitlisted for a kidney transplant reported scores with higher sexual functioning, while older respondents reported scores with lower functioning. The presence of depression was associated with worse lubrication and pain scores  while women who had experienced a previous cardiovascular event reported higher pain scores [-0.77 (-1.40- to -0.13)]. In conclusion, women in hemodialysis reported scores consistent with marked low sexual functioning across a range of domains; the low functioning appeared to be associated with comorbidity. Despite significant advances in the management of end-stage kidney disease (ESKD) including renal replacement therapy and the increasing availability of newer and more effective pharmacological interventions, there has been no marked improvement in patient survival, which remains 3–4 years on average –7. DepreHowever, previous research in this area has principally focused on erectile dysfunction in men, while sexual dysfunction among women on hemodialysis has received less attention . Our ColExploring the characteristics of individual sexual functioning domains may contribute to an improved understanding of the specific sexual experiences of women, when treated with hemodialysis, to inform a patient-centered research agenda. In this study, we assessed the prevalence and correlates of the individual domains of sexual functioning in women treated with hemodialysis within the same cohort of patients involved in the CDS study.CDS is a multinational, cross-sectional study involving women with ESKD receiving long-term outpatient hemodialysis for renal replacement therapy . In thisWe included consecutive women aged 18 years or older who had been treated with long-term hemodialysis for any duration within a convenience sample of clinics located in Europe  and South America (Argentina). The clinics were part of a collaborative dialysis network coordinated by Diaverum and were from communities and countries for which local investigators were highly committed to routine administration of a series of questionnaires and diagnostic instruments relating to depression, quality of life and sexual dysfunctions to patients within a selected period of time. We enrolled participants between January and June 2008. We excluded women who had major psychiatric disorder or who declined to participate in the study. Women were enrolled after having provided written informed consent to give information on sexual dysfunction, satisfaction and depression. We obtained ethics approval for analysis of routinely collected data from the University of Sydney Human Research Ethics Committee . The study was conducted according to the principles of the Declaration of Helsinki.http://mapigroup.com.Women were administered the Female Sexual Function Index  survey dQuestionnaires were completed anonymously. Demographic, clinical, laboratory and dialysis-related data were obtained from a centralized database linked using a unique identification code. Standardized clinical variables included age, gender, country of treatment, education level, presence of partner, occupational status, smoking history, physical activity, being on the waiting list for a kidney transplant, comorbidities including previous cardiovascular disease and diabetes, medication use, serum parameters including hemoglobin, phosphorus, parathyroid hormone, calcium and albumin, and dialysis characteristics.Baseline socio-demographic, clinical and dialysis-related characteristics were summarized as mean (standard deviation) or median (25th to 75th percentile) for continuous variables and frequencies and percentages for categorical variables. Prevalence of each domain of low female sexual functioning was reported as median (25th to 75th percentile). Frequency and percentages of each item of the FSFI have been also calculated.Women were classified as respondents when they answered all of the 19 questions of the FSFI questionnaire, incomplete respondents when one or more answers were missing. The clinical and socio-demographic characteristics of respondents and incomplete respondents were compared using standard univariate methods.For each domain, we conducted a stepwise multivariable linear regression to identify correlates of low or high scores controlling for the following covariates judged to have clinical importance: age, depression symptoms (CES-D score ≥ 18), pregnancy, occupational and menopause status, experience of a prior cardiovascular event , neurologic conditions , previous kidney transplant, wait-listing for kidney transplant, anxiolytics medication, time on dialysis, mean arterial pressure and serum phosphorus. We used α = 0.1 as a threshold for a covariate to both enter and exit the final model. Results were expressed as mean differences in domain scores along with their 95% confidence intervals (95% CIs). Finally, we performed a sensitivity analysis in those women who reported being sexually active.We considered two-sided P-value <0.05 as statistically significant. All analyses were performed using SAS Statistical Package Release 9.3 .Among 1472 consecutive women assessed for eligibility, 163 were excluded: 134 declined to respond to the routinely administered questionnaires, and 29 had a concurrent major psychiatric disorder precluding participation. The remaining 1309 (88.9%) received the FSFI questionnaire. 659 (50.3%) answered all of the 19 questions and were included in these analyses . The perth, 75th percentile) were (lower scores indicating higher difficulty): desire 1.2 (1.2 to 3), arousal 0.6 (0 to 3.3), lubrication 0 (0 to 3.6), orgasm 0 (0 to 3.6), satisfaction 2.4 (0 to 4.4), pain 0 (0 to 4.4).For each year increase in age, the desire score was reduced by -0.05 (95% CI -0.05 to -0.04)]. While women waitlisted for a kidney transplant [0.45 (0.21 to 0.70)] reported higher scores.Women waitlisted for a kidney transplant reported higher arousal scores [0.73 (0.38 to 1.08)]. Older women [-0.05 (-0.06 to -0.05)] and those who were retired [-0.49 (-0.93- to -0.04)] reported lower scores.Women waitlisted for a kidney transplant [0.71(0.30 to 1.13)] reported higher lubrication scores. Increasing age [-0.44 (-0.82 to -0.06)] and the presence of depression [-0.66 (-0.97 to -0.35)] correlated with lower scores.Women waitlisted for a kidney transplant reported higher orgasm scores [0.75 (0.33 to 1.17)]. Older women [-0.06 (-0.07 to -0.05)] and women who were retired [-0.63 (-1.17—to -0.09)] reported lower scores.Increasing age [-0.05 (-0.06 to -0.04)] was associated with reported lower satisfaction with overall sexual and relationship experiences. Women waitlisted for a kidney transplant [0.58 (0.15 to 1.00)] reported higher satisfaction.Women waitlisted for a kidney transplant [0.86 (0.37 to 1.34)] experienced lower pain during sexual activity. Increasing age [-0.06 (-0.08 to -0.05)] and depression [-0.37 (-0.72 to -0.01)] or the experience of a prior cardiovascular event [-0.77 (-1.40 to -0.13)] were correlated with higher pain.Domain scores were influenced by sexual activity in the FSFI questionnaire . We therefore assessed prevalence and correlates of each domain of sexual dysfunction in a sensitivity analysis restricted to sexually active women. Among responders, 232 (35.2%) women reported being sexual active in all domains and could be included in sensitivity analyses. Median scores of each domain of sexual dysfunction in these women were: desire 3.6 (3.0 to 4.2), arousal 3.9 (3.0 to 4.8), lubrication 4.2 (3.6 to 5.7), orgasm 4.4 (3.6 to 5.6), satisfaction 4.8 (3.6 to 5.6) and pain 5.0 (4.0 to 6.0). Respectively, 7.8% and 19% had very low/no and low desire; 7.8% and 12.5% had very low/no and low arousal; 4.7% and 6.9% reported that becoming lubricated was extremely difficult/impossible and very difficult; 36.2% and 31.9% reported that it was extremely difficult/impossible and very difficult to reach an orgasm; 9.5% and 10.3% were very dissatisfied and dissatisfied with sexual life; 3.0% and 3.9% had very high and high pain .In this cross-sectional study of 1309 women treated with hemodialysis, approximately half anonymously provided information about sexual function. Of these 659 women, 427 reported no sexual activity and 232 reported marked low sexual function across all measured domains including desire, arousal, lubrication, orgasm, satisfaction, and pain. Women waitlisted for a kidney transplant reported higher scores in all sexual domains, while older women reported lower scores. The presence of depression was associated with lower lubrication and higher pain scores; while women who had experienced a cardiovascular event also reported a higher pain score on average. The high prevalence of sexual issues and correlated characteristics were confirmed in the subgroup of women who reported being sexual active. These data suggest sexual function in women treated with dialysis is frequently very poor and may warrant further investigation to understand the clinical relevance of the data from a patient perspective. In our study women on hemodialysis didn’t report very high levels of dissatisfaction against their severe sexual problems. This may be consistent with the low sexual desire they reported that could show lack of interest in sexual activity as part of their life. Previous studies have already explored patients views regarding research priorities in dialysis setting , 21 but We performed a comprehensive evaluation of all individual domains of sexual function in women with end-stage kidney disease in a relatively large study. We assessed the prevalence and correlates of each domain adjusted for socio-demographic and clinical variables. Previous studies reporting individual domains of female sexual function in women on hemodialysis had smaller sample sizes and used a range of different tools for assessment –28. FiveThe strengths of our study are the inclusion of several hemodialysis centers within multiple countries, and the involvement of a sufficiently large number of women to facilitate adjustment for clinically relevant confounding variables.However, our study has limitations which need to be considered when interpreting the findings. First, the response rate of 50.3% may have introduced selection bias. While low, this response rate is similar or better than that of other patient survey studies of sexual health , 34, 35.Our study demonstrated a high prevalence of poor sexual functioning across all domains in women treated with hemodialysis. Despite a high frequency, treatment options for sexual dysfunction have not been adequately explored in this population . Our datIn conclusion, sexual function scores are severely impaired in women with end-stage kidney disease and appear to be associated with comorbidity. Additional patient-centered studies might assist greater understanding of the impact of sexual dysfunction on quality of life in this population.S1 Table(PDF)Click here for additional data file.S1 Fig(PDF)Click here for additional data file.S1 FileTable A. Baseline characteristics, Female Sexual Function Index and Center for Epidemiologic Studies-Depression (CESD) instrument. Table B. Legend.(ZIP)Click here for additional data file.