Stratification of patients with severe asthma by blood eosinophil counts predicts responders to anti-interleukin (IL)-5 (mepolizumab and reslizumab) and anti-IL-5 receptor α  therapies. This study characterized patients with severe asthma who could qualify for these biologics in a primary care setting.2-agonist (LABA), or theophylline filled on the same day. Patients’ asthma was considered severe also if they received a prescription for ICS with oral corticosteroids (OCS) or an additional prescription for omalizumab. Patient characteristics, asthma-related medications, and blood eosinophil counts were captured using observed care patterns for the year prior to ICS/LABA and/or OCS prescription. Health care resource use (HCRU) and costs were captured throughout the 1-year follow-up period.We retrospectively selected patients from July 1, 2010, to June 30, 2014, using a linked electronic medical records (EMR) database (IMS Evidence 360 EMR Canada) for > 950,000 patients in primary care in Ontario, Canada. Patients aged ≥ 12 years with ≥ 2 documented asthma diagnoses were identified as having severe asthma based on prescriptions for high-dosage inhaled corticosteroids (ICS) plus either a leukotriene receptor antagonist, long-acting βWe identified 212 patients who met the criteria for severe asthma. These patients required an average of 6.5 physician visits during the 1-year follow-up period , and 20 (9%) were referred to respiratory specialists. Overall, 56 patients (26%) with severe asthma had complete blood counts, of whom 23 (41%) had blood eosinophil counts ≥ 300 cells/μL and might be considered for anti-eosinophil therapies. Patients with severe asthma and blood eosinophil counts ≥ 300 cells/μL had more respiratory specialist referrals (17% vs. 12%) than patients with blood eosinophils < 300 cells/μL.Our data suggest that during 2010–2014, Ontario primary care patients with severe asthma and high blood eosinophil counts had greater HRCU than those with lower counts. Approximately 41% of patients with severe asthma could qualify for anti-eosinophil drugs based on blood eosinophil counts. However, the eosinophilic status of most patients was unknown. It is appropriate to increase awareness of the use of blood eosinophil counts to identify patients who could be considered for anti-eosinophil therapies. Approxisymptoms . Up to 2symptoms . New theIncreased understanding of the pathophysiology of asthma, as well as emerging biological therapies, has highlighted the need to consider factors beyond symptom control to manage individual patients optimally. The introduction of omalizumab, a humanized anti-immunoglobulin E antibody, highlighted the need to identify patients with an allergic component to their asthma . FurtherThe purpose of this study was to characterize and estimate the size of the population of individuals with severe asthma who may require treatment with an anti-eosinophil drug, such as benralizumab, in a primary care setting, along with the clinical and economic burden of their disease. This study was an exploratory analysis using routinely collected data from primary care clinics in Ontario, Canada.The primary aim of this study was to determine the prevalence and clinical characteristics of patients with severe asthma who may be responsive to anti-eosinophil therapies in a primary care setting in Canada. It was a retrospective, longitudinal, observational study of patients with severe asthma in primary care in Canada. This study is reported using the REporting of studies Conducted using Observational Routinely collected Data (RECORD) extension to the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement , 18.Patients aged ≥ 12 years with ≥ 2 documented asthma diagnoses were retrospectively selected over a 4-year period from July 1, 2010, to June 30, 2014, from a linked electronic medical records (EMR) database (IMS Evidence 360 EMR Canada) containing deidentified longitudinal records for > 950,000 patients in primary care in Ontario, Canada . The datPatients included in the study had to satisfy several selection criteria: ≥ 2 asthma diagnoses identified by OHIP diagnosis code 493  with at least one diagnosis in the selection period , 24; age2-agonists (SABA) were captured in the follow-up period. Number of physician visits, laboratory tests, sick notes, and specialist referrals were captured, along with the value of billings by physicians to the OHIP Schedule of Benefits for primary and secondary care. Costs for billing fees are expressed in 2015 Canadian dollars (Can $) based on the Canadian Consumer Price Index for Health Care Services. Data were stratified based on blood eosinophil counts: < 300 and ≥ 300 cells/μL. Emergency department visits and hospital admissions were not included because the data capture in the primary care medical records was not sufficient to create robust estimates.Patient demographics, smoking history, comorbidities, asthma-related medications, and blood eosinophil counts were obtained for the year prior to index (look-back period). Prescription of an oral corticosteroid, or prescriptions for short-acting βThe list of comorbidities included acute bronchitis (OHIP diagnosis code: 466), rhinitis (OHIP diagnosis code 477), sinusitis (OHIP diagnosis code: 461), anxiety disorders (OHIP diagnosis code: 300), eczema or rash (OHIP diagnosis code: 691), depression (OHIP diagnosis code: 311), diabetes (OHIP diagnosis code: 250), and pneumonia (OHIP diagnosis code: 486) .Clinical burden of disease was examined by incidence of an emergent (not same-day) prescription of an oral corticosteroid or SABA during the follow-up period. Adherence was measured using the percentage of days covered (PDC) on ICS , for allDescriptive statistics are presented for patient demographics and clinical characteristics. Categorical variables are expressed in terms of frequency counts and proportions. Continuous variables are expressed in terms of means, medians, and standard deviations. We did not perform formal statistical tests for between-group comparisons.The investigators had complete access to the IMS E360 EMR database. Data cleaning and correction were performed for the calculations of both body mass index and adherence. As in most databases, weight and height information fluctuations for a given patient were most likely caused by differences in reported units. We performed a correction for a few patients (< 10) to account for high volatility either by inputting the average values for a patient or by converting a value using the appropriate units.All data were sourced from IMS Evidence 360 EMR Canada. We performed patient-level linkage was performed across output tables using common deidentified patient numbers and visit identification information.From the 612,012 patients in the IMS Evidence 360 database during the selection period, 212 patients were identified as having severe asthma and meeting the eligibility criteria. The three most common reasons for patient exclusion were the presence of respiratory comorbidities , use of an LAMA (n = 200), and receipt of medium-dosage ICS/LABA , nonsmokers (83% vs. 58%), and recipients of ICS prescriptions 39% vs. 18%). Patients with eosinophil counts ≥ 300 cells/μL were also more likely to have acute bronchitis, rhinitis, and anxiety disorders than those with eosinophil counts < 300 cells/μL  were classified as adherent to ICS therapy  and eosinophil counts < 300 cells/μL, those with eosinophil counts ≥ 300 cells/μL required more respiratory specialist referrals 17% vs. 12%), incurred greater physician billing costs (Can $620 vs. Can $517) and more laboratory tests (46 vs. 34) . Patients with greater blood eosinophil counts also used more physician and laboratory health care resources than those with counts < 300 cells/µL. Complete blood counts  were performed only on a quarter of patients with severe asthma in primary care, yet a relatively high percentage of patients with CBC data (41%) had peripheral blood eosinophilia. Thus, few patients with severe asthma and blood eosinophilia are being identified and referred to respiratory specialists.We are not aware of any other real-world Canadian studies that have characterized disease burden for patients with severe asthma. However, our study is consistent with previous studies that have estimated the clinical, economic, and individual patient-reported burden of disease for Canadians with broader diagnoses of asthma. For example, our estimate of 7 physician visits annually sits midrange between estimates of 4–17 visits in other studies of adult patients with severe asthma . It is sFurthermore, we are not aware of other Canadian studies that have attempted to characterize the burden of asthma for patients with severe, eosinophilic asthma. Although there is still some uncertainty as to the value of using a single test to characterize the severity of eosinophilic inflammation –34, patiOne strength of our approach is that it is based on a large sample of patients and uses a single data structure, which avoids errors related to data linkage. We also used validated algorithms for identifying patients with asthma from administrative data , 42 and We made additional effort to minimize systematic errors or bias from confounding our estimates. For example, we chose to use PDC instead of a medication possession ratio (MPR) to estimate medication adherence. PDC provides a more conservative estimate of adherence and is preferred over MPR when patients frequently switch medications or use several medications concurrently within a drug class . Also, wOne potential limitation of our study is that it includes only primary care physician visits and does not capture patients who see emergency department physicians, respirologists, internists, or other health care specialists. However, a previous study of asthma burden in Ontario showed that 86% of claims to OHIP for nonpediatric asthma were from general practitioners and family physicians—few individuals received care from specialist physicians . AnotherThe use of electronic medical records from a primary care clinic also limits measures of adherence and laboratory data. Adherence in this study was captured by observing the initial prescription and does not capture whether the medication was subsequently dispensed and whether the patient then used the medication accordingly. Also, most patients were classified based on a single blood eosinophil measurement during the look-back period. As mentioned above, the value of using a single test to characterize the severity of eosinophilic inflammation is not certain. It is also possible that use of systemic corticosteroids during the look-back period may have influenced eosinophil measurements, particularly for the severe cohort, in which 19% of patients had a history of OCS use.Our study suggests that up to 41% of patients with severe asthma could qualify for new anti-IL-5 and anti-IL-5 receptor α therapies based on a single blood eosinophil count. Accepting an 8% prevalence of asthma in adults , 47, up Our data suggest that patients with greater blood eosinophil counts use more health care resources compared with those with lower eosinophil counts. Blood eosinophil counts were performed for only a quarter of patients with severe asthma in primary care. However, of these patients, approximately 41% had blood eosinophil counts ≥ 300 cells/µL and might be considered for anti-eosinophilic therapies. It is necessary to increase awareness of the use of blood eosinophil counts to identify patients who could qualify for anti-eosinophil therapies.


To assess whether circulating 25-hydroxyvitamin D We undertook a post hoc analysis of a cross-sectional study in adults with T2DM in whom we evaluated SCA. A total of 303 subjects with T2DM were included. Clinical variables and carotid ultrasound imaging were obtained. 2/dL2) product was positively associated with the presence of carotid plaques . An inverse association was observed between higher levels of 25OHD (≥30 ng/mL versus <20 ng/mL concentrations) and common carotid intima-media thickness  (βadj ± SE = −0.055 ± 0.024). We conclude that the CaP product is independently associated with the presence of established subclinical carotid atherosclerosis in patients with T2DM. We found no association of 25OHD with the presence of SCA. However, calcium phosphate (CaP; mg Patients with type 2 diabetes mellitus (T2DM) are at 2- to 4-fold higher risk of cardiovascular mortality compared with nondiabetic subjects . Further3, the circulating concentrations of 25-hydroxyvitamin D3 (25OHD) is the parameter that indicates the vitamin D deficiency/sufficiency status. Evidence from some association studies pointed to an association of vitamin D deficiency with subclinical atherosclerosis or established cardiovascular disease [The contribution of different factors involved in the regulation of mineral metabolism in the pathogenesis of atherosclerosis and subsequent cardiovascular events is supported by experimental and clinical evidence –11. Amon disease , 12, 13. disease . However disease .Although calcium and phosphate homeostasis is tightly regulated by vitamin D and parathormone (PTH), less attention has been paid to their potential involvement in the pathogenesis of atherosclerosis or as predictors of cardiovascular disease. Elevated concentrations of calcium and phosphate have also been related to the development of atherosclerosis and cardiovascular events –22. HoweConsidering all the evidence described above, we hypothesized that vitamin D and other markers of mineral metabolism are associated with the presence of carotid atherosclerotic plaques in patients with T2DM free from established chronic kidney disease and cardiovascular disease. Thus, the aim of this study was to test whether circulating vitamin D and other mineral metabolism-related factors, that is, calcium, phosphate, and intact parathormone, are associated with the presence of subclinical carotid atherosclerosis in type 2 diabetes mellitus patients.n = 180) or without (n = 123) subclinical atherosclerosis were included on the basis of availability of serum samples. The inclusion criteria were age from 40 to 75 years old, normal renal function (estimated glomerular filtration rate (eGFR) > 60 mL/min), and availability of the main study variables to perform the study assessments. The variables that were considered for this substudy were weight, height, waist, smoking habit, presence of dyslipidemia and hypertension, duration of diabetes and its treatment, lipid profile, age, sex, ethnicity, and the carotid ultrasound parameters.This is an ancillary study of a previous cross-sectional study in adult type 2 diabetic patients recruited at a single reference hospital in Catalonia, Spain. The primary objective of the current approach was to assess the potential association between subclinical atherosclerosis and 25OHD and other mineral metabolism factors: calcium, phosphate, and PTH. The study population has been recently described in the previous study that was designed to assess subclinical carotid atherosclerosis and cerebral microvascular disease in patients with T2DM . A totalThe exclusion criteria were defined as follows: established chronic kidney disease , previous supplementation with vitamin D and/or calcium, and previously known cardiovascular disease events or associated revascularization procedures, including coronary heart disease, cerebrovascular disease, or peripheral vascular disease (this included the diagnosis of diabetic foot disease). For this purpose, the patients' clinical records were thoroughly reviewed in addition to the anamnestic evaluation and physical examination.A detailed description of the study subjects and clinical procedures is provided elsewhere . Out of http://bibliodieta.umh.es/files/2011/07/CFA101.pdf) [Relevant demographic and clinical data were obtained from each subject. Weight, height, and waist circumference were measured using standardized clinical procedures. Patients were classified as having hypertension or dyslipidemia when they were receiving antihypertensive or lipid-lowering treatment, respectively. Laboratory variables were determined in fasting blood and spot urine samples. All analytical tests were performed using standard laboratory methods. Basic blood and urine biochemistry were determined using a Hitachi Modular DDPP analyzer . Hemoglobin A1c was measured using an HPLC Variant II Turbo . Intact parathormone was measured in an Elecsys E170 analyzer  by electrochemiluminescence immunoassay with 2.2% and 6% intra- and interassay variability, respectively. Serum 25OHD concentrations were measured using an Architect i2000SR analyzer  by a chemiluminescent microparticle immunoassay with an intra- and interassay variability values of 2.3% and 6.2%, respectively. Vitamin D deficiency was defined as a concentration of 25OHD below 20 ng/mL, and vitamin D insufficiency as values between 20 and <30 ng/mL, as defined by the Endocrine Society . These t101.pdf) . The sea101.pdf) .Subclinical carotid atherosclerosis (SCA) was defined as the presence of any atherosclerotic plaque in the carotid arteries. All participants underwent the same carotid ultrasound protocol performed by the same researcher, who was blinded to the characteristics of the study participants. Ultrasound images were obtained with a Siemens Sequoia 512 and a 15 MHz linear array probe. To identify the presence of plaques a 2D-mode and colour Doppler imaging, techniques were likewise used in longitudinal and transverse planes. The common carotid intima-media thickness (cIMT) was determined using conventional ultrasound procedures as measured from the media-adventitia interface to the intima-lumen interface. The intraobserver variability of the IMT image reading, calculated as the intraclass correlation coefficient, of the researcher performing this procedure is 0.93 . According to the Mannheim consensus , plaque t-test or Mann–Whitney U test that were used to compare quantitative variables  between two groups. A first multivariable logistic regression model was adjusted with all the clinically significant variables. The model was reduced by dropping one variable in each step, starting by the one with the highest nonsignificant p-value according to the likelihood ratio test (LRT). Calibration and discrimination for the final proposed logistic regression models were assessed by the Hosmer-Lemeshow goodness-of-fit test and the AUC. For the final linear regression model, the Kolmogorov-Smirnov goodness-of-fit test was performed and the coefficient of determination was provided. Adjusted association measures were the odds ratio (OR) and their 95% confidence interval (95% CI) with logistic regression models and effect (β) and standard error (±SE) with linear regression. The open source statistical analysis software package R [p < 0.05 were used.Quantitative variables were summarized using mean and standard deviation for those normally distributed (according to Shapiro-Wilks test) and as median and interquartile intervals otherwise. Qualitative variables were summarized using absolute and relative frequencies. For the variables showing a nonlinear relationship with any specific study outcome, some recoding options were tested. The relationship between potential risk factors and subclinical atherosclerosis was analyzed by adjusting multivariable logistic regression models for the presence of any plaque and by adjusting multivariable linear regression models for the common intima-media thickness. Logistic regression model building process was started by a bivariate analysis consisting of the chi-squared or McNemar tests that were used to compare qualitative variables and the ackage R  and a stp < 0.001). Subjects with SCA were also older than those without SCA . Hypertension was more frequent in patients with SCA , and also, as expected, they had higher systolic blood pressure . However, the study groups were similar in terms of BMI, waist circumference, physical activity, frequency of dyslipidemia, diabetes-related characteristics , and lipid profile.Clinical and biochemical characteristics of patients with T2DM according to their SCA status are shown in p = 0.341). Although serum calcium was similar in both groups, serum phosphate was higher in patients with SCA . The calcium phosphate (CaP) product was also increased in subjects with SCA . Additionally, PTH concentrations were lower in patients with SCA . Finally, there were no differences in terms of dietary calcium or vitamin D intake between groups. The multivariable analysis showed that there were no significant associations between female sex, 25OHD and PTH concentrations, and subclinical atherosclerosis (p < 0.001) and systolic blood pressure  were positively associated with the presence of carotid plaques (p = 0.012)  .https://doi.org/10.1155/2017/3498368. Vitamin D ≥ 30 ng/mL, as compared to vitamin D < 20 ng/mL, was associated with lower common cIMT . Age  and the presence of dyslipidemia  were positively associated with common carotid intima-media thickness. There was a negative association between female sex and cIMT . The age- and sex-adjusted model and the fully adjusted model are shown in Supplementary Table 2.Thereafter, a multivariable analysis for cIMT was also performed . A basicIn this study, we aimed to investigate the relationship between 25OHD and other mineral metabolism-related factors and the presence of subclinical carotid atherosclerosis, assessed by the presence of carotid plaques, in type 2 diabetic subjects. The study participants were free from chronic kidney disease without previous cardiovascular disease. Our results clearly show that increasing values of calcium phosphate product are associated with the presence of atherosclerotic carotid plaques. Concentrations of 25OHD in the higher range were negatively associated with lower cIMT in these subjects.Existing experimental and clinical evidence points to the involvement of phosphate and calcium in the development of atherosclerosis , 20. MosVery few additional studies were done in subjects without chronic kidney disease , 19. A vRegarding vitamin D, our results only showed that subjects with higher 25OHD concentrations (≥30 ng/mL) had lower cIMT. It should be pointed out that cIMT reflects initial morphologic changes in the intima of the artery wall. However, the existence of a plaque indicates that the atherosclerotic process is established; actually, cardiovascular events take place due to plaque complications. In our study, the concentrations of 25OHD were not at all associated with the presence of carotid plaques. These findings may indicate that 25OHD could be a marker of future cardiovascular disease only in early stages of the atherosclerotic process in diabetes. In contrast to the current results, Chen et al. described the association of lower 25OHD levels and the presence of carotid plaques in Chinese type 2 diabetic patients . PreviouThe current study has some limitations. First, this is a cross-sectional study that was not specifically designed to address the associations investigated in the current substudy. Additionally, this is not a population-based study, and this may limit the external validity of the current findings. Nevertheless, the characteristics of the included patients are very similar to those of the general diabetic population in our region . The curIn conclusion, the current findings indicate that the CaP product is associated with established subclinical atherosclerosis in patients with T2DM without previous cardiovascular disease or chronic kidney disease. Additionally, higher circulating 25OHD concentrations (≥30 ng/mL) are associated with lower cIMT. Given that this was a secondary analysis, the reported associations need to be confirmed in a prospectively designed study. This new research should include a comprehensive phenotyping of participants and should not focus in the study of an isolated factor of mineral metabolism but rather should assess the wide range of molecules that are involved in the complex cross-talk between parameters of mineral metabolism, that is, 25OHD, phosphate, calcium, PTH, and FGF-23.The information of supplementary materials are as follows: Supplementary Table 1. Multivariate analysis models for the presence of carotid plaques. Supplementary Table 2. Multivariate analysis models for common carotid intima-media thickness.


As its impact on transplant outcome remains open to debate, we decided to genotype it in a cohort of transplant subjects. A retrospective analysis of 439 first kidney recipients randomly divided into two subgroups  was performed to identify the best predictors of acute rejection (AR). The effect on transplant outcome was analyzed by an adjusted logistic regression model. Carriers of the A allele, associated with elevated TNF-α production, presented a higher risk of AR . Logistic regression analyses for AR showed an interaction between the polymorphism and treatment with thymoglobulin (p-interaction = 0.03). In recipients who did not receive thymoglobulin, carriers of A allele had higher risk of AR . Moreover, carriers of A allele not treated with thymoglobulin presented higher risk of AR than those who received thymoglobulin . The AUC of the model in the discovery cohort was 0.70 and in the validation cohort was 0.69. Our findings indicate that the −308G/A TNF-α polymorphism is associated with AR risk and it modulates the effectiveness of thymoglobulin treatment. This pharmacogenetic effect lets us propose this SNP as a useful predictor biomarker to tailor immunosuppressive regimens.The −308G/A SNP of Even after initial recovery of kidney function, acute rejection is associated with an increased risk of long-term graft failure . The ide B cells , 8. TNF-eability . Therefoα during acute rejection of liver [α has been also reported in human renal allograft biopsies and in rat models of acute and chronic rejection [Many researchers have reported increased serum concentrations of TNF-of liver , heart [of liver , and kidof liver , 13 alloejection , 15.α [α gene is located in HLA class III region of the major histocompatibility complex (MHC) on chromosome 6p21.3 [ TNF-α promoter region results in two forms related to their production, carriers of allele A, and GG genotype [α production [On the other hand, polymorphism in cytokine genes could explain differences in cytokine production and, therefore, in severity of rejection between individuals –18. Polyα . The TNFe 6p21.3 . G-to-A genotype . The pregenotype , 21 and oduction .α release promotes endothelial cell activation and intragraft leukocyte migration, increased production of TNF-α could trigger rejection [α polymorphism in acute graft rejection has been studied. Nonetheless, findings for the association between TNF-α and rejection are inconsistent. Some authors report that kidney recipients with the high-producing TNF-α −308A allele are at greater risk of rejection [As local TNF-ejection , 23, 24.ejection , 24–31, ejection –38. GiveBetween January 2005 and December 2012, a total of 623 Caucasian adult patients (≥18 years) received a deceased donor organ and were followed up for at least 24 months in our center. We excluded 184 patients . The datAn ultrasound-guided graft biopsy was performed when clinically indicated, that is, in patients with elevated serum creatinine levels. All patients with delayed graft function underwent protocol biopsy every 7 days until kidney function began to improve. A representative biopsy involved at least 1 artery and more than 7 glomeruli. All Banff-scored lesions were assessed . DepositPatients who received a kidney from a brain dead donor were treated mainly with tacrolimus, mycophenolate mofetil, and methylprednisolone; when the donors had expanded criteria or when ischemia time was long, they also received basiliximab or thymoglobulin. When the organ was donated after circulatory death, most patients received treatment with tacrolimus, mycophenolate mofetil, and methylprednisolone combined with basiliximab or thymoglobulin. In patients who received thymoglobulin, tacrolimus was introduced between days 4 and 6 after transplant. TNF-α polymorphism (rs1800629) was genotyped in a 7900HT Fast Real-Time PCR System using a TaqMan assay , as recommended by the manufacturer.Genomic DNA was extracted from EDTA-anticoagulated peripheral whole blood. The −308G/At-test or nonparametric tests where necessary. An adjusted logistic regression model was constructed and included variables with p < 0.15 in the univariate analysis or variables that were biologically relevant in the population analysis. Interactions with TNF-α polymorphism were evaluated. The p value for the interaction was obtained from the models constructed. The adjusted odds ratios (Adj. OR) are presented with their 95% confidence intervals. Discriminatory power was evaluated using area under the receiver operating characteristic (ROC) curves (AUC) of the predicted probabilities obtained in the model. Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test in both the discovery cohort and the validation cohort. Survival of the kidney transplants as functioning organs was analyzed using the Kaplan-Meier method with a log-rank test. Null hypotheses with an alpha error <0.05 were rejected. The statistical package used was SPSS version 15.0.Sample size was calculated based on an alpha risk of 0.05 and a beta risk of 0.2 in a 2-tailed contrast to detect a minimum relative risk of 2, assuming that 20% of patients not exposed to treatment would experience vascular rejection. It was calculated that 57 patients would be necessary in the high-producing group and 285 in the non-high-producing group . Kidney transplant recipients were randomly divided into two groups (2/3 and 1/3). The study of predictive factors was performed in 286 patients (discovery cohort) and subsequently validated in 153 patients . The influence of cytokine genotypes on acute rejection was expressed as a dichotomous variable, namely, low producers (GG) or high and intermediate producers (AA and GA). Qualitative variables were compared using the chi-square test or Fisher exact test and expressed as frequency distributions. Qualitative variables are expressed as mean (SD) or median (IQR) in the case of nonnormally distributed variables. They were compared using the  TNF-α was 82.9% (N = 364) for GG, 15.3% (N = 67) for GA, and 1.8% (N = 8) for AA.Of the total 439 patients in the cohort, 119 (27.1%) developed acute rejection (AR); of these, 83 experienced vascular involvement (18.9%). Median follow-up was 62.5 (39.9–87.2) months. The median time to rejection was 9 (7–15) days, and 96.6% of all rejections were during the first year after transplantation. The genotype distribution of −308A/GThe study of predictive factors was performed in 286 patients and subsequently validated in 153 patients. The distribution of risk factors was similar between the two cohorts . The res TNF-α (p = 0.03) .The model was adjusted to evaluate the development of acute cellular rejection and only the statistically significant variables were shown . In this = 0.03) . Carrier = 0.03)   . Further = 0.03) . The areAlloimmune responses and differences in susceptibility to rejection may be influenced by individual variations in cytokine genes. Indeed, cytokine gene polymorphism types have been extensively explored in transplantation because they are thought to explain the heterogeneous outcomes of the allograft and can thus help clinicians to tailor immunosuppression , 41–43.α polymorphism and acute rejection in kidney recipients of different populations; however, the results are apparently inconsistent and inconclusive. Our data support reports that found association of this SNP with a higher incidence of acute rejection [α high producers genotypes in the recipient were associated with an increased risk of acute allograft rejection. In this meta-analysis, authors recommended performing additional studies with large sample size and better study designs.Several studies have assessed the association between the −308A/G TNF-ejection , 24–31. ejection  concludeα polymorphism in kidney rejection could also arise because of differences in the immunosuppressive therapy used, as the type of medication administered is not usually included. The most common immunosuppressive agents are cyclosporine, prednisone, and azathioprine or mycophenolate [α in patients with the high producer genotype. TNF-α is mainly generated by monocytes and macrophages [α by macrophages [α.Discrepancies in previously reported findings may be due to a small size that compromised the statistical power and heterogeneity of the studies. Only few reports included cohorts of consecutive transplants performed over a specific time period , 34, 37 henolate –38. Our rophages  and it hrophages –48. Howerophages , the mairophages . Therefoα genotyping was not performed in the donor. Nevertheless, bearing in mind that most TNF-α is produced by macrophages, we think that more emphasis should be placed on the receptor genotype.Our study is limited by the fact that TNF-α polymorphism).Before a model can be relied upon to draw conclusions or predict future outcomes, it is important to ensure that it is correctly specified; that is, the data do not conflict with assumptions made by the model. Logistic regression is the most popular modeling approach for binary outcomes. The Hosmer-Lemeshow test makes it possible to compare goodness of fit by comparing observed and predicted risks across subgroups in a population. Prediction models allow clinicians to estimate prognosis , 52 and  TNF-α gene polymorphism that was previously associated with differential production of this cytokine is associated with AR risk and modulates the effectiveness of thymoglobulin treatment. Screening of this polymorphism will enable us to predict those patients  more likely to experience rejection and, therefore, require more intense immunosuppressive therapy. Similarly, it will enable us to identify patients with a potentially optimal response, who can be treated with less potent immunosuppression.The


The purpose of this study was to determine whether there were significant correlations between the pulse waveform in the capillary area of the optic nerve head (ONH) microcirculation shown by laser speckle flowgraphy (LSFG) and parameters of the systemic condition, especially the cardio-ankle vascular index (CAVI).We studied 130 men (ages 60.5 ± 10.9 years) who visited the Vascular Function Section of the Department of Cardiovascular Center of Toho University Sakura Medical Center. We evaluated the skew and blowout time (BOT) — which are parameters of pulse waveform analyses — using LSFG in the capillary area of the ONH for each patient. The CAVI, the E/e’ ratio as the measure of diastolic left ventricular function, and the mean intima-media thickness (IMT) were evaluated as systemic parameters. We performed a Pearson’s correlation analysis and a multiple regression analysis to determine independent factors for skew and BOT.t = 2.61, p = 0.01) were revealed as factors contributing independently to the skew by multiple regression analysis. Heart rate, the CAVI , the urinary albumin concentration, the mean IMT, spherical refraction, body mass index and pulse pressure were revealed as factors contributing independently to the BOT by multiple regression analysis.Heart rate, spherical refraction, and the CAVI (standard regression = 0.18, The CAVI was demonstrated to be an independent factor contributing to both skew and BOT in the capillary area of the ONH. Our findings clarified that large arterial function shown by the CAVI contributes to smooth hemodynamics of microcirculation, shown by LSFG. Systemic arteriosclerosis is an important contributing factor to cardiovascular disease and cerebrovascular disease, accounting for much of the mortality due to these diseases . An arteThere are also several reports of relationships between systemic arteriosclerosis and ocular diseases, such as retinal vein occlusion- and age-related macular degeneration –9. It isLaser speckle flowgraphy (LSFG), a noninvasive quantitative method of determining ocular blood flow , 12, is We have focused on the relationship between the pulse waveform and patients’ systemic conditions, and we reported that the pulse waveform in the ONH was significantly correlated with the CAVI, the left ventricular function obtained from echocardiography, and the carotid intima media thickness (IMT) as shown by ultrasonographic imaging, in healthy subjects , 18. OthThe purpose of this study was thus to determine whether there are significant correlations between the skew and BOT in the capillary area of the ONH shown by LSFG and parameters of the systemic condition, such as the CAVI, mean IMT and left ventricular diastolic function in patients with a variety of disorders.We analyzed the cases of 154 consecutive men who visited the Vascular Function Section of the Department of Cardiovascular Center of Toho University Sakura Medical Center in the years from April 1, 2007 to December 1, 2012. Patients who had glaucoma, moderate degree of cataract, vitreous and retinal diseases, and those who underwent intraocular surgery were excluded. The patients with the following conditions were excluded because these conditions can affect the CAVI and LSFG measurement: chronic atrial fibrillation had decreased the patient’s left ventricular function (ejection fraction <50 %), and peripheral arterial disease defined as an ankle-brachial index <0.9. In the end, 130 patients whose mean ± standard division (SD) age was 60.5 ± 10.9 years with the range 29 to 83 years met the study criteria. The Institutional Review Board of Toho University Sakura Medical Center approved the protocol of this study, and we began the research after all patients received information on the purpose and possible side effects of the research protocol and signed an informed consent. The procedures used conformed to the tenets of the Declaration of Helsinki.Echocardiography, CAVI measurement, and LSFG were performed after the patient rested for 10 min in a quiet, air-conditioned room with the temperature maintained at 24 ° C. All patients abstained from smoking, alcohol and caffeine for at least 24 h prior to the measurements. All evaluations were made between 15:00 and 17:00 h before a meal.Left ventricular diastolic function was assessed according to the recent consensus guidelines , 22 on dHigh-resolution ultrasonographic imaging of the carotid artery using the B-scan mode was performed using the EUB-8500 ultrasound system  with the probe frequency set to 7.5 MHz. The imaging was performed with the patient in the supine position with his head turned slightly away from the sonographer. The procedure involved scanning the near and far walls of the carotid artery every 1 cm proximal to the carotid bulb in the longitudinal view. The mean IMT was defined as the average of the maximal IMT 1 cm proximal and 1 cm distal to the carotid bulb , 25. TheThe measurements of the CAVI, blood pressure, and heart rate were performed using the program embedded in the VaSera VS-1000, a vascular screening system . A detailed explanation of the methods used to measure the CAVI has been reported . BrieflyWe calculated the parameters using LSFG Analyzer software . The software program then separated out the vessels using the automated definitive threshold and divided the ONH into the vessel area and the capillary area. The details of the determination of the LSFG measurements from fundus images were described previously , 26. In A similar explanation of the BOT values were obtained from the waveform analysis , 27, 28.Only the data from the right eye were used for the analysis.g for 10 min, and the supernatant was frozen immediately in polypropylene tubes and stored at −80 °C until its use in assays.The laboratory profile of each patient was comprised of the determination of the following: glycated hemoglobin A1c (HbA1c: %), homeostasis model assessment of insulin resistance (HOMA-IR), apolipoprotein-A1 (mg/dL), apolipoprotein-B (mg/dL), hematocrit (%), platelet count (×104/μL), cystatin C (mg/L) and urinary albumin concentration (UAC: mg/L) as an indicator of kidney function, and the total cholesterol (mg/dL) obtained from fasting morning blood and urine samples. The HbA1c is expressed based on the scale of the National Glycohemoglobin Standardization Program. HOMA-IR = fasting insulin (IU/ml) × fasting blood glucose (mmol/L)/22.5 . Blood a2), spherical refraction (diopters) assessed with the TONOREF 2 system , ocular perfusion pressure , and heart rate (beats per min). The OPP was defined as: (2/3MABP) – intraocular pressure. The intraocular pressure was obtained by applanation tonometry.The following parameters were measured: body mass index  was used for the statistical analyses.We considered The results of the characteristics of all patients are shown in Table r = 0.49, p < 0.0001), BMI , pulse pressure , spherical refraction , heart rate , HbA1c , hematocrit , mean IMT , the E/e’ ratio  and the CAVI . Cystatin C tended to be correlated with the skew but did not reach significance .Skew was significantly correlated with age , BMI , pulse pressure , spherical refraction , heart rate , HbA1c , hematocrit , cystatin C , UAC , mean IMT , the E/e’ ratio  and the CAVI .The BOT was significantly correlated with age  were heart rate , spherical refraction  and CAVI . The factors that were contributing independently to the BOT  were heart rate , the CAVI , UAC , mean IMT , spherical refraction , BMI  and pulse pressure .Tables This study was designed to determine whether systemic arterial stiffness shown by the CAVI significantly affects the skew and BOT, which are factors derived from a pulse waveform analysis, in the capillary area of the ONH. In our previous research, we reported that the BOT of the entire ONH was significantly correlated with age, mean IMT, left ventricular diastolic function, kidney function and the CAVI in the healthy subjects , 30, 31.The novel analysis method of LSFG can be used to separate the ONH into vessel and capillary areas for more detailed analyses of the ONH microcirculation. It was reported that the skew and BOT values in the capillary area of the ONH are important predictive factors for normal-tension glaucoma and silent brain infarction , 20.Based on the above-mentioned findings, we hypothesized that the systemic arterial morphological and functional status also affects the skew and BOT values in the capillary area of the ONH. The present study’s Pearson’s correlation analysis and multiple regression analysis revealed that heart rate, spherical refraction and the CAVI are factors that contribute to the skew. We also observed that the skew in the capillary area of the ONH increases in parallel with the increase in the CAVI. In other words, the peak of the MBR — as an indicator of the velocity of the erythrocytes — in the cardiac cycle moves leftward in parallel with the exacerbation of the CAVI.Our multiple regression analysis revealed that heart rate, the CAVI, UAC, mean IMT, spherical refraction, BMI and pulse pressure were factors contributing to the BOT. The BOT in the capillary area of the ONH decreased in parallel with the increase in the CAVI, UAC, mean IMT and pulse pressure. The BOT in the capillary area of the ONH was significantly correlated with these parameters, as was BOT in the entire ONH, as we reported previously , 30, 31.Several studies have reported that the CAVI increases not only with age but also with arteriosclerotic diseases, such as coronary artery disease, carotid arteriosclerosis, chronic kidney disease, and cerebrovascular disease –35. Our Our present findings also revealed that the systemic arterial function shown by the CAVI is one of the important contributors to ocular microcirculation. In other words, the microcirculation of the capillary area of the ONH calculated by LSFG provides a window for detecting the conditions of systemic large arteries. We believe our findings may be clues to the relationships between cardiovascular and cerebrovascular disease and ocular diseases, such as normal-tension glaucoma and retinal and choroidal vascular diseases.r > 0.60, p < 0.0001).In the present study, BMI was significantly positively correlated and spherical refraction was negatively correlated with BOT. These results provide new knowledge, and further detailed evaluations are needed to confirm these results. In any case, BMI and spherical refraction should be considered when interpreting blood flow data using LSFG. We excluded them from the multiple regression analysis, because the CAVI was strongly correlated with age (Our study has some severe limitations. First, only men were included in the study, and our findings should not be generalized to women. Second, the optic-nerve head has double blood circulation; one depends on branches of the central retinal artery while the other depends on the branches of the short posterior ciliary arteries. Both circulation routes function at different perfusion pressures . We evalIn conclusion, the CAVI was revealed as an independent factor contributing to both the skew and BOT in the capillary area of the ONH. Our study clarified that large arterial function shown by the CAVI contributes to smooth hemodynamics of microcirculation, which is shown by LSFG.


Impairment of physical function and abnormal body composition are the major presentations in patients with chronic kidney disease (CKD). The aim of this study is to investigate the relationship between body composition and physical function in CKD patients.This cross-sectional study enrolled 172 of CKD stages 1–5 from February 2013 to September 2013. Handgrip strength (upper extremity muscle endurance), 30-second chair-stand test (lower extremity muscle endurance) and 2-minute step test (cardiorespiratory endurance) were used as indices of physical function. Body composition, including fluid status , lean tissue index (LTI), and fat tissue index (FTI), was measured using a bioimpedance spectroscopy method.All patients with high ECW/TBW had lower handgrip strength and 30-second chair-stand than those with low ECW/TBW (P<0.001 and P = 0.002). CKD patients with high FTI had lower handgrip strength and 30-second chair-stand than those with low FTI (P<0.001 and P = 0.002). These patients with low LTI had lower handgrip strength than those with high LTI (P = 0.04). In multivariate analysis, high ECW/TBW was positively associated with decreased handgrip strength  in CKD patients. High FTI was significantly correlated with decreased times of 30-second chair-stand . There was no significant relationship between body composition and 2-minute step test.Our results show a significant association of impaired upper and lower extremity muscle endurance with high fluid status and fat tissue. Evaluation of body composition may assist in indentifying physical dysfunction earlier in CKD patients. Impairment of physical function is one of the major complications in patients with chronic kidney disease (CKD). Poor physical function is associated with not only low quality of life  but alsoCKD itself is a pro-inflammatory status . The redIn older populations, these metabolic waste products generated by malnutrition-inflammation contributes to skeletal muscular dysfunction, which has an important influence on impairment of mobility and physical performance, consequently increasing the risks for fractures, disability, hospitalization or mortality . HoweverThis cross-sectional study invited 172 of CKD stages 1–5 patients to participate in the study from February 2013 to September 2013 at one hospital in Southern Taiwan. All patients had been enrolled in our integrated CKD program for more than 3 months. The integrated CKD program provided multidisciplinary care plan, including physical, nursing and nutritional treatment. We monitored renal function every 3 months at least. CKD was staged according to K/DOQI definitions and the estimated glomerular filtration rate (eGFR) was calculated using the equation of the 4-variable Modification of Diet in Renal Disease (MDRD) Study . We exclThis study used handgrip, 30-second chair-stand test and 2-minute step test as indices of physical function. These examinations were performed at the same time with measurement of body composition and laboratory parameters. Handgrip strength (kgf) as an indicator of upper extremity muscle endurance was measured using a handheld dynamometer . Every participant was in a seated position and two consecutive measurements were performed at intermediate forearm position with the elbow flexed at 90 degree. The mean of the maximal values for each hand was used for analysis . Lower eth-90th percentile and >90th percentile of LTI and FTI relative to age and sex matched healthy population [Body composition was determined once by a bioimpedance spectroscopy method, Body Composition Monitor , at enrollment. BCM has been validated against standard reference measures for evaluation of body composition and fluid status in CKD and normal population ,17–20. TDemographic and clinical data of patients were obtained from interviews and medical records at enrollment. The body mass index (BMI) was calculated as the ratio of weight in kilograms divided by square of height in meters. Blood pressure was recorded as the mean of two consecutive measurements with 5-minute intervals, using one single calibrated device. Mean arterial pressure was calculated as 2/3 diastolic blood pressure plus 1/3 systolic blood pressure. Hypertension, diabetes, hyperlipidemia and gout were defined as those with a medical history through chart review. Cardiovascular disease was defined as a history of heart failure, acute or chronic ischemic heart disease, and myocardial infarction. Blood and urine samples were obtained at the same time of fluid status measurement. Patients were asked to fast for at least 12 hours before blood sample collection for the biochemistry study. The severity of proteinuria was determined using urine protein-creatinine ratio (PCR).th, 75th percentile), as appropriate, and categorical variables were expressed as percentages. Skewed distribution continuous variables were log-transformed to attain normal distribution. The significance of differences in continuous variables between groups was tested using independent t-test or the Mann-Whitney U analysis, as appropriate. The difference in the distribution of categorical variables was tested using the Chi-square test.Continuous variables were expressed as mean±SD or median  were CKD stage 1–2, and 128 (74.4%) were CKD stage 3–5. The mean of ECW/TBW, LTI and FTI was 46.6±3.1%, 14.0±2.7 kg/m2, and 9.7±4.2 kg/m2 respectively. CKD stage 3–5 patients had higher ECW/TBW than CKD stage 1–2. However, there was no significant difference of LTI and FTI among different CKD stages.The comparison of clinical characteristics between groups based on CKD stages is shown in v.s. 29.3±8.5kg, P<0.001, v.s. 108.5, P = 0.007) than CKD stage 1–2 patients.Of all CKD patients, the mean of handgrip strength and 30-second chair stand was 29.2±8.5 kg and 11.2±3.1 respectively. The median of 2-minute step was 105.5. CKD stage 3–5 patients had lower handgrip strength . After adjusting age, sex, BMI, eGFR, exercise capacity, and variables of P<0.05 in univariate analysis, 1% increase in ECW/TBW was correlated with 41.17kg decrease in handgrip strength .Low handgrip strength was significantly correlated with high ECW/TBW , high FTI , and low LTI .In univariate linear regression analysis, the times of 2-minute step were correlated positively with eGFR, but negatively with age . FurtherThis study assessed the relationship between body composition and physical function in patients CKD stages 1–5 not on dialysis. Patients with CKD stages 3–5 had lower handgrip strength and lower times of 30-second chair-stand than those with CKD stages 1–2. High ECW/TBW was significantly associated with low handgrip strength, and FTI was negatively correlated with times of 30-second chair-stand after adjustment for traditional risk factors for physical dysfunction in CKD patients.To our knowledge, this study is the first to evaluate the association between fluid status and physical function in CKD population, and we found that fluid overload was significantly associated with impaired upper extremity muscle endurance. Accumulating evidence has documented that malnutrition-inflammation was correlated with fluid overload . StoenoiMuscle structure and function are linked to physical function. A loss of lean tissue and an increase in whole-body or regional fat deposits affect muscle structure and function in older individuals . In patiFat tissue is an important endocrine organ that produces pro-inflammatory cytokines, such as interleukin-6, and anti-inflammatory cytokines, such as adiponectin . Excess 2 and the results show a significant association of handgrip strength with fluid status and LTI independent of age, sex and eGFR Click here for additional data file.S2 Fig(TIF)Click here for additional data file.S3 Fig(TIF)Click here for additional data file.


Construct validity, concurrent validity, and interday reliability were assessed by measuring toe (Portapres®)) and brachial blood pressure in 16 nondisabled participants on consecutive days. Construct validity was assessed by pedaling on a cycle ergometer (6 revolutions per minute) and comparing the measured toe blood pressure to an estimated value based on orthostatic factors. Concurrent validity was assessed by comparing toe and brachial blood pressure during supine rest and following 10 min of cycling exercise. Interday reliability was assessed by recording toe and brachial blood pressure during supine rest on a second day. Construct validity analysis shows that the toe blood pressure signal was moderately correlated with the changes in heart–toe distance and that changes in toe blood pressure during slow cycling were similar to the estimated value. Resting toe and brachial mean arterial blood pressure showed concurrent validity with only a fixed bias explained by the change in orthostatic pressure and the toe–brachial index. Furthermore, cycling exercise was associated with an increase in brachial and a decrease in toe mean blood pressure. The interday reliability analysis showed no proportional or fixed bias for mean arterial blood pressure. Our study showed the feasibility of using the Portapres® to measure toe blood pressure during movement and can be used to study the effect of movement‐related forces during cycling on toe blood pressure.The aim of the study was to assess the validity and reliability of using the Portapres Those measurement devices uses the volume‐clamp method, developed by J. Penaz, in association with photoplethysmography (PPG) to measure continuous arterial BP in the finger  , including the intra‐arterial method, the auscultatory method, the oscillometric method, and the noninvasive continuous (beat‐to‐beat) method  . TBP and blood oxygenation were measured in 10 healthy, young volunteers during rest at six different body tilt angles . They found a correlation of r = 0.87 (P = 0.01) between the Finometer® and theoretical values based on measured brachial blood pressure combined with calculated orthostatic pressure effect. They found similarities between their TBP measurements at various tilt angles with measurements obtained through instrumented catheters , and 0.905 and 0.898 on the left leg. The concordance correlation coefficient was 0.913 on the right leg and 0.915 on the left leg, which indicated concordance between the two devices.There has been other research that has investigated the validity of PPG for TBP measurements using laser Doppler (LD)  and interday reliability of the PortapresSixteen nondisabled, normotensive active participants  provided informed written consent before beginning the study. Participants were asked to refrain from consuming alcohol, caffeine, nicotine, or performing strenuous bout(s) of physical activity 1 day prior to both experimental days. Participants were well rested (6–8 h of sleep) the night before testing days, consumed their last meal 3 h prior to each testing session, and were well hydrated  leading up to testing. To minimize diurnal influences on cardiovascular function, participants attended the laboratory at approximately the same time of day for both testing sessions. All participants completed a Physical Activity Readiness Questionnaire (PAR‐Q) , resting supine TBP were compared to resting supine brachial BP before and after cycling exercise , and resting TBP measurements between two testing days (interday reliability).® front‐end unit was attached just proximal and anterior to the participants' right ankle.The study included 2 days of testing for each participant. On the first testing day, resting heart rate (HR) and right brachial BP were measured and recorded manually every minute for 5 min while the participant laid supine. TBP was measured simultaneously from the second toe of the right foot . The Portapres®, RacerMate Inc., Seattle, WA) with the seat adjusted to 100% of their right greater trochanter height .Starting with their foot at the top of the pedal crank, the participant pedaled at six revolutions per minute for 1 min to determine if the change in TBP corresponded to the change in toe height. The frequency of pedaling was controlled through auditory feedback from a metronome set at 60 beats per minute and the participant was required to be back at the top of the pedal crank every 10 beats. This condition was called the “slow orthostatic” trial, and was used to measure construct validity. An infrared marker was attached to the fifth metatarsal of the right foot. The right toe position was measured using an Optotrak Certusmax) , respectively. Heart rate was measured to ensure participants cycled at an intensity that elicited 60% of their HRmax.Heart rates, brachial BP, and TBP were measured using a Polar FT1 HR monitor , a Carescape v100 blood pressure monitor , and a Portapres® were sampled at a frequency of 200 Hz and analyzed using NDI First Principles™ software and custom MATLAB scripts.The three‐dimensional position of the fifth metatarsal and the output signal of the Portapres3) (Kenner 2), and diameter of pedal crank (0.36 m). The hypothetical value was equal to 27.9 mmHg.TBP data from the “slow orthostatic” trial were filtered at 0.3 Hz using a fourth‐order low‐pass Butterworth filter to subtract the systolic pulse from the measurement. The actual change in TBP due to corresponding fluctuations in orthostatic pressure was measured by calculating the difference between maximum and minimum TBP values for each pedal revolution during slow cycling. The theoretical change in TBP during slow cycling was determined by the multiplication of blood density (1053 kg/m) Kenner , accelerThe fifth metatarsal position data were filtered at 1 Hz using a fourth‐order low‐pass Butterworth filter to monitor pedal position and timing of the pedal revolution. The vertical changes in position of the fifth metatarsal  were extracted from the kinematic dataset and synchronized with the TBP data.T) and brachial mean arterial pressure (MAPB) measurements at two different parts of the experimental protocol: (1) during the initial rest period on the second testing day and (2) immediately following the cycling exercise bout. For this analysis, the TBP data were filtered using a 5‐Hz fourth‐order low‐pass Butterworth filter for all participants' data. The filtered TBP data were then extracted 15 sec before and 15 sec after the fourth minute manual brachial BP measurement. Maximum and minimum TBP values were classified as systolic TBP and diastolic TBP values, respectively. MAPT and MAPB were then calculated using systolic and diastolic TBP and brachial BP values measured at the fourth minute of rest using Equation Concurrent validity was assessed by comparing toe mean arterial pressure  for all participants to the theoretical value of 27.9 mmHg. Six TBP values were measured and compared against the theoretical value for each participant, which corresponded to the six full revolutions of the pedal crank. The D'Agostino and Pearson normality test was applied to all individual data points to ensure the data were normally distributed. Statistical significance determination was set at P < 0.05. A cross‐correlation analysis was used to assess the similarity between the participant's filtered kinematic and TBP waveforms.A one‐sample T  versus the change in MAPB  data. The changes in MAP were calculated by subtracting the MAP after exercise from the MAP before exercise for both the toe and brachial measurement sites.Concurrent validity was assessed by contrasting the brachial BP and TBP measurements at rest and following a bout of cycling exercise. The brachial BP and TBP at rest were analyzed using two different statistical methods: a model II ordinary least products (OLP) regression analysis and a method of differences  and the slope (b′) of the OLP regression line to determine biases. Fixed bias was determined by calculating the 95% confidence intervals (CI) for a′ and determining whether it included the value of “0”. If the 95% CI band did not include “0”, the data were classified as having a fixed bias. Proportional bias was defined as “one measurement that produces values that are greater (or lower) than those from the other by an amount that is proportional to the level of the measured variable” , and was chosen because it accounts for random error within both sets of measurements Ludbrook . For theLudbrook . TherefoB and MAPT (y‐axis) were plotted against the average of the two MAP measures (x‐axis). Proportional bias was determined by applying an ordinary least squares (OLS) regression to the Bland–Altman method of differences data. A one‐sample t‐test comparing a value of “0” to the slope of the method of difference data (OLS regression line) was used to determine proportional bias. Separately, a one‐sample t‐test comparing the mean difference data to a value of “0” was used to determine fixed bias.In the method of differences (Altman and Bland P < 0.05 (with a Bonferroni correction for multiple comparisons).The D'Agostino and Pearson normality test was applied to all individual data points to ensure that data were normally distributed . The OLS regression line was not normally distributed and was analyzed using the Wilcoxon signed‐rank test.All MAP, systolic, and diastolic TBP measurements acquired on two consecutive days were tested for interday reliability using OLP and Bland–Altman analyses. These OLP and Bland–Altman analyses used the same method as the concurrent validity analysis. For the OLP regression analysis, MAP, systolic, and diastolic TBP values for the first and second days were plotted on the An example of one participant's raw and filtered TBP Fig. A as wellFifteen participants provided 76 acceptable TBP values out of a maximum of 96 possible measurement, which were included in the construct validity analysis. One participant's data were excluded because TBP could not be measured. From the remaining 90 TBP values, 14 TBP data points were either absent or were unable to be extracted from the raw data due to participant error . Only one TBP value was deemed an outlier (75.0 mmHg) and was excluded from analysis due to being more than 3 SD from all participants overall mean (mean + 3 SD = 61.3 mmHg).n = 7) between the filtered TBP signal and difference in height between the heart and toe signal showed a moderate correlation (r = 0.66 ± 0.16) with no difference in the timing (lag = 0 ± 0.86 sec) between the two signals. Furthermore, the mean difference in TBP  was similar to the proposed theoretical difference of 27.9 mmHg .The cross‐correlation analysis  and average MAPB was 80 ± 5.5 mmHg . Ordinary least products (OLP) analysis indicated that there was fixed bias, but no proportional bias in MAP between the two measurement sites  and average MAPB was 89 ± 7.2 mmHg . The OLP analysis that was applied to the change in MAPT data versus the change in MAPB data showed a slope (b′) of 0.38 (95% CI's: −1.3 to 2.1), and a y intercept (a′) of 11.5 (95% CIs: −17.1 to 40.0) , whereas on day 2 it was 69.9 ± 13.2 mmHg . An OLP analysis showed that there were no fixed or proportional bias in MAP, systolic, or diastolic measurements in the toe between the two testing days (Table P < 0.05) but no fixed bias  within each revolution during cycling. Second, the concurrent validity of the Portapres® was determined by comparing the measured TBP to the brachial BP at rest and after a bout of cycling exercise. Third, the interday reliability of the Portapres® was determined by comparing resting TBP values on the first testing day to resting TBP values on the second testing day. The study was unique because it was the first one to use the Portapres® during any type of lower body movement. The study provided interesting findings, which adds to the literature as only a few other published studies have used a similar BP recording device on the toe while at rest ; however, they included some variability. Our results show that the TBP measured by the Portapresr = 0.87), which is higher than the one reported in this study (r = 0.66). Their measurements were collected under static conditions, and apparent differences in theoretical and actual measurements were found; however, these differences were not quantified. The difference between the Rosales‐Velderrain et al.  that are not present in controlled environments. In a previous study, Rosales‐Velderrain et al.  comparedn et al.  and thisSecond, the participants were instructed to keep a slow and steady cadence of six revolutions per minute during the 1 min slow orthostatic trial. At times, participants may have generated excessive forces on the pedal crank, which could have caused an increase in cuff pressure at the toe. If this was true, then larger pressures would be expected. Although pedal force was not measured in this study, the toe position versus time graphs showed very little deviation from the expected toe position curve in participants  and diastolic (minimum) blood pressures in one heart contraction may have also played a role in the changes of TBP compared to the change in foot height. One noticeable difference in the raw TBP waveforms was that they were not comparable between participants. Some participants showed very large and pronounced pulse pressures, whereas others showed very small pulse pressures. This difference between participants could be the result of many factors related to the alignment of the cuff or the toe temperature. However, the small difference in measurement magnitude between two consecutive days  when measuring TBP during a lower limb movement like cycling. One of the goals with slow cycling at six revolutions per minute was to observe any changes in TBP that were due to systolic and orthostatic forces. The systolic force was mostly attenuated from the raw TBP waveform by filtering, and was therefore believed to have very little effect on the TBP measurements during slow cycling. That said, it was difficult to predict how much of an effect the slow cycling movement had on the measured TBP values. Future studies should investigate ways to control for movement artifact when measuring the effect of the orthostatic force on TBP.With a measured change in TBP of 28.7 mmHg in comparison to the theoretical estimated value of 27.9 mmHg, this study shows that the Portapres® to measure TBP it was important to compare the measurements against another device and measurement site, as well as comparing the TBP values collected in this study to TBP values collected by others to determine their normalcy. The results of our study show that brachial MAP was approximately 10 mmHg  of −1.87 and a y intercept (aʹ) of −123.8 were calculated. The 95% CI for the bʹ was −0.4 to 3.4, meaning there was no proportional bias, and the 95% CI for aʹ was −235.5 to −12.0, meaning there was a fixed bias present in the data. Although the mechanisms behind this finding are not currently understood, it gives preliminary evidence that differences between upper and lower body measurement sites become larger when there is a greater average resting MAP between the two measurement sites.Another notable finding of the current study was how the difference in MAPsee Fig. . A trend® had very good interday reliability with only the Bland–Altman analysis showing a proportional bias for diastolic measurements. However, the limits of agreement in the TBP measurements were greater than the acceptable limit of agreement of 10 mmHg that has been suggested for clinical practice  to detect changes in blood flow (LD3) and heart beats (LD0.03). Their results showed limits of agreement that were well above 10 mmHg as well , and were comparable to results of the current study because of the lower TBP magnitude found in their at‐risk population (approximately 60 mmHg vs. 72 mmHg in this study).The results of this study show that TBP measured using the Portapres® cannot, at this time, be used to measure TBP in a clinical population until it can provide lower limits of agreement between measurements on separate days . For example, according to the TBP values found using our findings, a group of patients with peripheral artery disease taking part in an exercise intervention study over an extended period would have to provide very large changes in TBP  to show any sign of actual benefit from the exercise. The large amount of change in TBP is probably not feasible in a disabled population considering they have very low TBP to begin with. Therefore, it would not be appropriate to expect such large changes in this population due to exercise. Future studies should investigate other measurement protocols to increase interday reliability with the Portapres® in attempt to lower the limits of agreement, so peripheral artery disease detection and rehabilitation progress can be measured using the device.The significance of these findings is that the Portapres® was able to collect TBP in 16 nondisabled participants at rest and while cycling at a very slow cadence with mixed results regarding construct and concurrent validity as well as interday reliability. Construct validity has been established through the moderate cross‐correlation and similar magnitude of changes between the measured TBP and the changes in height between the heart and the toes during slow cycling. We found differences in concurrent validity depending on whether the measurements were recorded at rest or after cycling exercise. Brachial BP and TBP had fixed but no proportional bias at rest prior to exercise, which is a promising result. This result was not found after exercise which is believed to be due to different regional effect in vascular resistance. Finally, the Portapres® did not show acceptable limits of agreement when testing for interday reliability , but our findings do provide information to determine sample size calculations in future studies. Finally, the results from this study show the possibility of using the Portapres® to study the effect of movement‐related increases in arterial blood pressure (Sheriff et al. In conclusion, we have shown that the PortapresNone declared.


The aim of this study was to assess target diabetic goal achievements and to explore variables associated with them. A cross-sectional study was conducted between December 2015 and April 2016 on 188 type 2 diabetic patients attending Ayder Referral Hospital's outpatient diabetic clinic. Glycemic control was assessed using fasting plasma glucose values and total cholesterol and triglyceride were used to evaluate lipid profiles. Bivariate and multivariate logistic regression analyses were done to identify factors associated with poor glycemic control, hypertension, and dyslipidemia.P = 0.013) and marked month to month fasting plasma glucose (FPG) variability as measured by large standard deviation  were significantly associated with overall poor mean FPG results. Female sex was also significantly associated with dyslipidemia . Mean duration of diabetes was 6.5 years. Combined glycemic, lipid, and blood pressure targets were achieved only in 8.5% of the participants. More males achieved combined targets than females. Separately, while above two-thirds of the patients had poor glycemic control (67%), more than half of the participants have had poor lipid (58.5%) and blood pressure (52.1%) control. A significant portion of the patients (68.1%) had also comorbidities other than hyperglycemia. In bivariate and multivariate analyses, longer duration of diabetes disease (AOR: 3.4;  The study showed that achievements of combined diabetic goals are generally poor.  More than 422 million 8.5%) adult people were living with diabetes at the end of 2014. Tens of millions suffer disabling and life-threatening complications of diabetes such as heart attack, stroke, kidney failure, blindness, and amputation . Diabete% adult pOptimal control of plasma glucose, lipid profile, and blood pressure is central to the management of diabetes mellitus. These are the key factors in reducing morbidity and death from the disease. Several large studies have proven that achieving these diabetic goals averts or considerably delays life-threatening complications of diabetes, enabling people with diabetes to live longer and healthier lives , 7. DespA cross-sectional study was conducted in type 2 diabetic patients attending outpatient diabetic clinic of Ayder Referral Hospital, Mekelle University, between December 2015 and April 2016 to evaluate the extent of diabetic target achievements and factors associated with them. All type 2 diabetic patients who were attending the outpatient diabetic clinic during the data collection period were included in the study provided that they met all of the following inclusion criteria: visited the diabetic clinic during the data collection period, had been diagnosed with diabetes at least six months earlier, had regular follow-up at diabetic clinic of Ayder Referral Hospital for at least 6 months prior to data collection, and agreed to sign consent form. During their regular follow-up, study participants were recruited into the study by trained data collectors. Patients were allowed to participate only once during the six-month period. Patients whose follow-up was not regular (those who missed three or more follow-ups within six months), patients with less than six-month follow-up, and newly diagnosed diabetic patients (less than six-month duration) were excluded from the study.Data on sociodemographic variables , lifestyle variables , and self-monitoring and management practices were collected by trained diabetic nurses using face-to-face interviews and structured questionnaires. After face-to-face interview, information on anthropometric measurements, blood pressure, duration of diabetes, diabetic medications, coexisting comorbidities and other medications, lipid profiles, and current and previous five-month records of fasting plasma glucose (FPG) was collected through clinical laboratory investigation and review of patients' medical records.Ethical clearance and approval for undertaking this study were obtained from Research and Community Service Council (RCSC) of Mekelle University, College of Health Sciences, before starting the actual data collection. Subsequent permission was obtained from the authorities of Ayder Referral Hospital, including medical director and the head of diabetic clinic. After explaining the aim and objectives of the study, verbal and written informed consent was obtained from each participant.We evaluated achievements of diabetes goal by assessing glycemic control, lipid profile, and blood pressure targets. We used mean and single FPG measurements for glycemic control and total cholesterol and triglyceride test for lipid profile assessments. Glycemic control was classified as good or poor based on the criteria of the American Diabetes Association (ADA)  [Lipid profiles, blood pressure, and body mass index values were also categorized as normal and high based on criteria of ADA and US National Cholesterol Education Program. Accordingly, hypercholesterolemia was considered when total cholesterol level is ≥200 mg/dl and hypertriglyceridemia refers to a level ≥ 150 mg/dl. Dyslipidemia was defined as the presence of one or both of these abnormalities in serum. Hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg or use of antihypertensive medications , 14.∗ HbA1c) − 77.3 [Month to month variability of FPG was also assessed using mean, standard deviation (SD), and coefficient of variation (CV) . Mean an) − 77.3 .2O2, one of the reaction products, is measured quantitatively in a peroxidase-catalyzed reaction that produces a color. The color intensity is proportional to triglyceride concentration present in the sample. Absorbance is measured at 500 nm.Fasting serum value of FPG, total cholesterol, and triglyceride were determined according to their measurement principles and guidelines using Hitachi 902 Autoanalyzer . For total cholesterol determination, cholesterol esters in serum are hydrolyzed by cholesterol esterase in the reagent. The free cholesterol is then oxidized by cholesterol oxidase to the corresponding ketone liberating hydrogen peroxide, which is then converted to water and oxygen by the enzyme peroxidase. Para-aminophenazone (4-aminophenazone) takes up the oxygen and together with phenol forms a pink-colored quinoneimine dye and the absorbance was measured at 515 nm wavelength. Triglycerides were measured enzymatically in serum using a series of coupled reactions in which triglycerides were hydrolyzed to produce glycerol. Glycerol is then oxidized using glycerol oxidase, and HAll data were entered into Epi Info software (version 7.1) and analyzed using Statistical Package for the Social Sciences (SPSS) software (version 20.0). First, data were cleaned, edited, and checked for completeness before analysis.P value of <0.05 was considered as a statistically significant level. All variables with a P value < 0.3 were considered for multivariate logistic regression to determine independent factors predicting poor diabetic control. Model fit to the data  was assessed by the likelihood ratio χ2 test and Hosmer-Lemeshow goodness-of-fit test.Chi-square test was used to measure the significant differences among different proportions. Binary logistic regression analysis was carried out to identify factors associated with poor glycemic control, hypertension, and dyslipidemia with their 95% confidence interval. At the same time, we performed covariate analysis between continuous variables. A From the total 188 participants, 104 (58.9%) were males. The median age of the study population was 54 years, ranging from 18 to 80 years. 34% of the study participants were illiterate and 17% were rural residents. Less than one-fifth (16.5%) of the participants have had regular physical exercises and 66% had food selection for their diabetes management. From participants with dietary restriction, 23.4% avoided sugar, salt, and fatty foods, while the rest used vegetables (13.8%), barley (8%), and teff (8%). Majority of the participants visited the diabetic clinic only 3-4 times in the last six months. Only 11.2% patients had their own glucometer for self-monitoring practices . Table 1Mean duration of diabetes since diagnosis was 6.5 years. A larger proportion of patients (55.3%) were taking oral hypoglycemic agents followed by insulin (37.8). In addition to diabetic treatments, about 40% of the patients were taking other medications. Based on self-report and clinical record review, comorbidities other than hyperglycemia were described in 68.1% of the patients. Peripheral vascular disease (46.8%), hypertension (44.7%), gastrointestinal problems (42.2%), renal diseases (22.3%), retinopathy (18.6%), and heart problems (5.9%) were among the reported comorbidities. Except hypertension, female proportions were higher in all comorbidities .∗ 3 < mean). Only 35 (18.6%) patients had HbA1c test record during the last six months. From these, 26/35 had HbA1c value ≥ 7% (poor control). The detailed clinical characteristics of the study's patients are indicated in Based on coefficient of variation of FPG, 93 (49.5%) had marked month to month glycemic variations (CV: FPG ≥ 25) and 61 (32.44%) failed to achieve target SD for FPG  had poor glycemic control. After calculating HbA1c values from the corresponding mean FPG values, 110 (58.5%) had HbA1c value ≥ 7 (poor control), while 52.2% of patients were hypertensive and 58.5% had dyslipidemia and either hypercholesterolemia or triglyceridemia or both. Combined glycemic, lipid, and blood pressure targets were achieved only in 8.5% of the participants. While majorities (41.5%) achieved only one of these three goals, 22.3% did not achieve all the three targets. More proportion of males achieved combined targets than females .P value less than 0.3 in binary logistic regression analysis were included in multivariate logistic regression analysis after checking for confounders. In multivariate analysis, these variables retained their significant association  had also comorbidities other than hyperglycemia. Our result is lower as compared to the previous study in Israel, which found 13% of combined target achievements . HoweverIn this study, we used FPG test as a tool for assessing glycemic control status. Despite the fact that assessment of FPG is insufficient to obtain optimal glycemic control –29 and tFor blood pressure targets, we found comparable results with studies from Israel (51%)  and SoutIn bivariate and multivariate analyses, longer duration of diabetes disease (AOR: 3.4) and wide month to month FPG variability as measured by large CV of FPG and large SD (AOR: 2.5) were significantly associated with overall poor mean FPG results. None of these variables were associated with single FPG values. Association of marked FPG variability (CV ≥ 25) with poor mean FPG control, but not with single FPG value, indicates that FPG variability mainly affects the overall long-term results. This can be interpreted as follows: diabetic patients who failed to narrow their month to month FPG variability and maintain its stability are less likely to achieve their long-term control. This may be in turn the reflection of low treatment adherence, low self-management practices, or irregular food intakes.β-cell function and insulin secretion as the disease progresses over time.In accordance with our result, Assunção et al. and Juarez et al. also found significant association between longer duration of diabetes and poor glycemic control , 31. ThiP < 0.05). The association of high BMI with hypertension and female gender and high FPG with dyslipidemia is consistent with the pathogenesis and risk of these diseases. However, the association between presence of coexisting morbidities and hypertension is hard to explain, since frequencies were generated from the data collected by combination of self-report and review of clinical records.Similarly, in bivariate analysis, patients with higher BMI (BMI ≥ 25), taking drugs other than antidiabetics, and having coexisting morbidities were more likely to be hypertensive and failed to achieve blood pressure targets. Female diabetic patients and patients with high FPG were also at high risk of developing dyslipidemia . In order to improve combined diabetic goal attainment, patients should be advised to minimize month to month FPG variation and maintain consistent glycemic control.


To evaluate changes in intraocular pressure (IOP) and intracerebral pressure (ICP) reflected by the optic nerve sheath diameter (ONSD) in patients undergoing robotic-assisted laparoscopic prostatectomy (RALP) in permanent 45° steep Trendelenburg position (STP).Fifty-one patients undergoing RALP under a standardised anaesthesia. IOP was perioperatively measured in awake patients (T0) and IOP and ONSD 20 min after induction of anaesthesia (T1), after insufflation of the abdomen in supine position (T2), after 30 min in STP (T3), when controlling Santorini’s plexus in STP (T4) and before awakening while supine (T5). We investigated the influence of respiratory and circulatory parameters as well as patient-specific and time-dependent factors on IOP and ONSD.p = 0.013). Univariate mixed effects models showed peak inspiratory pressure (PIP) and mean arterial blood pressure (MAP) to be significant predictors for IOP increase. Mean ONSD values (mm) were T1 = 5.88, T2 = 6.08, T3 = 6.07, T4 = 6.04 and T5 = 5.96. The ONSD remained permanently >6.0 mm during RALP. Patients aged <63 years showed a 0.21 mm wider ONSD on average (p = 0.017) and greater variations in diameter than older patients.Average IOP values (mmHg) were T0 = 19.9, T1 = 15.9, T2 = 20.1, T3 = 30.7, T4 = 33.9 and T5 = 21.8. IOP was 14.0 ± 7.47 mmHg (mean ± SD) higher at T4 than T0 (The combination of STP and capnoperitoneum during RALP has a pronounced influence on IOP and, to a lesser degree, on ICP. IOP is directly correlated with increasing PIP and MAP. IOP doubled and the ONSD rose to values indicating increased intracranial pressure. Differences in the ONSD were age-related, showing higher output values as well as better autoregulation and compliance in STP for patients aged <63 years. Despite several ocular changes during RALP, visual function was not significantly impaired postoperatively.Z-2014-0387-6. Registered 8 July 2014. Prostate cancer is the most common cancer in men 31.9%) and the third leading cause of cancer death (11%) in Germany .9% and t, 3. ActuThe aim of this study was to investigate the influence of capnoperitoneum and permanent 45° STP on IOP and ONSD in patients undergoing RALP. We also analysed the influence of age, body mass index (BMI), peak inspiratory pressure (PIP), mean arterial blood pressure (MAP), duration of surgery and STP on IOP and ONSD during RALP. Perioperative and postoperative complications were also recorded.This single-centre, prospective and nonrandomised study was approved by the local institutional review board (Protocol no. 14-101-0107) and registered at the local Centre for Clinical Studies (Z-2014-0387-6. Registered 8 July 2014). Informed consent was obtained from 51 patients scheduled for elective prostatectomy at the Department of Urology in Regensburg. All patients were recruited between January 2015 and August 2015. Main exclusion criteria were pre-existing eye disease , history of eye surgery, age >80 years, BMI >40, American Society of Anaesthesia (ASA) physical status > III, known cardiac insufficiency and pulmonary hypertension.The anaesthesia protocol was standardised for drugs used during RALP and exclusively conducted by the same 2 anaesthesiologists throughout the entire study. After baseline IOP measurement, patients received 2 mg of midazolam for premedication and 0.2 mg of piritramid per kilogramme (kg) body weight for the placement of a PiCCO radial artery catheter  for invasive blood pressure measurement under local anaesthesia. Anaesthesia was induced with propofol (2–3 mg/kg), remifentanil (1.5 μg/kg bolus and continuous application of 0.3 μg/kg/min) and rocuronium (0.5 mg/kg). After tracheal intubation, anaesthesia was continued with propofol as total intravenous anaesthesia guided by the Bispectral Index™  between 40 and 50; remifentanil was reduced to 0.2 μg/kg/min. Neuromuscular transmission was monitored with a peripheral nerve stimulator to maintain one twitch of the train-of-four (TOF). Relaxation with rocuronium was repeated in the case of TOF >1/4 and finished 45 min before the end of the procedure. Arterial blood pressure was kept stable with a maximum decrease of 20% of its pre-induction value. Controlled ventilation maintained end tidal CO2 (etCO2) between 30 and 40 mmHg. Pneumoperitoneum was created by intraperitoneal insufflation of CO2 with the patient in supine position. All patients were then placed in STP , which is the maximal Trendelenburg angle of the Maquet surgical table  , which does not require any topical anaesthesia of the cornea. The tonometer was calibrated according to the manufacturer’s guidelines before each application. IOP was bilaterally measured in each patient at 6 predefined time points Table . The ONSPostoperative all patients were observed in the recovery room, 8 h later on the ward and the next day and received a clinically visual and perimetric examination.p values are two-sided, and a p value of 0.05 is considered the threshold of statistical significance. Because of the explorative nature of this study, no adjustment for multiple testing was done. Data were analysed with the software SAS 9.4 .Due to the exploratory nature of this study and the lack of a primary endpoint with expectable effect sizes, no sample size calculation was performed a priori. To get robust effects in a feasible amount of time, we decided to include about 50 patients into this study. To analyse the influence of the variables age, BMI, intravenous infusion, PIP and MAP on IOP and ONSD, linear mixed models were used. These models account for correlated measurements within each patient because of several time points. Each variable was analysed in a separate model, containing time as an additional factor. The covariance structure between the time points was set to autoregressive. Effect estimates of significant variables are presented as slopes (effect on IOP and ONSD per one unit change of the variable) with corresponding 95% confidence intervals. All reported Fifty-one male patients were enrolled in this study. We registered IOP and ONSD for 102 eyes of 51 patients. Patient characteristics and common surgical variables are shown in Table P < 0.0001). In contrast, IOP at T3 (P = 0.008) and T4 (P = 0.013) was significantly higher than at T0. IOP was highest at STP (T4). In 14% of patients, IOP at T4 was higher than 40 mmHg, and the highest IOP measured was 59.6 mmHg. BMI, duration of surgery and STP did not influence IOP. A linear relationship between PIP and IOP was observed: IOP rose significantly with increasing airway peak pressure , P = 0.018). PIP in STP reached levels above 30 cmH2O most of the time .Average IOP (± SD) of all eyes (mmHg) for each time point was as follows: T0 = 19.9 ±3.6), T1 = 15.9 ±4.8), T2 = 20.1 (±6.6), T3 = 30.7 (±6.3), T4 = 33.9 (±7.4) and T5 = 21.8 (±4.3)  in patients aged <63 years (median age) and showed greater variations in diameter than in older patients  ONSD (mm) for each time point was as follows: T1 = 5.88 (±0.44), T2 = 6.08 (±0.52), T3 = 6.07 (±0.49), T4 = 6.04 (±0.50) and T5 = 5.96 (±0.49). The ONSD increased by about 0.2 mm (3.4%) after the start of capnoperitoneum (T2). During STP, the ONSD remained increased and was higher at the end of surgery (T5) than at the initial level , which may depend on the fact that we measured IOP with a rebound tonometer without topical anesthesia in the awake patient , 13. IndMolloy found that baseline IOP and duration of surgery were the only factors predicting increased IOP . In our On the basis of this study, we were able to quantify the changes in IOP throughout the procedure. We therefore concluded that patients treated with robotic prostatectomy reach IOP levels comparable to those observed in patients with glaucoma. However, possible adverse ocular effects as a consequence of IOP changes have not yet been investigated. In our study, no patient experienced ischaemic optic neuropathy after RALP clinically represented by scotoma or significant visual loss.In this study, the ONSD did not significantly exceed the initial value . Another study reported that the ONSD increased by 12.5% 0.6 mm) during CO2 pneumoperitoneum and STP for 20 patients undergoing RALP . Chin et mm durinHowever, we found an age-related difference (median 63 years) in the changes in the ONSD during RALP. Younger patients had a significantly higher baseline ONSD under mechanical ventilation, suggesting higher elasticity of the dura mater. Over the course of STP (T3 to T4), the ONSD decreased in younger patients, which may indicate better adaptability of the ONSD or intracranial pressure, respectively Fig. .Because of logistic preoperative constraints, we did not measure the ONSD prior to intubation. Neither ocular nor neurological complications were observed in our defined cohort. Larger prospective studies with RALP are required to further evaluate the relationship between STP and permanent ocular changes and to make recommendations regarding the prevention and treatment of increased intraoperative IOP.In conclusion, we found that IOP and ONSD increased significantly in a time-dependent way in patients undergoing RALP in 45 ° STP. IOP doubled and the ONSD rose to values indicating slight increased intracranial pressure, but no patient reported visual impairment or at worst POVL. We observed age-related differences in the ONSD with a higher initial value and better autoregulation in STP for younger patients. RALP is associated with significant measurable ocular changes, namely an increase of IOP and ONSD.


Because quality improvement metrics and treatment guidelines are used to conduct research, evaluate care quality, and assess population health, they should, ideally, align. We used electronic medical record data to analyze variation between blood pressure control estimates calculated by using thresholds derived from National Quality Forum 0018 (NQF 0018) and Joint National Committee (JNC) treatment guidelines in a cohort of patients with hypertension. Percentage of patients with controlled blood pressure derived from each quality improvement or treatment guideline cutoff varied up to 16.1 percentage points. This variance demonstrates that discrepancies in blood pressure thresholds produce considerable variation in estimates; thus, treatment guidance and metrics should be selected carefully. Hypertension affects 1 in 3 Americans and results in adverse outcomes and significant health care expenditures . AlthougBy using electronic medical record (EMR) data, concordance was assessed between 3 BP control algorithms. These algorithms applied BP thresholds derived from 2 treatment guidelines  and one clinical quality metric  used in hypertension care . The folThe Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7): Patients without diabetes or chronic kidney disease: systolic BP <140 mm Hg, diastolic BP <90 mm Hg; patients with diabetes or chronic kidney disease: systolic BP <130 mm Hg, diastolic BP <80 mm Hg : Patients aged <60 y, who have diabetes, or who have chronic kidney disease: systolic BP <140 mm Hg, diastolic BP <90 mm Hg; patients aged 60 y or older: systolic BP <150 mm Hg, diastolic BP <90 mm Hg : Systolic BP <140 mm Hg, diastolic BP <90 mm Hg .We analyzed encounter-level EMR data, including demographics, diagnoses, and vital signs from 19 community health centers. Data spanned approximately 3.5 years (September 2013–March 2017). Because data were collected by the Massachusetts Department of Public Health for quality improvement, review by an institutional review board was not required.International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] and International Classification of Diseases, 10th Revision, Clinical Modification [ICD-10-CM], codes 401.*/I10) was assembled. Primary hypertension was selected because clinical priorities may be different when hypertension is secondary to other conditions. Patients were included in the cohort if they had a diagnosis of primary hypertension any time prior or up to 6 months into the measurement period. Patients could meet this criteria via 1 of 2 pathways: 1) a pre-existing hypertension diagnosis, ascertained by presence of an ICD code in a historical diagnosis file , or a diagnosis of hypertension at any visit during the 2.5 years of data preceding the 1-year measurement period; or 2) patients newly diagnosed with hypertension who had a diagnosis at any visit in the first 6 months of the measurement period. In addition, during the 1-year measurement period, patients had to be aged 18 to 85 years, could not be pregnant, and had to have had at least 1 visit with a health care provider (the BP data recorded at this visit was used to estimate BP control). The algorithm used to construct the cohort is similar to that used for NQF 0018 but with a few deviations  research that explores BP control can be validly synthesized into meta-analyses and systematic reviews to inform practice, because even minor differences in algorithms may result in incongruent findings; and 2) BP control estimates across different populations or clinics are comparable and generalizable. Finally, if metrics used for assessing quality do not align with treatment guidelines, guidance should be provided to clinicians on how to appropriately integrate these different algorithms into clinical practice.A limitation of this analysis is that these results cannot be extended beyond patients with primary hypertension. Regardless, our findings indicate that minor discrepancies in BP control algorithms affect estimates of BP control; thus, mindfulness of these discrepancies is necessary when providing guidance to clinicians, interpreting data, comparing population-wide estimates, and generalizing findings of research.