Background: Corticosteroids are associated with reduced bone mineral density (BMD), as well as water and salt retention, leading to hypertension. They are substrates for P-glycoprotein, a protein coded by the highly polymorphic ABCB1 gene. We hypothesized that one ABCB1 polymorphism, rs1045642, is associated with blood pressure and BMD parameters at 1-year post kidney transplantation (KT).Methods: Rs1045642 was genotyped using pyrosequencing in 40 KT recipients. Both dominant (CC vs. CT + TT) and codominant (CC vs. CT vs. TT) genetic models  were adjusted for confounding variables .Results: Rs1045642 genotypes were significantly associated with systolic (SBP) and diastolic (DBP) blood pressure 1-year post-transplantation, independent of the genetic model used . A non-statistically significant trend was observed for an association between rs1045642 and BMD change at 1-year post-KT.Conclusions: Rs1045642 is significantly associated with higher BP 1 year after KT. Further investigations are necessary to confirm the role of rs1045642 in corticosteroid-related adverse effects. Corticosteroids continue to be used after kidney transplantation (KT) in immunosuppression protocols worldwide. Among the known adverse effects associated with prednisone use, dyslipidemia, diabetes, hypertension, and cataracts have been well evaluated in contexts other than KT  and diastolic blood pressure (DBP) are risk factors for graft failure and cardiovascular disease after KT  transporters. ABC proteins transport several molecules across extra- and intracellular membranes. More specifically, P-GP is a member of the multidrug resistance (MDR) family known as the MDR/TAP subfamily  affects the P-GP protein either by being in linkage disequilibrium with others functional SNPs, or by allele-specific differences in the codon usage affecting the protein folding and changing the substrate specificity  in the context of corticosteroids, has been previously evaluated  measurements], at 1-year post-KT. We hypothesize that rs1045642  is associated with higher blood pressure and increased loss of BMD at 1 year after transplantation.Our study aims to identify the association between This pharmacogenetics, cohort pilot study is a single center, monogenic association study evaluating the relationship between the SNP rs1045642 and corticosteroid-induced adverse events, defined as blood pressure and changes in bone mineralization phenotypes at 1 year, among KT recipients.The primary outcomes were SBP and DBP measurements at 1 year post-KT. Secondary outcomes were changes in BMD and t-score at 1-year post-KT. The methods and results are reported according to STrengthening the REporting of Genetic Association Studies (STREGA), an extension of the STROBE Statement  in the week following transplantation and at 1 year post-KT; and informed and written consent provided for the genetic and retrospective medical record analyses. The exclusion criteria were as follows: non-Caucasian ethnicity; post-KT protocol not involving the use of a corticosteroid; corticosteroid use during the 12 months before transplantation; or treatment for a humoral or tubulointerstitial rejection episode during the first post-KT year.2) and the baseline BMD (g/cm2); and t-score change at 1-year post-KT, defined as the difference between the 1-year t-score and the baseline t-score. These outcomes were all continuous variables.The following outcomes were defined and used as outcome variables: SBP and DBP at 1-year post-KT; BMD change at 1-year post-KT, defined as the difference between the 1-year BMD (g/cm2), estimated from the creatinine-based formula developed by the Chronic Kidney Disease Epidemiology Collaboration −1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black]. Scr is serum creatinine in μmol/L; κ is 61.9 for females and 79.6 for males; α is −0.329 for females and −0.411 for males; min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1. The equation does not require weight because the results are reported normalized to 1.73 m2 body surface area, which is an accepted average adult surface area.The following covariables were also evaluated: age at the time of transplantation (years); sex; glomerular filtration rate  that complied with the standards from the British Hypertension Society protocol for the evaluation of blood pressure measuring devices  and the corresponding t-scores were measured during the first week post-transplantation (t0) and at 1-year post-transplantation (t1) by DXA using bone densitometers  with a coefficient of variation of repeated measurements varying between 1.0 and 1.5%, as previously reported , CT (or GA), and TT (or AA).DNA was extracted using the Gentra® Puregene Blood kit  according to the manufacturer's instructions from 3-mL blood samples collected in ethylenediamine tetra-acetic acid–coated tubes. RS1045642 was determined by pyrosequencing using an assay developed for this study. Primers were designed with Primer3 .Frequency of the C allele has been reported to vary between 43 and 48% among Caucasians  and was found to be not significant. The 95% confidence intervals were calculated using Rmisc (https://cran.r-project.org/web/packages/Rmisc/Rmisc.pdf). Analysis of variance (ANOVA) for linear model fits were performed in R using lm and ANOVA functions for both univariate and multivariate analyses  was tested in Stata 14.1 using a chi-square test (p = 0.13). Regarding hypertension treatment, there were no differences according to genotypes in the number of antihypertensive drugs taken, before transplantation (p = 0.98) and at 1 year post transplantation (p = 0.65). There were also no statistically significant differences among genotype groups in the proportion of patients with rejection diagnosed at last follow-up, the proportion taking tacrolimus or cyclosporine at 1 year, or the trough levels of tacrolimus or cyclosporine at 1 year (data not shown).In this study, we included 40 patients who provided informed and written consent and fulfilled the inclusion and exclusion criteria. The patients' main baseline characteristics are presented in Table F = 5, p = 0.012], with an R2 of 0.2. Similarly, significantly higher SBP and DBP values  were identified at 1 year among KT recipients carrying the C allele according to the codominant model, as well as in the CC genotype when using the dominant model . This study is the first report linking genetic polymorphism to the development of corticosteroid-related adverse events after KT. Prolonged use of corticosteroids after KT is still a matter of debate  is probably substantial and likely overshadowed any potential effects of rs1045642 on bone-associated outcomes. Our main outcome was a single office measurement of BP, and the absence of repeated measurements and/or 24-h ambulatory measurements prevents us from making broad conclusions.In conclusion, this pilot study demonstrated that rs1045642 polymorphism may be associated with office SBP and DBP measurements at 1-year post-KT. The polymorphism also exhibited a trend toward being associated with changes in bone mineralization phenotypes at 1-year post-KT; this association was clinically, although not statistically, significant. These, preliminary results require confirmation in a larger independent cohort to further explore the potential use of rs1045642 determination in tailoring corticosteroid based-regimens for individual KT recipients to avoid the development of corticosteroid side effects.YB and KH: Designed research; YB and LS: Performed research; YB and BP: Collected data; YB, LS, BP, SF, and KH: Analyzed data; AP-G: Contributed important reagents; YB, LS, BP, AP-G, and KH: Wrote the paper.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In unadjusted Cox proportional regression analyses OSA was not associated with higher all-cause mortality risk (Hazard Ratio(HR) = 1.20; 95% Confidence Interval(CI): 0.50–2.85). No association was found between the presence of OSA and the rate of progression of CKD or all-cause mortality in prevalent kidney transplant recipients.Obstructive sleep apnea(OSA) is one of the most common sleep disorders in kidney transplant recipients, however its long-term consequences have only rarely been investigated. Here, we hypothesized that the presence of OSA would be associated with higher risk of mortality and faster decline of graft function in kidney transplant recipients. In a prospective cohort study 100 prevalent kidney transplant recipients who underwent one-night polysomnography at baseline and were followed for a median 75 months. Generalized linear mixed-effects models and Cox regression models were used to assess the association between OSA and the rate of progression of chronic kidney disease(CKD) and mortality. The estimated slopes of estimated glomerular filtration rate(eGFR) in patients with and without OSA were compared using a two-stage model of eGFR change including only OSA as a variable. In this model patients with OSA (eGFR versus time was −0.93 ml/min/1.73 m Obstructive sleep apnea (OSA) is one of the most clinically important forms of sleep-related breathing disorders. The prevalence of moderate and severe obstructive OSA (AHI ≥ 15 and the presence of daytime symptoms of OSA) is 2–4% in the general population2456Previous studies have shown high prevalence of OSA (16–54%) in patients with chronic kidney disease (CKD)8Despite the potential clinical relevance, the long-term consequences of OSA have only rarely been investigated among kidney transplant recipients. The association between OSA and hypertension, accelerated atherosclerosis and vascular damage was confirmed in patients with CKDWe designed this prospective cohort study to determine the association between presence of OSA and long-term outcome, such as the decline of graft function and all-cause mortality in a randomly selected sample of stable, prevalent kidney transplant recipients. OSA was assessed using polysomnography at baseline. Based on the previous findings we hypothesized that the presence of OSA would be associated with faster decline of graft function and higher risk of mortality.The SLeep disorders Evaluation in Patients after kidney Transplantation (SLEPT) - study cohort was described previouslyThe percentage of male patients was significantly higher among patients with versus without apnea-hypopnea index (AHI) ≥ 15/h. The prevalence of mild (5/h ≤ apnea-hypopnea index (AHI) < 15/h), moderate (15/h ≤ AHI < 30/h) and severe OSA (AHI ≥ 30/h) was 18%, 11% and 14% in our kidney transplant recipients2/yr (95% CI: −1.55 to −0.78) (2/yr (95% CI: −1.75 to −0.11) had a similar slope than patients without OSA (eGFR versus time was −1.24 ml/min/1.73 m2/yr (95% CI: −1.67 to −0.81)  . Figure o −0.81) . Similaro −0.81) . Howevero −0.81) . Additioo −0.81) . Similaro −0.81) .2/year as a cut-off level (2/year (2/year (not shown) or >8 ml/min/1.73 m2/year as a cut-off level for rapid decline (not shown). A similar result was found when we adjusted for baseline eGFR (not shown). Moreover, neither the high desaturation index  nor the desaturation index (as a continuous variable) was associated with the rapid decline of eGFR using >4 ml/min/1.73 m2/year  nor the AHI index (as a continuous variable) was associated with the rapid decline of eGFR using >4 ml/min/1.73 mff level . Similar  was 47.8/1000 patient-years . The unadjusted mortality rate was similar among patients with and without OSA ; AHI < 15/h group: 45.6/1000 patient-years (95%CI: 29.1–71.5); p = 0.68). Time to death was also similar in patients with versus without OSA, as shown on the Kaplan-Meier plot . We foun1 point increase = 1.28; 95% CI: 1.04–1.58) (04–1.58) .Moreover, neither the high desaturation index  nor the desaturation index (as a continuous variable) was associated with the all-cause mortality . SimilarIn this prospective cohort study, which is one of the largest studies using polysomnography in kidney transplant recipients, there was no association between the presence of OSA and the rate of decline of graft function in prevalent kidney transplant recipients. In addition, we could not find any association between presence of OSA and all-cause mortality in this population.In this dataset the prevalence of OSA was higher than published by Mallamaci et al. recentlyThe rate of decline of graft function was similar in transplant recipients with and without OSA. This is surprising as previous data showed strong correlation between severity of CKD and prevalence of OSA in CKD population1617We previously showed that high risk of OSA is an independent predictor of graft loss among female kidney transplant recipientsThere was no association between OSA and all-cause mortality or combined outcome in our patients. OSA is an independent predictor of mortality in the general population22829Post hoc power calculations suggest that this study was powered to detect 0.25 or lower hazard ratio of the mortality between the non OSA versus OSA groups with a power of 80%, but the power is insufficient to detect a smaller difference. Based on this data, we can conclude that our study was underpowered and further, larger studies are needed to confirm or reject our results. Patients from a single center were enrolled; therefore, our results are not to be generalized without further considerations. Finally, a substantial proportion of transplant recipients refused to participate  Study”) potentially eligible patients were selected from all prevalent adult transplant recipients  who were regularly followed at a single outpatient transplant center on December 31, 2006. After applying exclusion criteria  on dialysis or transplant, active and acute respiratory disorder, acute infection, hospitalization within 1 month, surgery within 3 months) 1198 patients remained . From this “base population” we randomly selected and approached 150 patients (“Tx study sample”) using the simple random sampling strategy offered by SPSS 15.0 . From thStandard, attended overnight polysomnography was performed in our sleep laboratory . Recordings were manually scored by two somnologists. Sleep stages were determined in 30 s epochs according to Rechtschaffen and Kales34Laboratory, demographic, anthropometric, medication data and single pool (sp) Kt/V were extracted from the medical records. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease (MDRD) study formulaComorbidity was assessed by the modified Charlson Comorbidity Index (CCI)37Transplantation related information collected included current medications, transplant and dialysis “vintage” , time spent on dialysis prior to transplantation, type of transplantation (deceased donor or living donor), history of cumulative acute rejection, HLA mismatch, titer of pre-transplant panel reactive antibodies (PRA), cold ischemic time (CIT), age and gender of donor and history of delayed graft function. Time elapsed since the initiation of the first treatment for ESRD (cumulative ESRD time) was also calculated. Standard maintenance immunosuppressive therapy generally consisted of prednisolone, either CsA or tacrolimus, combined with MMF or azathioprine, everolimus or sirolimus.2 the last value was the last available eGFR or the last value below 15 ml/min/1.73 m2 and no further data was collected. The “rapid decline of graft function” status was defined if the deterioration of eGFR was higher than 4 ml/min/1.73 m2/year. The secondary outcome variable was all-cause mortality, which included all deaths with a functioning graft and deaths occurring after the graft failure . Deaths and re-initiations of maintenance dialysis were ascertained from the hospital database. Deaths were validated by cross-referencing with data from the Hungarian Central Office of Administrative and Electronic Public Service, which is the government agency maintaining official vital status records. In addition, we also performed a sensitivity analysis using combined outcome, defined as death of any cause or return to dialysis or rapid decline of graft function (deterioration of eGFR was higher than 4 ml/min/1.73 m2/year) of graft function. None of our patients were treated for OSA at baseline or during the follow-up period, however CPAP treatment was offered all of them.Patients were followed for an average 75 months . The primary outcome variable was deterioration of graft function. We collected each patient's eGFR in every 6 months for the entire follow-up period. If a patient was started on dialysis or re-transplanted or eGFR was less than 15 ml/min/1.73 mThe study was approved by the Ethics Committee of the Semmelweis University (4/2007). Before enrolment, patients received detailed verbal and written information about the aims and protocol of the study and signed an informed consent. All experiments were performed in accordance with relevant guidelines and regulations.Statistical analyses were carried out using the STATA 12.1 software. Results are presented as percentage, mean  or medians . Continuous variables were compared using Student's t-test or the Mann-Whitney U test and categorical variables were analyzed with chi-square test. In all statistics, two-sided test were used and the results were considered statistically significant if p was less than 0.05.For multivariate analysis, logistic- and Cox regressions were applied. Independent variables were included in the multivariate models based on theoretical considerations. Variance influence factors (VIF) were used to indicate collinearity between independent variables. The association between baseline AHI level and all-cause mortality was assessed using Cox proportional regression analysis and Kaplan-Meier plots with log rank test. Proportional hazards assumptions were tested using scaled Schoenfeld residuals.The association between the presence of OSA (using different AHI cut-off levels) and the slopes of eGFR versus time were examined in generalized linear mixed-effects models allowing for a random intercept and slope using the “XTMIXED” command in STATA. The change in eGFR from baseline until death, start of dialysis, or re-transplantation (whichever occurred first) was studied in all transplant recipients who had at least three serum creatinine measurements  by using a two-stage model formulation. In such a model, the level 1 change describes intra-individual changes in eGFR, and the level 2 model describes how the change coefficients differ across participants. The covariate of interest (AHI as independent variable) is thus included in the level 2 models to explain interindividual differences in intra-individual change (slope).Supplemental tables and figure


Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension.Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (June 2016). Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD. Of 2,846 articles in the initial search, 36 were eligible. IPD were provided from 25 trials, including 1 unpublished study. Data for the primary outcomes—change in mean clinic or ambulatory BP and proportion controlled below target at 12 months—were available from 15/19 possible studies . Overall, self-monitoring was associated with reduced clinic systolic blood pressure (sBP) compared to usual care at 12 months . However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone , to a 6.1 mmHg  reduction when monitoring was combined with intensive support. Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities. Ambulatory BP data at 12 months were available from 4 trials , which assessed self-monitoring with little or no co-intervention. There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group . Results for diastolic blood pressure (dBP) were similar. The main limitation of this work was that significant heterogeneity remained. This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies.Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions  leads to clinically significant BP reduction which persists for at least 12 months. The implementation of self-monitoring in hypertension should be accompanied by such co-interventions. In an individual patient data meta-analysis of randomized trials, Katherine Tucker and colleagues examine the evidence for the effectiveness of self-monitoring of blood pressure in hypertension. Self-monitoring of BP appears to lower BP in people with hypertension, over and above usual care.Implementation of self-monitoring has been inconsistent, perhaps because important evidence gaps remain regarding how best to use it and for which patient groups.To better understand the effect of self-monitoring on BP lowering and BP control.Specifically, to examine the effect of self-monitoring in combination with various co-interventions, and in different groups of patients.We undertook a systematic literature search to identify all studies that included self-monitoring of BP in people with high BP.For studies published since the year 2000 with at least 6 months of follow-up data and at least 100 patients, we contacted authors to gain access to the original data collected for each individual patient .We then used these data to perform IPD meta-analysis to evaluate the effect of self-monitoring on BP levels and in the control of hypertension using 1 year of follow-up as our primary end point.We predefined levels of intensity of co-intervention and subgroups of patients for further analysis.Self-monitoring worked best when combined with more intensive interventions such as self-management, systematic medication titration, or lifestyle counselling, but had little or no effect on its own.Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities.Self-monitoring can be recommended to lower BP when combined with co-interventions involving individually tailored support.Self-monitoring alone does not seem to lower BP but may be useful for other reasons including engaging with patients or reducing clinician workload. Treatment of hypertension results in significant reductions in risk of subsequent cardiovascular disease ,2. DespiSelf-monitoring is well tolerated by patients and has been shown to be a better predictor of end organ damage than clinic measurement –8. This Previous meta-analyses have shown that self-monitoring reduces clinic BP by a small but significant amount compared to conventional care around 4/1.5 mmHg) /1.5 mmHg–14. AnalThe aim of this work was therefore to use individual patient data (IPD) from relevant trials to assess the effectiveness of BP self-monitoring on BP reduction and hypertension control, evaluating how best to utilise self-monitoring of BP and to determine which subpopulation is most likely to benefit.This study systematically reviewed the existing literature to identify randomised trials examining the efficacy of self-monitoring of BP compared to control. Authors of all eligible trials were approached for access to IPD. A protocol with detailed methods has been published previously . The metMedline, Embase, and the Cochrane Library were searched for trials using BP self-monitoring in hypertensive patients (Two reviewers (RM and KT) independently assessed the articles for eligibility and inclusion; disagreements were resolved by discussion. Randomised trials were eligible that recruited patients with hypertension being managed as outpatients using an intervention that included self-measurement of BP. Self-monitoring had to be without medical professional input  and using a validated monitor, with or without other co-interventions, and where a comparator group had no organised self-measurement of BP. Included studies were required to have involved at least 100 patients, followed up for at least 24 weeks, and to have been published since 2000. This was to ensure that self-monitoring equipment was likely to be relevant to contemporary medical management . Relevant outcomes were systolic blood pressure (sBP) and/or diastolic blood pressure (dBP) measured in clinic, by researcher or by ambulatory measurement, and achievement of BP control.Authors whose trials met the inclusion criteria were approached for provision of IPD including demographic details, comorbidities, antihypertensive medications, lifestyle factors, and BP end points (clinic and/or ambulatory). Study-level data were extracted where available from published articles and checked by the original authors. In particular, any co-interventions were carefully documented and prospectively allocated to 1 of 4 levels of interventional support based on a previous classification ). All subgroup analyses were adjusted for age, sex, baseline clinic BP, level of intervention, and individual study .Subgroup analyses examined the effect of self-monitoring on BP mean and control by age, sex, baseline sBP, the presence and number of antihypertensive medications prescribed, and comorbidities  ≥ 30 kg/mSensitivity analyses included incorporation of aggregate data from studies that did not contribute IPD –23, exclThere were no deviations from the protocol . Five poAll analyses were conducted using STATA version 13.1 , using the ipdmetan package . Data arOf 2,846 unique studies from the combined searches, 132 were assessed in full and 36 studies were deemed potentially eligible . One stuOverall, the information from the included trials was judged to be at low risk of bias: most studies used computerised generation of randomisation sequences , appropriate allocation concealment , and all used an intention-to-treat approach with either multiple imputation for missing data or analysis of complete cases. Most studies  followed up more than 80% of participants, but only 12/25 (48%) used blinded assessment of outcome . An inflI2 = 76%, P < 0.001. Self-monitoring was also associated with reduced dBP at 12-months follow-up  and significant heterogeneity remained   . Signifi< 0.001) . Similar< 0.001)  Figs.Clinic BP control was improved at 12-months follow-up (RR of uncontrolled BP 0.7 [95% CI 0.56 to 0.86]) again with significant heterogeneity between groups . SimilarP < 0.001). Within predefined categories of intensity of co-intervention, significant heterogeneity remained, apart from within level 2.The reductions in clinic sBP varied with different levels of intervention: level 1 (with no co-intervention) −1.0 mmHg, [95% CI −3.3 to 1.2 mmHg]; level 4  −6.1 mmHg, [95% CI −9.0 to −3.2 mmHg]  (heterogP < 0.001). Within predefined categories of intensity of co-intervention, significant heterogeneity remained in levels 1 and 4.A similar pattern of reductions was seen in dBP: level 1 (with no co-intervention) −1.1 mmHg, [95% CI −2.4 to 0.2 mmHg]; level 4  −2.3 mmHg, [95% CI −4.0 to −0.6 mmHg]  (heterogP < 0.001). Heterogeneity within levels of intervention in this analysis was low for levels 2 and 4 of co-intervention, although the I2 remained above 50% for level 1. Similar results were seen at 6-months follow-up (21 studies) and at 18-months follow-up (5 studies)  or automated feedback only . No change was seen in ambulatory sBP associated with self-monitoring  ; these were studies with no co-intervention   or ambul3, 2.5]) . At 6 moNo ambulatory data were available at 18 months.I2 ≤ 20% for all subgroups).Subgroup analyses using data from 12-months follow-up showed little difference in either reduction of systolic or diastolic clinic BP or likelihood of uncontrolled BP depending on history of MI or presence of CKD or diabetes Figs , 7 and 8I2 = 77%, P = 0.04), though this difference was not observed for dBP or maintained in the likelihood of control analysis . Post-hoc analyses showed that the distribution of number of medications between stroke and non-stroke patients was similar  but not in the likelihood of uncontrolled BP . Considering the effect of obesity, there was no difference in the effect on systolic clinic BP reduction  but there was some evidence of heterogeneity of effect for dBP  and the risk of uncontrolled BP .However, a history of stroke was associated with a reduced effectiveness of self-monitoring in terms of clinic sBP lowering . Similarly, the post-hoc analysis plotting change in sBP against medication changes was consistent with the hypothesis that self-monitoring interventions resulted in BP decreases via increases in prescribed medication  combined with self-monitoring, with little or no effect from self-monitoring alone.These results held whether systolic or diastolic clinic BP or clinic BP control were assessed and were consistent at both 6 and 12 months. No data were available from studies with intensive co-interventions which used ambulatory BP monitoring to measure outcomes at 12 months or longer, and those with little or no co-intervention showed similar effects to the clinic BP data (no effect in either case). There was a suspicion of attenuation of the effect of self-monitoring in the few studies to date that have followed up patients for longer than 1 year but data were sparse. Future research might be directed towards longer studies with ambulatory BP measurement (or other measurements to reduce the white coat effect) for outcomes. Self-monitoring appeared most effective at lowering BP in people on fewer BP medications at baseline, and there was a suggestion of a greater effect with higher BP—provided BP was not 170 mmHg or above. Analyses considering those with apparent resistant hypertension at baseline suggested that self-monitoring works less well in this group, but this analysis was not prespecified, could not take into account dose of antihypertensive medication, and should be interpreted with caution. In terms of comorbidities, the effects of self-monitoring were similar whether or not an individual had a history of MI, diabetes, or CKD. In people with previous stroke, there may be a reduced effect of self-monitoring but this did not reflect more intensive treatment prior to randomisation.To our knowledge, this is the first analysis of self-monitoring of BP to use IPD from a wide range of self-monitoring trials from North America, Australia, and Europe and including both specialist and primary care settings. IPD allowed for standardised adjustment of outcomes and sufficient power to detect differences between subgroups.An important issue in IPD analysis is selection of studies. The BP—SMART collaboration has gained access to a large number of datasets; nevertheless, some studies were not available due to unavailability of data or lack of response. Despite this, only 4 studies eligible for the primary outcome (14% of available patient data) were unable to provide data, and sensitivity analyses suggested no material change in the results when the published aggregate data from these studies were included.Quality of included studies was adequate in terms of randomisation sequences, appropriate allocation concealment, and analyses. Follow-up was high for most studies but only half used blinded assessment of outcome. However, a post-hoc sensitivity analysis showed no difference in results from blinding, perhaps because in most studies BP was assessed using automated monitors reducing the chance of bias.Despite the use of IPD and the division of studies into subgroups, significant heterogeneity remained, which limited the ability to do meta-analysis. However, this does not negate the conclusion that the evidence for both BP reduction and control is stronger for higher-intensity interventions and weak for self-monitoring alone. The hypothesis that effect would vary with level of intervention was prespecified and the categorisation of studies into 4 levels of intervention was agreed to by all study investigators before results were available.P values ≤ 5% for heterogeneity across these 18 tests are unlikely to be all due to chance alone and the tests were prespecified.Whilst all included studies compared self-monitoring of BP to control groups without self-monitoring, inevitably different investigators used different protocols and therefore studies differed in inclusion criteria, self-monitoring regime, and target BPs. These issues could at least in part explain the remaining heterogeneity between studies. The exclusion of studies which did not use lower BP targets for self-monitored BP did not change the results, but even IPD analysis is unable to take differences between studies entirely into account and this may be reflected in the heterogeneity which remained. Significance tests should be interpreted with caution when, as in Figs Most outcome data were based on clinic measurement of BP, which is what was used by the majority of trials of outcome of hypertension treatment . AmbulatEven with IPD, issues such as loss to follow-up may be important. Included studies had rates of follow-up between 58% and 98% at 12 months with most studies following-up around 90%. In the main analysis, formal methods for handling missing data were not used since methods for imputation in IPD meta-analysis are in their infancy; however, the impact of each individual study on the overall results as assessed by the influence analysis suggests that factors such as differential follow-up between studies were unlikely to have affected the results .The outcomes included in this review are all related to BP. Whilst BP is directly related to stroke and coronary heart disease risk, it is nevertheless an intermediate outcome. Ideally, such hard outcomes would be directly measured in trials. However, because of relatively short follow-up and small numbers of participants, few included individual trials did so.There have been previous systematic reviews of trials of self-monitoring ,13,14,53Self-monitoring in the absence of such a co-intervention had little effect on BP. This is not to say that self-monitoring alone should be discouraged, for it brings other advantages both theoretical   and pracObese patients had similar BP reductions to non-obese individuals but greater chance of BP control, which does not reflect differences in mean BP. The findings concerning patients with previous stroke and resistant hypertension require some caution, particularly the latter which was a post-hoc analysis, but have not been previously described. In the case of stroke, the results do not appear to be due to baseline intensity of antihypertensive treatment and warrant further study as more data become available.Combining self-monitoring with increased collaboration between patient and either a nurse, physician, or pharmacist can result in important decreases in BP (6 mmHg systolic on average for the more intensive co-interventions) and improved control. The mechanisms for these reductions in BP could include lifestyle changes (no data available); increased adherence to medication (no data available) ; or incrThe recent SPRINT trial results suggest that more intensive BP interventions are likely to be important in terms of morbidity and mortality . IncreasThe effects appear to be independent of age, sex, and a range of comorbidities , but there was a suggestion that people receiving less intensive antihypertensive treatment, and those with the highest BPs (up to 170 mmHg systolic), may have the most to gain, presumably because they are not already receiving sufficient doses of medication. Conversely, with resistant hypertension there appeared to be little effect from self-monitoring. Similar results for stroke should be interpreted cautiously and warrant further study.The data presented appear to indicate a potential attenuation of the beneficial effects of self-monitoring over time see  Figs. WeFinally, we know from the individual trials that only a proportion of those with hypertension will be suitable for self-monitoring. Despite this, the numbers of people with hypertension and access to their own BP monitor are likely to be well into the tens of millions internationally and represent an important population to engage with ,59.Several unanswered questions remain. Ultimately, trials including cardiovascular endpoints would provide the strongest evidence for self-monitoring in the management of hypertension but may not be appropriate given the strong evidence linking BP to outcome. Further consideration of self-monitoring in the presence of comorbidities seems warranted, particularly for stroke. Furthermore, this review has not included economic outcomes (available from 6 of the included studies) or quality of life measures (available in 8 of the included studies), and these outcomes form part of the next series of investigations for this collaboration.Self-monitoring of BP combined with co-interventions involving individually tailored support lowers clinic BP but has little effect on its own. Self-monitoring supported by such co-interventions should be recommended as part of routine clinical practice in international guidelines and further research should determine the most cost-effective means of supporting implementation.S1 PRISMA Checklist(DOC)Click here for additional data file.S1 Text(PDF)Click here for additional data file.S1 TableLevels used to describe the included self-monitoring interventions. * 1:1 contact or support in this context refers to contact over and above that in usual care. Abbreviation: BP, blood pressure.(DOCX)Click here for additional data file.S2 Table+Data at 6 months follow-up were available from 8,563/12,822 (67%) of patients randomised. Abbreviation: IPD, individual patient data.*Data were available from trials including 7,138/8,292 (86%) of patients randomised. (DOCX)Click here for additional data file.S3 Table*Due to the nature of the intervention, the participants in all studies were aware that they were in the self-monitoring group.(DOCX)Click here for additional data file.S4 TableTable showing the funding of the included studies.(DOCX)Click here for additional data file.S5 Table(DOCX)Click here for additional data file.S1 FigFlow diagram of the systematic review and selection of studies for the IPD.(DOCX)Click here for additional data file.S2 FigAn example search from Medline.(DOCX)Click here for additional data file.S3 FigChange in sBP adjusted for age, sex, baseline clinic BP, and history of diabetes. Abbreviations: BP, blood pressure; sBP, systolic blood pressure.(TIF)Click here for additional data file.S4 FigChange in dBP adjusted for age, sex, baseline clinic BP, and history of diabetes. Abbreviations: BP, blood pressure; dBP, diastolic blood pressure.(TIF)Click here for additional data file.S5 FigRR of uncontrolled BP adjusted for age, sex, baseline clinic BP, and history of diabetes. Abbreviations: BP, blood pressure; RR, relative risk.(TIF)Click here for additional data file.S6 FigChange in sBP adjusted for age, sex, baseline clinic BP, and history of diabetes. Abbreviations: BP, blood pressure; sBP, systolic blood pressure.(TIF)Click here for additional data file.S7 FigChange in dBP adjusted for age, sex, baseline clinic BP, and history of diabetes. Abbreviations: BP, blood pressure; dBP, diastolic blood pressure.(TIF)Click here for additional data file.S8 FigRR of uncontrolled BP adjusted for age, sex, baseline clinic BP, and history of diabetes. Abbreviations: BP, blood pressure; RR, relative risk.(TIF)Click here for additional data file.S9 FigChange in sBP adjusted for age, sex, baseline clinic BP, history of diabetes, and level of intervention. Abbreviations: BP, blood pressure; sBP, systolic blood pressure.(TIF)Click here for additional data file.S10 FigChange in dBP adjusted for age, sex, baseline clinic BP, history of diabetes, and level of intervention. Abbreviations: BP, blood pressure; dBP, diastolic blood pressure.(TIF)Click here for additional data file.S11 Fig*Four studies containing aggregate data only: Varis et al. , Rinfret(TIF)Click here for additional data file.S12 FigChange in sBP at 12 months. *Patients from TASMINH1 Click here for additional data file.S13 FigChange in sBP at 12 months. Change in sBP adjusted for age, sex, baseline clinic BP, history of diabetes, and level of intervention. Abbreviations: ABPM, ambulatory blood pressure monitoring; BP, blood pressure; sBP, systolic blood pressure.(TIFF)Click here for additional data file.S14 FigChange in sBP at 12 months. Change in sBP adjusted for age, sex, baseline clinic BP, history of diabetes, and level of intervention. Abbreviations: ABPM, ambulatory blood pressure monitoring; BP, blood pressure; sBP, systolic blood pressure.(TIFF)Click here for additional data file.S15 FigRR of uncontrolled BP adjusted for age, sex, baseline clinic BP, and history of diabetes. Abbreviations: BP, blood pressure; RR, relative risk.(TIF)Click here for additional data file.S16 FigRR of uncontrolled BP adjusted for age, sex, baseline clinic BP, and history of diabetes. Abbreviations: BP, blood pressure; RR, relative risk.(TIF)Click here for additional data file.S17 FigChange in sBP adjusted for age, sex, baseline clinic BP, and history of diabetes. Abbreviations: BP, blood pressure; sBP, systolic blood pressure.(TIF)Click here for additional data file.S18 FigsBP change at 12 months analysed without adjusting for medication changes at follow-up (11 studies). Change in sBP adjusted for age, sex, baseline clinic BP, and history of diabetes. Abbreviations: BP, blood pressure; sBP, systolic blood pressure.(TIF)Click here for additional data file.S19 FigsBP change at 12 months analysed adjusting for medication changes at follow-up (11 studies). Change in sBP adjusted for age, sex, baseline clinic BP, history of diabetes, and medication changes at 12 months follow-up. Abbreviations: BP, blood pressure; sBP, systolic blood pressure.(TIF)Click here for additional data file.S20 FigEach line indicates pooled meta-analysis results with that study omitted from the results. Abbreviation: sBP, systolic blood pressure.(TIFF)Click here for additional data file.S21 FigP = 1.00) would indicate little influence of publication bias. Abbreviation: sBP, systolic blood pressure.The standard error is plotted against the mean change in sBP at 12 months. An Egger’s test of zero ((TIFF)Click here for additional data file.S22 Fig*Test for trend using a fixed-effects linear regression model adjusted for study. †The HOMERUS and TCYB trials, and studies by Godwin et al.  and Leiv(TIFF)Click here for additional data file.S23 FigThe STATA code used to perform the meta-analysis and figures.(DOCX)Click here for additional data file.


Chronic kidney disease (CKD) eventually progresses to end-stage renal disease (ESRD). However, risk factors associated with CKD progression have not been well characterized in Japanese patients with CKD who are less affected with coronary disease than Westerners.2]. The primary endpoint was a composite of time to a 50 % decline in eGFR from baseline or time to the initiation of renal replacement therapy (RRT). The secondary endpoints were the rate of decline in eGFR from baseline, time to a 50 % decline in eGFR from baseline, time to the initiation of RRT, and time to doubling of serum creatinine (Cre) concentration.A large-scale, multicenter, prospective, cohort study was conducted in patients with CKD and under nephrology care, who met the eligibility criteria  and increased albumin-to-creatinine ratio  at baseline were significantly associated  with the primary endpoint.2966 patients  were enrolled. The incidence of the primary endpoint increased significantly  contains supplementary material, which is available to authorized users. Chronic kidney disease (CKD) eventually progresses to end-stage renal disease . The proportion of patients with CKD is higher in Japan than in foreign countries. The estimated number of CKD patients is approximately 13.3 million, representing about 13 % of the Japanese adult population .The Chronic Kidney Disease Japan Cohort (CKD-JAC) study was planned in consideration of the Chronic Renal Insufficiency Cohort (CRIC) study in the US , 4. The The CKD-JAC study established the Steering Committee, the Event Assessment Panel, as well as the Data Coordinating Center and determined 17 participating medical institutions, the central laboratories, and scientific advisors. The study protocol was approved by the institutional review boards at the institutions, and the study was conducted in accordance with the Declaration of Helsinki of 1975, as revised in 2005, and in compliance with the current regulations.The CKD-JAC study was designed as a large-scale, multicenter, prospective, cohort study . The design and cohort thereof have been reported previously −0.287 × [serum creatinine (mg/dL)]−1.094; and for females, eGFR (mL/min/1.73 m2) = 194 × [age]−0.287 × [serum creatinine (mg/dL)]−1.094 × 0.739. A 50 % decline in eGFR from baseline was detected at the first of three consecutive visits when the renal event occurred. Furthermore, the correlations of serum creatinine (Cre) concentrations measured at respective institutions and the central laboratories were examined, and the former concentrations corrected with the latter ones were used to address the interinstitutional heterogeneity of the data obtained. Furthermore, the functional relationship analysis estimating errors in the values measured at respective institutions and the central laboratories was conducted to make necessary corrections. The central laboratories measured serum Cre, urinary excretion of albumin (Alb), parathyroid hormone, and fibroblast growth factor (FGF) 23 concentration.The primary endpoint was defined as a composite of two renal events: time to a 50 % decline in eGFR from baseline or time to the initiation of RRT. The following formulae for Japanese individuals were used to calculate eGFR by gender : for malThe following four renal events were established as the secondary endpoints: (1) rate of decline in eGFR from baseline. The slope of the regression line was calculated based on all eGFRs that had been determined between the onset of the study and the final determination point of eGFR and on the number of days from the onset of the study; (2) time to a 50 % decline in eGFR from baseline; (3) time to the initiation of RRT; and (4) time to doubling of serum Cre concentration. The number of days before the first of three consecutive visits after the onset of the study, at which serum Cre concentration doubled against the baseline value, was determined.Among traditional and nontraditional risk factors, we examined the following as candidate risk factors for CKD progression to ESRD that were assessed with the renal event-based primary and secondary endpoints: age, gender, complication of DM, history of CVD, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), concurrent medications , hemoglobin (Hb), Alb, C-reactive protein, blood urea nitrogen (BUN), Cre, eGFR, and urine albumin-to-creatinine ratio (UACR).Patients were categorized to two BP groups , and these two groups were then compared with respect to the primary endpoint.Patients were categorized to the following seven BP groups according to the Japanese Society for Hypertension’s criteria: optimal (<120 mmHg in SBP and <80 mmHg in DBP), normal (120–129 mmHg in SBP and/or 80–84 mmHg in DBP), high normal (130–139 mmHg in SBP and/or 85–89 mmHg in DBP), grade 1 hypertension (140–159 mmHg in SBP and/or 90–99 mmHg in DBP), grade 2 hypertension (160–179 mmHg in SBP and/or 100–109 mmHg in DBP), grade 3 hypertension (≥180 mmHg in SBP and/or ≥110 mmHg in DBP), and isolated systolic hypertension (<140 mmHg in SBP and <90 mmHg in DBP), and seven groups were then compared with respect to the primary endpoint.The associations of risk factors with CKD progression to ESRD were analyzed according to the Cox and Poisson regression models, preceded by the confirmation of correlations among risk factors and of multicollinearity. Regression diagnosis using the lever and covariate ratios was made to assess the observed values with a great association. The log–log plots were prepared in Cox regression, while residual diagnosis was made in Poisson regression. The models considering interactions were applied to both Cox and Poisson regressions in an attempt to select risk factors according to the stepwise method. The multivariate Cox proportional hazards models were used to explore the risk factors for the primary and secondary endpoints mentioned above. We did not establish the threshold for correlation coefficient but verified that all variables used had a correlation coefficient of less than 0.6, thus showing no severe multicollinearity (variance inflation factor: <10). Multivariate analyses were made using the data from 1331 patients about whom all variables had been measured in the complete case analysis, and we used the multiple imputation method to handle the missing data.P < 0.05 was considered statistically significant. All statistical analyses were made using SAS version 9.4 .The Kaplan–Meier curves were prepared to estimate the cumulative incidence of the primary endpoint, and the log-rank test was conducted to compare two and seven groups with respect to BP patterns 1 and 2, respectively. A two-tailed value of 2. The median duration of follow-up was approximately 3.9 years. In concert with CKD stage at baseline, the higher values (P < 0.0001) were obtained with respect to age, history of CVD, SBP, pulse pressure, BUN, uric acid (UA), UACR 300–999 mg/g Cre, UACR ≥1000 mg/g Cre, ESAs, and sodium bicarbonate, as well as serum Cre, phosphorus, parathyroid hormone, and log FGF23; the lower values (P < 0.0001) were obtained with respect to BMI, eGFR, and Hb, as well as serum Alb, calcium (Ca), and lipids.A total of 2966 patients were enrolled Fig. , and patP < 0.0001) in concert with CKD stage at baseline.The Kaplan–Meier curves for primary endpoint renal event-free Japanese patients with CKD according to CKD stage at baseline are shown in Fig. P value of <0.0001: elevated SBP at baseline  and increased UACR at baseline   by eightfold faster than those who had a UACR of <300 mg/g Cre.The rates of decline in eGFR per year exhibited a significant tendency to be higher for greater CKD stage and higher UACR .Time to a 50 % decline in eGFR from baseline.Multiple Cox regression analysis revealed that the following risk factors were significantly associated with time to a 50 % decline in eGFR from baseline: male gender, and administration of ESAs; increases in BMI, SBP, serum phosphorus, 300–999 mg/g Cre, and ≥1000 mg/g Cre; and decreases in eGFR, UA, serum Alb, and Hb (Supplement 2).Time to the initiation of RRT.Multiple Cox regression analysis revealed that the following risk factors were significantly associated with time to the initiation of RRT: younger age, male gender, history of CVD, and administration of sodium bicarbonate; increases in SBP, UACR 300–999 mg/g Cre, UCAR ≥1000 mg/g Cre, serum Cre, and log FGF23; and decreases in eGFR, serum Alb, and Hb (Supplement 3).Time to doubling of serum Cre concentration.Multiple Cox regression analysis revealed that the following risk factors were significantly associated with time to doubling of serum Cre concentration: younger age, male gender, and administration of ESAs; increases in BMI, SBP, UACR 300–999 mg/g Cre, and UCAR ≥1000 mg/g Cre; and decreases in eGFR, UA, serum Alb, and Hb (Supplement 4).The incidence rates (1000 person-years of follow-up) of both the primary and secondary endpoints increased in nearly full association with CKD stage at baseline Table .Table 4IP < 0.0001) in the ≥140 mmHg in SBP and/or ≥90 mmHg in DBP group. The incidences of the primary endpoint were compared among the following seven BP category groups according to BP pattern 2: the optimal group; the normal group; the high normal group; the grade 1 hypertension group; the grade 2 hypertension group; the grade 3 hypertension group; and the isolated systolic hypertension group. The Kaplan–Meier curves for primary endpoint renal event-free Japanese patients with CKD according to BP pattern 2 in seven groups are shown  was found among the seven groups with respect to the primary endpoint.The incidences of the primary endpoint were compared between the following two BP pattern groups according to BP pattern 1: the ≥140 mmHg in SBP and/or ≥90 mmHg in DBP group; and the <140 mmHg in SBP and <90 mmHg in DBP group. The Kaplan–Meier curves for primary endpoint renal event-free Japanese patients with CKD according to BP pattern 1 are shown Fig. a. The inP < 0.0001) among the three UACR groups.The incidences of the primary endpoint were calculated in three UACR  categories. The Kaplan–Meier curves for Japanese patients with CKD according to these three categories of UACR at baseline are shown in Fig. P < 0.0001, respectively) with the primary endpoint; and (2) the deterioration of a powerful predictor of ESRD, proteinuria (which was translated into higher UACR), accelerated CKD progression to ESRD extensively. These findings are in concert with previous clinical studies indicating that lower eGFR and higher UACR are independently associated with the increased risks of CVD and ESRD.The present study is the first, large-scale, multicenter, prospective cohort study in Japanese patients with CKD under nephrology care, which aimed at identifying risk factors for CKD progression to ESRD. Our study disclosed the following facts: (1) elevated SBP and increased UACR, both at baseline, were significantly associated  were under control to the levels at which the target BPs were almost reached. Our study is distinguishably featured by the precise assessment of renal events, including the rate of decline in eGFR from baseline, through the more meticulous care  of patients as compared with previous studies in Westerners.Voormolen et al.  reportedOur study has several limitations. First, patient characteristics were determined only at baseline and once. Second, the GFR to assess the renal function of patients was not precisely calculated based on inulin clearance but was estimated with the serum creatinine-based equation. Third, selection bias cannot be ruled out, because patients were mostly enrolled at large-sized hospitals that can provide nephrology care.In conclusion, elevated SBP and increased UACR were the risk factors significantly associated with CKD progression to ESRD in Japanese patients with CKD. Therefore, clinicians should constantly give heed, in the routine clinical setting, especially to advanced CKD patients with poorly controlled hypertension and increased UACR in an attempt to curb CKD progression to ESRD.Supplementary material 1 (DOCX 64 kb)Supplementary material 2 (DOCX 62 kb)Supplementary material 3 (DOCX 63 kb)Supplementary material 4 (DOCX 63 kb)Below is the link to the electronic supplementary material.


To investigate the clinical and morphological characteristics associated with risk factors for the rupture of bifurcation-type middle cerebral artery aneurysms (MCAAs).A total of 169 consecutive patients with 177 bifurcation-type MCAAs were reviewed from August 2011 to January 2016. Based on the clinical and morphologic characteristics findings, the risk factors of aneurysm rupture were assessed using statistical methods.MD) of the parent and two daughter arteries was negatively correlated with rupture. Aneurysms with irregularity, depth, width, maximum size, aspect ratio, depth-to-width ratio, bottleneck factor, and size ratio were positively correlated with rupture. The multivariate logistic regression model revealed that irregular shape (odds ratio (OR) 2.697) and aspect ratio (OR 3.723) were significantly and positively correlated with rupture, while cerebral atherosclerosis (OR 0.033), CAD (OR 0.080), and MD (OR 0.201) were negatively correlated with rupture. Receiver operating characteristic analysis revealed that the threshold value of the aspect ratio and MD were 0.96 and 2.43 mm, respectively.Age, cerebral atherosclerosis, no hypertension, hypertension grade 2 and coronary artery disease (CAD) were negatively correlated with aneurysm rupture. The mean diameter (MD (<2.43 mm) are likely better predictors of rupture.Cerebral atherosclerosis and CAD are protective factors against rupture. Morphological characteristics such as an aneurysm with an irregular shape, a high aspect ratio (>0.96) and a small  The prevalence of intracranial aneurysms (IAs) is estimated to be 2%-10% of the general population –6. The IMiddle cerebral artery aneurysms (MCAAs) are common, accounting for 18% to 40% of all IAs , and areThis retrospective study was approved by our institutional ethics committee . Signed written informed consent was obtained from all patients before the examination. A total of 22378 consecutive patients who underwent head computed tomography angiography (CTA) examinations were enrolled from August 2011 to January 2016. Out of 1176 (5.2%) patients with IAs, 220 (18.9%) presented MCAAs. Aneurysms belonging to the bifurcation type were selected, excluding proximal (n = 23) and distal aneurysms (n = 11). Subjects who had mycotic (n = 1), traumatic (n = 2), reoperated (n = 3), or fusiform aneurysms (n = 3), cases associated with arteriovenous malformations (n = 3) and poor image quality (n = 5) were also excluded. Finally, 169 patients (67 ruptured and 102 unruptured) with 177 IAs (67 ruptured and 110 unruptured) were available for analysis. Sixty-three ruptured intracranial aneurysms (RIAs) were managed with both treatment (coiling or clipping), and four patients died before surgery. Seventy UIAs were managed because of clinical symptoms , and 40 UIAs were observed with no growth or rupture signs.The clinical data for the study were extracted from the hospital medical records by KJ Mou, who was the only person to faithfully recorded clinical data like patients with cerebral atherosclerosis or without, and blinded to the rupture or unrupture status. Cerebral atherosclerosis, coronary artery disease (CAD), and diabetes mellitus were recorded as either present or absent. Cerebral atherosclerosis was defined as diffuse atherosclerosis of the brain, luminal stenosis and small vessel occlusion, the diagnosis was made on the basis of CTA, transcranial ultrasound, or MRA. Hypertension was defined as a systolic blood pressure (BP) ≥140 mm Hg, a diastolic BP ≥90 mm Hg, or the use of antihypertensive agents. Hypertension was divided into the following 4 grades: a systolic BP <140 mm Hg or a diastolic BP<90 mm Hg as no hypertension; a systolic BP (140–159 mm Hg) or a diastolic BP (90–99 mm Hg) as grade 1; a systolic BP ≥180 mm Hg or a diastolic BP ≥110 mm Hg as grade 3; and a BP in between as grade 2. Alcohol consumption and smoking were classified as never, former and current. The history of subarachnoid hemorrhage (SAH) was defined as a history of rupture of aneurysm at another location. In cases with multiple aneurysms, the ruptured aneurysm was determined based on the location of the hemorrhage on computed tomography (CT), angiographic or operative findings.MCAAs were evaluated with CTA using a 64-slice CT machine . All of the images were transferred to the GE Advantix workstation (Advantage Windows 4.5) to generate 3D reconstructions and morphological measurements.Two categorical morphological variables included the shape of the aneurysm (simple lobed or irregular shape) and the neck types. An aneurysm with lobular or daughter sacs was defined as having an irregular shape . The necDmax), aspect ratio (AR), depth-to-width ratio (DW), bottleneck factor (BF), size ratio (SR), daughter artery ratio (DAR), mean diameter (MD) of the parent and two daughter arteries, flow angle, and lateral angle ratio (LAR) were examined. These variables have already been defined and are depicted clearly in the literature [All measurements were performed by two observers and the average value was calculated for statistical analysis. Twelve continuous morphological variables such as aneurysm depth, width, neck width, maximum size  were further analyzed using forward multiple logistic regression to calculate the odds ratios (OR) and 95% confidence intervals (CI) for the likelihood of aneurysm rupture. Then, receiver operating characteristic (ROC) curve analysis to determine the sensitivity and specificity using the area under the curve (AUC).Statistical analyses were performed using the Statistical Package for Social Sciences . Kappa consistence test was used for the inter-observer reliability of numerical measurements. The variables were expressed as the means ± standard deviation or number of patients (%). Independent t test was used for continuous data, and chi-squared test was used for categorical data. All variables with a The clinical characteristics of the 169 patients are shown in Dmax, AR, DW, BF, SR and MD were associated with rupture risk.The level of agreement between the two observers for numerical measurements was satisfactory, with κ coefficients of 0.89 (p<0.0001). The morphological characteristics of bifurcation-type MCAAs are listed in . IrregulP≤0.2) were entered into a univariate logistic regression model to determine the risk factors for aneurysm rupture. Of these variables, 13 independent variables were associated with aneurysm rupture (P≤0.05). Then, these variables were entered into a forward conditional multiple logistic regression model (MD (OR 0.201) were associated with a decreased risk of aneurysm rupture. On the contrary, aneurysms with an irregular shape (OR 2.697) and AR (OR 3.723) increased the risk of aneurysm rupture. The threshold values of the AR and MD were 0.96 and 2.43 mm, respectively  expression than that of UIAs. We plan to synthesize the MRI probe targeted to MMP-9. Based on the enhancement degree of the aneurysms wall after injection of the probe, the rupture risk may be evaluated. All these are under our investigation.AR and a small MD are more prone to rupture; more attention should be paid to the aneurysm with these characteristics during our clinical practice.Based on the clinical records and CTA findings from patients with bifurcation-type MCAAs, we find that cerebral atherosclerosis and CAD are likely protective factors against aneurysm rupture. On the other hand, since aneurysms with an irregular shape, a high S1 TableP< 0.05).CAD, coronary artery disease; Bleeding history, history of ruptured aneurysm in other locations. †Variables showing significant difference by univariate analysis ((DOCX)Click here for additional data file.S2 TableP< 0.05).DAR, daughter artery ratio; LAR, lateral angle ratio. †Variables showing significant difference by univariate analysis ((DOCX)Click here for additional data file.S3 TableCI, Confidence intervals; CAD, coronary artery disease; β, partial regression coefficient.(DOCX)Click here for additional data file.S4 TableSen, sensitivity, the chances of false negatives; Spe, specificity, the chance of false positives; CI, confidence intervals; Threshold value, the cut off for the aspect ratio and mean diameter.(DOCX)Click here for additional data file.S1 Checklist(DOC)Click here for additional data file.S1 Dataset(XLS)Click here for additional data file.


The presence of left ventricular hypertrophy (LVH) in patients with Chronic Kidney Disease (CKD) is associated with worsening cardiovascular outcomes. There is a dearth of data on LVH in Ghanaian CKD patients.This was a cross sectional study carried out at the Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana. A questionnaire was used to obtain information on clinical features of CKD. The MDRD-4 equation was used to calculate eGFR. Information on the prevalence and factors associated with electrocardiographic left ventricular hypertrophy were obtained during the initial assessment.About 64.5% of the 203 participants were male and the mean age was 43.9 ± 17.8 years. Most subjects (79.8%) had stage 5 disease. The mean systolic and diastolic blood pressures were 167.86 ± 39.87 and 101.8 ± 24.4 respectively. Approximately 43% of respondents had LVH. eGFR correlated negatively with LVH. High systolic pressure , high diastolic pressure  increased pulse pressure , increased body mass index  as well as male gender  were associated with the presence of LVH.LVH is common in our cohort. High pulse pressure, high DBP, increased BMI and male gender are significant associated factors. Adequate treatment of high blood pressure as well as early detection of LVH and interventions aimed at prevention and/or regression of LVH are to be encouraged. Chronic Kidney Disease (CKD) is a worldwide public health challenge with adverse outcomes of kidney failure, cardiovascular disease and premature death . CKD patThis was a cross sectional study carried out over a 1-year period at the Komfo Anokye Teaching Hospital (KATH). KATH is the second largest hospital in Ghana and caters for patients in middle and northern zones of the country. The hospital provides clinical services for both adult and paediatric renal patients. Haemodialysis is the main mode of Renal Replacement Therapy (RRT). Chronic Kidney Disease (CKD) patients attending the renal clinic over a 1 year period were eligible for inclusion in the study. Consecutive patients diagnosed with CKD based on the case definition age 18 years and above were eligible for inclusion. Eligible patients were not to be undergoing dialysis. Patients attending the renal clinic with diagnosis other than CKD and CKD patients who did not provide informed consent were excluded from this study. Informed consent was obtained from all study participants or their legal representatives prior to inclusion in the study. A questionnaire was administered to each patient to obtain the demographic data and clinical history. A detailed clinical examination was performed on all respondents to obtain information including: weight, height, systolic and diastolic blood pressure. The height was measured with the patient standing barefooted on flat surface. Blood pressure was measured using Intellisense™ M3 automatic Blood Pressure monitor . The pulse pressure was calculated as the difference between the systolic and diastolic blood pressures. A midstream urine sample was analysed for proteinuria using dipstick testing  and the degree of proteinuria classified as absent .Abdominopelvic ultrasonography was done to assess the architecture of the kidneys. The haemoglobin (Hb) level and Hb indices were measured at KATH haematology laboratory with an auto analyser . Liver function tests (LFT), blood urea nitrogen (BUN) and serum creatinine levels (based on modified Jaffe method) were measured at the KATH biochemistry laboratory using an auto-analyser . Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD-4) equation and the stage of CKD noted.ECG measurement and interpretation: ECG was measured at a paper speed of 25mm/s, at a gain of 10mm/mV (or 5mm/mV) using an AT 200 ECG machine . Sokolow-Lyon LVH was defined as sum of S wave in lead V1 and R wave in lead V5 or V6 ≥ 35mm and/ or R wave in lead aVL ≥ 11mm. ECG interpretations were done by a Physician Specialist and verified by another senior Physician.Ethical statement: The study was approved by and conformed to the ethical guidelines of the Committee on Human Research Publications and Ethics (CHRPE) of the School of Medical Sciences, Kwame Nkrumah University of Science and Technology and the Komfo Anokye Teaching Hospital.Definition of terms: 1) CKD was defined as the presence of kidney damage, manifested by abnormal albumin excretion or decreased kidney function, quantified by measured or estimated glomerular filtration rate (GFR) that persists for more than three months. In the absence of previous data on eGFR or markers of kidney damage, chronicity was inferred from clinical presumption of kidney disease for >3 months; 2) Proteinuria was classified as absent (urine dipstick negative), or present (urine dipstick positive); 3) Hypertension was defined as the presence of a persistently elevated systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg in patients, and/or the use of antihypertensive drugs and/or past medical history of hypertension; 4) Hypertension was noted as the cause of renal disease in cases if medical record indicated hypertension was present before onset of kidney disease and if there was absence of proteinuria, normal renal function indices, and preserved renal sizes in presence of hypertension early in the illness. 5)Anaemia was defined as haemoglobin (Hb) level < 11 g/dL.Statistical analysis: Continuous variables are presented as means ± SDs and as percentages for dichotomous variables. Differences in characteristics in subjects with and without LVH were evaluated using χ2 (chi square test). Associations between LVH and parameters were analysed using multivariate logistic regression modeling. Epi Info version 7.1.2.0 was used for analysis and a p value <0.05 was considered statistically significant.A total of 203 participants were recruited into the study. The baseline demographic and clinical characteristics of participants are represented in The prevalence of left ventricular hypertrophy as determined by the Sokolow-Lyon LVH was 43.3%. There was a negative correlation between eGFR and LVH . There were more males than females (35.5% versus 7.8%) with LVH . Ninety-two percent (92%) of patients with LVH were aged < 60 years. Majority (81.8%) of cases with LVH had stage 5 CKD (95% CI 72.9-89.9). CKD stages 3 and 4 accounted for 12.5% and 5.7% of cases with LVH respectively .The abdominopelvic ultrasound results are represented in The analysis of association between LVH and risk factors is presented in The mean age of study participants was 43.9 ± 17.8 years. This is in agreement with other published studies that found CKD to be commoner in the third to fifth decades of life . There wThere was an inverse relationship between left ventricular hypertrophy and the estimated glomerular filtration rate. Patients with low eGFR (corresponding to more advanced CKD), are more likely to have left ventricular hypertrophy. Complications such as hypertension, anaemia, fluid overload and arterial stiffening are more common in advanced CKD. These factors contribute to the development of LVH, hence the high incidence of LVH observed in the later stages of CKD. Levin and colleagues  demonstrThe overall high prevalence of LVH 43.3%) by Sokolow-Lyon criteria is in agreement with the 45% by Chijioke et al  working 3.3% by SThere was a positive correlation between LVH and SBP, DBP as well as pulse pressure. The very high prevalence of LVH among the respondents at such early age appear to be related to late presentation and poor control of blood pressure, as LVH is a recognized evidence of end organ damage from uncontrolled hypertension. Among all study participants, the mean systolic and diastolic blood pressures of 167.9 ± 39.8 and 101.8 ± 24.4 respectively are rather high. High blood pressure potentiates the decline in GFR in patients with established diabetic and non - diabetic kidney disease . On the It is also important to emphasise utilisation of antihypertensive agents that can result in regression or even prevent development of LVH. Attainment of LVH regression is desirable as it reduces adverse outcomes like cardiac arrhythmias and sudden death , 30. LefNo echocardiographic assessment of LVH was done in our study, so we were unable to determine the diagnostic test performance of ECG LVH in this population. Although our sample size was moderately large, we may have missed relationships that may have been significant if the strength of the relationship was not high. Finally, ambulatory Blood pressure monitoring would have been a preferred means of confirming high blood pressure.In conclusion, there is a high prevalence of left ventricular hypertrophy among CKD patients in Kumasi, Ghana. High diastolic blood pressure, high pulse pressure and increased BMI as well as male gender were found to be significantly associated with the presence of LVH in this cohort. Adequate control of blood pressure is important to forestall the development of CKD and other end organ damage. Early detection of LVH and interventions aimed at prevention and/or regression of LVH are to be encouraged.CKD patients are at significantly increased risk for both morbidity and mortality from cardiovascular disease;There is data from the developed world on the incidence of left ventricular hypertrophy and its impact on cardiovascular outcomes in CKD patients.To the best of our knowledge, this study is the first report of the high burden of LVH in Ghanaian CKD patients;Our study found pulse pressure, high DBP, increased BMI and male gender to be significant associated factors of LVH in our Ghanaian CKD cohort.The authors declare no competing interest.


Two very effective antihypertensive medications with well-established and significant cardiovascular outcome studies have been combined and used for the first time in early combination therapy in the TALENT study. Results from this multicentre, prospective, randomised, doubleblind trial were announced at the 2010 European Society of Hypertension (ESH) congress held in June in Oslo, Norway, and highlighted the rapid, safe and effective blood pressure-lowering action of this combination.1The TALENT  enrolled 405 patients with office systolic blood pressure at a baseline of ≥ 135 mmHg and with a high cardiovascular risk because of diabetes, the metabolic syndrome, and echocardiographic/ECG evidence of left ventricular hypertrophy or microalbuminuria. Patients could be admitted to the trial if other antihypertensive medication  could be safely withdrawn.Patients were randomised to initial administration of telmisartan (80 mg/day) plus nifedipine GITS (20 mg/d), telmisartan alone, or nifedipine GITS alone in a 2:1:1 ratio. Treatment was continued for 24 weeks, shifting the monotherapy groups to combination therapy after eight weeks .Office and ambulatory blood pressure was measured after two, eight, 16 and 24 weeks and after eight, 16, and 24 weeks, respectively. Up-titration occurred when needed but not to blood pressure levels below 120 mmHg.Initiating treatment with the combination therapy resulted in earlier blood pressure control. This was maintained throughout the study period both with regard to office and ambulatory blood pressure control, which was reduced by 14.2/3 mmHg and 10/4.7 mmHg, respectively.Both combination and monotherapy substantially lowered systolic and diastolic blood pressure. The 24-hour data showed that the effect was consistent throughout the 24-hour period. Of importance is that longer-term control was similar, irrespective of the initial monotherapy treatment strategy followed or whether the combination was initiated first.In terms of the evidence-based reduction of cardiovascular outcomes, telmisartan in the ONTARGET


Ultrasound is routinely performed at our transplant unit within the first 48 h of kidney transplantation (KTX). The objective of this study was to evaluate the association of ultrasound results and, in particular, elevated resistance indices (RIs) with the occurrence of surgical complications and allograft outcomes.N = 329). Ultrasound examination was performed on 315 recipients (95.7%).The study included all kidney allograft recipients undergoing transplantation at our center between January 2010 and December 2011 (p = 0.032). A lack of arterial signal was detected in eight patients (2.5%), of whom five had a vascular complication that required surgical therapy. In 12 patients (3.8%), RI was 1 without any other signs of vascular impairment. Even though such values can be a sign of venous thrombosis, no case was observed in any of these patients.Delayed graft function was more common in subjects with a high RI (≥0.7) than in patients with an RI < 0.7 (47.2 vs. 28.2%; The results of our study suggest that ultrasound evaluation of the transplanted kidney shortly after transplantation is a valuable tool not only for detecting vascular complications but also as a predictor of graft outcome regarding delayed graft function. Kidney transplantation (KTX) has become the gold standard for treatment of end-stage renal disease. However, even though continuous improvements in immunosuppressive therapy and surgical technique have led to excellent short-term patient and graft survival rates , surgicaEven though vascular complications have become uncommon after KTX, arterial or venous thrombosis still represents a substantial risk for graft loss. The overall risk for vascular complication ranges between 2 and 4%, with renal artery occlusion being the most common cause , 6. GiveUltrasound is cheap, noninvasive, widely available, and efficient for evaluating the allograft and not only depicting the anatomy of the transplanted kidney but also assessing the vascular supply, which is especially at risk in the early phase after KTX. The intrarenal resistance index (RI) calculated from the pulsatile flow-velocity waveform is one marker assessed routinely. Additionally, perirenal fluid retention can be detected, which may indicate any kind of bleeding or compression of vital structures. Moreover, it has been shown that both early and late RI may be predictive of transplant outcome , 8. ImpeHowever, even though ultrasound of the transplanted kidney is performed in most centers worldwide, the clinical significance of early ultrasound examination is still debated. In this large retrospective study, we sought to investigate whether and to which extent the results of ultrasound examination shortly after surgery are associated with allograft function in the early post-transplant period.All kidney transplant recipients undergoing transplantation between January 2010 and December 2011 at the Medical University of Vienna were included in this retrospective analysis. Overall, 329 patients were analyzed for this study. The study was reviewed and approved by the institutional review board of the Medical University of Vienna (IRB no.: 1541/2013).Following KTX, ultrasound was routinely performed within the first 48 h of transplantation Fig. . The intAll data were collected from patients’ charts, laboratory records, and a prospective transplant database. Kidney function was assessed and labeled as delayed graft function , slow graft function  or primary non-function , as appropriate. Surgical complications were defined as any complications within 3 months associated with the KTX that required surgical therapy.U test or t test. Binary outcome variables were compared with Fisher’s exact test and the chi-square test. Furthermore, we used logistic regression models with RI as predictor variable to assess the effect of RI on the studied endpoints. Factors influencing the RI were analyzed using univariate linear regression models. Significant variables were further tested in a multivariate model. The risk of death and graft loss depending on the RI is shown in a Kaplan–Meier graph and analysis was performed by using a log rank test. A p value of < 0.05 was considered statistically significant.Statistical analysis was performed using GraphPad Prism, version 5  and SPSS software (version 20.0). Continuous data are expressed as median with range or mean ± standard deviation (SD). Analysis was performed with the Mann–Whitney Baseline characteristics are shown in Table p = 0.002; Fig. In eight patients, a lack of arterial perfusion was noted 2.5%). Vascular thrombosis was confirmed by further diagnostic steps including computed tomography (CT) angiography in five of these cases. After further diagnostic steps including CT angiography, three results were false positive giving a positive predictive value (PPV) of 62.5%. The remaining five patients with confirmed lack of perfusion were scheduled for surgery. There were three patients (1%) showing arterial thrombosis and two patients (0.6%) showing venous thrombosis. Despite immediate surgical intervention, four of these five patients lost their graft. In one patient with arterial thrombosis, successful thrombectomy was performed after flushing the kidney with preservation solution. Overall, patients with a lack of perfusion in the early ultrasound examination had a significantly diminished graft survival compared with patients without (.5%. Vascp < 0.0001). Conversely, patients with DGF had a significantly higher RI compared with patients with immediate graft function . Even though there was a high rate of delayed graft function within this cohort (75%), there was no association with patient or graft survival. In line with these findings, kidney function was significantly impaired at higher RI values. Logistic regression revealed a significantly higher probability of DGF at a higher RI (.8%. Evenp = 0.854) or the incidence of biopsy-confirmed acute rejection  was observed. Notably, there was no difference between patient- (p = 0.987) or death-censored graft survival (p = 0.214) between high or low RI  and CIT (p = 0.016) were significantly associated with vascular resistance, donor age and body weight showed no correlation with RI. These findings were further specified in a multivariate analysis, which showed a significant correlation between RI and recipient age (p = 0.001) but not CIT (p = 0.072).To assess variables influencing RI values, recipient age, donor age, body weight, and cold ischemia time (CIT) were imputed in a univariate linear regression model. Whereas recipient age , an incidence similar to that described in the literature , 6. MostThe predictive value of RI has been shown by various authors , 8. We cIn conclusion, our results reinforce the value of ultrasound as a diagnostic tool for evaluating the transplanted kidney. In addition to information regarding vascular supply, RI can serve as a fair predictor of outcome.


Malnutrition is common in elderly and is a risk factor for pressure ulcers.The aim of the present study was to determine the prevalence of malnutrition in geriatric and palliative patients hospitalised in long-term care facility, and to examine the influence of nutritional status on the prevalence of pressure ulcers (PU).Descriptive, observational and cross-sectional study including 2099 patients admitted to the Hospital during a 24 month period (January 2013 to December 2014). We recorded: demographic data, body mass index (BMI), Braden score, laboratory parameters of interest  and presence or absence of malnutrition and pressure ulcers.The pressure ulcer prevalence was 12.9% (256 out of 2099). Based on the BMI classification, 61.7% of patients had a good nutritional status, 27.4% were undernourished, and 2.1% were considered malnourished. Nutritional status was statistically significantly different between patients with and without PU (p < 0.0001). This study also showed that hypoproteinemia, hypoalbuminemia, low RBC was positively associated with PU prevalence.The results highlight the impact of nutritional status on the prevalence of pressure ulcers in hospitalised geriatric and palliative population. It is of paramount importance to correctly evaluate the presence of malnutrition in patients at risk of pressure ulcers. A pressure ulcer (PU) is localised injury to the skin and/or underlying tissue usually over a bony prominence, as a result of pressure or pressure in combination with shear. It leads to ischemia, progressive destruction and necrosis of the underlying soft tissues . PressurThe prevalence of PUs in long-term settings ranges from 11 to 29% -6. DevelMalnutrition is a very common problem that affects approximately 30-50% of hospitalised patients. It is estimated that at least one-third of patients has some degree of malnutrition upon admission to the hospital (7). Additionally, among patients who are not malnourished upon admission, about one third may become malnourished while in the hospital (8). Among the elderly residents of long-term care institutions, the prevalence of in-hospital malnutrition has been estimated to be between 12.5 and 78.9% in different studies . OverallHospital malnutrition is associated with an increase in morbidity, mortality, a higher readmission rate, functional disabilities and physical complications, and, therefore, higher healthcare costs. Malnutrition is closely related to frailty, a clinical syndrome characterised by increased vulnerability to adverse health outcomes including acute illness, the decline in physiological reserve, and increased risk for disability, falls, hospitalisation, need for long-term care, and death .The principal objective of this study was to assess the prevalence of malnutrition in elderly patients hospitalised in the long-term care facility. The secondary objective was to examine the influence of malnutrition on the prevalence of pressure ulcers.This observational study was carried out at the Geriatric and Palliative Care Hospital “13 November” in Skopje, Macedonia, the largest specialised geriatric and palliative hospital in the country that attends to patients through the Public Health System. The study design was approved by the Hospital Ethics Committee. Informed consent was waived because of the study’s observational nature.Consecutive patients admitted to the hospital were enrolled from January 2013 to December 2014. We collected data using a case report form and recorded information about demographics, main diagnosis, BMI, laboratory findings, the presence of PU and PU characteristics.Body mass index (BMI) was calculated using the formula: weight in kilogrammes/height in meters2. Using BMI classification, patients were classified as severely underweight, underweight, normal weight, overweight, severely obese or morbidly obese.The Braden scale was used to assess the risk of developing PUs. The total score can range from 6 to 23 with a lower score indicating a higher risk .The risk for PU development was assigned according to the stratification determined by the scale, into four groups; according to the Braden score . The risDescriptive statistics was used to describe the study population, with continuous outcomes summarised as a mean and range, and categorical outcomes presented as a percentage. Chi-square test was used to analyse categorical variables. Independent t-test was used to analyse continuous variables. P-values < 0.05 were considered statistically significant.During the study period, two thousand and ninety-nine patients were consecutively admitted. Baseline characteristics of the study population are shown in Braden score ranged from 6 to 23  and 1948 (92.8%) had a risk for pressure ulcers .2 = 25.350; p < 0.0001).In this retrospective study involving 2099 geriatric and palliative patients in a long-term setting, the following variables were significantly more frequently documented in patients with PU compared to those without PU: malnutrition measured as BMI, hypoproteinemia, hypoalbuminemia and anaemia .Malnutrition is defined as a state of nutrition in which a deficiency or excess of energy, protein and other nutrients causes measurable effects both on tissue/body structure and function .The causes of malnutrition are multiple and complex . In eldeMalnutrition has numerous effects, including impaired collagen synthesis, and immune function. Wound healing refers to the complex and dynamic process of restoring cellular structures and tissue layers. In each phase of wound healing, poor nutritional status can delay the healing process or cause inadequate healing when nutritional deficiencies are not corrected , 21.A number of studies have demonstrated that the relationship between malnutrition and pressure ulcers is bidirectional -24. A diPatients with chronic PUs - wounds that remain unhealed for more than six weeks - experience a continuous cycle in which they lose protein through excess exudate, resulting in delayed wound healing.Our results revealed marked hypoproteinemia and hypoalbuminemia in patients with PUs. Protein-energy malnutrition reduces fibroblastic cellular activity and delays angiogenesis in the proliferative stage and reduced collagen synthesis and maturation in the remodelling stage, leading to increased wound dehiscence. Furthermore, proteins are lost in wound exudates, which can contain as much as 100 g of protein per day . A deficOlder people are at risk of malnutrition if they have a BMI below 24, and malnutrition is indicated by a BMI of less than 20 . The WorMalnutrition in a hospital setting may be prevented by using strategies that include assisting patients into a position conducive to swallowing safely and comfortably; implementing food charts to ensure accurate documentation of intake; and using fluid charts to record input and output to calculate fluid balance .Maintaining nutritional status and preventing malnutrition aims to ensure that energy, protein and other micronutrients are available to prevent pressure ulcer development. No biochemical marker on its own offers a satisfactory screening test for malnutrition. Serum proteins synthesised by the liver have been used as markers of nutrition—albumin, transferrin, retinol-binding protein and thyroxine-binding albumin. Serum albumin has been most widely adopted; however, the long half-life of albumin means that serum albumin does not respond to short-term changes in protein and energy intake.Nutrition and hydration play an important role in preserving skin and tissue viability and in supporting tissue repair for PU healing .In the older population, undernutrition rather than overnutrition is the main cause for concern . MalnourPressure ulcers are debilitating chronic wounds. Prevention of PUs in hospitalised elderly patients is an important health priority, one that requires clear identification of risk factors. Effective management of malnutrition requires collaboration among multiple clinical disciplines and all members of the clinical team .In conclusion, malnutrition is a problem of high prevalence and impact in geriatric and palliative patients. Given the high prevalence of malnutrition among patients with pressure ulcers, performing a routine nutritional screening should result in early identification of residents with the risk of development of pressure ulcer.