The study aims to assess the influence of the stage of chronic kidney disease and glomerular filtration rate on prevalence and degree of erectile dysfunction.This transversal study, conducted from May 2013 to December 2015, included patients with chronic kidney disease in conservative treatment, stages III/IV/V. Erectile dysfunction was evaluated by the International Index of Erectile Function. Data classically associated with erectile dysfunction were obtained by medical record review. Erectile dysfunction, degree of erectile dysfunction, and other main variables associated with erectile dysfunction were compared between patients with chronic kidney disease on conservative treatment stages III versus IV/V using the Chi-square test. The relationship between score of the International Index of Erectile Dysfunction and glomerular filtration rate was established by Pearson correlation coefficient.Two hundred and forty five patients with chronic kidney disease in conservative treatment participated of the study. The prevalence of erectile dysfunction in patients with chronic kidney disease in stages IV/V was greater than in stage III. Glomerular filtration rate positively correlated with score of the International Index of Erectile Dysfunction.The study suggests that chronic kidney disease progression (glomerular filtration rate decrease and advance in chronic kidney disease stages) worsen erectile function. Hypothetically, diagnosis and treatment of erectile dysfunction may be anticipated with the analysis of chronic kidney disease progression. Erectile dysfunction (ED) is a persistent inability to attain and/or maintain an erection sufficient to satisfactory sexual performance . This seMany studies have analyzed ED in patients with CKD. The ED prevalence found in these works was usually high -10. Age,Some studies specifically evaluated patients with ED and chronic kidney disease on conservative treatment (CKDCT) -14. In tThis transversal study, conducted from May 2013 to December 2015, was approved (registration no. 090/2011) by the Ethics Committee of the Federal University of Goiás Clinical Hospital, in accordance with Helsinki Declaration of 1975 revised in 1983.For practical purposes, CKDCT was defined as structural or functional abnormalities of the kidney, present for more than 3 months, with health implications, in patients who did not receive renal replacement therapy, dialysis, or renal transplantation.Male patients, volunteers, heterosexuals, carriers of CKDCT, from two hospitals in the city of Goiânia (Brazil), without cognitive or communication impairment and that signed an informed consent form were included in this study. The patients were classified into CKD stages according to the criteria of the Kidney Disease Outcomes Quality Initiative (2012)  Table-1Table-1. 2, or without data to estimate it , were excluded.Patients with creatinine clearance, estimated by the Cockcroft-Gault equation , greaterPatients were individually approached, before their scheduled medical visit, in nephrology services, previously cited. They received a brief explanation about the research and were instructed to read and interpret questions about erectile function of the International Index of Erectile Function (IIEF). Life habits, sociodemographic characteristics, clinical and laboratory data were obtained from medical records review made by five researchers.The variables evaluated were: age, marital status, body mass index, systemic arterial hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, time of CKD, smoking, pack years of smoking, alcohol use, antihypertensive numbers, antidepressants and anxiolytics use, hematocrit, cholesterol, high density lipid cholesterol, low density lipid cholesterol, and triglycerides.ED was assessed by erectile function domain of the IIEF (questions numbers 1 to 5 and 15) . Accordi® Excel 2007 and analyzed by Statistical Package for Social Sciences for Windows 16. Descriptive analysis was done for ED and its categories (according to IIEF), life habits, sociodemographic characteristics, and clinical and laboratory data. Categorical variables were assessed by ED proportion in each category and continuous variables by ED proportion in categories created to facilitate interpretation of results. ED prevalence, ED degrees, and each categorical variable of patients with CKDCT stage III were compared with their corresponding stage IV/V, using Chi-square test. Severe ED was compared with other ED degrees in patients in stage III using the previous test. Stage IV/V patients were grouped and similar comparison was done. P equal or less than 0.05 was considered statistically significant. Relationship between IIEF score and GFR was analyzed by Pearson correlation coefficient.Data were tabulated in Microsoft2 in same stages, respectively. CKD stages, ED, and severe ED distribution of patients are presented in The study assessed 338 patients with CKDCT, 245 (72.49%) patients were included and 93 (27.51%) excluded. Mean age was 63.36±13.74, 67.16±14.43, and 66.52±12.27 years in stages III, IV, and V, respectively. Creatinine clearance (estimated) means were 33.34, 23.07, and 12.14mL/min/1.73mPotential factors that can influence erectile function occurred in similar frequency in patients with CKD stage III and IV/V. Only body mass index was not similar between them .ED proportion in patients with CKD stage III was lower than in stage IV/V . HoweverIncrease of IIEF score followed the increase of GFR with a weak relationship .The first reference of sexual disorder prevalence, in patients with CKDCT, estimated 9% in both sexes . Other wSome studies registered influence of CKD stages and GFR on erectile function , 18, 23.Influence of CKD stages and GFR in erectile function is not always found. ED was observed in 72.3%, 81.5%, and 85.7% of 81 outpatients with CKD stages III, IV, and V, respectively. These ED rates were not statistically different . PatientThe present study found lower GFR levels and/or more advanced stages of CKD associated with worse erectile function. Some works have shown that worse kidney function increases the chance and severity of sexual disorders , 18, 23.Assuming conditions resulting from CKD that directly cause damage to erectile function are magnified in the more advanced disease, it could also be assumed that the more severe the CKD is, the greater severity and frequency of ED. Another hypothesis is that the more serious, poorly treated, or uncontrolled diabetes and/or hypertension are, the more serious the CKD and ED resulting from them are. Therefore, the studied patients with CKD stages IV/V may had higher ED prevalence than patients with CKD stage III, because the first are more expose to directly deleterious effects of CKD in the penis or could have worse, more poorly treated or uncontrolled diabetes and/or arterial systemic hypertension than patients with CKD stage III. The present work did not evaluate severity and control of diabetes or arterial systemic hypertension, a limitation of the study.The work has other characteristics that may have affected the results. This is an observational study. Therefore, association among studied variables can be found, but causal relationships cannot be proved among them. Non-random samples were used in this work, thus the samples may have been subject to bias. Evaluation of some variables cited as influential in erectile function  was not performed in the present research , 33. TheIn conclusion, this study suggests that CKD progression (GFR decrease and advance in CKD stages) worsen erectile function. Hypothetically, diagnosis and treatment of ED may be anticipated with the analysis of CKD progression. Therefore, activity and sexual health may be preserved or re-assumed by CKD patients, and their quality of life may be improved.


Essential hypertension is associated with reduced pain sensitivity of unclear aetiology. This study explores this issue using the Cold Pressor Test (CPT), a reliable pain/stress model, comparing CPT-related EEG activity in first episode hypertensives and controls. 22 untreated hypertensives and 18 matched normotensives underwent 24-hour ambulatory blood pressure monitoring (ABPM). EEG recordings were taken before, during, and after CPT exposure. Significant group differences in CPT-induced EEG oscillations were covaried with the most robust cardiovascular differentiators by means of a Canonical Analysis. Positive correlations were noted between ABPM variables and Delta (1–4 Hz) oscillations during the tolerance phase; in high-alpha (10–12 Hz) oscillations during the stress unit and posttest phase; and in low-alpha (8–10 Hz) oscillations during CPT phases overall. Negative correlations were found between ABPM variables and Beta2 oscillations (16.5–20 Hz) during the posttest phase and Gamma (28.5–45 Hz) oscillations during the CPT phases overall. These relationships were localised at several sites across the cerebral hemispheres with predominance in the right hemisphere and left frontal lobe. These findings provide a starting point for increasing our understanding of the complex relationships between cerebral activation and cardiovascular functioning involved in regulating blood pressure changes. Hypertension is a leading risk factor for cardiovascular disease and a major contributor to healthcare costs worldwide . Given tThe central nervous system (CNS) has also been implicated in the aetiology and maintenance of some forms of EH. The CNS is a target of the disease which, if untreated, progresses to blood pressure (BP) levels threatening the integrity of cerebral vessels, potentially inducing stroke .Considerable evidence supports the connection between pain perception and BP regulation. It has been proposed that acute BP increases may reduce pain, thus establishing hypertension through instrumental learning . HypoalgThe layman concept that stress can cause hypertension still lacks strong empirical support. A review of studies examining the relationship of stress and hypertension  concludePain sensations, consisting of sensory, affective, and cognitive experiences, modulate EEG oscillations across a wide range of frequency bands, presumably reflecting the mechanisms involved in cortical activation and inhibition , 10. SevTaking into consideration the issues presented above, the current study attempted an integrative approach to the factors interacting in the setting of hypertension. The objective was to compare well-characterised, untreated hypertensives and matched normotensive controls in terms of (i) arterial blood pressure variables (24-hour ambulatory blood pressure monitoring (ABPM)), (ii) CNS electrophysiological responsiveness (EEG), and (iii) behavioural responsiveness (pain perception and tolerance) under exposure to sympathoexcitatory stress and pain induced by the CPT.Although the impact of experimental pain on EEG has attracted experimental interest, the existing available data do not warrant the formulation of specific hypotheses regarding the relationship between brain oscillations and newly diagnosed, untreated hypertension. Therefore this axis of our design has an exploratory character.The hypertensive (HT) group consisted of 22 newly diagnosed untreated hypertensives  referred to the hypertensive centre of the Department of Clinical Therapeutics . The normotensive control (NT) group included 18 healthy volunteers . All 40 participants were ambulatory and the two groups were matched for sex, age, and body mass index. They all fulfilled the following inclusion criteria: (1) no previous antihypertensive treatment; (2) absence of clinical signs or laboratory evidence of hypertension-related complications  or of secondary causes of arterial hypertension; (3) absence of any other systematic disease; (4) absence of psychiatric disorders or psychiatric medication; (5) at least three valid BP measurements per hour over 24 hr ambulatory blood pressure monitoring (ABPM: 75% successful measurements). The cohort was initially evaluated by 24-hour ABPM and subjects were divided into 2 groups in terms of their ABPM measurements objectively on the basis of this measurement. Individuals with 24-hour ambulatory BP <130/80 mmHg were placed in the NT group; individuals with 24-hour ambulatory BP ≥130/80 mmHg were placed in the HT group. All subjects gave their informed consent for participation in the study, and the study protocol was approved by the hospital ethics review committee to ensure that the procedures followed were in accordance with the institutional guidelines.Participants were instructed to abstain from alcohol, cigarette smoking, coffee/tea, and exercise for at least 30 minutes prior to testing. The study flow diagram can be seen in 24-hour ABPM was conducted on all subjects on a usual working day by means of the Spacelabs 90217 ambulatory blood pressure monitor . The appropriate sized cuff was placed around the nondominant arm and 3 consecutive blood pressure determinations were recorded along with sphygmomanometric measurements to verify that there was no difference greater than 5 mmHg on the average of the 2 sets of values. Throughout the 24-hour monitoring readings were obtained automatically at 15-minute intervals and all subjects had at least 3 valid readings per hour. The resulting 80 to 96 pairs of systolic and diastolic BP readings per recording with the corresponding recording time were used to calculate blood pressure derivatives. All subjects were instructed to maintain their usual daytime activities between 6:00 AM and 10:00 PM and rest-sleep between 10:00 PM and 6:00 AM . In thisThe CPT is a method commonly used to evoke a sympathoexcitatory stress response , 16. TesEEG data collection and analysis: for acquiring the EEG data, the EMOTIV Epoc EEG system was used . This device has a wireless amplifier, and 14 wet saline electrodes, corresponding at the positions AF3, F7, F3, FC5, T7, P7, O1, O2, P8, T8, FC6, F4, F8, and AF4 according to the international 10–20 system see .The device has also an embedded 16-bit ADC which was used to digitize the data with 128 Hz sampling frequency per channel. The data were sent via Bluetooth to a computer with the EMOTIV Control Panel software installed, allowing the visual monitoring of the impedance of the electrode contact to the scalp. The EMOTIV Epoc EEG device is part of a number of low-cost EEG systems, which have been recently applied for research aims. However, recent research assessing their reliability provides converging evidence indicating their capacity to measure consistently EEG signals –20.Two electrodes located just above the subject's ears  were used as reference. Electrode resistance was kept constantly below 5 kΩ. The EEG signals were band-passed filtered with Butterworth 0.5–8 Hz, 8–12 Hz, 12–28 Hz, and 28–45.5 Hz filters.Wx, that permits the accurate decomposition of EEG waveforms into a set of component waveforms allowing the isolation of all scales of waveform structure [t), to be convolved with the original signal, x(t). This convolution leads to a new signal, WxΨ, with b denoting the translation parameter and a the wavelet's scaling parameter. This signal consisted of coefficients which denote the correlation between the EEG signal and the wavelet function. In order to approximate the continuous wavelet transform, the convolution with the signal has to be done N times for each scale, where N is the number of points in the signal time series. Although the choice of N could be arbitrary, given the fact that the exact number of time segment data points of all CPT phases was known beforehand, the appropriate choice of repeated convolutions was made resulting in comparable wavelet coefficients for all time segments. Nevertheless, the wavelet transforms at each scale a have to be directly comparable to each other and to the transforms of other time series, so the wavelet function was normalized to have unit energy at all times. The wavelet power spectrum was then computed as |Wx2| or as |Wx2| in terms of translation and shifting parameters.In order to analyse the data from the experimental setup, a wavelet-based analysis was performed using EEGLAB 13.5.4b , an opentructure . AccordiFurthermore, certain coefficients will be generated corresponding to the noise affected zones and some other coefficients will be generated in the areas corresponding to the actual EEG. Although these coefficients are associated with frequency components, they are modified in the time domain, where each coefficient corresponds to a time range. An appropriate choice of wavelet coefficients would result in removing the noisy part of the EEG signal to some extent, while retaining the useful part of the signal . Noise fFor each electrode the total measurements were divided into four time segments based on the previous described experimental procedure. The wavelet coefficients were split into the following eight standardized bands: Delta (1–4 Hz), Theta1 (4–6 Hz), Theta2 (6–8 Hz), Alpha1 (8–10 Hz), Alpha2 10–12 Hz), Beta1 (12.5–16 Hz), Beta2 (16.5–20 Hz), Beta3 (20.5–28 Hz), and Gamma (28.5–45 Hz). The wavelet cycles of the transform were dynamically increased so that the time width of the wavelet corresponding to the highest frequency of the Gamma band is to be half the time width of that related to the lowest frequency of the Delta band, thus, allowing a higher frequency resolution (resulting from 3 cycles at 1 Hz to above 67 cycles at 45 Hz). The wavelet coefficients were averaged over time and then scales contained within each frequency band were summed together to yield the absolute activity within each band  Hz, Beta. For eacStatistical analysis was performed with the STATISTICA 12.0 software for Windows. A first analysis involved a between-group, Repeated Measures design. Power spectrum density of EEG recordings from 14 electrodes was expressed as Delta, Theta1, Theta2, Alpha1, Alpha2, Beta1, Beta2, Beta3, and Gamma values. Each frequency was analysed as a dependent variable in separate, 1-way Repeated Measures ANOVAs. In each ANOVA, the independent variable was Group Membership ((1) normotensive controls versus (2) hypertensives); the Repeated Measures factor was phase, which included four levels corresponding to the stages of the Cold Pressor Test ((1) pretest resting phase, (2) stress unit phase, (3) tolerance phase, and (4) posttest resting phase). Special attention was given to interactions as those would provide the strongest evidence as to differential response profiles of hypertensives versus controls. The overall relationship among the clinical and the EEG variables was further investigated by Canonical Analysis; in order to ascertain the relative significance of the variables they showed the highest individual association with the two states of the subjects . On the left side of the equation we chose those EEG variables that clearly and statistically significant showed an interaction effect via the standard Repeated Measures ANOVA paradigm. Each subgroup of these variables was analysed separately so four Canonical Analyses were carried out, one for each group, that is, Gamma, Alpha1, Alpha2, Delta, and Theta1. On the right side of the equation we chose Maximum Diastolic Blood Pressure of the day (Max DBP day), Minimum Heart Rate of the day (Min HR day), Mean Blood Pressure 24 hours (Mean MBP24), and Minimum Diastolic Blood Pressure of the day (Min DBP day) by performing Discriminant Function Analysis that included all clinical variables and controls/hypertensives as the dependent variable.t-test to check for differences between the groups regarding the behavioural performance in the pain tolerance of the subjects.We also performed the standard Student's p = 0.059).There was no significant difference between normotensives and hypertensives although a tendency was revealed towards greater pain tolerance in hypertensives measured as self-determined duration (min) of exposure to the cold bath . Overall, signals tended to rise during the tolerance phase and drop during the posttest resting phase.However, the central finding was the interactions observed between Group Membership and phase. Analyses revealed interactions in Delta, Theta1, Alpha1, Alpha2, Beta2, and Gamma values. In examining this relationship we encountered four distinct response patterns which support our hypothesis that hypertensives have a differential electrophysiological response profile to environmental stimuli as those are simulated by the phases of the Cold Pressor Test.DBA at F3 and P8 leads had higher values for hypertensives than controls overall and particularly in the tolerance and posttest phases. A similar finding was noted for electrode O2 but with a greater difference between the two groups, with controls showing a continuous value decline from pretest to posttest. In the control group, lead F4 showed a sharp value drop at the posttest phase, whereas hypertensives demonstrated a slight increase at the same phase. In the control group the AF4 lead revealed a steady drop from the beginning of the procedure to the end, similarly to the O2 lead; in contrast, the hypertensives group sustained the same level of activity in all four experimental phases  and 7. ATBA 1 at F3 and AF4 leads produced a statistically significant interaction , with hyOverall, ABA 1 values at O2 and P8 leads were higher in hypertensives than controls throughout the experiment, whereas controls showed a significant drop in the posttest resting phase  and 7. Tp = 0.001) rather than between the groups as noted in most measurements.In the case of Alpha1 electrode P8 the statistically significant interaction was due to the within the control group drop in the Power Spectral Density value at the posttest phase compared to the pretest  rather than between the groups as noted in most measurements.As in the case of Alpha1 electrode P8 the statistically significant interaction in Beta2 electrode T8 was due to the within the control group rise in the Power Spectral Density value at the posttest phase compared to the stress unit phase  and the tolerance phase (p = 0.000) whereas no such changes were observed in the controls group whose values remained similar throughout the entire experiment.Once more, the statistically significant interaction for Gamma electrode AF3 was due to statistically significant differences in the Power Spectral Density values what were noted in the hypertensives group who had a sharp rise from the pretest to the stress unit phase  = 67.373 p = 0.14224). This was followed by Alpha2  = 64.833 p = 0.05315), Gamma  = 53.749; p = 0.26380), Alpha1  = 32.951 p = 0.42043), and Beta1  = 22.403; p = 0.13073).The obtained results revealed that Delta values where the most strongly associated with the clinical state of the subjects  and electrophysiological responsiveness (EEG activity) elicited by exposure to sympathoexcitatory stress/pain induced by the CPT in untreated hypertensives and normotensive controls.Although the two groups differed significantly in all arterial blood pressure variables, a Discriminant Function Analysis revealed that the most robust group differentiators were four: Maximum Diastolic Blood Pressure of the day (Max DBP day), Minimum Heart Rate of the day (Min HR day), Mean Blood Pressure 24 hours (Mean MBP 24), and Minimum Diastolic Blood Pressure of the day (Min DBP day).An initial series of ANOVA analyses determined significant group differences in CPT-induced EEG oscillations, which were then covaried with the four most robust cardiovascular differentiators by means of Canonical Analyses. This revealed positive correlations between cardiovascular variables and Delta oscillations (1–4 Hz) during the tolerance phase; in high-alpha oscillations (10–12 Hz) during the stress unit and posttest phase; and in low-alpha oscillations (8–10 Hz) during all four CPT phases.In contrast, negative correlations were noted between cardiovascular variables and Beta2 oscillations (16.5–20 Hz) during the posttest phase and Gamma oscillations (28.5–45 Hz) during all four CPT phases.These associations were localised at several sites across the cerebral hemispheres, predominantly in the right one, and in left frontal lobe.p = 0.059). This is in line with previous findings indicating hypoalgesia in hypertensives. Hypertension-associated hypoalgesia has important clinical implications, the first of which relates to the phenomenon of silent myocardial ischemia and infarcts which are significantly more common in hypertensives than in normotensives [On the behavioural level, pain tolerance measured in terms of self-determined exposure to the CPT ice bath beyond the obligatory 1 min stress unit phase revealed a tendency towards greater tolerance in hypertensives, although this did not reach statistical significance  appear compatible with previous human and animal studies suggesting that increased cerebral activity in the spectrum of DBA is associated with increased arterial pressure, probably mediated through suppressed baroreflex control of heart rate , 27. DBADBA correlations were noted in the left frontal and the right occipital areas. This is consistent with evidence that DBA is involved in cortical communication over long distances . Yener aOur findings revealed positive correlations between cardiovascular variables and high (10–12 Hz) alpha oscillations during the CPT stress unit and posttest phases and in low (8–10 Hz) alpha oscillations during the 4 CPT phases overall. The high-alpha subband (A2BA) is considered an index of task-specific sensorimotor activity regulation , mainly The low-alpha subband (A1BA) is considered an index of general tonic alertness . The difIt is a reasonable assumption that the pretest brain oscillations noted in our study may be explained in terms of anticipation of pain. Such anticipation can cause mood changes and behavioural adaptations which may influence subsequent pain perception , 40. It A negative correlation was noted between cardiovascular variables and B2BA during the posttest phase. Given that Beta brain activity plays a role in motor processing, a possible interpretation of this correlation is that pain-related B2BA modulations reflect the preparation and execution of a defensive response . This viA negative correlation between GBA and cardiovascular group differentiators emerged from our study. GBA is considered to play a crucial role in cortical integration and perception . Brief pIn contrast, longer-lasting painful stimulation (perception of tonic pain) does not appear to be encoded by GBA in the somatosensory cortex, but rather in the medial prefrontal cortex, close to premotor and cingulate cortices . This GBPrevious studies have shown that GBA is enhanced during attentional selection of sensory information . AdditioIn the service of adaptive environmental engagement low coping capacity has been associated with a more pronounced decrease in GBA . Hence tAs a whole, the correlations we noted between brain oscillations and cardiovascular parameters may be better understood in the light of reports suggesting that cognitive alterations depend upon the degree of hypertension. It is established that the systolic and diastolic blood pressures have effects on distinct cognitive domains , 55. AnsFurthermore, the relative scalp locations of differences in magnitude of cerebral activation between the two hemispheres could determine the overall changes in blood pressure and heart rate. This idea is supportive to the view, which states that the two cerebral hemispheres act in concert to promote changes in cardiovascular functioning; however, the right hemisphere predominantly modulates sympathetic efferents, while the left hemisphere predominantly modulates parasympathetic efferents, of the autonomic nervous system .In conclusion, our results add to a growing body of evidence that the brain is implicated in the initiation of high blood pressure while it is itself altered by early disease processes. Thus the brain and vasculature may be independently and concurrently targeted by the factors inducing essential hypertension .Previous studies have thoroughly evaluated the impact of TR of BP variation on target organ damage. A cross-sectional study in 514 normotensive and uncomplicated hypertensive patients demonstrated that the 24-hour rate of systolic BP variation was greater in hypertensive than in normotensive subjects and was the only office or ambulatory BP monitoring parameter that was linearly and independently associated with carotid intima-media thickening . AdditioOur results also demonstrate the advantage of simultaneous EEG recording under well-defined pain inducing conditions. Our approach of factoring contributions from multiple, interconnected brain processes is relevant to all studies which attempt to link evoked brain responses with behaviour and demonstrates that exploiting these interactions leads to a more complete understanding of brain response to stimulation and the psychophysiological emergence of the experience of pain.A number of limitations must be considered when interpreting the findings of the current study. First, the study relied on a relatively small sample. Second, we employed CPT as a measure of pain. Although this approach is consistent with the literature, we cannot necessarily generalize the current results to other types of painful stimuli, such as thermal stimuli. Third, an additional limitation relates to the fact that EEG and cardiovascular measurements were noncontemporaneous. This potentially limits the findings in that the two measures were not precisely coupled. Fourth, data were collected in a single testing session. Therefore, we cannot comment on the stability of the relation between hypertension and EEG activity over time.Nevertheless, the study adds to the understanding of the role of brain oscillations evoked by stress and/or pain stimulation in the underlying mechanisms of hypertension. Our data suggest that brain oscillations in response to stress and/or pain challenge may give greater insight into underlying systems and the mechanisms of hypertension.EEG recorded in the course of the CPT provides a measure of cortical activity, on the basis of which untreated hypertensives may be differentiated from healthy controls. Furthermore, the method utilized in this study helps isolate pain-related features in the EEG during CPT in association with cardiovascular variables. This lends credibility to the hypothesis that top-down and bottom-up control mechanisms are implicated in the development of hypertension. Future applications of the methodology may help identify specific EEG features related to the neuronal processing of pain perception in hypertension.


The burden of uncontrolled hypertension in Low-and-Middle Income Countries (LMICs) is high, with an increased risk of cardiovascular diseases and chronic renal failure in these settings.To assess the factors associated with uncontrolled blood pressure control in a cross-section of Ghanaian hypertensive subjects involved in an on-going multicenter epidemiological study aimed at improving access to hypertension treatment.A cross-sectional study involving 2,870 participants with hypertension with or without diabetes who were enrolled at 5 hospitals in Ghana . Data on demographics, medical history, lifestyle factors, anti-hypertensive medications and treatment adherence were collected. The 14-item version of the Hill-Bone compliance to high blood pressure therapy scale was used to assess adherence to treatment in 3 domains namely adherence to medications, salt intake and clinic appointments. Questionnaires on knowledge, attitudes and practices on hypertension, sources of antihypertensive medications and challenges with accessing these medications were also administered. Blood pressure, weight and height were measured for each subject at enrollment. Factors associated with uncontrolled blood pressure (>140/90mmHg) were assessed using a multivariate logistic regression model.The mean ± SD age of study participants was 58.9 ± 16.6 years, with a female preponderance (76.8%). Among study participants, 1,213 (42.3%) study participants had blood pressure measurements under control. Factors that remained significantly associated with uncontrolled blood pressure with adjusted OR (95% CI) included receiving therapy at a tertiary level of care: 2.47 (1.57–3.87), longer duration of hypertension diagnosis: 1.01 (1.00–1.03), poor adherence to therapy: 1.21 (1.09–1.35) for each 5 points higher score on the Hill-Bone scale, reported difficulties in obtaining antihypertensive medications: 1.24 (1.02–1.49) and number of antihypertensive medications prescribed: 1.32 (1.21–1.44).We have found high rates of uncontrolled blood pressure among Ghanaian patients with hypertension accessing healthcare in public institutions. The system-level and individual-level factors associated with poor blood pressure control should be addressed to improve hypertension management among Ghanaians. Hypertension is a major global public health challenge with nearly 1 billion individuals affected worldwide and projected to reach 1.56 billion by 2025 . Recent In LMICs, health systems are not well equipped to provide care for non-communicable diseases (NCDs) such as hypertension which are often life-long diseases requiring sustained access to healthcare for control. Among populations in LMICs, awareness about hypertension control and the need for continuous treatment are low. Many other factors including limited resource allocation, lack of training in hypertension treatment among many professionals, and low health literacy among patients contribute to poor blood pressure control. These factors have contrived to create a looming epidemic of Cardiovascular Diseases (CVDs) in these settings. One of the key Sustainable Development Goals adopted by the World Health Assembly in 2013 was to lower the prevalence of raised blood pressure by 25% by 2025 . In ordeTo address the aforementioned challenges in blood pressure control in LMICs, both community and hospital based studies are urgently needed. Such studies will provide the needed information on the key local drivers of the poor rates of hypertension control –13 and hThe Ghana Access and Affordability Program (GAAP), a public-private partnership aims to improve the management of hypertension and type II diabetes through improved access to medicines for the control of these conditions. In this report we present a comprehensive analysis of factors associated with blood pressure control among 2,870 Ghanaian hypertensive patients enrolled as part of the GAAP pilot study. Our objective was to understand the unique factors associated with uncontrolled blood pressure among Ghanaians with hypertension under routine health delivery settings. The patient population in the present study received medical care from clinics located in primary, secondary and tertiary facilities across the country.This study protocol was approved by the Committee on Human Research Publications and Ethics of the Kwame Nkrumah University of Science and Technology and the Ghana Health Services Ethical Review Committee. It was declared as exempt by the Institutional Review Board at the Johns Hopkins Bloomberg School of Medicine. Written informed consent was obtained from all study participants before enrollment into the study. All relevant data are included in the manuscript and The present report is a cross-sectional analysis of baseline data of a prospective cohort study of hypertensive and diabetic patients in the GAAP pilot study.The GAAP Pilot study was conducted at 5 hypertension and diabetes specialty and general clinics in urban, peri-urban and rural locations in Ghana. These sites were conveniently selected based on the ecological zones of northern savannah, central forest -mixed zone and the coastal belt. Briefly, the study sites included:The Agogo Presbyterian Hospital, (APH) is a peri-urban, district, secondary level health institution situated in the middle belt of Ghana.The Atua Government Hospital, (AGH) is a peri-urban, district, secondary level health institution situated in the southern belt of Ghana.The Komfo Anokye Teaching Hospital, (KATH) is an urban, tertiary level health institution situated in the middle belt of Ghana,The Kings Medical center, (KMC) is a rural, primary level health institution situated in the Northern belt of Ghana.The Tamale Teaching Hospital, (TTH) is an urban, tertiary level health institution situated in the Northern belt of Ghana.Participants were eligible if they were 18 years or older with known diagnosis of hypertension and/or type II diabetes presenting for routine care at either a general polyclinic  or a dedicated diabetes/hypertension clinic, . Participants were excluded if they had hypertensive urgency/emergency or glycemic complications such as hypoglycemia or a hyperglycemic emergency at initial contact for enrollment. During the 6-month enrollment period of the study, each consecutive participant meeting the eligibility criteria was invited for enrollment by research assistants after explaining the objectives of study and obtaining informed consent.Trained Research Assistants interviewed study participants and collected demographic and household information such as age, gender, educational attainment, employment status, number of dependents on monthly income and health expenditures. Study participants were also interviewed on their lifestyle behaviors such as alcohol use, cigarette smoking, and level of physical activities. A detailed medical history including duration of hypertension or diabetes diagnosis and compliance with hypertension treatment was assessed using the 14-item version of Hill-Bone compliance to high blood pressure therapy scale which has demonstrated good validity and internal reliability . The scaThe vital signs of study participants including measurements of blood pressure and pulse rates were performed by trained study nurses following a standardized study protocol. Briefly, each site was provided with an automated blood pressure measurement device (Omron HEM-907XL) for blood pressure and pulse measurements. Each study participant rested for at least 5 minutes prior to blood pressure measurements while sitting in a chair with both feet flat on the floor. Both arms were supported at the level of the heart on a table. Two consecutive blood pressure readings from the same arm taken 2 minutes apart were recorded and averaged for the present analysis.Anthropometric evaluations including measurement of weight, height and waist circumference were performed by Study nurses. Weight was measured using a pre-calibrated Secca scale with participants wearing light clothing and barefooted. Weight was rounded off to the nearest 1 kg. Height was measured with the participant standing upright against a wall using a previously affixed height measuring device. Body mass index (BMI) of each participant was then derived by dividing the weight in kilograms by the square of the height in meters. Waist circumference was measured in the mid-axillary line midway between the lower rib and the superior iliac crest using a standard non-stretchable tape.Alcohol intake was categorized into never, former drinker or current drinker. Quantity of alcohol consumed by current drinkers was classified according to amount of alcohol ingested in the past month into daily, 5–6 days per week, 3–4 days per week, 1–2 days per week and 1–3 days per month. Cigarette smoking status was defined as never, former, or current smoker. We defined current smokers as individuals who smoked any tobacco in the past 12 months and included those who had quit within the past year. Former smokers were defined as those who had quit more than a year earlier. Physical activity was assessed by asking if participants frequently performed physical activities that caused a small increase in breathing or made their heart rate increase, such as (fast/brisk) walking, jogging, bicycling and how much they spent during physical activity.Stroke was self-reported if participant had ever experienced sudden onset of weakness or sensory loss on one side of the body, sudden loss of vision, or sudden loss of speech. Heart failure was self reported if participant had ever experienced shortness of breath on exertion, on lying down as well as swelling of both feet.To ensure standardization across all study sites, an International Organization for Standardization (ISO)-certified and quality-assured laboratory was contracted to run all biochemical panels which included serum creatinine, lipid profile and hemoglobin A1C for subjects with diabetes. Samples were transported to the laboratory by trained phlebotomists on the same day of collection often within 4 hours or where not feasible (KMC and AGH sites), samples were stored in a freezer before transported to the laboratory the next day.Means and medians were compared using either the Student’s t-test or Mann-Whitney’s U-test for paired comparisons. Proportions were compared using the Chi-squared tests or Fisher’s exact test for proportions with subgroupings <5. Correlations between two continuous variables were assessed using the Pearson’s correlation coefficient. A multivariate logistic regression analysis was performed to identify factors independently associated with the risk of clinic blood pressure reading not on target of <140/90mmHg. We evaluated blood pressure control as a binary variable—poor control or well controlled. Independent variables evaluated included the following categorical variables: age (categorized as <60 years vs ≥60 years), gender, monthly income, location of residence , level of healthcare institution , comorbid diabetes status and employment status. The following continuous variables were evaluated in the model: duration of hypertension history, number of antihypertensives prescribed, scores on 14-item version of Hill-Bone compliance to high blood pressure therapy scale. In building our model, factors associated with the outcome variable at a p-value of <0.05 in unadjusted analyses were included in the multivariate analysis. We investigated putative factors associated with poor blood pressure control among Ghanaians based on literature search, clinical understanding of hypertension management and empirical evidence from our data . In all analyses, two-tailed p-values <0.05 were considered statistically significant. Statistical analysis was performed using SPSS version 19.The present analysis involves 2,870 participants, of which 1685 (65.0%) were known to have hypertension alone and 1,005 (35.0%) had a dual diagnosis of type II diabetes and hypertension. The mean (± SD) age of study participants was 58.9 ± 16.6 years, with a female preponderance (76.8%). It was found that 41.7% resided in urban locations, 22.0% in semi-urban and 36.2% in rural dwellings. As shown in 1,213 (42.3%) study participants had blood pressure measurements below 140/90mm Hg and were considered to be on target whilst the remainder (57.7%) were classified as uncontrolled. There were no significant differences between the two groups with respect to age, gender, educational status or household monthly income as shown in Using the 14-item version of the Hill-Bone Adherence scale we found that most of study participants were moderately adherent to therapy with a mean score of 20.7 ± 3.8. Adherence scores were significantly higher among those with uncontrolled hypertension (20.9±4.0) compared with a score 20.4 ± 3.4 among those on target, p = 0.002. Overall, average scores on adherence to medications and appointment keeping domains of the Hill-Bone scale were significantly poorer among the group with poorly controlled hypertension than those with controlled blood pressure as shown in Among study participants, 63.2% knew the meaning of the term hypertension but only 6.2% and 3.1% respectively had accurate knowledge on what the systolic and diastolic blood pressure cut-offs should be for hypertension diagnosis. As shown in 98% of study participants obtained their antihypertensive medications from hospital pharmacy at the study sites. In addition, 35% and 7% obtained their medications from Community Pharmacies and Licensed Chemical sellers respectively when medications were not available in the hospital pharmacy. Nearly 52% of participants reported being referred from the Hospital pharmacy to either a Community Pharmacy or Licensed Chemical seller for their antihypertensive medications at some point over the preceding 6 months. Over the previous 6 months, 20.5% reported experiencing difficulty obtaining medications at hospital pharmacies, 6.5% at community pharmacy and 1% at Licensed chemical seller as shown in In decreasing order, commonly prescribed classes of antihypertensive medications included Calcium channel blockers (82.2%), Angiotensin converting enzyme inhibitors (43.2%), Angiotensin receptor blockers (27.3%), diuretics (26.3%), centrally acting agents (13.9%), beta blockers (9.8%) and peripheral vasodilators (1.5%). The median (IQR) number of antihypertensive medications per participant was 2 (2–3). Notably, participants whose blood pressure was uncontrolled were on a significantly higher number of antihypertensive medications, mean (±SD) of 2.20 ± 0.95 compared with 1.90 ± 0.94, p<0.0001 among those with controlled blood pressure as shown in Variables significantly associated with poor blood pressure control in unadjusted analyses included location of residence, employment status, level of health care, duration of hypertension diagnosis in years, adherence to hypertension therapy, reported difficulties in obtaining antihypertensive medications and the number of antihypertensive medications subjects were taking as shown in This study to the best of our knowledge is the first in Ghana to robustly evaluate patient-level, health systems-level and access factors influencing blood pressure control among patients receiving care for hypertension. From this multicenter study, we found that 58% of participants had uncontrolled blood pressure. Although >99% of all study participants had valid health insurance cover and were eligible for subsidized essential antihypertensive medicines, one-fifth of study participants reported encountering difficulties accessing these medications at the point of care. Additionally, we found that adherence to hypertensive therapy was not optimal for a significant majority of study participants. Furthermore, knowledge on hypertension and its management among patients was low, despite the average duration of hypertension diagnosis being 8 years. Although urban dwellers were being managed at tertiary hospitals within dedicated hypertension clinics, blood pressure control was poorest in this category compared with rural dwellers receiving care at primary healthcare facilities. Consequently, patient-level factors such as duration of hypertension, compliance with treatment, disease-related factors such as number of antihypertensive medications, and system-level factors such as availability of medications at point of care and the tier of health institution were significantly associated with poor hypertension control.The rates of blood pressure control in the present study is comparable with that from many other studies in sub-Saharan Africa where control rates rarely exceeded >45% –46 althoInterestingly, although socio-demographic factors such as age, gender, income level and educational status were not significantly associated with hypertension control in the present study, some previous studies have identified associations with these factors albeit inconsistently across studies ,57. It iIn the Prospective Urban Rural Epidemiology (PURE) study,  control Lack of health literacy about hypertension was a common theme among study participants, but there were no consistent trends in responses observed between the two groups. Similar studies conducted on knowledge, attitudes and practices in sub-Saharan Africa –66 have Poor adherence to hypertension treatment captured under three domains namely medication adherence, salt usage and appointment keeping by the Hill Bone questionnaire was as expected a key determinant of blood pressure control. Indeed, for each 5-points higher (higher scores means poor adherence), the risk of poor blood pressure control increased by 21% (p = 0.0006). We found that participants whose blood pressure were not on target reported higher tendencies to miss scheduled clinic appointments, to forget to get prescriptions filled, to run out of medications, to skip medications before coming to clinic and to miss pills when careless. Compositely, medication adherence and appointment keeping scores were significantly better among those with uncontrolled blood pressure but not salt usage which was similar between the two groups. Reasons for non-adherence are multi-factorial and are often contributed to by a mix of patient related, physician related and health system-related factors. This makes adherence to therapy for chronic diseases such as hypertension a major challenge worldwide –74. HencAn important finding worth highlighting is the reported difficulties encountered by patients in accessing antihypertensive medications. Unlike the scenario in many LMICs, nearly all study participants in the present study were covered by an insurance scheme which ensured access to essential antihypertensive medications for blood pressure control at the point of care within a hospital pharmacy. However as we have shown, up to 20% of study participants reported encountering difficulties in obtaining medicines, highlighting the frailties of the insurance scheme. Where medications were unavailable, patients would have to obtain medicines from other sources, which required out-of pocket payments for these non-insured medications further increasing the possibility of non-adherence. Hence access and affordability of essential antihypertensive medications for the treatment of hypertension in LMICs may constitute yet another important barrier to blood pressure control.Although we have attempted to assess various factors that might influence blood pressure control, the study is limited in not assessing health professional level of knowledge on hypertension management. Given our finding that tertiary centers were associated with poor control of hypertension, further investigation is warranted on quality of care provided at the tertiary level of healthcare in Ghana. Other important factors of relevance to blood pressure control such as therapeutic inertia and resistant hypertension were not assessed in the present study. Again, the Hill Bone adherence questionnaire subjectively evaluated the reported adherence of participants and is liable to recall bias. Similarly, history of stroke and heart failure were elicited from participants based on self-reports and are subject to recall bias. We defined current cigarette smoking as smoking a cigarette over the past 12 months but current cigarette smoking is typically assessed as smoking 100 or more cigarettes in lifetime and smoking at least a cigarette over the past 30 days and therefore there is a measurement bias with the corollary of overestimating the frequency of current smokers in our study. Finally the associations observed between the selected variables and blood pressure control in a cross-sectional study design does not connote causal relations.In this multi-centre hospital-based study among Ghanaian hypertensive patients, we found more than half (57.4%) of study participants had uncontrolled blood pressure. Health system level factors such as access and affordability of antihypertensive medications at hospital pharmacies and patient-level factors such as adherence to hypertension treatment and knowledge on hypertension should be addressed urgently to prevent the high cardiovascular risk associated with uncontrolled hypertension among Ghanaians.S1 Table(XLSX)Click here for additional data file.


Our aim was to examine the impact of early MgSO4 administration on local cerebral microcirculation during microsurgical clipping of SAH-related aneurysms.In patients with subarachnoid hemorrhage (SAH), vasospasm remains one of the major complications. The application of intravenous magnesium sulfate  and lasted a maximum of 60 min.The non-invasive laser-Doppler spectrophotometry system “Oxygen-to-See (O2C)” was used in 14 consecutive patients  with aneurysmatic SAH. A subdural probe measured capillary venous oxygenation (SO2), relative hemoglobin content (rHb), blood cell velocity (velo) and blood flow (flow) in 7 mm tissue depth. Data samples were recorded as baseline immediately before intraoperative application of MgSO4 was administered 2.8  hours after onset of symptoms. Median flow increased significantly by 20.8% . Velo increased 4.9% (1–17%), rHb decreased 1.5% (3–34%) and SO2 decreased 9.4% (8–38%) by trend compared to the baseline values. FiO2 correlated positively with velo , whereas arterial HCO3 correlated negatively with SO2 . Of 14 patients, 2 had symptomatic vasospasm.MgSO4 in patients with SAH. Using a non-invasive laser-Doppler spectrophotometry system, this technique is feasible for continuous real-time monitoring of cerebral microcirculation.Our data suggest an increased cerebral blood flow after early intraoperative administration of MgSODRKS00013047, retrospectively registered on September 21st, 2017.DRKS ,  Subarachnoid hemorrhage (SAH) caused by a ruptured aneurysm occurs in about 700.000 individuals per year worldwide with an approximate incidence of 9 per 100.000 person years , 3. AfteA variety of treatment options aiming at the relaxation of smooth muscle in cerebral arteries to prevent CVS and avoid infarctions have been reported, including the application of calcium antagonists, statins, or endothelin receptor antagonists . As inteUnfortunately, several randomized controlled trials and meta-analysis could not clearly show the positive benefit of magnesium therapy. The MASH trial suggested a reduction of delayed cerebral ischemia and related poor clinical outcome . HoweverThere are several possible explanations for the lack of evidence in pooled studies. In most randomized trials, time from SAH to magnesium administration has been >24 h after bleeding, and no homogenous timing of administration or dosing schedules were applied –14. The Patient recruitment started in January 2014 at the Department of Neurosurgery, University Hospital Erlangen. This study complied with the laws of the Federal Republic of Germany and followed the Declaration of Helsinki. It was approved by the Ethical Board of the Friedrich-Alexander University of Erlangen-Nuremberg (reference number 4570). Written informed consent was obtained from all subjects or a legal surrogate.Inclusion criteria were: a) age 18–85 years, b) supratentorial craniotomy, c) microsurgical clipping of an intracerebral aneurysm causing SAH, and d) craniotomy size >3 cm in diameter. Exclusion criteria were a) aneurysm of the posterior circulation, b) decompensated renal or liver insufficiency, c) acute coronary syndrome, d) severe comorbidity  ≥3), e) pregnancy.After verification of SAH and identification of the intracerebral aneurysm by digital subtraction angiography or CT angiography, patients were transferred to the operating room immediately. Every patient received an external ventricle drainage prior to craniotomy. Also, 2 g cefazolin was given as an intravenous antibiotic prophylaxis.After fixing the skull in the Mayfield clamp, we set up the SEP monitoring . Bilateral median nerve stimulation at the wrist or posterior tibial nerve stimulation at the ankle was applied  for the other three parameters. Validity as well as reliability of the obtained variables was tested and proved sufficient in several studies, including invasive cerebral blood flow measurements with colored microspheres in animals [The measurement technique of the laser-Doppler spectrophotometry system “O2C” has been described in detail elsewhere , 20. In  animals –20.4 and 10 min thereafter, another data sample of 60 s was taken. The neurosurgeon was blinded to the exact beginning of the MgSO4 administration and the result of the vascular neuromonitoring parameters obtained by the O2C system during the operation.After microsurgical opening of the dura, the O2C probe was carefully inserted subdurally and placed at the distal supply territory of the parent aneurysmatic vessel under continuous irrigation to avoid damage of brain tissue Fig. . The pro1) and sevoflurane (1.5–2.0 vol%). In addition, patients received rocuronium  to faciliate deep anesthesia. Along with MgSO4 10%, intravenous esketamine was administered continuously at a rate of 0.1 mg kg-1 h−1 during surgery. All patients were ventilated controlled . Ventilation was set to keep an arterial carbon dioxide tension of 30-35 mmHg and whenever possible, a positive endexspiratory pressure was avoided. The core temperature was kept at 35–36 °C by Bear Hugger™ . Right before clipping the aneurysm, the mean arterial blood pressure was reduced in a controlled setting to 50-60 mmHg and simultaneously the FiO2 was increased to 50%.Standard monitoring included ECG, pulsoxymetry, noninvasive blood pressure, and was extended with invasive blood pressure, central venous line, capnometry, temperature-sensing urinary catheter and stomach tube. Neurosurgery was performed under general anesthesia with endotracheal intubation according to a standardized protocol, which was based on sufentanil  and was administered over a maximum of 60 min. The dose was based on previous studies to rapidly evoke an effective magnesium concentration [4.Magnesium sulfate MgSOntration , 22. SerPatient data were automatically recorded and stored online. For further processing, relevant data were extracted from patient record using NarkoData .After surgery, patients were admitted to our ICU for 10 to 14 days. All patients were treated in accordance with the guidelines of our department. We recorded neurological outcome and clinical status using the modified Rankin Scale (mRS) at discharge from hospital and 12 months later. Outcome measures were surgery-related morbidity and mortality as well as appearance of neurological deficits as documented during hospital stay. Cerebral vasospasm was detected either by transcranial Doppler ultrasound using the Lindegaard ratio ≥ 3 and a mean flow velocity of ≥120 cm/s  or digit4 administration. A Shapiro-Wilk-Test was performed to identify normal distribution for each continuous variable. We used a paired t test in cases with Gaussian distribution, otherwise the non-parametric Wilcoxon signed-rank test was used for paired comparisons (before/after) of independent variables. To identify possible confounding factors, we examined correlation of O2C parameters with the following anesthesiological parameters: bladder temperature, systolic/diastolic blood pressure, mean arterial blood pressure, heart rate, end-tidal partial carbon dioxide pressure (etCO2), temperature corrected partial carbon dioxide pressure (pCO2 (T)), fraction of inspired oxygen (FiO2), hemoglobin oxygen saturation (SaO2), hemoglobin (Hb), hematocrit (Hct) and arterial bicarbonate (HCO3). Here, Spearman’s rank correlation coefficient was calculated. Statistical significance was set at P < 0.05.The SPSS Version 21.0 for Windows  was used for statistical analysis. Results are given as median values and one standard deviation (SD). Dependent variables were “SO2”, “rHb”, “velo” and “flow”. Independent variables were the presence or absence (before/after) of MgSO4-administration were detected. All O2C parameters were not normally distributed. Cardiorespiratory and anesthesiological parameters were kept constant throughout the operation. The median time between onset of symptoms and application of MgSO4 was 2.8  hours. Median serum magnesium levels were 1.3 ± 0.3 mmol/L.All recordings were performed successfully in every patient. No adverse events of MgSOp = .001), which was 20.8%. All other parameters showed no statistically significant differences. Blood cell velocity had a tendency to rise from 52.4 ± 10.7 AU  to 54.1 ± 11.4 AU , which means a slight increase of 4.9%. SO2 decreased 9.4% by trend from 48.4% ± 16.9  to 43.4% ± 14.0 . Hemoglobin content (rHb) tended to decrease slightly by 1.5% . A typical time course of MgSO4 application is given in Fig. Statistical analysis revealed a significant increase of median flow from a baseline value of 313.6 ± 77.8  to 375.3 ± 79.4 AU  as a surrogate marker for relative blood volume appears along with a higher blood flow, causing a larger shift of blood volume per time.2  and a strong negative correlation of SO2 with HCO3 . An overview of anesthesiological values is given in Table We identified two anesthesiological parameters that affected the O2C measurement values. We found a strong positive correlation between velo and FiOIn two patients, SEP monitoring was not possible due to a high impendance and internal system measurement error, most likely related to the skin flap size and retraction. In 8 of 12 patients, pathological SEP values correlated to an ischemia-related post-operative neurological deficit.Cerebral vasospasm was detected in 8/14 patients, however, only two out of these eight patients suffered from symptomatic vasospasm with an apparent ischemia as documented by CT and the corresponding neurological deficit. Thus, the rate of clinical relevant vasospasm causing a delayed cerebral ischemia was 2/14 (14%) in our patient group  succumbed to the severity of their SAH, which caused multiple infarctions, malignant brain edema and ultimately, transtentorial herniation of brain tissue leading to central dysregulation and death during their hospital stay. Complications occurred in 3 patients (21%). Two patients suffered from cerebral infarctions due to surgical manipulation of the recurrent artery of Heubner and perforators (No. 1 and 5). Patient No. 10 had a brain abscess, which was evacuated 23 days after clipping and treated with an abscess drainage and i.v. antibiotics.4. Analysis of possible confounding factors revealed a strong positive correlation between velo and FiO2, which is probably due to the measurement method of the O2C-System. One explanation of the negative correlation seen in SO2 and HCO3 might be that a reduction in capillary-venous oxygen saturation is associated with a reduction in partial venous oxygen pressure. This reduction could be part of the oxidative metabolism, which causes an increase of carbon dioxide. The latter is buffered by the carbonic acid – bicarbonate system and consequently, a higher HCO3 concentration is found.Based on our clinical observations over the past years, we wanted to test the hypothesis that early administration of magnesium sulfate increases local cerebral microcirculation in patients with SAH in this preliminary study. To achieve this, we used a novel combined laser-Doppler flowmetry and tissue spectrophotometry system. The intraoperative non-invasive real-time measurement of microcirculatory parameters revealed an increase in blood flow and blood cell velocity with a tendency of increase in capillary-venous oxygen saturation and decrease in the capillary filling pressures, indicating a higher local cerebral blood flow. This phenomenon was observed approximately 10–15 min after the early intravenous administration of MgSOMagnesium sulfate has neuroprotective properties such as relaxation of cerebral arteries and arterioles in a concentration-dependent manner. Studies suggest that it is capable to reverse postischemic cerebral vasospasm, and offers neuronal protection through direct metabolic depression of glucose, or blocking of excitatory neurotransmitters , 26. MagDrawbacks of the application of magnesium in humans are e.g. hypotension, bradycardia, loss of reflexes or respiratory depression , 29, 30.Magnesium can cross the blood brain barrier in humans and animals, however, serum levels cannot reliably be compared to the concentration of magnesium in the cerebrospinal fluid.Although there are several studies that suggest a neuroprotective effect during neurosurgical procedures associated with ischemia , three l4 is crucial, as the acute phase of SAH determines subsequent pathophysiological mechanisms such as early brain injury and the extent of cerebral vasospasm or delayed ischemic deficits at a later point in time (see below). Moreover, serum magnesium levels were not measured as study parameters in MASH-2, making comparison to the other RCTs difficult [There are several possible reasons for those results. First, comparisons in meta-analysis are confounded by the heterogeneity in methodology and patient groups. Examples are 1) initiation and timing of magnesium administration, 2) dose and concentration levels, 3) duration of administration, 4) no study information about the clinical correlation of hypoxemia, morphological changes in MRI/CT and angiographic vasospasm. The mean time from symptom onset to initiation of therapy was 31.7 h in IMASH and 33 h in MASH-2. In our opinion, the time of administration of MgSOifficult . The magifficult .4 was applied within a median time span of about 3 h after onset of symptoms. We regulated the infusion rate based on the MAP to maintain stable cerebral perfusion pressures. As the semiquantitative variables of the O2C system are not validated by invasive measurements of cerebral blood flow in this study, the relative increase in local cerebral blood flow cannot be depicted in absolute values. Even though we observed a delayed cerebral ischemia in 14% of our cases, and this rate is below the reported incidence of 30–40% in SAH patients, our vasospasm rate was 50% [In our patient group, MgSO was 50% . Therefo4 acts as a non-competitive inhibitor of the intracellular IP3-gate calcium channel and voltage-dependent calcium channels, it can intensify the vasodilatory effect of ketamine. Moreover, ketamine protects brain tissue by maintaining intracellular magnesium levels due to NMDA and quisqualate receptor blockade [Another important factor of this study is the comedication of esketamine in all of our patients. As an N-methyl D-aspartate (NMDA) receptor antagonist, ketamine is known to have a vasodilatory effect in cerebral blood vessels and can increase regional and global cerebral blood flow alike. There is evidence that this vasodilatation is calcium-mediated . As MgSOblockade , 34.The fact that augmentation of cerebral blood flow does not automatically convert into better clinical outcome of patients with post-SAH vasospasm has been under investigation since the results of the Clazosentan trials. Despite reversal of angiographic vasospasm after application of the selective endothelin(ET)-1 receptor antagonist, morbidities and functional neurological outcome remained unchanged . Other p4 application on cerebral microcirculation using non-invasive vascular real-time monitoring in patients with aneurysmal SAH. The system used is a novelty, as is combines both techniques, laser-Doppler flowmetry and tissue spectrophotometry, in one device. Although there is one previous study investigating the feasibility of this method in intracranial aneurysm surgery, it did not handle the scientific subject of magnesium application and moreover, continuous real-time monitoring was not performed [To the best of our knowledge, this work is the first study on the impact of early MgSOerformed .4 in a randomized, double-blinded design. Microcirculatory parameters as assessed by the O2C system are only of semiquantitative nature. Regarding the statistical calculation of O2C variables with a small sample size, an a priori power analysis could not be carried out due to the lack of reference values, which is another limiting factor of our study and the interpretation of results [3. Even though the system has the advantage of recording blood flow as well as metabolism modalities, the interaction of pathophysiological mechanisms and the disturbance of the blood-brain barrier as well as cerebral autoregulation can be confounders to our results.The data of this study are preliminary without a control group receiving placebo instead of MgSO results . We did 4. A randomized, double-blinded controlled trial is needed for the proof of concept.Future studies should deal with the exact concentration of MgSO4 in blood serum and CSF to determine the optimum rate and duration of early magnesium infusion for the prevention of cerebral vasospasm and the associated delayed neurological deficit. Non-invasive vascular neuromonitoring could be a useful tool to detect the impact on cerebral microcirculation to guide the application of MgSOThe early intravenous application of magnesium sulfate in patients with aneurysmatic subarachnoid hemorrhage affects local cerebral microcirculation. Our preliminary data using non-invasive continuous real-time monitoring suggests an increased cerebral blood flow. Further trials are needed to underline the potential benefit of the point in time, dosage and application rate of magnesium as well as the vascular neuromonitoring to prevent vasospasm and subsequently, a delayed ischemic neurological deficit.


Deep vein thrombosis (DVT) is one of the major complications of total joint arthroplasty (TJA). Chronic kidney dysfunction (CKD) has proven to promote a proinflammatory and prothrombotic state and is prevalent among patients undergoing TJA. The purpose of this study is to identify whether CKD increase the risk of DVT following TJA. In a retrospective study, 1274 patients who underwent primary TJA were studied. CKD is graded in 5 stages. Univariate and multivariate analysis were used to identify the association of CKD and its severity with postoperative DVT. There were 1139 (89.4%) participants with normal kidney function, 103 (8.1%) with mildly decreased kidney function, and 32 (2.5%) with stage 3 and 4 CKD. A total of 244 patients (19.2%) were diagnosed with DVT. Sixty-four patients (5.0%) developed symptomatic DVT. Advanced age, female gender, malignancy, and eGFR showed significant association with total DVT. BMI, thrombosis history, malignancy, and eGFR were associated with symptomatic DVT. After adjusting for age, gender, BMI, and malignancy, eGFR was found to be related to both total and symptomatic DVT. CKD is an important risk factor for both total and symptomatic DVT following TJA. Postoperative prophylaxis should be made a priority in this population. Total joint arthroplasty (TJA) is an effective surgical procedure which can improve the quality of life and function of patients affected by end-stage arthritis of the hip or knee , 2. OutcChronic kidney dysfunction (CKD) is a clinical situation with prevalence rising from 10% in 1994 to 13% in 2004 in the United States . It is e2, mildly decreased kidney function as eGFR between 60 and 89 mL/min per 1.73 m2, and stage 3 to 4 CKD as eGFR between 15 and 59 mL/min per 1.73 m2. eGFR is calculated using creatinine measurement, along with age, sex, and race. The equation is based on the data of 454 Chinese patients with CKD as follows [We conducted a retrospective analysis of the patients consecutively admitted for primary unilateral TKA and THA in our institution from October 2010 to August 2014. If patients received staged bilateral knee or hip surgeries during this period, only the first procedure was included. In addition, all THA were done using direct transgluteal approach. We excluded subjects with incomplete information, with severe organs insufficiency except kidney, or undergoing bilateral simultaneous surgery . The fol follows : (1)eGFRAll surgeries were performed by 2 experienced surgeons. All the patients received recommended thromboembolism prophylaxis regimen (low-molecular-weight heparin) and underwent unified rehabilitation program after surgery. All the patients received 0.3 mL  of low-molecular-weight heparin from the same company subcutaneously once daily. The dosage level used as prophylaxis is considered to be moderate. In addition to drug thromboprophylaxis, bilateral lower limbs of all patients were compressed by pressure pump rhythmically to prevent DVT starting on the first postoperative night.Routine venography of the operated lower limb was performed at 3–5 days after operation. For patients with contradictions to venography examination, color Doppler ultrasound was applied. Once confirmed by venography, color Doppler ultrasound, or symptoms of DVT, which is characterized by the presence of pain and swelling of the leg, skin discoloration, and a positive Homans' sign  or Neuhot-test. The association of CKD with total DVT and symptomatic DVT was investigated using logistic regression analysis after adjustment for age, gender, BMI, malignancy, hypertension, diabetes, thrombosis history, and smoking by using logistic regression analysis.Statistical analysis was performed using SPSS 19.0 system software . Numeric data are shown as mean ± standard deviation; categorical data are shown as numbers with percentages. Qualitative variables including gender, hypertension, insulin resistance, smoking, malignancy, heart disease, and thrombosis history were compared by a chi-square test. Continuous variables including age, BMI, and DVT were analyzed by the Student 2 (SD 52.3 mL/min per 1.73 m2). There were 1139 (89.4%) participants with normal kidney function, 103 (8.1%) with mildly decreased kidney function, and 32 (2.5%) with stage 3 and 4 CKD. The mean eGFR among the participants with stage 3/4 CKD was 43.0 mL/min per 1.73 m2 (SD 15.1 mL/min per 1.73 m2).A total of 1274 subjects (500 TKA and 774 THA) were included in this study. There were 870 females and 404 males. The mean age was 65.2 ± 12.7 years (range: 18–93 years). The mean eGFR was 144.6 mL/min per 1.73 mTwo hundred and forty-four patients (19.2%) with DVT were documented by venography or color Doppler ultrasound. Sixty-four patients (5.0%) developed symptomatic DVT within 30 days after surgery. There was no fatal pulmonary embolism (PE) as a result of the DVT. Patients with DVT had a greater mean baseline age, BMI, and higher prevalence of diabetes and hypertension than those without incident DVT.P < 0.001), female gender (P = 0.007), malignancy (P = 0.046), and eGFR (P < 0.001) showed significant association with total DVT. BMI (P = 0.012), thrombosis history (P < 0.001), malignancy (P = 0.035), and eGFR (P < 0.001) were associated with symptomatic DVT. Malignancy  and eGFR  were related to both total DVT and symptomatic DVT. After adjusting for age, gender, BMI, and malignancy  was found to be related to both total DVT and symptomatic DVT.According to univariate analysis , advancelignancy , eGFR (O2, the OR for total DVT for those with mildly decreased kidney function and stage 3/4 CKD patients were 1.03 and 2.68. The OR for symptomatic DVT for those with mildly decreased kidney function and stage 3/4 CKD patients were 2.82 and 3.55. For further examination of the relationship between kidney function and DVT, the predicted OR for DVT for those with eGFR of 75, 60, 45, and 30 mL/min per 1.73 m2 were 1.84, 2.68, 4.99, and 5.90, respectively, compared with individuals with eGFR of 90 mL/min per 1.73 m2.As shown in The aim of this study was to investigate the relationship between CKD and the incidence of postoperative DVT and to further determine its influence on the severity of this complication. We hypothesized that CKD patients have a higher risk of developing both symptomatic and asymptomatic DVT following TJA compared with patients without CKD. In this study, CKD was found to be an independent risk factor for DVT of patients undergoing TJA. Patients with stage 3/4 CKD had a 2.68-fold increased risk for DVT compared with those with normal kidney function, which was consistent with the data from previous studies. Using data of 19,000 middle-aged and elderly adults, Wattanakit et al.  reportedFor the first time, this study also investigated the influence of CKD on the severity of the DVT. Proximal DVT including the popliteal vein, femoral vein, and iliac vein thrombosis has been reported to propagate more often than distal DVT , always The mechanism explaining the greater risk for VTE in CKD remains unclear. Hypercoagulability can be potentially induced by the increased inflammatory state associated with CKD. It was reported that the levels of various cytokines, such as interleukin-6, are elevated . Adams eDespite the fact that our data was derived from a large retrospective study, several limitations still existed in our study. First, we only tested early postoperative DVT by using venography or color Doppler ultrasound, which may therefore lead to missing cases with DVT after discharge. However, it has been reported that more than 80% of DVT after TJA occurs within 3 days postoperatively . MoreoveCKD can increase the risk of both total and symptomatic DVT after TJA. Our analysis suggests that postoperative prophylaxis should be made a priority in patients with CKD especially stage 3/4 CKD.


Despite knowing that resveratrol has effects on blood vessels, blood pressureand that phytostrogens can also improve the endothelium-dependentrelaxation/vasodilation, there are no reports of reveratrol's direct effecton the endothelial function and blood pressure of animals with estrogendeficit .To verify the effect of two different periods of preventive treatment withresveratrol on blood pressure and endothelial function in ovariectomizedyoung adult rats. 3-month old female Wistar rats were used and distributed in 6 groups: intactgroups with 60 or 90 days, ovariectomized groups with 60 or 90 days, andovariectomized treated with resveratrol (10 mg/kg of body weight per day)for 60 or 90 days. The number of days in each group corresponds to theduration of the experimental period. Vascular reactivity study was performedin abdominal aortic rings, systolic blood pressure was measured and serumnitric oxide (NO) concentration was quantified. Ovariectomy induced blood pressure increase 60 and 90 days after surgery,whereas the endothelial function decreased only 90 days after surgery, withno difference in NO concentration among the groups. Only longer treatment(90 days) with resveratrol was able to improve the endothelial function andnormalize blood pressure. Our results suggest that 90 days of treatment with resveratrol is able toimprove the endothelial function and decrease blood pressure inovariectomized rats. Among them, we can mention its action on estrogen receptorα (ERα) and the reduction of oxidative stress.6In order to reduce some negative effects of estrogen deficiency, hormone replacementtherapy (HRT) is commonly indicated. However, studies indicate that this treatmentmay be associated with adverse cardiovascular events, increased risk of thedevelopment of breast cancer and deep vein thrombosis in women with a predispositionto these conditions.9In an attempt to find alternatives to HRT with fewer side effects, resveratrol has shown promising effect because of its similarity todiethylstilbestrol (a synthetic estrogen) and can be regarded as a phytoestrogen. Inaddition, resveratrol can exert its action on estrogen receptors and may then beregarded as a SERM (selective estrogen receptor modulator).4 and that studies indicate the effectof resveratrol on blood pressure and blood vessels,11 thereare not many reports of its direct effect on both the endothelial function and bloodpressure in animals with estrogen deficit only. Thus, the objective of this studywas to verify the effect of two different preventive treatment protocols withresveratrol on blood pressure and endothelial function in young ovariectomizedfemale rats.Despite knowing that both phytoestrogens and SERMs are reported in the literature asacute improvers of endothelium-dependent relaxation/vasodilationThe experimental protocol was performed in accordance with the guidelines of theBrazilian College for Animal Experimentation (COBEA) and was approved by theEthics Committee of the Federal University of Sao Carlos - UFSCar(2-043/2013).Rattus norvegicus albinis) female rats (90 daysold at the beginning of the experiment) were housed under controlled dark-lightcycles (14h/10h from 6:00 pm to 8:00 am) and temperature (22 ± 2 °C)receiving standard diet and water ad libitum for 60 or 90days.Sixty Wistar , ovariectomized - 60 days (OVX 60), ovariectomized + resveratrol -60 days (OVX + RES 60), intact - 90 days (INT 90), ovariectomized - 90 days (OVX90) and ovariectomized + resveratrol - 90 days (OVX + RES 90). The number ofdays in each group represented the duration of the experimental period. Theanimals in the intact groups received no intervention; the ovariectomized groupswere ovariectomized and treated with a 0.9% saline solution (0.1ml/100g of bodyweight per day) by gavage until the end of the experimental period. Those in theovariectomized + resveratrol group were ovariectomized and treated daily with asolution of 10mg/kg of body weight of resveratrol per day , also by gavage for 60 or 90 days. At the end of the experimentalperiod, the rats were anaesthetized with isoflurane and euthanized bydecapitation. Blood and aorta artery were collected for experimentalanalysis.12 two daysbefore the animals were killed by decapitation at the end of eachexperimental period. The average of four consecutive measurements was takenas the mean systolic blood pressure of each animal.Systolic blood pressure (SBP) was measured by tail-cuff plethysmography innon-anesthetized animals, as described elsewhere by Rodrigues etal.,13 The aortas were carefullydissected and mounted as ring preparations (≅4 mm in length) and placed inbath chambers (5 mL) containing Krebs solution at 37 °C  continuously bubbled with 95%O2 and 5% CO2, pH 7.4, in a Mulvany-Halpernisometric myograph  and recorded by aPowerLab8/SP data acquisition system . The aortic rings were submitted to a tension of 1.5 g, whichwas readjusted every 15 min for a 60-min equilibration period beforeaddition of the given drug. Experiments were conducted in aortic rings withintact endothelium and also in endothelium-denuded aortic rings. Endothelialintegrity was assessed by the degree of relaxation induced by1µmol/l acetylcholine (Ach) in the presence ofcontractile tonus induced by phenylephrine (0.1µM).The ring was considered as with intact endothelium if relaxation withacetylcholine was higher than 80%. In endothelium-denuded aortas, therelaxation to Ach was lower than 5%. After the endothelial integrity test,aortic rings were pre-contracted with phenylephrine(0.1µM). When the plateau was reached,concentration-effect curves to acetylcholine (0.1nM to 0.1mM) in intactendothelium aortic rings or to sodium nitroprusside (SNP) inendothelium-denuded aortic rings were constructed. The potency(pD2) and the maximal relaxant effect (ME) were measured.The thoracic aortas were isolated, cleaned of adherent connective tissues,and placed in Krebs solution, as described elsewhere.2-) and nitrate (NO3-), collectively known as NOx. The NO/ozonechemiluminescence method was performed using the NO Analizer 280i . The NOx concentration was corrected by the factorobtained by the quotient of the measured NOx and expectedconcentrations of sodium nitrate , yielding a standard curve.14Serum nitric oxide levels were obtained by measuring the serum concentrations ofits stable end-products nitrite  was verified by the Kolmogorov-Smirnov test. Differences in meansamong the groups in each experimental period were compared by one-way analysisof variance (ANOVA). When significance was indicated, a Newman-Keuls post hocanalysis was used with statistical significance set at p<0.05 .Acetylcholine, phenylephrine and sodium nitroprusside, were purchased fromSigma-Aldrich . Resveratrol was purchased from CaymanChemical .In In The main finding of this study was that the treatment with resveratrol for 90 daysprevented the changes in blood pressure and endothelial function induced by estrogendeficiency. In this trial period, we have verified that ovariectomy was effective toinduce endothelial dysfunction and elevation of blood pressure. The 60-day estrogendeficiency was not enough to induce changes in endothelial function in aortic ringof rats; however, this period was enough to increase the blood pressure value andresveratrol treatment did not modify endothelial function and blood pressure. 15 whotreated Wistar ovariectomized rats with frozen grape powder (in which one of thecomponents is resveratrol). Still, the authors suggest that the effect ofovariectomy on blood pressure is induced by elevation in oxidative stress triggeredby estrogen deficit and the effect of frozen grape powder may be related to itsstrong antioxidant effect,15 afeature also verified with resveratrol.16The increase in blood pressure due to ovariectomy and its subsequent reduction in thegroup treated with resveratrol in the 90-day experimental protocol also was observedpreviously by Patki et al,10 in stroke-prone spontaneouslyhypertensive ovariectomized rats, supplemented dietetically with 5mg/kg of bodyweight of resveratrol. However, these authors indicate that the effect of thesubstance on the endothelium is through the increased bioavailability of NO, asreported by other studies18, a fact not confirmed by ourstudy.The decrease in endothelium-dependent relaxation in aortic rings and consequentincrease with the treatment with resveratrol in the 90-day experimental protocolagrees with the results presented by Mizutani and colleaguesAn interesting result was that only prolonged resveratrol treatment (90 days) wasable to improve the endothelial function and normalize blood pressure. Sixty daysafter surgery, no endothelium dysfunction was verified, and no improvement wasinduced by resveratrol. Thus, our result suggests that the improvement in theendothelial function induced by resveratrol normalizes the blood pressure in OVXrats by a NO independent mechanism. 4 point out that inaddition to NO there are other endothelium factors which can induce vasodilation,including the endothelium-derived hyperpolarizing factor(EDHF). Furthermore, Dolinsky et al11 suggested that the effect of resveratrol on bloodpressure can be different in accordance to the experimental model used, and thesedifferences could result from the distinct mechanisms of hypertension developing.Considering that there are few studies that have evaluated the effect of estrogendeficiency on blood pressure and endothelial function in young/adult animal models,the results of this study represent an important contribution of resveratrol as apreventive treatment for postmenopausal cardiovascular effects.Vanhoute et alOur results suggest that ninety days of treatment with resveratrol (10 mg/kg bodyweight per day) is able to normalize the endothelial function and blood pressure ofovariectomized rats via a NO-independent mechanism.


The purpose of this retrospective study is to clarify the difference in plantar pressure distribution during walking and related patient-based outcomes between forefoot joint-preserving arthroplasty and resection-replacement arthroplasty in patients with rheumatoid arthritis (RA).Four groups of patients were recruited. Group1 included 22 feet of 11 healthy controls (age 48.6 years), Group2 included 36 feet of 28 RA patients with deformed non-operated feet , Group3 included 27 feet of 20 RA patients with metatarsal head resection-replacement arthroplasty , and Group4 included 34 feet of 29 RA patients with metatarsophalangeal (MTP) joint-preserving arthroplasty . Patients were cross-sectionally examined by F-SCAN II to evaluate walking plantar pressure, and the self-administered foot evaluation questionnaire (SAFE-Q). Twenty joint-preserving arthroplasty feet were longitudinally examined at both pre- and post-operation.st MTP joint, Group4 showed higher pressure distribution (13.7%) than Group2 (8.0%) and Group3 (6.7%) (P<0.001). In the 2nd-3rd MTP joint, Group4 showed lower pressure distribution (9.0%) than Group2 (14.5%) (P<0.001) and Group3 (11.5%) (P<0.05). On longitudinal analysis, Group4 showed increased 1st MTP joint pressure  and decreased 2nd-3rd MTP joint pressure  distribution. In the SAFE-Q subscale scores, Group4 showed higher scores than Group3 in pain and pain-related scores  and in shoe-related scores .In the 1st MTP joint and lower 2nd-3rd MTP joint pressures than resection-replacement arthroplasty, which were associated with better patient-based outcomes.Joint-preserving arthroplasty resulted in higher 1 Rheumatoid arthritis (RA) is frequently associated with painful foot deformities, which is reported in 75% of patients within four years of diagnosis, increasing to approximately 90% during the course of the disease , 2. ThesThere is a trend toward joint-preserving arthroplasty instead of conventional resection-replacement arthroplasty of forefoot deformities with recent advances in the pharmacological treatment of RA , 14. MorThe purpose of this retrospective study was to evaluate and compare the effects of both forefoot resection-replacement arthroplasty and joint-preserving arthroplasty on walking plantar pressure distribution and its relevance to patient-based outcomes in RA.Four groups of patients were recruited from April 2012 to December 2015. The recruiting criteria was all of the RA patients who underwent forefoot arthroplasty during this period, and RA patients without operation who had forefoot symptoms. Group1 included 22 feet of 11 healthy controls (age 48.6 years), Group2 included 36 feet of 28 RA patients with symptomatic deformed non-operated feet , Group3 included 27 feet of 20 RA patients with metatarsal head resection-replacement arthroplasty , and Group4 included 34 feet of 29 RA patients with metatarsophalangeal joint-preserving arthroplasty  were enrolled. The operation procedures were selected at the discretion of each senior rheumatoid surgeon and performed from January 2000 to December 2015. In operated patients, postoperative evaluation was performed only for those who completed more than 6 months of follow-up.2 cells), which has relatively high resolution compared to other foot pressure measurement systems [st MTP joint, 2nd-3rd MTP joint, 4th-5th MTP joint, and heel) were defined by matching with each patients’ standing feet X-rays as shown in Walking plantar pressures were evaluated using the F-SCAN II system  as previously described . Briefly systems . All sub systems , and regAt the same time as the F-SCAN II assessment, patients were radiographically evaluated and asked to answer the postoperative SAFE-Q. The main body of the outcome instrument consists of 34 questionnaire items, which provide five subscale scores , and each subscale score ranges from 0 to 100 points .The clinical characteristics of each group are shown in This study was conducted at single center and in accordance with the ethical standards of the Declaration of Helsinki which was approved by the Institutional Ethics Review Board . Written, informed consent was obtained from each patient.Representative radiographs and plantar peak pressure distributions of each groups are shown in As for the joint-preserving arthroplasty, most patients  were treated by the combination of modified Scarf osteotomy of the hallux with the medial longitudinal approach  and off-In both groups, proximal interphalangeal (PIP) joint resection arthroplasty of the lesser toes with a dorsal approach was added if patients had rigid flexion deformities of the PIP joint, and the lesser toes were temporarily fixed with 1–1.2-mm-diameter Kirschner wires for 2–3 weeks . After rU test, or the chi-squared test, as appropriate. Changes in each score from before to after surgery at specified time points within each study group were compared using the nonparametric Wilcoxon signed-rank test. Results are expressed as means ± standard error. A P value < 0.05 indicated significance. All tests were performed using IBM SPSS Statistics version 22 software .Differences between the groups were tested using analysis of variance (ANOVA), the Mann-Whitney Patients’ clinical characteristics and operation-related outcomes of each group when performing F-SCAN II are shown in st MTP joint pressure. As for radiographic parameters, the HV angle  and the M1M5 angle  were significantly smaller in the joint-preserving group than in the resection-replacement group  are shown in st MTP joint, 2nd-3rd MTP joint, 4th-5th MTP joint, and heel) are shown in st MTP joint pressure  and higher 2nd-3rd MTP joint pressure . Compared to the deformed-RA group, the resection-replacement group showed similar 1st MTP joint pressure (8.0% vs. 6.7%), but lower 2nd-3rd MTP joint pressure . Finally, compared to the resection-replacement group, the joint-preserving group showed higher 1st MTP joint pressure  and lower 2nd-3rd MTP joint  and 4th-5th MTP joint  pressures. No significant differences were observed in heel pressure between the groups.Peak pressure distributions (%) of the ROIs  and decrease in 2nd-3rd MTP joint  and 4th-5th MTP joint  pressure distributions after the operation Click here for additional data file.