Hypertensive syndromes in pregnancy are one of the leading causes of obstetric admissions into intensive care units. They are related to changes in the central nervous system caused by a decrease in cerebral perfusion pressure, indicated by an increase in intracranial pressure. These changes in pressure usually result from acute injuries or a decrease in the mean arterial pressure due to iatrogenic action or shock. However, other vascular disorders may contribute to similar occurrences.A 15-year-old girl was admitted to our hospital complaining of severe headaches since the eighth month of pregnancy, and presented with an arterial blood pressure of 180/120 mmHg. The diagnostic hypothesis was pre-eclampsia. Our patient's blood pressure levels remained elevated, and she was submitted to a cesarean section. After the procedure, she was referred to our infirmary, presenting with a blank distant look and with no interaction with the environment, dyslalia, and labial and upper and lower right limb paresis. She was confused and unable to speak, but responded to painful stimuli as she conveyed abdominal pain at superficial and deep palpation. The hypothesis of post-partum psychosis was suggested. She was then transferred to our intensive care unit, maintaining an impassive attitude in bed but reacting to external stimuli. Results of a computed tomography scan revealed ischemic infarction of the territory of her left middle cerebral artery. A selective cerebral arteriography showed bilateral occlusion of her internal carotid artery in the intracranial position, prebifurcation and angiodysplasia in the cervical segments of her internal carotid artery. Sixteen days after hospital admission, our patient died.This data shows the need for careful monitoring of hypertensive syndromes in pregnancy cases, especially in cases with a history of chronic hypertension or with vascular alterations, It also highlights the need for constant supervision of blood pressure levels during the use of anti-hypertensive medications. Cardiovascular diseases during pregnancy are represented primarily by gestational hypertension syndromes and are an important cause of maternal morbidity, accounting for about 20-50% of obstetric admissions in the intensive care unit, and 15% of gestational deaths in Brazil [Besides general systemic alterations, hypertensive syndromes in pregnancy (HSP) are related to changes in the central nervous system caused by the decrease of the cerebral perfusion pressure, indicated by the increase of the intracranial pressure. This can result from acute injuries or a decrease in the mean arterial pressure (MAP) due to iatrogenic action or shock. However, other vascular disorders may contribute to similar occurrences. The nervous system maintains cerebral autoregulation as a response mechanism to alterations in blood pressure levels. This adjusts the balance between cerebral perfusion pressure and cerebrovascular resistance, contributing to the perfusion of the nervous system, and also responsible for the balance of blood flow to vital organs .In the current study we present the case of a pregnant woman with altered blood pressure levels, signs of loss of cerebral autoregulation and impairment of cerebral perfusion pressure, related to the manipulation of MAP and previous presence of carotid angiodysplasia.A 15-year-old girl was admitted to our hospital complaining of severe headaches since the eighth month of pregnancy, which had worsened in the last five hours. The following information was observed in the prenatal card: G1P0A0; gestational age: 37 weeks ; type O+ blood and negative serology. On examination our patient presented an arterial blood pressure of 180/120 mmHg, her uterine cervix was 20% effaced, with impervious external orifice and cephalic presentation. The diagnostic hypothesis was pre-eclampsia and routine investigations were requested to diagnose the HSP. After the tests, the diagnostic hypothesis changed to gestational hypertension. As our patient continued with elevated blood pressure levels, she was submitted to a cesarean section on the fourth day in hospital, delivering a male live baby with no intercurrences. After the procedure, she was referred to our infirmary, presenting a blank distant look and with no interaction with the environment. On examination she presented with dyslalia, and labial and upper and lower right limb paresis. During an examination six days after hospital admission, our patient was confused and unable to speak, but responded to painful stimuli as she conveyed abdominal pain at superficial and deep palpation. Moreover, she had a hematoma on the upper region of the surgical wound and physiological lochia. The hypothesis of post-partum psychosis was suggested and a careful neurological evaluation requested. She was administered the following drugs in hospital: nifedipine 1 mg, methyldopa 500 mg, 750 mg paracetamol, betamethasone, oxytocin, tenoxicam, promethazine, diclofenac sodium, cephalexin, and haloperidol. She was then transferred to the teaching hospital on the same day, and admitted to our intensive care unit, maintaining an impassive attitude in bed but reacting to external stimuli. She also emitted incomprehensible sounds, presented a blank look, with upward conjugated deviation of the eyes and mydriatic pupils reactive to light. She had Glasgow Coma Scale (GCS) score of nine points (2 +5 +2). Our patient was then submitted to orotracheal intubation with mechanical ventilation and central venous access through her right internal jugular vein, in addition to continuous sedation. Computed tomography (CT) of her skull and pelvis were requested. Results revealed tomography findings consistent with ischemic infarction of the territory of her left middle cerebral artery, but no pelvic alterations were observed. Our patient showed progressive worsening of the neurological symptoms, hyperthermia, tonic-extensor crisis, difficulty in breathing and scored four points in the GCS. A repeat skull CT revealed ischemic lesions in the mean cerebral system affecting her basal ganglia and parietal lobe, with proper filling of venous sinuses and no signs of meningeal inflammation. During this period, her blood pressure levels remained elevated (MAP 140-150 mmHg) and refractory to medication. In addition, our patient presented with neuropsychomotor agitation and periods of tachycardia and systemic arterial hypertension alternating with bradycardia and normotension. An urgent selective cerebral arteriography was requested; this showed bilateral occlusion of her internal carotid artery in the intracranial position, pre-bifurcation and angiodysplasia in the cervical segments of the internal carotid artery. Sixteen days after hospital admission, there was a worsening of our patient's condition and she died. Brain death as a consequence of bilateral obstruction of the internal carotid was certified as the cause of death.In this case, our patient presented with elevated blood pressure levels and had an initial diagnostic of HSP. Although hypertension is one of the parameters for the diagnosis of HSP, other aspects must be considered; for example, the development of brain alterations, frequent in severe cases of HSP . HoweverBrain alterations are related to changes in MAP, but when they exceed the levels of regulation they are associated with a reduction of cerebral blood flow , being dAnother diagnostic hypothesis related to the neurological alterations presented was post-partum psychosis. About 0.1-0.2% of psychiatric disorders during the post-partum period are represented by psychosis, characterized by the sudden onset of periods of psychotic mood with serious mental disorders within two to three weeks of birth. The classical symptoms are mental confusion, psychomotor agitation, anxiety and insomnia, evolving to manic, melancholy or even catatonic forms . DespiteCarotid angiodysplasia was diagnosed by angiography as the underlying disease. Vascular malformation or angiodysplasia is characterized by endothelial hyperplasia and can be classified as hemangioma or as vascular malformation itself. Histologically, hemangiomas are characterized by endothelial hyperplasia during the proliferative phase, and by fibrosis, fatty infiltration and cell decrease in the involution phase. They are not present at birth, developing during the first months of life, and in 95% of cases they undergo a regression process that can be short or extend until the age of ten. As for malformations, the lesions are present at birth, grow at the same rate as the body and do not regress spontaneously. They consist of abnormal collections of blood vessels with the endothelium preserved and can be subdivided into arterial, venous and lymphatic vessels or a combination of them all ,9. AlthoThe present study demonstrated a case of a hypertensive pregnant patient with carotid angiodysplasia and decompensation of cerebral autoregulation possibly caused by the use of anti-hypertensive drugs. This data shows the need for careful monitoring of HSP cases, especially in cases with a history of chronic hypertension or with vascular alterations, as well as constant supervision of the blood pressure levels during the use of anti-hypertensive medications.Written informed consent was obtained from the patient's Father for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no competing interests.VRP made significant contributions to the conception and acquisition of the data and was engaged in the design of the present study. LPR and CSOG participated in the sequence alignment and drafted the manuscript. BBT participated in the design and coordination of the study. MAR and RRMC were involved in drafting the manuscript and revising it critically for important intellectual content, providing general supervision for the research group and approved the final version to be published. All the authors read and approved the final manuscript.


This randomized controlled trial aimed to evaluate whether the serum procalcitonin (PCT) level can be utilized to guide the use of antibiotics in the treatment of acute exacerbations of asthma.A total of 293 consecutive patients with suspected asthma attacks from February 2005 to July 2010 participated in this study. 225 patients completed the study. Serum PCT levels, and other inflammatory biomarkers of all patients were measured. In addition to the standard treatment, the control group received antibiotics according to the attending physicians’ discretions, while the patients in the PCT group were treated with antibiotics according to serum PCT concentrations. Antibiotics usage was strongly discouraged when the PCT concentration was below 0.1 μg/L; discouraged when the PCT concentration was between 0.1 μg/L and 0.25 μg/L; or encouraged when the PCT concentration was above 0.25 μg/L. The primary endpoint was the determination of antibiotics usage. The second endpoints included the diagnostic accuracy of PCT and other laboratory biomarkers the effectiveness of asthma control, secondary ED visits, hospital re-admissions, repeated needs for steroids or dosage increase, needs for antibiotics, WBC count, PCT levels and FEV1%.2 = 21.97, p < 0.001. RR = 0.561, 95% CI 0.441-0.713). PCT and IL-6 showed good diagnostic significance for bacterial asthma . The degrees of asthma control in patients were categorized to three levels and were comparable between the two groups at the six weeks follow-up period . There were no significant difference regarding other secondary outcomes (p > 0.05).At baseline, two groups were identical regarding clinical, laboratory and symptom score. Probability of the antibiotics usage in the PCT group (46.1%) was lower than that in the control group (74.8%) (χThe serum PCT concentration can be used to effectively determine whether the acute asthma patients have bacterial infections in the respiratory tract, and to guide the use of antibiotics in the treatment of acute asthma exacerbations, which may substantially reduce unnecessary antibiotic use without compromising the therapeutic outcomes.ICTRP ChiCTR-TRC-12002534 Acute attacks of asthma are episodes that occur suddenly and may also occur repeatedly over time. The attacks seriously disturb the patient’s daily and work life, which impose great burdens on the family and the society. There are various causes for acute asthma, including allergen provocation, drugs, respiratory viruses, bacterial infections and so on. Since bacterial infection seems to only play a minor role in acute exacerbations of asthma, guidelines for asthma management do not recommend routine use of antibiotics . The majProcalcitonin (PCT) is the prehormone of calcitonin. The serum PCT level significantly increases in patients with bacterial infections but not viral infection or other inflammatory diseases, granting the PCT test high potential in discriminating bacterial and non-bacterial infections -5. There2 saturation <95%, a peak expiratory flow (PEF) at randomization ≤80% of their known best (within the last 12 months) or, in the absence of this information, of their predicted PEF [From February 2005 to July 2010 in the emergency department of the fifth people’s hospital of Shanghai, 293 suspected acute exacerbation of asthma patients were screened for eligibility to participate in this study. Of these, 265 patients meeting the Bronchial Asthma Guide were eligible and 255 patients completed the study, including 123 male patients and 132 female patients. Patients were eligible for the intervention if they met all the following criteria: 1) ≥ 18 years old; 2) has any, or all, of the following clinical features as defined by the Global Initiative for National Asthma (GINA) Guidelines: dyspnea, wheeze, acute cough, increased work of breathing, increased requirement for beta2-agonist from baseline use, OWe conducted a randomized, controlled trial. All eligible patients were assigned to either the PCT-guided antibiotics therapy group or the control group, in which the attending physicians decide the use of antibiotics according to usual practice. The flowchart of patients was summarized in Figure We appointed an independent investigator team blinded to the group assignment to monitor the adherence to the protocol, the safety and efficacy of the intervention, as well as primary and secondary outcomes during the six-week follow-up period. All patients, laboratory technicians, investigators and research designers were blinded to patient assignments until the data analysis was completed. There were no protocol violations during the study.1% were assessed.Our primary endpoint was the use of antibiotics, which was evaluted by the antibiotic prescription rate and the relative risk of antibiotic exposure in patients with acute exacerbations of asthma. The secondary endpoints were patients’ clinical, laboratory, and lung function outcomes at the follow-up visit (6 weeks). During the six-week follow-up period, secondary ED visits, hospital re-admissions, repeated needs for steroids or dosage increase, needs for antibiotics, white blood cell count (WBC), PCT levels and FEV1) was collected before and after treatment. The symptom scores of asthma were also recorded. The patients were categorized into mild, moderate, and severe subgroups based on the severity level of their asthma, according to which antibiotics use was analyzed. The patients were re-categorized during the six-week follow-up period to assess the asthma control.The serum PCT tests were done using a time-resolved amplified cryptate emission (TRACE) technology assay  with a functional assay sensitivity of 0.06 g/L, about four-fold above the mean normal PCT level. And several laboratory parameters of the patients, including the levels of high sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), as well as WBC, were measured and collected. Arterial blood gas analysis was also performed on all patients. The usage of antibiotics in two groups was recorded. Forced expiratory volume in one second  of 65%.2 test, two-sampled t test, Mann–Whitney U test, as appropriate. Correlation analyses of the level of serum PCT and levels of hsCRP, IL-6, TNF-α and WBC were performed using Spearman rank. A p value less than 0.05 was defined as significant. Data were analyzed using statistical software .Discrete variables are expressed as counts (percentages) and continuous variables as mean ± SD. Comparability of groups was analyzed by χThe patients were aged between 19 and 78 years old and the average age was 53 ± 15 years old. Detailed baseline characteristics of the studied population are presented in Table 1 score of both groups was significantly improved after treatment compared with that before treatment. Thirty-two (25.0%) patients in PCT group received corticosteroids therapy, while 36 (28.3%) patients received corticosteroids therapy in the control group . Eight (6.3%) patients in PCT group and nine (7.1%) patients in the control group  received mechanical ventilation treatment.The FEVp < 0.05). Other inflammatory parameters that we tested showed no significant difference between patients with mild-moderate asthma and severe-critical asthma. Spearman analysis showed that the serum PCT level didn’t correlate with the level of any laboratory biomarkers except for IL-6 .Table 2 = 21.97, p = 0.000, RR = 0.561, 95% CI 0.441-0.713). Table p <0.01). There was no significant statistical difference in the usage of antibiotics between patients with severe and critical asthma in the two groups.As shown in Table 2 =1.62, p = 0.45)  of 65% on asthma control. Second, our results should not be generalized to other settings such as hospital-acquired pneumonia and chronic obstructive pulmonary disease. Third, we did not conduct a formal cost-benefit study. Larger clinical trials are needed to explore the overall clinical and economic impact of the reduction of exposure to antibiotics in asthma patients.The authors declare that they have no competing interests.LW carried out the investigation, participated in study design and drafted the manuscript. YL and ZY carried out the investigation, participated in the laboratory measuring. XJ participated in the study design, carried out the investigation. LG participated in the design of the study and performed the statistical analysis. YCH carried out the investigation, participated in the laboratory measuring. TJG conceived the idea of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.Co-first author Wei Long.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/596/prepub


The authors present a novel approach to nonresectional therapy in major hepatic trauma utilizing intraabdominal perihepatic vacuum assisted closure (VAC) therapy in the porcine model of Grade V liver injury.A Grade V injury was created in the right lobe of the liver in a healthy pig. A Pringle maneuver was applied  and a vacuum assisted closure device was placed over the injured lobe and connected to suction. The device consisted of a perforated plastic bag placed over the liver, followed by a 15 cm by 15cm VAC sponge covered with a nonperforated plastic bag. The abdomen was closed temporarily. Blood loss, cardiopulmonary parameters and bladder pressures were measured over a one-hour period. The device was then removed and the animal was euthanized.Feasibility of device placement was demonstrated by maintenance of adequate vacuum suction pressures and seal. VAC placement presented no major technical challenges. Successful control of ongoing liver hemorrhage was achieved with the VAC. Total blood loss was 625 ml (20ml/kg). This corresponds to class II hemorrhagic shock in humans and compares favorably to previously reported estimated blood losses with similar grade liver injuries in the swine model. No post-injury cardiopulmonary compromise or elevated abdominal compartment pressures were encountered, while hepatic parenchymal perfusion was maintained.These data demonstrate the feasibility and utility of a perihepatic negative pressure device for the treatment of hemorrhage from severe liver injury in the porcine model. This is a proof-of-concept investigation using the swine model of grade V exsanguinating liver trauma. The aim of the investigation was to determine if the internal application of a modified vacuum-assisted closure device to the injured liver could control hemorrhage.• High grade, exsanguinating liver injury requires rapid control.• Application of a negative pressure device to exsanguinating liver injury is a variant of "packing" that may offer several advantages.• In this proof-of-concept investigation using an animal model of liver trauma, application of a negative pressure device rapidly controlled hemorrhage.The liver is the most commonly injured intraperitoneal organ . TreatmeShort of formal resection, adequate debridement of non-viable hepatic parenchyma is generally advocated and performed, since it is thought to be vital in minimizing septic complications . Liver tPerihepatic packing has been utilized to treat liver injury since the Second World War. Success in civilian trauma has revitalized this modality as a temporizing measure to control hemorrhage, particularly in cases complicated by the deadly triad of hypothermia, hypocoagulability and acidosis -11. SimiAdjuncts to this approach including angiography with selective vessel embolization, computed tomography directed drainage of abscess or biloma, and endoscopic retrograde cholangiopancreatography with biliary stenting have recently been integrated into the nonoperative management strategy of liver trauma with encouraging results .Liver packing, although a life-saving maneuver is not without complications. Placing sponges between the liver and diaphragm to tamponade bleeding compromises venous return, impairing cardiopulmonary function in patients with already limited reserve. Re-bleeding and intraabdominal abscess formation after pack removal has also been described. In patients who require massive resuscitation, visceral edema and elevated intraabdominal pressures may lead to subsequent abdominal compartment syndrome with the use of perihepatic packing.Abdominal compartment syndrome may cause compromise of cardiac performance and respiratory function, renal function, splanchnic perfusion, and may impair cerebral perfusion -17. The Vacuum assisted closure (VAC), also referred to as negative pressure wound therapy, has gained wide acceptance for use in the management of a range of acute and chronic wounds as well as for temporary abdominal closures in cases of abdominal compartment syndrome and damage control laparotomy ,21. VAC The porcine or swine model has been used extensively to simulate, experimentally, human liver injury -38. A reGiven the complications associated with traditional hepatic packing, the authors present a novel approach to nonresectional therapy in major hepatic trauma utilizing intraabdominal perihepatic vacuum assisted closure or Liver VAC (L-VAC) therapy in the porcine model. We propose this as a new method for control of hepatic hemorrhage without concomitant cardiopulmonary compromise or development of abdominal compartment syndrome.All experimental methods were conducted in accordance with standard and humane animal laboratory regulations. The study protocol was approved by the Institutional Animal Care and Use Committee at the Kansas University Medical Center.A healthy, female, 32kg Chester White pig was fasted overnight. The animal was then sedated with intramuscular Telazol (5mg/kg) and Rompun (2mg/kg). General anesthesia was then maintained by inhalational Isoflurane after the animal was orotracheally intubated. The right femoral artery and vein were cannulated via cutdown technique and connected to a continuous monometer. Monitoring included heart rate, blood pressure, hemoglobin-oxygen saturation urine output, end-tidal carbon dioxide or partial pressure of carbon dioxide, respiratory rate, central venous pressure, blood pressure, core temperature, and bladder pressure. Baseline labs consisting of hemoglobin and hematocrit, arterial blood gases, and arterial lactate were obtained from the arterial line and measured at 30 minute intervals throughout the experiment. Intravenous infusion of Lactated Ringer’s crystalloid was used as needed  to maintain hemodynamic stability.A generous midline laparotomy incision was made sharply and entrance to the abdomen was obtained. The bladder was cannulated with a suprapubic catheter and placed to dependent drainage after measurement of bladder pressure. The portal triad structures were mobilized and isolated with a Rumel tourniquet. The right medial lobe of the liver was selected for the site of injury and retracted by manual elevation Figure . After pThe abdomen was temporarily closed with a second negative pressure device. The intraabdominal contents were covered with a large 10cm ×10cm plastic drape. A large black abdominal sponge was placed over the drape, followed by the suction pad. This negative pressure device was connected to 70cm of water suction . At initial device placement there was 75ml of immediate blood return. Continued losses after applying the device to suction were negligible over the next 60 minutes. Immediate blood loss after removal of the device was 270 ml (8.4 ml/kg) for a total blood loss of 625ml (19.5 ml/kg) for the entire procedure. Hemoglobin counts were 12.2 g/dl, 11.5g/dl, and 9.6g/dl at 0, 30, and 60 minutes, respectively. No blood products were administered.Figure Initial and serial arterial lactate levels were 1.1, 5.8, and 6.8mol/l at 0, 30, and 60 minutes, respectively.2O at 0, 30, and 60 minutes, respectively. Urine output was 73 ml (2.2ml/kg) at 60 minutes.The bladder pressure was 12, 17, and 12 cm HMean arterial pressure (MAP) and systolic blood pressure (SBP) averaged 79 mmHg and 121 mmHg, respectively, during L-VAC compression (using 51 mmHg suction) over one hour. Mean hepatic perfusion pressure (MAP minus L-VAC compression pressure) averaged approximately 28 mmHg and the mean systolic perfusion pressure (SBP minus L-VAC compression pressure) averaged approximately 70 mmHg  and maintained at 70 cm water (51 mmHg) without evidence of vacuum leak. The device was easily deployed with readily available materials, a strength of current therapeutic modalities including perihepatic packing with laparotomy sponges.Application of this device in clinical practice may be affected by minor anatomic differences between the swine and humans. Specifically, mobilization of the phrenohepatic and triangular ligaments may be necessary to allow for adequate sealing of the device. The author’s personal experience in human cadavers has shown favorable results with no technical difficulties. Given the initial learning curve with this novel application of the L-VAC device, it is the author’s recommendation that clinicians practice in a cadaveric model prior to attempting operative placement in the acute traumatic setting. Careful patient selection is also warranted based on injury location. Injuries to the more medial portions of the liver may impair sealing of the device.The device demonstrated successful control of ongoing hemorrhage. Significant bleeding was encountered after creation of the injury and prior to control of the porta hepatis, as well as after final removal of the device. Ongoing blood losses after application of the L-VAC device to suction were 75ml, initially, after which they became negligible over the remainder of the 60 minute experiment. Total blood loss was 625 ml (20ml/kg). This corresponds to class II hemorrhagic shock in humans. While no controls were performed comparing this novel method to traditional therapies, the amount of blood loss with the L-VAC compares favorably to that reported in the current literature. Reported mean estimated blood losses approach 3,700ml in swine with similar injures treated with packing and hemostatic bandages.Hepatic parenchymal perfusion was maintained by keeping L-VAC pressures well below the mean and systolic blood pressure throughout the experiment Figure . The livNo post-injury cardiopulmonary compromise was encountered during use of the L-VAC. Venous return to the heart was unaffected as central venous pressures and SBP remained within normal limits throughout the experiment and serum lactate levels elevated in proportion to the level of hemorrhage.Traditional packing methods rely on compressing the liver between the abdominal wall and the spine for hemostasis. Pressure is also directed posteriorly toward the retroperitoneum and the retrohepatic vena cava. This impediment of venous return is poorly tolerated in the hypovolemic patient and may exacerbate already compromised cardiac output. Given the circular geometry of the L-VAC device, the force vectors are directed inward toward the liver parenchyma. This allows for pressure application to the injured organ without a concomitant decrease in venous return, a distinct advantage over traditional perihepatic packing.Perihepatic packing has also been shown to result in pathologic intra-abdominal hypertension . In thisThe applicability of the swine model for human liver injury has been well described in the literature. This model, however, is not without its limitations. The compression of the portal inflow during creation of the liver laceration minimized initial blood losses. In the clinical setting, uncompensated hypovolemic shock may result in the ‘bloody vicious cycle’ of hypothermia, acidosis, and coagulopathy. Obtaining hemostasis from bleeding viscera in the face of these physiologic derangements can be quite challenging. In this regard, the model used for this experiment was artificial given that the pig was well compensated hemodynamically, with functioning coagulation cascades. However, given the mechanism of action of the VAC device, the authors contend that L-VAC placement may be the ideal therapy for control of hemorrhage in such cases. Consideration is being given to repeating this experiment in animals that are hypothermic and coagulopathic.Future areas of investigation should be directed toward comparing this innovative method to well-established therapies such as packing, mesh wrapping, and application of hemostatic agents.In summary, these data demonstrate the feasibility and utility of a perihepatic negative pressure device for the treatment of hemorrhage from severe liver injury in the porcine model. This method is potentially applicable in the clinical setting and may afford advantages over traditional damage control procedures such as perihepatic packing.The authors declare that they have no competing interests.BT initially conceived the study idea. BT, CE, and MM were all involved in the study design and procedure. CE drafted the initial case report. Case report revisions and final report submission were all conducted by BT, CE, MM. All authors read and approved the final manuscript.This study was funded in part by funds from the Kansas University Medical Center, and the Wesley Medical Center Trauma Research Fund.This study was approved for implementatin by the IACUC of the Kansas University Medical center.


One of the observer errors associated with blood pressure (BP) measurement using a mercury sphygmomanometer is end digit preference (EDP) which refers to the occurrence of a particular end digit more frequently than would be expected by chance alone. Published reports, mainly from outside Africa, have shown a high prevalence ranging from 22 to 90% of end digit zero in BP readings taken by healthcare workers (HCWs). This study examined the prevalence of EDP and patients’ and physicians’ characteristics influencing the occurrence of EDP.A retrospective review was undertaken of BP readings of 114 patients seen over a two-month period at our hypertension specialty clinic.p < 0.001; DBP: 98.5 vs 64.3%, p < 0.001). Among the physicians, the consultant staff displayed the least preference for end digit zero compared to resident doctors. There was no statistically significant difference in gender, age, weight, height and BMI of those with BP readings with end digit zero compared with those with non-zero end digits.Nurses and physicians displayed a high frequency of preference for end digit zero in systolic blood pressure (SBP) and diastolic blood pressure (DBP) readings. The preference for end digit zero was, however, higher for nurses than for physicians (SBP: 98.5 vs 51.2%, The high prevalence of EDP for zero argues for the training, retraining and certification of HCWs in BP measurement and the institution of a regular monitoring and feedback system on EDP in order to minimise this observer error. The toxicity of mercury notwithstanding, the mercury sphygmomanometer remains the most widely used apparatus for blood pressure (BP) measurement in Nigeria.20End digit preference (EDP) refers to the occurrence of a particular end digit more frequently than would be expected by chance alone and it is a widely accepted indicator of low-quality BP measurement.If BP measurements are done strictly according to guidelines, the expected prevalence of each of the digits should be 20%. However, various studies have shown that there is an increased prevalence of end digit 0 (zero), ranging from 22 to 90%, depending on the clinical setting , the skill or qualification of the healthcare worker who took the BP, and the presence of feedback-monitoring systems for EDP.20End digit preference leads to over- or underestimation of actual BP. Underestimation of BP could mean missing the diagnosis of hypertension in a patient, which can result in significant morbidity and mortality due to lack of treatment.23Furthermore, EDP had been associated with difficulty in assessing associations between blood pressure and other potential cardiovascular risk factors by reducing the power of statistical tests.There is a dearth of publications on EDP in BP measurement from Africa, despite the fact that one of the earliest publications on this clinical entity was from South Africa.We retrospectively reviewed the medical records of patients with hypertension attending the Hypertension Clinic of Ladoke Akintola University of Technology Teaching Hospital, Osogbo, Osun State, Nigeria over a two-month period (1 February to 31 March 2010). In our hypertension clinic, a patient’s blood pressure is first taken by a nurse using a mercury sphygmomanometer and the value is recorded in the patient’s folder. The physician repeats the BP measurement during the same visit as part of the clinical evaluation of the patient.Only folders of patients with at least three clinic visits before the commencement of the study and with proper documentation of the BP values by nurses and doctors were selected for the study. The latest three BP readings by the nurses and doctors were extracted from the medical records of the patients.The designation of the attending doctor at each clinic visit was also recorded. The nurses involved in BP measurements of patients in our clinic during the study period were registered nurses and they were in the same cadre. Ten doctors and two nurses were responsible for taking the readings included in this analysis.2 (kg/m2).Patients’ gender, age, height (m) and latest weight (kg) were recorded. Body mass index (BMI) was calculated from weight/heightEthical approval for the study was obtained from the Research Ethics Committee of Ladoke Akintola University of Technology Teaching Hospital, Osogbo, Osun State, Nigeria.Continuous variables were summarised as means ± standard deviation and categorical variables were displayed as percentages. Distribution of end digits of systolic and diastolic blood pressure values was noted and Chi-square comparison was performed to examine the significant differences in the occurrence of 0, 2, 4, 5, 6 and 8 end digits reported for both systolic and diastolic BP readings by nurses and doctors. Differences in zero and non-zero end digits of BP values by different cadres of doctors were also evaluated.t-test for continuous variables in the group of patients with zero EDP and the group with non-zero end digits. All p-values less than 0.05 were considered to be statistically significant.The last clinic attendance BP value was used to assess the demographic characteristics of patients that may influence EDP by physicians. The demographic parameters were compared using Chi-square for categorical and Student’s Statistical analysis was done using Statistical Package for Social Sciences (SPSS) software, version 15 . Figures were drawn using the Microsoft Office Excel 2007 version.The study population consisted of 114 patients  and their demographic features are shown in There was no statistically significant difference in the mean SBP and DBP of males and females. The means of the nurse–doctor SBP difference and nurse–doctor DBP difference were –4.36 mmHg (range –60 to +32 mmHg) and 1.22 mmHg (range–44 to +40 mmHg), respectively.The nurses and the doctors took 342 BP readings each. p < 0.001). For DBP, 98.5% of nurses’ readings ended in the digit 0 while 64.3% of doctors’ readings ended in the digit 0 (p < 0.001).Nurses had a statistically significantly higher occurrence of SBP zero EDP compared to doctors (p < 0.001). Although the consultant staff recorded a higher frequency of end digit 0 for DBP than SBP (42.3%), the frequency of end digit 0 was still lower than that by registrars (67.8%) and senior registrars (77.8%), and this difference was statistically significant (p < 0.001).A comparison of the characteristics of the patients was made in those whose SBP and DBP readings ended with end digit 0 and those with non-zero end digits et al.A zero EDP of 98.5% of SBP and DBP readings by nurses in our clinic was much higher than the 22.2–40.8% of SBP and 21.8–53.6% of DBP readings by hypertension nurse specialists at the Mayo Clinic, Rochester, as reported by Graves The zero EDP of 51.2% of SBP and 64.3% of DBP readings by doctors in our clinic was much higher than the expected 20%. Although a zero EDP of 51.2% of SBP readings was lower than the 60–84% reported in most clinical practice-based studies,et al.,et al.,et al.,et al.The zero EDP of 64.3% of DBP readings in our study is similar to the 64% obtained by Kim Subgroup analysis of the readings by doctors showed that the consultant staff had the least preference for end digit zero in their BP measurements, although the findings of a zero EDP of 25.4% of SBP and 42.3% of DBP were higher than the expected 20%. The lower frequency of zero EDP in the BP readings by consultants was not unexpected, taking into consideration their years of training and practice, and the fact they are more likely to be conversant with guidelines for BP measurement.et al.The senior residents showed a higher frequency for zero EDP than the junior residents, a finding which was unexpected, considering the senior residents’ knowledge base and years of training. However, many publications have pointed out the lack of formal training and assessment in BP measurement during undergraduate and postgraduate medical training, and this could have been responsible for our findings.et al.,et al.,We did not find any impact of patient-related factors such as gender, age, weight and BMI on the occurrence of EDP. Our results differ from earlier reports by Graves Publications abound in the literature on the debate over whether mercury sphygmomanometers should be phased out in clinical practice.29Although the use of automated BP measuring devices may help in eliminating EDP,28Studies have also shown that training, retraining and certification of healthcare workers in BP measurement with regular monitoring and feedback on end digit and number preference help to reduce or eliminate end digit and other observer bias and errors associated with BP measurement.28Our cohort consisted of patients being managed for hypertension, and good BP control can be defined as SBP < 140 mmHg and/or DBP < 90 mmHg. Only two (3.8%) out of 53 patients with SBP < 140 mmHg had SBP of 138 mmHg and two 2.4%) out of 84 patients with DBP < 90 mmHg had DBP of 88 mmHg. Therefore, the occurrence of an 8 as end digit was not related to treatment thresholds..4% out o4The means of the difference in the nurse–doctor SBP measurements was –4.36 mmHg, indicating that the SBP readings by the nurses were on the average lower than those by doctors. However, the nurse–doctor DBP difference of 1.22 indicates that DBP recorded by the nurses were on the average higher than that recorded by doctors.et al.et al. (1.22 vs –7.9 mmHg), the ranges of the difference were similar (–44 to +40 vs –44 to +31 mmHg).30The means and range of the nurse–doctor SBP differences in our study of –4.36 mmHg and –60 to +32 mmHg was comparable to –6.3 mmHg and –67 to +66 mmHg reported by La Batide-Alanore This study had a few limitations. The high frequency of zero EDP in our study is an indication that the various healthcare workers involved in this study were rounding the BP readings to the nearest 10 mmHg. In view of the retrospective nature of the study, we could not tell whether the readings were rounded down or up. Second, we had few missing data on weight (one subject) and height (nine subjects). Third, in view of its retrospective nature, we could not assess whether the BP measurements were done according to the guidelines on BP measurement. Lastly, although the number of our observations may appear small, most publications on this subject with larger number of observations involved multiple centres with electronic storage of BP readings.29We found a high frequency of zero EDP in BP measurements in our hypertension specialty clinic, particularly from among the nursing staff and resident doctors. Our findings argue for the training, retraining and certification of nurses and doctors in BP measurement and the institution of a regular monitoring and feedback system on EDP in order to minimise this observer error.


The use of atypical antipsychotic agents has rapidly increased in the United States and worldwide in the last decade. Nonetheless, many health care practitioners do not appreciate the significance of the cardiovascular side effects that may be associated with their use and the means to minimize them. Thus, atypical antipsychotic medications can cause cardiovascular side effects such as arrhythmias and deviations in blood pressure. In rare cases, they may also cause congestive heart failure, myocarditis, and sudden death. Patients with schizophrenia have a higher risk of cardiovascular mortality than healthy individuals, possibly because of excessive smoking, the underlying disorder itself, or a combination of both factors. Increased awareness of these potential complications can allow pharmacists and physicians to better manage and monitor high risk patients. Accurate assessments are very important to avoid medications from being given to patients inappropriately. Additionally, monitoring patients regularly via blood draws and checking blood pressure, heart rate, and electrocardiogram can help catch any clinical problems and prevent further complications. Finally, patient and family-member education, which pharmacists in particular can play key roles in, is central for the management and prevention of side effects, which is known to reflect positively on morbidity and mortality in these patients. The risk of cardiovascular-related morbidity and mortality is known to increase in patients with schizophrenia. Patients with schizophrenia have an increased risk of sudden death and are 2–4 times more likely to die prematurely compared to the general population . The secAntipsychotics have been used for more than five decades for the treatment of psychosis, which can result from a number of disorders including bipolar disorders, delirium, delusional disorders, psychotic depression, paranoia, schizophrenia, Tourette's syndrome, and substance-induced psychosis and various neurologic conditions such as dementias, Huntington's disease, multiple sclerosis, and parkinsonism. The first generation antipsychotic medications (FGAs), also commonly referred to as “neuroleptics,” which include phenothiazines, butyrophenones, and thiothixenes, treat many of the symptoms of psychosis but have undesirable side effects such as akathisia, tardive dyskinesia, dystonia, and parkinsonism, collectively referred to as “extrapyramidal side effects” (EPS). The newer atypical antipsychotics SGAs;  have beeAs indicated before, it is well established that patients with mental disorders have a higher prevalence of modifiable risk factors for cardiovascular disease that may include obesity, hypertension, diabetes mellitus, and dyslipidemia. For example, obesity can be 1.5 to 2 times more prevalent in people with schizophrenia and affective disorders than in the general population . Recent The association between SGAs and hypertriglyceridemia has been established in wide range of studies . In addioptimal use of drugs,substantial reduction of adverse drug reactions,fewer complications related to drug treatment,reduced morbidity and mortality by minimizing medication-related problems,improved laboratory monitoring of drug therapy,improved patient satisfaction.In summary, adverse reactions to drugs  are very costly and cause pain and suffering for the patient, resulting in potential disability or sometimes death . In factIntegrating the activities of traditional pharmacy practice , pharmacist clinician activities require an understanding of the advancements made in collaborative practice and cognitive services. Cognitive service is a component of pharmaceutical care that pharmacists have been providing for many years. Cognitive service is defined as services provided by the pharmacist for the patient or other health care professionals for the purposes of promoting optimal health and/or drug therapy, not necessarily drug product or drug distribution related . These sto be a BCPP (board certified in psychiatric pharmacy) or its equivalent training or experience like residency in psychopharmacy and/ or BCPS with psychiatry background;to be competent to interpret ECG (Lead II);to be trained to take vitals and listen to and interpret heart sounds S1 and S2;to be able to interpret laboratory reports accurately.Mechanisms for assuring the competence of specialist pharmacists to monitor cardiovascular side effects in our opinion may include but not limited to the following:A professional function of a pharmacist is to provide drug therapy directed at definite outcomes that improve quality of life for patients. The profession of pharmacy has an obligation to the public to ensure that pharmacists provide safe, effective, timely, and compassionate care to patients. However, specialized areas may require specialized knowledge and skills, attained only through additional training.Based on these considerations and given the shortage of primary care practitioners in general and in mental health/psychiatric facilities in particular, the present paper not only underscores but also provides guidance for the management of cardiovascular complications/manifestations in patients receiving treatment for schizophrenia.The definition of orthostatic hypotension is the decrease of 20 mmHg or more in systolic pressure or the decrease of 10 mmHg or more in diastolic pressure within three minutes of standing . OrthostHypotension, including orthostatic hypotension, is a significant side effect encountered with atypical antipsychotic drugs. Adrenergic blockade may result in number of risks, such as syncope, falls, fractures, increased anginal episodes, and orthostatic hypotension. The agents that most commonly cause hypotension include clozapine, quetiapine, and risperidone. Olanzapine does not block alpha adrenergic receptors and has not been linked to orthostatic hypotension, although dizziness has been reported in some patients. Risperidone can occasionally cause orthostatic dizziness, hypotension including orthostatic hypotension, and reflex tachycardia. The least hypotensive effects are reported with ziprasidone. Atypical antipsychotic drugs in combination with cardiovascular medications such as methyldopa, diuretics, adrenergic blockers, calcium antagonists, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, nitrates, and others may aggravate the hypotensive effects.Orthostatic hypotension can contribute to the increase in risk for injury  and falls in the elderly population. This is because the elderly are frailer and have a higher incidence of osteoporosis compared to the younger population. It is recommended that those who take these psychotropic medications should be aware of dizziness. Recommendations of taking appropriate orthostatic blood pressure assessment are to have the patient lie supine for ten minutes, obtain blood pressure and heart rate, then take blood pressure and heart rate immediately after the patient arises, and ask about dizziness . Heart rThe SGAs that are associated with hypertension include clozapine, olanzapine, and ziprasidone. Quetiapine and risperidone appear to have the lowest risk of hypertension. Assessing the patient's pre-existing illness and/or monitoring the patient's blood pressure and heart rate at baseline and then periodically during treatment can help control and prevent further complications from arising.An electrocardiogram (ECG) measures the electrical activity of the heart and can serve as a diagnostic aid to determine possible heart complications. The phases of the ECG are summarized in twisting because the peaks are at their smallest in one lead, and largest in another lead (Torsades de pointes (TdP) is a polymorphic ventricular tachycardia associated with a prolonged QTc interval. The ECG pattern is distinctive and is called her lead . Torsadeher lead . Patientr) channel. Although olanzapine, quetiapine, and risperidone bind to the Ikr channel, it is unclear whether they cause TdP or not. Some of the psychotropic drugs that can possibly cause TdP are listed in Potassium channels play an important role in ventricular arrhythmias . The potassium channel that is most involved in drug-induced QT syndromes is the potassium rectifier  . Not allIn this connection, there have been case reports providing evidence for the association of ziprasidone with torsades de pointes , 21. ForAssessment and monitoring of patients are needed to determine their wellness. Determining the patient's history of heart disease (including family members) and inquiring about other types of psychotropic, heart, or over-the-counter medications are needed to start any drug therapy. A thorough physical examination and ECG monitoring are important in determining the heart rate and blood pressure. Lastly, taking blood samples periodically is needed to determine patient's potassium levels. It is important because low levels of potassium can increase the risk of TdP. There is no known mechanism on how sudden death occurs, but it is known that it may possibly be caused by cardiac arrhythmias, notably TdP following ventricular fibrillation. The common feature is delayed repolarization of the myocardium which causes a prolongation of the QT interval of the ECG. This leaves the myocardium vulnerable to ventricular tachycardia and in some serious cases sudden death.A study by Ray and his colleagues followed nearly 0.5 million Tennessee Medicaid enrollees for 2.5 years  and founMyocarditis, inflammation of the heart muscle, is a rare complication of clozapine therapy. In one study, the estimated incidence was between 0.7% and 1.2% of clozapine-treated patients . The mecMyocarditis can be detected from a physical exam showing irregular and/or abnormal heart beats or sounds, fluids in the lungs, skin, and/or the legs. Other examinations include ECG, chest X-ray, WBC, RBC, and blood cultures for infections. Treatment includes an evaluation and treatment of the underlying problem. This may require use of antibiotics for infection and low-salt diet to avoid retaining water. Diuretics are also given to remove body water. Steroids and anti-inflammatory medications are used to reduce inflammation. Abnormal heart rhythm may require the use of additional medications, a pacemaker, or even a defibrillator. If a blood clot is present in the heart chamber, anticoagulants may be given as well. It is important to treat as soon as possible to prevent complications such as heart failure, pericarditis, or cardiomyopathy.Clozapine, which is (the only drug) indicated for resistant schizophrenia, has a “black box” warning for causing an increased risk of fatal myocarditis. One study reported 23 cases  of clozapine-associated cardiovascular complications: 15 of myocarditis and eight of cardiomyopathy . Of the Antipsychotic medications can cause various types of cardiovascular complications . Increased awareness of these potential complications can allow pharmacists and clinicians to better manage and monitor at-risk patients. Accurate assessments are very important to avoid medications from being given to patients inappropriately. In addition, monitoring patients regularly via blood draws and checking blood pressure, heart rate, respiration rate, and ECG can also help catch any clinical problems as well as prevent further complications from occurring. Lastly, educating patients, family, and caregivers on what to look out for and how to handle certain side effects is very important. By doing so, the risk of mortality for patients with mental and behavioral disorders may be further reduced. Pharmacists practicing in mental health facilities, by virtue of their job functions and responsibilities, are in a unique position to play a pivotal role in minimizing the cardiovascular adverse effects of antipsychotic drugs.


R2 (.43). This model presented a sensitivity of 80.86% and specificity of 81.22% in the training set and, respectively, 45.65% and 65.15% in the test sample. For men BMI, WC, HC, and WHC showed the best prediction with the lowest deviance (57.25), misclassification (.16), and the higher pseudo R2 (.46). This model had a sensitivity of 72% and specificity of 86.25% in the training set and, respectively, 58.38% and 69.70% in the test set. Finally, the result from the classification tree analysis was compared with traditional logistic regression, indicating that the former outperformed the latter in terms of predictive power.The present study investigates the prediction of increased blood pressure by body mass index (BMI), waist (WC) and hip circumference (HC), and waist hip ratio (WHR) using a machine learning technique named classification tree. Data were collected from 400 college students (56.3% women) from 16 to 63 years old. Fifteen trees were calculated in the training group for each sex, using different numbers and combinations of predictors. The result shows that for women BMI, WC, and WHR are the combination that produces the best prediction, since it has the lowest deviance (87.42), misclassification (.19), and the higher pseudo  Waist-hip ratio was not a significant predictor for men (P = 0.369) or women (P = 0.070), with a cutoff of 0.92 cm for the first  and 0.85 cm for the second . Finally, BMI presented a cutoff of 23 kg/m2 for men  and 23.3 kg/m2 for women . Although less employed in the study of health conditions related to obesity, hip circumference is pointed as a variable that can increase the predictive power of the other anthropometric variables and should be included in the obesity studies [Body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR) are among the most practical and cost effective measures for evaluation of obesity, with the advantage that both WC and WHR present positive correlations with the amount of visceral fat, and together effectively predict cardiovascular risk , 7. Furt studies . It seem studies , 12.From the usual methods employed to study the relationship between anthropometric variables and obesity, the receiver-operating characteristic (ROC) curve analysis is the technique used to provide and to verify the quality of the cutoff points. This statistical method is highly recommended in epidemiological studies  because Health researches could benefit from employing machine learning techniques to verify the combination of variables that best predict a given outcome, as well as to verify their cutoff values. Machine learning is a relatively new science field focused on the construction and study of systems that can automatically learn from data , generatclassification and regression tree (CART) is of special interest for health studies, since it is useful: (1) to discover which variable, or combination of variables, better predicts a given outcome  and (2) to identify the cutoff values for each variable that maximally predicts the chosen outcome.Among the techniques of machine learning, the CART is a type of supervised learning technique  for recum, representing region Rm, with Nm observations, letk observations in node m. We classify the observations in node m to class m. Different measures of node impurity (⋯) include the following:Two main indexes, misclassification and deviance, can be used to indicate the quality of the prediction. Hastie et al.  explain Misclassification error: Cross entropy or deviance: Misclassification is the index indicating the total amount of wrong predictions made or its rate . Deviance is an index that is sensible to both the misclassification and the purity of the feature space partitions. As pointed by Hastie et al.  and by GR2 and AUC). In the present study we will analyze which variable, or combination of variables , better predicts increased blood pressure (prehypertension or hypertension) and which cutoff values are maximally predictive of it. Fifteen models, or trees, with different number and combination of predictors will be compared for each sex, in a training sample. Then, the best tree will be tested in a testing sample for cross validation.The present study has as the main goal to introduce and to apply the machine learning technique named classification and regression tree (CART) in the context of increased blood pressure. The machine learning field is a set of innovative techniques that provides state-of-the-art predictions in terms of accuracy. CART is becoming popular in different science fields since its interpretability is straightforward; the result of the prediction is easily understandable by experts of the field; it is applicable to a wide range of problems, can use any kind of variable as predictor, is a nonparametric technique, and is sensible to the impact of additional variables in the predictive model. Through the application of the CART analysis we expect to contribute with future studies focusing on the prediction of increased blood pressure by any kind of variable . Additionally, we are going to compare the results from the CART analysis with traditional logistic regression analysis, in terms of strength of the prediction (pseudo-The data was collected in a convenience sample composed of 400 undergraduate students (56.3% women) aged between 16 and 63 years old (mean = 23.14 and standard deviation = 6.03), from a private university of Vitória da Conquista, Bahia, Brazil. All participants signed an informed consent agreeing to participate in the research. Weight was measured using a digital scale , to the closest 0.1 Kg. Height was measured using a stiff tape placed vertically on a flat wall, on subjects standing erect and head in the Frankfurt plane . BMI washttp://dx.doi.org/10.6084/m9.figshare.845664; (2) men's dataset can be downloaded at http://dx.doi.org/10.6084/m9.figshare.845665. All analyses were made using the tree package [tree classification procedure was fitted by binary recursive partitioning using as outcome the presence of increased blood pressure: at least prehypertension (systolic blood pressure > 120.0 mmHg) for women and hypertension (systolic blood pressure > 140.0 mmHg) for men. We are not investigating systolic hypertension in the weman sample because only 8% of them presented a systolic blood pressure equal to or greater than 140 mmHg. When the prevalence of one category of the outcome variable is very low, the classification tree fits a model that only predicts more abundant category. This problem is typical of the machine learning methods, which suffer in the presence of unbalanced datasets [The systolic blood pressure was assessed and the subjects with increased blood pressure were identified. The data were first split into two subsets, one for each sex. Then, each subset was randomly split into two sets (training and testing) with almost the same number of people for cross-validation. The dataset is freely available in a web repository for reproducible purposes , 26: (1) package  from thedatasets . Geurts datasets  suggest R2 was calculated for each model, using the following formulae:Fifteen random trees were calculated (grown) from the training set for each sex, in order to identify which variables, or which combination of variables, were suitable to predict the presence of increased blood pressure. Each random tree had one or more predictors, as can be seen in All the ethical principles contained in the Declaration of Helsinki were followed in the current study, as well as all the Brazilian specific laws.2), WC (median = 84 cm), HC (median = 103 cm), and WHR (median = 0.83) than women. The latter showed the following medians: a SBP of 117 mmHg, a BMI of 22 kg/m2, a WC of 76 cm, a HC of 100 cm, and a WHR of 0.76.None of the variables employed in the current study presented a normal distribution, as pointed by the Shapiro-Wilk's test of normality see . Men preR2 for each of the fifteen models investigated in the training sample. Waist circumference alone was the worst predictor for the women sample (tree 2), since it presented a deviance of 149.30, a misclassification error rate of 0.40, and a pseudo-R2 of only 0.03. Tree 13 presented the best model, with the lowest deviance (87.42), a misclassification error rate of 0.19, and a pseudo-R2 of 0.43. Comparing the variables alone, body mass index was the best predictor, explaining 32% of the variance of increased systolic blood pressure for women, against only 3% for waist circumference and hip circumference and 9% of waist-hip ratio. When added to BMI as predictors, WC and HC worsen the prediction, decreasing the percentage of explained variance from 32% to 29% and the misclassification from 0.27 to 0.26 and increasing the deviance from 104.50 to 109.50 and 108.90, respectively. All combinations of three variables provided a better prediction than the variables alone or combined two by two. Tree 11, for example, had BMI, WC and HC as predictors of increased blood pressure and resulted in a better model then tree 1 , decreasing deviance from 104.50 to 94.24, misclassification from 0.26 to 0.22 and increasing the percentage of explained variance from 32% to 39%. So, WC and HC together with BMI have an incremental validity that adds 4% of explanation to the predictive model. However, the best model, represented by tree 13, showed that WC and WHR combined with BMI add 11% of variance explanation to the predictive model, compared to BMI alone (tree 1), decrease the percentage of misclassification from 26% to 19%, and decrease deviance from 104.50 to 87.42. So, WC and WHR have a considerable impact on the prediction of increased blood pressure in women when combined with BMI, presenting incremental validity over the latter.Systolic blood pressure presented a moderate correlation with all the anthropometric variables. Only 10.89% of SBP's variance was explained by BMI, 12.25% was explained by WC, 6.25% by HC, and 9.61% by WHR. Increased blood pressure was found in 42% of women (SBP > 120 mmHg) and in 47% of men (SBP > 140 mmHg). R2 of 0.11. Tree 15 presented the best model, with the lowest deviance (57.25), a misclassification error rate of 0.16, and a pseudo-R2 of 0.46. Comparing the variables alone, body mass index was the best predictor, explaining 16% of the variance of increased systolic blood pressure for men, with a deviance of 89.35 and a misclassification of 0.26, a result slightly better than tree 3 in which HC alone explained the same amount of increased SBP's variance with deviance of 89.59 and a misclassification of 0.26. When added to BMI as predictors, WC, HC, and WHR increase the percentage of variance explanation to 33%, 25%, and 25%, respectively, with deviance of 71.07, 80.17, and 79.90 and with misclassification error rate of 0.21, 0.25, and 0.23. All combinations of two variables lead to a better prediction than every variable alone. When added to BMI and WC, hip circumference worsens the prediction by decreasing the percentage of increased systolic blood pressure's variance explanation from 33% (tree 5) to 32% (tree 11), increasing deviance from 71.07 to 72.66, and misclassification error rate from 0.21 to 0.23. However, when waist-hip ratio is added to BMI, WC, and HC as predictors, deviance, misclassification, and pseudo-R2 are improved. If we compare tree 15 with tree 1 it is possible to argue that WC, HC, and WHR together present incremental validity in the prediction of increased systolic blood pressure in men, increasing 30% of its variance explanation, improving 10% of misclassification, and decreasing deviance from 89.35 to 57.25.Considering the men's result, waist-hip ratio alone (tree 4) presented the worst prediction model, with deviance of 95.09, misclassification error rate of 0.29, and pseudo-2 and WHR is smaller than .685 cm, the person is classified as having systolic pre-hypertension (classified as PRE). When BMI is higher than 27.27 kg/m2 and WHR is higher than 0.80, the person is also classified as having systolic pre-hypertension (classified as PRE). Averaging the percentage of women with increased blood pressure (or systolic pre-hypertension) classified as having pre-hypertension in each node results in a correct prediction of 80.86%; in other words this is the overall tree sensibility. In the same line of reasoning, averaging the percentage of women with regular blood pressure classified as having a regular pressure in each node results in a correct prediction of 81.22%; in other words this is the overall tree specificity. However, the cross-validation of tree 13 in women's testing sample showed that the sensibility decreased to 45.65% and the specificity to 65.15%. The percentage of women with SBP greater than 120 mmHg in the training sample was 43.75% and in the testing sample was 41.07%.R2 of 0.43, with an overall tree sensibility of 80.86% and specificity of 81.22%, while the logistic model with higher pseudo-R2 and AUC was the model 11, presenting 0.023 and 0.566, respectively  requires caution to verify which variables better predict obesity. A smaller P does not indicate a stronger relationship between independent and dependent variables, and statistical significance does not indicate practical importance [Anthropometric variables are among the most practical and low-cost obesity diagnostic methods , regardiportance . The ROCportance  because portance , being lclassification and regression tree (CART) of the machine learning field. The CART techniques are of special interest for health studies to discover which variable, or combination of variables, better predicts a given outcome  and to identify the cutoff values for each variable that maximally predicts the chosen outcome. Health studies have been employing machine learning methods in different applications that go from sustained weight loss investigation [A conjoint of techniques that can provide sensitive information about incremental validity is the tigation , obesitytigation , to genetigation  and meditigation .In the current study, classification tree models were used to verify which combination of BMI, WC, WHR, and HC best predicted increased blood pressure for women and men. The best model for women showed that adding WC and WHR to BMI increased 11% of the variance explanation in the predictive model, decreased the percentage of misclassification from 26% to 19%, and decreased deviance from 104.50 to 87.42. As pointed before, WC and WHR have a considerable impact on the prediction of increased blood pressure in women when combined with BMI. The overall sensibility for the best model (tree no. 13) was 80.86% and the overall specificity was 81.22%. The complex model represented by tree 13 see  exceededR2, sensibility, and specificity for both men and women.The best model for men showed that WC, HC, WHR, and BMI together presented an incremental validity over BMI alone in the prediction of hypertension, increasing 30% of the variance explanation, improving 10% of misclassification, and decreasing deviance from 89.35 to 57.25. The overall sensibility and specificity for the best model (tree no. 15) was 72% and 86.25%. As happened with the women result, the complex model represented by tree 15 see  exceededvariance issue [In spite of the high sensibility and specificity of the best models for both men and women in the training sample, the cross validation applied in the test sample revealed a different scenario. The cross-validation of tree 13 in women's testing sample showed that the sensibility decreased to 45.65% and the specificity to 65.15%, and the cross-validation of tree 15 in the men's testing sample showed that sensibility decreased to 52.38% and the specificity decreased to 69.70%. The observed difference in sensibility and specificity between the modeled training set and the cross-validation in the test set is known in the machine learning literature as the ce issue . It meance issue  can be ace issue . Finallyhttp://www.who.int/gho/ncd/en/index.html) [Using machine learning techniques to discover new relations in data, to verify incremental validity of additional predictors, and to make accurate predictions for new data sets may help the health scientists to find new robust diagnostic parameters. The clinical usefulness of the present study relies on the possibility of using new algorithms to classify and predict increased blood pressure, with higher accuracy than usual cutoff points. Although most of the clinicians can measure both blood pressure and the anthropometric variables simultaneously, there are several parts of the world, such as many countries from Africa or several places in Latin America, where material resources are scarce. So, the application of complex algorithms, as the presented one in the current paper, can be a help for those professionals that can rely only on very simple and cheap instruments, such as a measure tape. Furthermore, the present study applied a new method for prediction of health outcomes, which in spite of being incipient in the literature, can provide new insights and discoveries since it outperforms traditional techniques (such as logistic and linear regression), making possible to compare the impact of new variables on the prediction of the chosen outcome . Traditional techniques are based on several assumptions, as the normality of the distribution, linear relationship between independent and dependent variables, homoscedasticity, and so on. The Machine learning techniques can handle any kind of variable , with no assumption about distribution, linearity, or homoscedasticity. Moreover, it can be used to extract useful information and to discover new relations in very huge data sets provided by some international databases, such as the World Health Organization Global database on noncommunicable diseases (see ex.html) . As quotex.html)  approach


Hypertension is a risk factor for cardiovascular disease, and the prevalence of hypertension tends to increase with age. Current treatments for hypertension have adverse side effects and poor adherence. The purpose of this study is to evaluate the effects of moxibustion on blood pressure in individuals with pre- or stage I hypertension.Forty-five subjects with pre- or stage I hypertension will be randomized into three groups: treatment group A (2 times/week), treatment group B (3 times/week), and the control group (non-treated group). The inclusion criteria will be as follows: (1) aged between 19 and 65 years; (2) prehypertension or stage I hypertension ; (3) the participants are volunteers and written consent obtained.p < 0.05).The participants in the treatment group A will undergo indirect moxibustion 2 times per week for 4 weeks, and the participants in the treatment group B will undergo indirect moxibustion 3 times per week for 4 weeks. The participants in the control group (non-treated group) will maintain their current lifestyle, including diet and exercise. The use of antihypertensive medication is not permitted. The primary endpoint will be a change in patient blood pressure. The secondary endpoints will be the body mass index, lipid profile, EuroQol and Heart Rate Variability. The data will be analyzed with the Student’s t-test and analysis of variance (ANOVA) (The results of this study will help to establish the optimal approach for the care of adults with pre- or stage I hypertension.Clinical Research Information Service KCT0000469 Hypertension is an important risk factor for cardiovascular diseases including stroke, myocardial infarction, congestive heart failure, kidney disease, and peripheral vascular disease -3.It is estimated that in 2025, 1.56 billion adults will have hypertension . AccordiArtemisia vulgaris) at acupoints or other specific parts of the body to treat or prevent diseases. This technique is typically used to treat and prevent cold syndrome, deficiency conditions and chronic diseases [Moxibustion involves the application of ignited mugwort  concerning moxibustion treatment for prehypertension. A systematic review on the effects of moxibustion on hypertension revealed no evidence that moxibustion is beneficial to people with hypertension. However, the differences between specific and non-specific effects should be examined in a future study that includes appropriate control groups .The aims of this pilot study are to evaluate the effects of moxibustion on blood pressure in patients with pre- or stage I hypertension, to test the methods used and to calculate the sample size required for future randomized trials.This study will be a prospective randomized controlled trial, and participants will be recruited from Woo-suk University Hospital using notices at the hospital and newspaper advertisements.In this pilot clinical trial, patients with pre- or stage I hypertension will be analyzed to determine the safety and efficacy of moxibustion, and basic analysis will be performed on the results. The study participants will voluntarily sign clinical trial consent forms, and all examinations and tests will be performed according to the clinical trial plan. Eligible subjects will be chosen based on specific inclusion and exclusion criteria. Participants will be randomized before the first treatment. Forty-five subjects with pre- or stage I hypertension will be randomized into three groups: treatment group A (2 times/week), treatment group B (3 times/week), and the control group (non-treated group). During each moxibustion treatment, each acupoint will be treated five times. The treatment will continue for 4 weeks. The follow-up assessment is designed to evaluate the long-term effects of moxibustion. Upon completion of the 4-week-long treatment, follow-up tests will be conducted at weeks 8,12,16,20 and 24 after randomization .The systolic and diastolic blood pressures will be measured in the arm using an automatic blood pressure meter . The subjects will be fitted with a BP cuff on both arms. A trained researcher will measure the blood pressure carefully in the arm with higher BP while the subject is in the seated position. The blood pressure will be measured three times after the subject has rested for at least 10 min. All BP measurements will be taken in a temperature-controlled room. The three measurements will be carried out at 5-min intervals. The mean of these three measurements will be used in the data analysis. The participants will be instructed not to drink caffeinated drinks such as coffee or tea and not to exercise, smoke or eat 2 h before the blood pressure test. In addition, they will be instructed to avoid drinking heavily the day before the test .The practitioner has had more than 3 years of clinical experience since completing 6 years of study at the College of Korean Medicine and has received a Doctor of Korean Medicine.This study is designed as a pilot study to calculate the appropriate sample size for future randomized clinical trials. Allowing for a 20% dropout rate, each group will include 15 participants, which is the minimum sample size necessary to evaluate the effect of moxibustion ,14. In tThis protocol adheres to the principles of the Declaration of Helsinki and has been approved by the institutional review boards of the Woo-suk University Hospital, where the study will take place (WSOH IRB 1205-02). Before any treatment is given, written consent will be obtained from each participant. All patients will have the right to withdraw from the trial at any time.Inclusion criteria were as follows: (1) aged between 19 and 65 years; (2) pre- or stage I hypertension (JNC 7); (3) the participants are volunteers, and written consent was obtained.Exclusion criteria were as follows: 1) taking medications to control blood pressure; (2) secondary hypertension; (3) history of cerebrovascular disease, cardiovascular disease, malignant tumors, kidney diseases, liver diseases, thyroid gland diseases, active tuberculosis, or other infectious diseases; (4) diabetic patients taking insulin or anti-diabetic medications; (5) drug or alcohol dependence; (6) taking hemorrhagic disease and anticoagulation medications (excluding aspirin); (7) receiving systemic steroid therapy or immunosuppressive therapy; (8) taking medications that could affect blood pressure such as central nervous system depressants or stimulants; (9) pregnancy or the possibility of pregnancy; (10) hypersensitivity reactions following moxibustion therapy; (11) received oriental medicine treatment related to hypertension in the past month; (12) participants deemed unsuitable for the trial, as judged by the person in charge of the clinical trial  will receive no treatment. The subject in this group will be asked to maintain their normal lifestyle, including diet, exercise and workload.Brochures containing information on dietary changes, living habits, and exercise regimens that help prevent and alleviate hypertension will be distributed to all groups, and the subjects will decide for themselves whether to incorporate the suggested changes into their daily lives.All groups will be prohibited from undergoing active treatment to lower the blood pressure for the duration of their participation in this clinical trial. After the completion of the clinical trial, during the assessment period, the subjects will be allowed to decide for themselves whether to receive additional treatment. Any other related information will be recorded in detail.The use of birth control pills and central nervous system stimulants or depressants, which can affect blood pressure, will remain prohibited. The practitioner will be allowed to converse with the subjects about daily care and treatment details while carrying out the required examination.The primary outcome measurement in this study is the change in blood pressure before randomization (baseline) and 4 weeks after randomization. Blood pressure will be taken at every visit.The secondary outcome measures will be the mean pulse pressure, body mass index (BMI), heart rate variability (HRV), the Modified Stress Response Inventory (SRI-MF), the Pittsburgh Sleep Quality Index (PSQI), the Fatigue Severity Scale (FSS), EuroQol (EQ-5D), general assessments and blood tests including fasting blood sugar (FBS), uric acid, lipid profile, high sensitivity C-reactive protein (hs-CRP), liver function test (LFT), hemoglobin A1c (HbA1C), and complete blood count (CBC).The pulse pressure refers to the difference between the systolic pressure and the diastolic pressure. This value reflects the degree of stiffness of the blood vessels. An increase in the pulse pressure after midlife is recognized as a risk factor for cardiovascular diseases . The BMIFollow-up tests will be conducted at 8, 12, 16, 20 and 24 weeks after randomization. The follow-up assessment is designed to evaluate the long-term effects of moxibustion.The results of the intention-to-treat (ITT) analysis will be used to assess the validity of the study as a whole. The per-protocol (PP) analysis results will be used as a reference. The ITT analysis will be used as the main safety assessment technique.Continuous data will be represented by the average, standard deviation, minimum value, and maximum value, whereas categorical data will be represented by a frequency table. For the comparison of the results among the groups, the analysis of variance (ANOVA) test will be used when the data are normally distributed; the Kruskal-Wallis test will be used otherwise. In addition, the chi-square test will be performed for categorical data.After 4 weeks, the differences in systolic and diastolic pressure will be summarized for each group using descriptive statistics, including the median, average, standard deviation, and interquartile range. In addition, we will evaluate the effectiveness of the treatment using an analysis of covariance as the dependent variable, the baseline score as the covariate, the group as the fixed factor, and the hypertension stage as the stratified variable. In addition, we will compare the results for the stratified groups with the results for the whole subject pool (non-stratified) to determine whether hypertension stage is a suitable stratification variable. The differences in the systolic pressure and diastolic pressure following the treatment for each group will be analyzed using a paired t-test or a Wilcoxon signed rank test, and the 95% confidence interval will be presented. To assess the difference in the tendency for each visit, repeated measures analysis of variance will be performed. A significance level of 5% will be used in all analyses.The average pulse pressure, change in the baseline blood pressure following the treatment, BMI, EQ-5D, Ankle Brachial Pressure Index(ABI index), Brachial-Ankle Pulse wave velocity(PWV index), heart rate variation , and blood test results will be analyzed using the same techniques used to analyze the validity of the assessment variable. To determine whether there are differences in the distribution of the change in symptoms among the groups, analysis will be performed on each item using the chi-squared test.All adverse reactions manifested will be listed with detailed explanations. The frequency of abnormal reactions that are correlated with the treatment and abnormal reactions that do not have such correlations will be recorded. A Fisher’s exact test will be performed to determine whether there are any differences among the groups with respect to the incidence of abnormal reactions as reported by the subjects. Furthermore, technical analysis will be performed to identify differences in the degree of severity and in the type of abnormal reactions among the groups.The safety evaluation will be based on adverse events, which are expected to include blisters, redness, and burns. Adverse reactions refer to undesirable and unintentional signs , symptoms or diseases following the treatment. There does not necessarily have to be a cause and effect relationship with the treatment. The subjects will be instructed to voluntarily report any information regarding abnormal reactions to the practitioner on a regular basis.Any adverse events during treatment will be recorded. When abnormal reactions appear, the date of appearance, the date of disappearance, the degree of the abnormal reaction, measures taken related to the treatment, correlation with the treatment, names of suspicious drugs taken outside of the treatment, whether the abnormal reactions were treated and any other related information will be recorded in detail. Any medical conditions or diseases present prior to the start of the treatment will be considered abnormal reactions only if they worsen after starting the treatment.Abnormal test values or results will be considered abnormal reactions only if they cause clinical symptoms, if they are considered clinically significant or if treatment is needed.This study is a preliminary study targeting individuals with pre- or stage I hypertension, who will be randomly divided into treatment group A (2 times/week), treatment group B (3 times/week), and the control group (non-treated group). Basic analysis will be performed to assess the validity and safety of moxibustion for the treatment of pre- or stage I hypertension. The following results will be presented: the extent of stimulation provided by moxibustion, differences in the effect according to the frequency of treatment, and how long the efficacy of the treatment last. These results will be based on long-term follow-up observation.This trial is currently recruiting participants.JNC-7: Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; RCTs: Randomized controlled trials; BMI: body mass index; HRV: heart rate variability; SRI-MF: modified stress response inventory; PSQI: Pittsburgh Sleep Quality Index; FSS: Fatigue Severity Scale; EQ-5D: EuroQol; FBS: fasting blood sugar; LFT: liver function test; hs-CRP: high sensitivity C-reactive protein; HbA1C: hemoglobin A1c; CBC: complete blood count; NDI: neck disability index; ITT: intent to treat; PP: per protocol; ANOVA: analysis of variance; ABI index: ankle brachial pressure index; PWV index: brachial-ankle pulse wave velocity.The authors declare that they have no competing interests.KMS participated in the design of the study, coordinates the study and drafted the manuscript. JEP, YL, HJJ, SYJ, MHL, KWK, THY, and SMC provided technical advice and wrote the relevant sections of the manuscript. All authors participated in read, and approved the final manuscript.KMS, JEP and KWK: Senior researcher of Medical Research Division, Korea Institute of Oriental Medicine.SMC: Director of Medical Research Division, Korea Institute of Oriental Medicine.YL, HJJ, SYJ and MHL: Researcher of Medical Research Division, Korea Institute of Oriental Medicine.THY: Professor of the Department of Acupuncture & Moxibustion, Woosuk University.


The aim of this study was to investigate the prevalence of interankle systolic blood pressure difference (sIAND) and its influencing factors in community population.This study included 2849 (65.1±9.4 y) subjects. Blood pressure (BPs) of four limbs was simultaneously measured with 4 electronic sphygmomanometers after 10 min rest in supine position. The difference of systolic BP (SBP) between two ankles was calculated as DETASBP. The criterion for abnormal sIAND was ≥10 mmHg of absolute DeltaSBP, in which the criterion for 1o sIAND was 10–19 mmHg and for 2o sIAND was ≥20 mmHg. Age, gender, smoking, hypertension, family histories of hypertension and diabetes were recorded. Fasting blood glucose and lipids, circumference of hip and waist, and body mass index (BMI) were measured.The SBP was higher in the right ankle than in the left ankle  and mean DeltaSBP was 6.08±6.26 mmHg. Similar difference was found in both genders. The prevalence of abnormal was 18.5%, in which, the prevalence 1o sIAND was 15.3% and that of 2o sIAND was 3.1%. Multivariate regression analysis showed that age, waist circumference and blood glucose level were the positive factors for DeltaSBP. The normal upper limit for DeltaSBP was 16.7 mmHg in this population, the prevalence of sIAND by≥16 mmHg was 5.8%.Aging, hypertension, obesity and abnormal glucose metabolism are positive factors for inter-ankle SBP difference. The guidelines for hypertension and blood pressure measurement point out that for the first blood pressure (BP) taking, two arms should be measured to evaluate interarm BP difference (IAD) Increasing data show that IAD is not only a sign for diagnosing subcravian and brachial artery stenosis, left ventricular hypertrophy, but also a predictor of adverse cardiovascular outcomes In recent years, some studies suggested that simultaneously measuring BP of four limbs can provide more valuable information, for example, an ankle-brachial index (ABI). A low ABI (<0.9) is an important sign for intermittent claudication and other peripheral vascular disease. Meanwhile, ABI is also a useful predictor for cardio-cerebrovascular diseases Like arms, two ankles in some patients may show significantly different BP, i.e., interankle BP difference (IAND). Recently, some studies showed that IAND could predict the risk for overall and cardio-cerebrovascular events . Because IAND was not widely studied, in the previous studies various diagnostic criteria were used: mean values, or quartile, or ≥10 mm Hg, or ≥15 mm Hg One reason for this confusion phenomenon is no data about the prevalence of IAND in community population. This study was to investigate the prevalence of IAND in community population and to evaluate the possible influencing factors for IAND.This study enrolled 3311 adult community residents of two different communities during Sept–Dec of 2011, one in Nanchang City of Jiangxi province and the other in Shunde City of Guandong province. The information on age, sex, smoking , family history of hypertension, histories of hypertension and diabetes were obtained with questionnaires and medical records. Waist and hip circumference, body mass index (BMI), fasting blood glucose, total cholesterol (TC), triglyceride (TG), high and low density lipoprotein cholesterol (HDL-C and LDL-C) were measured. Ratios of LDL-C/HDL-C and LDL-C/TC were calculated. The participants under antihypertensive therapy or with BP of 140/90 mmHg or more at investigation were diagnosed as hypertensive patients. Subjects with arrhythmias and known intermittent claudication were excluded. Finally, 2849 subjects of ≥40 years  with complete measurement data were included.This study focused on systolic IAND (sIAND). After 10-minute supine rest, supine BP of four limbs were measured simultaneously using 4 electronic sphygmomanometers (Omron HEM7101) for three times with a 2-minute interval. Their averages were used to calculate absolute interankle SBP difference (DETA BP). When DETASBP was 10–19 mm Hg class 1 sIAND (1o s IAND) and DETASBP was ≥20 mmHg class 2 sIAND (2o sIAND) were diagnosed The higher SBP of two arms and the lower SBP of two ankles were used to calculate sABI, and sABI of <0.9 was considered as abnormal.The proposal and the consent procedures of this study were approved by the Ethic Committees of the Second Affiliated Hospital of Nanchang University, and of the Sixth Hospital of Nanchang city, and of Guizhou Hospital of Fushan city. All patients provided verbal informed consent for BP measurement of four limbs as this measurement is a non-invasive clinical examination.All data are presented as Mean ± Standard Deviation (Mean±SD). The SPSS10.0 statistical package  was used for Student's t-test and Chi-square test in this study. Linear correlation analysis was used for the relationship between DeltaSBP or DeltaSBP/SBP and other variables.was the reference value range of 95% on<mean+1.64SD. Statistical significance was defined as P<0.05.In multivariate analysis, the independent variables were SBP and SBP/SBP, and the dependent variables were age, gender , BMI (kg/m2), waist circumference, hip circumference, smoking , history of hypertension , diabetes , coronary heart disease , TG, TC, LDL-C/HDL-C, LDL-C/TC and blood glucose levels. The definition of the normal upper limit of DETASBP The general information is shown in The right ankle SBP, either in males or in females, was about 1.7 mmHg higher than the left ankle SBP. Although the SBP was higher in males, DeltaSBP had no gender difference. In this population the normal upper limit for DeltaSBP was 16.7 mmHg.Increased sIAND was found in 526 subjects (18.4%), of them, 437subjects (15.3%) were diagnosed 1o sIAND and 89 subjects (3.1%) 2o sIAND. The prevalence of 10 sIAND was significantly higher in males than in females, but the prevalence of 20 sIAND was similar between two gender groups .Linear correlation analysis showed that DeltaSBP and DeltaSBP/SBP were positively correlated with age, BMI, waist circumference, hip circumference, blood glucose and TC levels. Meanwhile, DETASBP and DETASBP/SBP were positively correlated with baseline SBP also .Multivariate regression analysis showed that age, waist circumference, blood glucose levels and hypertension history were the positive factors for DeltaSBP. Meanwhile, age, waist circumference and blood glucose levels were the positive factors for DeltaSBP/SBP .The sABI was slightly higher in the female group than in the male group, but the prevalence of abnormal sABI was similar between two gender groups. A negative correlation was found between sIAND and sABI  . In thisTraditionally, leg BP indicates the popliteal artery BP. Normally, the popliteal artery SBP is 20–40 mmHg higher than the brachial artery SBP. As ankle BP can be easily taken using electronic sphygmomanometer, it is used more often in clinical practice. Ankle BP is correlated with arm BP and the augmentation of central BP Intermittent claudication is a common disease caused by leg artery stenosis or occlusion. At present, palpation of dorsal artery of foot is often used to diagnose this disease. Because palpation method is insensitive, the diagnosis of intermittent claudication may be missed, especially in the early stage. On the basis of the value of systolic IAD for diagnosing subclavian or brachial artery stenosis This phenomenon will limit the use of sIAND in clinical practice. Combining our results and the previous data, we may suggest ≥16.0 mmHg as a cut-off value for sIAND in adults aged 40 years and over. The present study demonstrated that age, waist circumference and blood glucose levels were positively BP-independent factors for increased sIAND, because they were positively correlated not only with DeltaSBP, but with DeltaSBP/SBP. Although hypertension history was positively associated with DeltaSBP, but not with DeltaSBP/SBP, it may be a SBP-dependent factor for sIAND. Meanwhile, the present study indicated that sIAND is independent of gender as both genders had similar DETASBPs and gender was not correlated with DeltaSBP and DeltaSBP/SBP. Even the prevalence of 10 sIAND was higher in males (17.9% vs14.2%), this gender difference for the prevalence of 10 sIAND may come from other factors existing in male group, such as higher mean age and smoking rate. Because aging, obesity and abnormal glucose metabolism are important risk factors of atherosclerosis, we consider that underlying mechanism of the increased DeltaSBP is leg artery atherosclerosis in middle-aged and elderly people.The present study showed a negative relationship between sIAND and sABI. The reason for this relationship is clear, as increased sIAND and decreased sABI are related with leg artery stenosis. However, the clinical value of sIAND could not be replaced by sABI as they are dependent on the pathological condition of different limbs. If a patient has stenosis in both arms and in a leg, his or her sABI (as well as systolic interarm BP difference) may be “pseudomorphic normal”. In this case, only sIAND can provide valuable information. Meanwhile, IAD and ABI could not be correctly evaluated in some patients, for example, the renal inadequacy patients with an artificial arteriovenous fistula in one arm. Furthermore, this study showed that the overlapping rate between sIAND ans sABI was not so high, only 37 of 165 cases with sIAND by ≥16 mmHg were included into the 79 cases with abnormal sABI. Even in the 89 cases with 20 sIAND, only 31 cases with abnormal sABI. These results mean that sIAND or sABI has itself application area.In addition, the prevalence of sABI was 2.8% on the higher SBP of two arms and the lower SBP of the two ankles. The prevalence of sABI was more lower, only 1.8% on the SBP from right side limbs and 1.4% from the left side limbs. Using the SBPs of four limbs to identify sABI may be more reasonable for better screening intermittent claudication.Palpation of the leg artery is usually used to diagnose intermittent claudication in clinical treatment, but this method is insensitive. For correct diagnosis, artery imaging form computer tomography or catheterization is needed. Compared with the above-mentioned expensive or invasive examinations, evaluating sIAND is simpler and cheaper. So sIAND may be a useful index for screening asymptomatic intermittent claudication.Although we suggest DETA BBP≥16 mmHg as a reference of cut-off value for sIAND in adults aged 40 years and over, its clinical value should be demonstrated by artery imaging evidence in the future.In a community population, 18.5% of subjects showed DETASBP of ≥10 mmHg, but only 5.8% had DETA SBP of ≥16 mmHg, a normal upper limit suggested by this study. Aging, obesity and abnormal glucose metabolism are SBP-independent positive factors for increased sIAND.