Guidelines for the management of blood pressure (BP) in primary care generally suggest that decisions be made on the basis of specific threshold values (e.g. BP 140/90 mmHg); but this fails to adequately accommodate a common cause of variation – the play of chance.To determine the impact of chance variability in BP readings on the clinical decision making of general practitioners (GPs) regarding anti-hypertensive treatment and cardiovascular risk management.We used an internet based study design, where 109 GPs were assigned to manage one of eight case vignettes (guidelines would recommend treatment for only one of the eight) and presented with blood pressure readings that were randomly selected from an underlying population.Seventeen  GPs consulted the vignette for whom treatment was recommended, but only 7/17 (41.2%) GPs prescribed treatment, whereas 14/92 (15.2%) GPs prescribed medication to the other vignettes. When deciding to follow-up a vignette GPs were influenced by threshold values for systolic and diastolic BP, but not by the overall cardiovascular risk. If the first reading was a low BP  GPs were highly likely to discharge the vignette and follow-up a high BP reading (diastolic >90 or systolic BP≥140). Similar factors predicted the decision to prescribe a drug, although the vignette’s cardiovascular risk (>20%) was now statistically significant (p = 0.03).GP decision making, whilst generally consistent with guidelines, appears to be compromised by chance variation leading to under and over treatment. Interventions to adequately accommodate chance variability into clinical decision making are required. Like many other countries, guidelines in the United Kingdom (UK) determine whether a patient is recommended antihypertensive treatment based on their measured blood pressure and their ten-year cardiovascular risk Although guidelines are clear, the decision to start a patient on treatment is not straightforward because within the same individual, measured blood pressure varies. Measured blood pressure exhibits variation of two types: systematic and random (or chance). Systematic variation is caused by a range of patient factors such as flu, the white-coat effect or pain The intrinsic biological variability of blood pressure gives rise to “chance like” variation in blood pressure from beat to beat, minute to minute and day to day. To try and take account of blood pressure variability, clinical diagnosis is based on the average of a number of blood pressure measurements: in an attempt to estimate the true, but unknown, mean blood pressure.Since blood pressure measurement is used as a diagnostic test, variability of blood pressure can lead to false positives – where normotensives misclassified as hypertensive - and false negatives - hypertensives misclassified as normotensive. The Positive Predictive Value Investigating the effect of blood pressure variation on clinical decision-making in clinical practice is challenging because patients with different blood pressures also differ in characteristics such as age, gender or other cardiovascular risk factors and the act of measurement, treatment and management interfere/confound the estimation of the true underlying blood pressure. However simulation, using case vignettes, is one approach to investigating the impact of chance variation on the clinical decision making process because it avoids some of these challenging problems TM sought ethical approval from the South Birmingham Research Ethics Committee and was advised that the project did not require ethical review. All data were handled anonymously.A website was developed that presented one of eight typical case vignettes of a patient consulting for a routine check up in primary care. The eight case vignettes described a 40, 50, 60 and 70 year old white man and a 40, 50, 60 and 70 year old white woman. In each case the vignette was a non smoking, non diabetic, who drank alcohol in moderation and exercised twice a week, with a body mass index of 25 kg/m2. The total cholesterol level and HDL cholesterol level were the mean for a person of this age and sex based on the Health Survey for England of 1998 Participants who accessed the website were presented with information on the patient’s characteristics, with summaries of current UK guidelines and a hyperlink to an on-line cardiovascular risk calculator On accessing the website, participants were randomly allocated to one of the eight case vignettes and presented with a first consultation blood pressure reading. Participants were asked to indicate which of three possible decisions they would take. These decisions were coded as 1 to 3 . If the At subsequent consultations participants were provided with further randomly selected blood pressure drawn from a population of two hundred. If the patient had been started on treatment the subsequent blood pressure was drawn from a population of two hundred blood pressures with a slightly lower mean, reflecting the effects of treatment. Treatment effects were determined from the average effects reported in meta-analysis We aimed to recruit UK based GPs, so participants were recruited by emailing members of a number of the Primary Care Cardiovascular Society, the Royal College of General Practitioners and MidRec (the Midlands Research network). Advertisements were placed in Pulse (a UK magazine read by GPs) to draw attention to the study. All participants could opt to be included in a draw with a prize of £100. Participants were asked to provide basic details: their age, gender and clinical specialty.Party Package ROur exploratory analysis involved the use of Classification and Regression Trees (CART) which are a statistical data mining based technique for constructing decision trees by recursively splitting or partitioning patients into homogenous groups lme4RWe used the insights from the tree models to construct two random effects models logistic regression models using the The first model focused on the decision to follow-up (decision 2) the patient and the second model focused on the decision to prescribe medication (decision 3). These two decisions were considered the most important in our study . The covariates in the random effects models were the patients age (years), patients gender , GPs age (years), GPs gender , patient’s first visit (yes/no), patients systolic BP≥120 (yes/no), patients diastolic BP≥90 (yes/no) and CVD Risk ≥20% (yes/no). We investigated two way interactions between the blood pressure variables and first visit and retained only those interactions which were statistically significant at the 5% level. GPs were included as random effects as were our eight vignettes  Our use and choice of threshold values for systolic BP, diastolic BP and CVD Risk was based on values commonly indicated in clinical guidelines (BP 140/90) which were also seen in our exploratory tree models.Between September 2007 and July 2008, 109 UK GPs, 65 male and 44 female with an average age of 40.28 years (SD: 9.44), accessed the website and answered questions relating to the case vignettes.Specifically if the patient  had a low BP  then the GPs discharged the patient . If the patient  had a low diastolic BP (≤89) but a high systolic BP (>138) then GPs were more likely to invite the patient for a follow-up  and less likely to discharge the patient (5/18 27.7% were discharged). Finally, a high diastolic reading  was most likely to result in a follow-up visit , with 8/67 (11.9%) being discharged and 1/67 (1.5%) being prescribed a drug. The decision to prescribe was related to a one-off high BP reading (systolic 175 and diastolic 107) in vignette eight, which equates to ten year CVD risk calculated with this blood pressure reading would be 20.9% (compared to true underlying CVD risk of 13.9%). At the end of the first consultation, 34% (37/109) of GPs had discharged the patient, whereas 65% (71/109) invited the patient for a follow-up consultation and 1 GP had prescribed medication.If the patient,  was on treatment and presented with a high diastolic BP (>94) then on these occasions, GPs were most likely to add another medication , although in 20/56 such occasions GPs invited the patients for follow-up, on 4/56 such occasions the medication was changed and on one such occasion (1/56) a drug was stopped.If the patient  was on treatment and presented with a low diastolic BP (≤94) then on these occasions, GPs were most likely to invite the patient for a follow-up (74/102), although in 13/102 occasions GPs prescribed an additional BP drug, on 11/102 occasions GPs discharged the patient, on 3/102 occasions GPs stopped one medication and one occasion (1/102) the GP changed the medication.If the patient  was not on treatment and presented with a high diastolic BP (>91) then on these occasions GPs were most likely to invite the patient for a follow-up (44/49), although on 4/49 occasions GPs discharged the patient and on one occasion (1/49) the GP started the patient on medication.If the patient  was not on treatment and presented with a low diastolic BP (≤91) and a low systolic BP (≤137) then in 39/63 such occasions GPs discharged the patient, whilst in 24/63 occasions GPs invited the patient for follow-up.If the patient  was not on treatment and presented with a low diastolic BP (≤91) and a high systolic BP (>137) then in 27/31 such occasions GPs invited the patient for follow-up, whilst on four (4/31) occasions GPs discharged the patient.We further investigated the decision to follow-up the patient using a random effects logistic regression model  and founWe further investigated the decision to prescribe medication using a random effects logistic regression model  and founTo our knowledge this is the first study to explicitly explore how clinician decision making is influenced by chance variation in blood pressure. We found that when deciding to follow-up the patient, GPs appeared not to consider if the vignette’s overall cardiovascular risk was ≥20%, but were influenced by threshold values for systolic and diastolic BP. Furthermore, whilst GPs decisions to prescribe a drug were also affected by similar thresholds, the patient’s cardiovascular risk (>20%) was now seen to be statistically significant. Since cardiovascular risk is only valid in untreated populations we would expect it to influence only the decision to intiate treatment. Finally, we saw evidence of under treatment and over treatment. Under half of practitioners prescribed for the only patient who would be recommended treatment under UK guidelines and about 15% of GPs prescribed medication to non-recommended patients.Treatment seemed to be determined more by blood pressure than by estimated risk of cardiovascular disease. This observation has also been made in UK clinical practice A weakness of this website based study design is that theoretical decisions are made about a theoretical patient, although we found no evidence of nonsensical decision making, indeed the decisions appeared rational. However as observed earlier, this is the only practical design that can investigate the effects of blood pressure variation on standardised patients. Our participating GPs are self-selected volunteers with an average age of 40.3 years and 59.6%  are male. In the UK 52.6% of GPs are male and in England mean age is about 46 A key question about the study design is whether the variability of blood pressure in the vignettes adequately represents what is seen in clinical practice. The coefficient of variation of blood pressure used in the case vignettes (9.9%) is consistent with published reports which range from 7.2% to 10% In the UK it has recently been recommended that 24-hour ambulatory blood pressure measurement be used for diagnosis of hypertension when blood pressures are close to a treatment threshold Whilst further studies to determine the impact of chance variation on clinical decision making would be useful, it is also worth noting that there is little in the clinical guidelines to mitigate against chance variation and interventions that can help clinicians and patients understand and appropriately react to chance variability are also needed, especially because our findings suggest that addressing chance variability could be a promising strategy for reducing under/over treatment and their associated costs.


Background: Movement dysfunction may be expressed in terms of symptoms experienced in non-physiological postures, and head-down crooked kneeling (HDCK) is a posture frequently assumed by Muslims during prayer activities. The purpose of this study was to investigate the cardiovascular responses in the HDCK posture. Methods: Seventy healthy volunteers, comprising 35 males and 35 females, participated in the study. Cardiovascular parameters of blood pressure and pulse rate of the participants were measured in rested sitting position and then at one and three minutes into the HDCK posture. Two-way ANOVA was used to determine the differences between cardiovascular responses at rest and in the HDCK posture, and the Student t test was utilized to determine gender difference in cardiovascular responses at rest and at one and three minutes into the HDCK posture. Results: The study showed a significant decrease in systolic and diastolic blood pressures at one minute into the HDCK posture and an increase in pulse rate at one and three minutes into the HDCK posture, as compared to the resting values. Rate pressure product also rose at one minute into the HDCK posture, whereas pulse pressure increased at one and three minutes into the HDCK posture, as compared with the resting values. However, no significant change was observed in the mean arterial pressure values. Conclusion: The findings from this study suggest that no adverse cardiovascular event can be expected to occur for the normal duration of this posture during Muslim prayer activities. These two postures  are unusual in daily life activities. However, in physiotherapy procedures, tilting position combined with deep breathing exercise, percussion, and vibration helps remove excess secretions in pulmonary conditions.2-5 Moreover, acrobats, children, and military personnel sometimes assume momentary tilted or inverted positions during play and maneuvers.Cardiovascular variables such as blood pressure and pulse rate are influenced by a wide range of factors such as emotion, lifestyle, and physical activities including changes in posture.6 On assumption of a passive head-down tilt, blood is shifted towards the upper thorax and head, consequently, the forearm blood flow and arterial blood pressure increase and heart rate decreases.7,8 Mengesha,9 and Balogun et al.10 reported that systolic and diastolic blood pressures as well as mean arterial blood pressure (MAP) and pulse pressure (PP) were not affected by aerobic training and head-down inversion, but pulse rate and rate pressure product (RPP) during head-down inversion were significantly reduced.Several studies have been conducted to investigate the physiological responses during non-physiological postures and activities. Head-down position during long periods of sitting decreases heart rate, increases ejection duration, and causes shift in the myocardial oxygen supply/demand ratio.11-13 From the extant literature, the majority of studies on cardiovascular responses during non-physiological postures have been conducted in the industrialized nations,8,14,15 and the few relevant studies from the developing countries were conducted over two decades ago.10 In physiotherapy clinics, patients usually present with problems such as limitation in daily life activities, which may include limitations in assuming postures, e.g. during various prayer positions. The assessment of cardiovascular responses during orthostatic stress resulting from varying postures may provide important information on the regulation and control of blood pressure across different races and genders.16 There are a total of 34 prostrations in the usual five daily obligatory prayers, during which each HDCK posture lasts for approximately 10 to 15 seconds. In the unusual or periodic non-obligatory prayers observed during the Ramadan fasting period or Taraweeh and the late night prayer or Tahajjud, prostration usually lasts for up to 2 minutes or even longer. In Muslim prayer activities, postures assumed encompass standing, bowing or Ruku’u, and head-down crooked kneeling (HDCK) or Sujood (prostration), and sitting in that order. Head-down inversion in Sujood is similar to poses used in hatha yoga, which is a practice that focuses on relaxation, body awareness, and meditation.None of the previous studies has explored cardiovascular responses during the HDCK posture, assumed during Muslim prayer activities. The objective of this study was to investigate the cardiovascular responses of healthy subjects during prostrations in Muslim prayers. We hypothesized that there would be no significant difference in cardiovascular parameters at rest and during Sujood and that there would be no significant gender difference in cardiovascular parameters at different time points during Sujood.Participants Seventy healthy young students of the University of Maiduguri and staff of the University of Maiduguri Teaching Hospital  participated in the study. Subjects with a known history of chronic headache, glaucoma, hypertension, or other related heart diseases were excluded and informed consent was obtained from the participants before data collection.InstrumentsThe following instruments were used for the collection of data in the study: digital electronic device to monitor blood pressure and pulse rate (Beurer D-89077 Germany), bathroom scale, Standiometer, stop watch, table mat, and data collection instruments such as data forms and pens. The study was conducted at the gymnasium of the Department of Physiotherapy, University of Maiduguri Teaching Hospital.Study ProcedureA repeated measurement design was utilized for this study. The participants were interviewed for medical history of any cardiovascular ailment, and those who met the inclusion criteria were given a consent form to sign. A pilot study was carried out prior to the main study, which revealed that the participants started experiencing discomfort at three minutes into Sujood.The participants were advised not to eat kola nuts (kola nitida) and avoid drinking caffeine-containing beverages 24 hours before the commencement of the study. All the measurements were taken in the morning because of the hot weather condition during the study period. On arrival at the lab, the participants received explanation about the protocol of the study and their heights and weights were measured using a Standiometer and a bathroom scale, respectively. Afterward, the participants assumed sitting position.Five minutes after the assumption of sitting position, resting period blood pressure and pulse rate were measured. The measurements were repeated at the seventh minute and the average of the two readings was recorded. Subsequently, the participants assumed prostration and stayed in that position for up to three minutes, during which time, blood pressure and heart rate were monitored at one and three minutes into prostration. The participants then returned into sitting position and their blood pressure and pulse rate were monitored for a duration of five minutes before discharge.17 RPP is a valid predictor of myocardial oxygen demand, and PP is a good predictor of stroke volume.10For each participant, MAP, RPP, and PP, as dependent variables, were computed. MAP is an important predictor of cardiac output,The ethical approval of the Ethics Committee of the University of Maiduguri Teaching Hospital was obtained before the commencement of this study.Data AnalysesData analysis was performed using Statistical Package for Social Sciences (SPSS version 16.0). Descriptive statistics of mean and standard deviation were drawn upon to describe the participants’ physical characteristics and to describe the cardiovascular responses at rest and at different time points during the HDCK position, i.e. at one and three minutes into prostration.t-test was employed to determine differences in the physical characteristics between the male and female participants, and the analysis of variance (two-way ANOVA) was utilized to determine differences in the cardiovascular responses between the male and female participants at rest and during the HDCK position. Least Significance Difference (LSD) was used as a post-hoc test to probe significant main effects, and a significance level of 0.05 was adopted in the study.Inferential statistic of the independent The mean age of the participants was 27.73±6.64 years. The mean height and weight of the male participants were significantly higher than those of the females, as is shown in Post-hoc analysis revealed that the significant differences (P<0.001) in systolic blood pressure were between baseline (118.14±10.90) and at one minute into the HDCK position (114.60±11.93) and between baseline (118.14±10.90) and at three minutes into the HDCK position (116.23±12.78). Diastolic blood pressure was significantly reduced (P<0.001) at one minute into the HDCK position (74.49±10.9) from the baseline value (80.81±11.75), and it also significantly decreased (P=0.005) at three minutes into the HDCK position (77.09±10.72) from the baseline value. For pulse rate, responses were significantly elevated (P=0.014) at three minutes into the HDCK position (76.33±11.84) from the baseline value (72.29±10.27), and also after the third minute (76.33±11.84) from the first minute (74.64±11.22) into the HCDK position. MAP was significantly reduced (P<0.001) at one minute into the HCDK position (88.52±10.41) from the baseline value (93.26±10.48), and was also significantly reduced (P=0.021) at three minutes into the HDCK position (90.13±10.26) from the baseline value (93.26±10.48). A significant difference (P=0.003) was found only between the first and third minutes into the HDCK position for RPP, with the value significantly higher at three minutes into the HDCK position (8843±1537.81) than at one minute into the position (8497.79±1402.20) (not shown in the table).18 which reported a significant decrease in systolic and diastolic blood pressure response among subjects in side-lying, 10° head-down tilt. The finding is, however, inconsistent with that of LeMarr et al.19 which reported a consistent increase in systolic blood pressure during a three-minute inversion. Also, contrary to the Klatz et al.20 and Ballantyne,21 studies, which showed an average increase of 20 mm Hg for systolic blood pressure during inversion, our findings revealed a lower increase of 7 mm Hg in systolic blood pressure at one minute into the HDCK position. The aim of this study was to investigate the cardiovascular responses of healthy subjects during the HDCK position, which is assumed in Muslim prayers. We hypothesized that there would be no significant difference between the cardiovascular parameters of the male and female participants at different time points during Sujood. The main finding was that systolic and diastolic blood pressures were significantly reduced in both male and female participants following Sujood, in comparison with the baseline values, but these reductions were not sustained through the third minute into the position. This finding is relatively concordant with that of the the study of White and Mawdsley,19-21 may be attributed to the different position and duration of tilting and inversion used. In contrast to the present study, inversion and tilting in all the previous studies were assumed for longer durations. It is also possible that the attenuation response in blood pressure to inversion in this study was due to the adaptation of baroreceptors to head-down fatigue in the participants insofar as the majority of them were Muslims, who frequently adopt this position during their daily prayers.The inconsistency with respect to systolic and diastolic blood pressures between our findings and those of some previous studies20 who found no increase in pulse rate during more than 90° head-down inversion among healthy young subjects, a significant increase in pulse rate was found at three minutes into inversion in the present study. The increase in heart rate response from the resting value, found in the present study, was very much expected because anxiety, albeit subtle, always occurs during unusual positions and can trigger a sympathetic pressure response.22 According to the law of hydrostatics, circulatory pressure differences are produced by the three phenomena of gravity force, blood density, and the vertical distance between the two points being measured. Also, Starling’s law stipulates that both cardiac output and systemic blood pressure are expected to rise following changes in postures. This situation would probably influence pulse rate in either way. A decrease may result from blood distribution, which would influence the baroreceptors to cause vagal stimulation and augment response, hence giving rise to the reflex vasodilatation of the peripheral bed.13 An increase may also result to ensure continued evacuation of blood from the dependent region in the unusual posture, especially in less efficient circulation as in sedentary participants. This could be more likely since the veins and muscles of the upper part of the body are not specially adapted as the veins and muscles of the legs to aid venous return to the heart.Contrary to the finding of Klatz et al.10 These changes in MAP and RPP, which were not observed between the baseline values and at three minutes into the position, suggest an initial reduction before an upward trend in these values as the subjects assumed the HDCK position. Consistent with the study of Balogun et al.10 our findings show a decrease in MAP at one minute into prostration , an increase at three minutes into prostration , and a decrease in MAP at three minutes into prostration  (P>0.05).Our results, documenting a rise in MAP and RPP between the first minute and third minute into the HDCK position and no change in PP throughout the maneuver, are consistent with those of Balogun et al.12 Perhaps gender is not a personal individual factor that can influence or determine differences in cardiovascular responses following varying postures. Contrary to the expectation that cardiovascular responses following Sujood would be different between males and females, it is worth noting that the changes in the cardiovascular parameters at different time points during the HDCK position were not significantly different between the male and female participants in this study. This finding in our sample seems to confirm the conclusions that blood pressure responses to varying positions are comparable irrespective of the gender and race of the participants.There are some limitations to this study, which should be noted when interpreting the findings. First, the external validity of the study may be low because the participants were recruited through a convenience sampling technique and were limited to people with a potentially higher educational status . Second, the measurement was not performed at a similar time for all the participants, and it is possible for cardiovascular responses to inversion to vary at different time points during the day when the measurements are taken. Also, the environmental temperature during the procedure was not measured, which may preclude the generalization of our findings to different seasons in Maiduguri, Nigeria. Despite these limitations, however, the findings from the present study can be used as a basis for further exploratory studies on the cardiovascular responses to inversion during Muslim prayers, and can also elucidate on the body of knowledge on the effects of postural changes on cardiovascular responses in the general population. This study revealed a significant decrease in systolic and diastolic blood pressures and an increase in pulse rate at different time points during Sujood. Also, our findings showed no significant gender difference in the effect of Sujood on cardiovascular parameters at different points in time. These findings indicate that the blood pressure of the healthy subjects was not elevated within the first three minutes into Sujood and suggest that there may be no adverse effect or danger attributable to this prayer position. The present study is confirmation that Sujood is safe and no adverse cardiovascular effect can be expected to arise from it in the usual obligatory Muslim prayers or even longer durations for which the unusual or periodic non-obligatory prayers are held.


Chronic kidney disease is an important public health threat. Such patients present high morbidity and mortality due to cardiovascular disease, with low quality of life and survival, and also high expenditure resulting from the treatment. Arterial hypertension is both a cause and a complication of kidney disease; also, arterial hypertension is a risk factor for cardiovascular disease among patients with kidney diseases. There is some evidence that exercise interventions may be beneficial to chronic kidney disease patients, but previous studies included only end-stage patients, i.e. those undergoing dialysis. This study aims to evaluate the effect of exercise on kidney function, quality of life and other risk factors for cardiovascular disease among non-diabetic chronic hypertensive kidney disease patients who are not undergoing dialysis.2. The randomization will be done in fixed-size blocks of six individuals such that 75 participants will be allocated to each group. At baseline, information on demographic, socioeconomic, behavioral, anthropometric, blood pressure and quality-of-life variables will be collected, and laboratory tests will be performed. The intervention will consist of three weekly physical exercise sessions lasting 60–75 minutes each, with a total duration of 16 weeks. The outcomes will be the kidney function progression rate, quality of life, blood pressure, lipid profile, hemoglobin level, ultrasensitive C-reactive protein level, and ankle-arm index. The patients in both groups (intervention and control) will be reassessed and compared partway through the study (8th week), at the end of the intervention (16th week) and in the 8th week after the end of the intervention.The participants will be located through screening hypertensive patients attended within the public healthcare network in Pelotas, a city in south of Brazil. Eligible individuals will be those with glomerular filtration rate between 15 and 59 ml/min x 1.73 mThere is still a scarcity of data relating to the effect of physical exercise among the most numerous group of individuals with kidney disease, i.e. patients undergoing conservative treatment. In particular, there is a lack of randomized controlled studies. This study will help fill this gap. Studiessing age . Patientsing age , with losing age .These patients present diminished kidney function most frequently as a result of diabetes mellitus or systemic arterial hypertension. Systemic arterial hypertension is both a cause and a complication of chronic kidney disease and hypertension is a risk factor for cardiovascular diseases among these patients . Kidney Among the general population, physical activity is associated with lower cardiovascular risk . IndividData on the effect of physical exercise among the most numerous group of individuals with chronic kidney diseases, i.e. patients at less advanced stages of the disease who are still receiving conservative treatment, are still scarce . FurtherThe aim of the present study is to evaluate the effect of an exercise program on non-diabetic hypertensive patients with chronic kidney disease with regard to disease progression and quality of life. The hypothesis is that patients with chronic kidney disease who perform physical exercises (intervention group) will present less deterioration of kidney function and an increase in the quality-of-life score. Quality of life will be measured by means of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), using the Portuguese version translated and validated by Ciconelli .Additionally, the efficacy of the physical exercise will also be assessed by comparing the intervention and control groups regarding the following variables: (a) blood pressure and the need to use antihypertensive medications; (b) serum levels of total cholesterol, HDL cholesterol, triglycerides, albumin, ultrasensitive C-reactive protein, hemoglobin and hematocrit; (c) excretion of proteins and creatinine in urine; (d) ankle-arm index;2  Diabetics – we opted to exclude patients with diabetes because they present different prognosis as compared to chronic kidney disease patients without diabetes ;b) Individuals with severe physical disabilities ;c) Individuals with a history of acute myocardial infarction over the last six months;d) Individuals with kidney transplants or who are undergoing dialysis treatment.2 were identified. In this subsample, the glomerular filtration rate of non-diabetic hypertensive patients in stages 3 and 4 of chronic kidney disease was 48.47 ± 9.61 ml/min x 1.73 m2. To identify a post-intervention difference greater than or equal to 10% between the intervention and control groups that is significant at the 5% level (two-tailed), with a power of 80% at the end of 16 weeks, it will be necessary to include 63 patients in each group of the study. We decided to expand the sample to 75 patients per group in order to take follow-up losses into account based on previous trials with chronic kidney disease patients. This sample size also allows detecting baseline vs. post-intervention differences of 10% or greater in both groups.Due to the lack of baseline population-based Brazilian data on kidney function, we carried out a pilot study in a subsample of hypertensive patients registered in eight primary health care units in the city of Pelotas in 2010 in order to obtain the estimates needed for the sample size calculation. Through reviewing 3800 medical files, 290 patients with glomerular filtration rates of less than 60 ml/min x 1.73 mRandom allocation will be performed after the individuals who agreed to participate have been interviewed and have undergone a physical examination. The allocation list will be concealed and patients will be allocated to either the intervention or the control group. In order to balance the groups in terms of numbers of participants, we will use the technique of randomization in fixed-size blocks of six individuals. For each group of six individuals, we will make a draw for the order of entry in each group (intervention or control).The individuals identified from the “HiperDia” records will be visited at home and invited to participate in the study. After recruitment, a baseline study will be conducted to assess the individuals of both groups before the intervention. The main variables to be collected will be: demographic and socioeconomic data ; behavioral characteristics ; anthropometric data ; clinical data ; venous blood and urine sample collection for laboratory analyses ; and quality of life. The blood and urine samples will be collected at home following an overnight fast (~12 hours) by a nursing technician, and will be sent to the support laboratory, packed in refrigerated boxes at a temperature of approximately 4 °C. Interviewers will be blinded to the interventions or control status of each patient.th week), just after the end of the intervention (16th week) and in the 8th week after the end of the intervention , and from weeks 11–16, we will also include low-intensity plyometric training. In terms of muscle power training, we will conduct 2–3 repetitions of 4–6 simple horizontal jumps in the first 14 weeks. In the last two weeks, vertical jumps will also be included .th and 16th weeks after the start of the intervention and in the 8th week after the end of the intervention, similarly to what will be done with patients from the intervention group.The control group will continue to receive the usual attendance provided by the primary health care unit, in accordance with the guidelines of the Ministry of Health’s primary healthcare manuals for clinical prevention of cardiovascular, cerebrovascular and chronic kidney diseases . The conSince the aim of the study is to assess the efficacy of the intervention, strategies for ensuring follow-ups with complete adherence will be used. At the start of the study, the participants will be informed about the importance of the follow-up, and the names, addresses and telephone numbers of two individuals who are close to the participant and who might be able to inform where the participant can be found will be recorded. Over the course of the study, the participants in the intervention group will be contacted by telephone on the day preceding the physical activity sessions. Participants will be offered a snack at the end of each intervention session, transportation vouchers for them to come to the sessions and a pair of training shoes and sports clothes to use at the physical exercise sessions. Participants who do not come to one of the sessions will be sought in their homes to find out why they had been absent. If necessary to ensure adherence, the study will provide door-to-door transportation, free of charge for participants. The intervention will take place between August 2011 and July 2012. The sessions will be administered by physical education professionals, through an agreement with the School of Physical Education of the Federal University of Pelotas, within the premises of the school.th and 16th weeks after the start of the intervention and in the 8th week after the end of the intervention. Protein excretion in urine will be evaluated through the proteinuria ratio in milligrams per deciliter (mg/dl) and the creatininuria ratio (mg/dl), taking the index to be normal when it is less than 0.3. A secondary outcome is quality of life, which will be measured using the Medical Outcomes Study Short Form 36 item (SF-36). It comprises eight scales, each scored from 0 to 100.Progression of kidney disease will be assessed according to glomerular filtration rate measurements, estimated from the four variables formula for Modification of Diet in Renal Disease (MDRD). The glomerular filtration rate will be estimated in the intervention and control groups from serum creatinine measurements obtained at the baseline, in the 8Blood pressure: for measurements of systolic and diastolic blood pressure, the mean from two measurements made five minutes apart, with the patient seated, will be used. In order to maintain precision, an automatic device for blood pressure measurement will be used (Omron HEM-705-CP), and the adult cuff size will be selected . The patients will remain seated, with the arm supported at heart level. They will remain at rest for five minutes before the measurement and should not have had coffee or smoked within the preceding 30 minutes.Medications: to measure the consumption of medications, the questionnaire standardized by Bertoldi and colleagues  will be Blood and urine samples: will be collected after the participants have been under fasting conditions for 12 hours. Assays to determine serum levels of total cholesterol, HDL cholesterol, triglycerides, blood glucose, ultrasensitive C-reactive protein, hemoglobin and hematocrit will be performed. Protein and creatinine concentrations will be measured in urine samples. Proteinuria will be assayed using the colorimetric method, with pyrogallol red in a photometric device. Plasma and urinary creatinine will be analyzed by means of kinetics, Jaffe’s method with distilled water and using Roche reagent. Total cholesterol and HDL cholesterol will be measured by means of a colorimetric cholesterol esterase enzymatic method.Ankle-arm index: this index will be measured with the patient in dorsal decubitus, as the mean of two systolic pressure measurements on the dominant brachial artery , to obtain the proximal pressure; and on the posterior tibial of the ipsilateral leg to obtain the distal pressure . These mIn addition to these variables, physical activity before and after the intervention will be quantified. Physical activity practice during leisure time and as a means of transport will be evaluated using the long version of the International Physical Activity Questionnaire (IPAQ) . This ouAt the baseline, in addition to data on sociodemographic, behavioral and anthropometric characteristics, length of time with the diagnosis of hypertension and laboratory parameters, information on the following factors will be gathered:1. Medications:a) Use of antihypertensive agents that block the angiotensin system (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) that may be associated with diminished progression of kidney disease;b) Use of non-steroidal anti-inflammatory drugs, which, on the contrary, may increase the progression of chronic kidney disease.c) Level of physical activity before the start of the study.The day-to-day progress of the study will be closely monitored by the coordinator, who will be available to resolve any queries that may arise over the course of the fieldwork. The physical exercise sessions of the intervention group will be monitored by a research assistant, who will record the names of those who are present, identify those who are absent and organize home visits within the next 24 hours after the session for the participants who did not attend. According to the reason for the absence, appropriate measures will be taken in order to ensure maximum adherence to the study among the participants.T-test. We will use confidence intervals for estimating treatment effects.Data will be double-entered into the Epi-Info software in order to make subsequent comparison and thus ensure greater data quality. Automatic data checking will be performed, at the time of data entry, using the check function of Epi-Info, in order to verify range and consistency. To identify and correct inconsistencies of coding, revision and data entry, data cleaning will be performed by obtaining the frequencies of the variables gathered, using the Stata 11.0 software. This software will also be used for the data analysis. A two-tailed significance level of 5 % will be used for all the analyses. The two groups will firstly be compared in terms of the frequencies of the independent variables , blood pressure levels, glomerular filtration rates and other dependent variables. All analyses will be conducted using intention to treat, i.e., each individual will be analyzed in the group to which he or she was initially allocated, independent of dropouts from the intervention group or any beginning of physical activity among members of the control group. Outcome variables  will be compared in the two groups using The research ethics committee of the Federal University of Pelotas has approved this study. Likewise, the study has been authorized by the City Health Department and by the coordinators of the health care clinics involved in this study. The results from this study will be communicated to the Health Department of Pelotas and to the Regional Healthcare Coordination Office. Interviewees will be asked to give their written informed consent to their inclusion and will be assured of the right not to answer any part or the whole questionnaire, and their right to withdraw from the study at any time, without any onus on the participant or his/her family.After the end of the study, if any benefits relating to the disease are found, we will offer the same activity under the same conditions to all participants in the study.The authors declare there are no financial competing interests to declare in relation to this manuscript.FCB made substantial contributions to conception and design of the study. PH conceived the study, and participated in its design and coordination and helped to draft the manuscript. IS involved in drafting the manuscript and revising it critically for important intellectual content. GM participated in the design of the study. FBV is in charge of the exercise intervention. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/13/90/prepub


To study the prevalence and define deferential risk factors for ‘Resistant’ hypertension (RHT) in a hypertensive population of South Asian origin.A descriptive cross-sectional study was carried out among hypertensive patients attending clinics at the Cardiology Unit, Colombo from July-October 2009. All the patients with hypertension who provided informed written consent were recruited to the study (n = 277). A pre-tested interviewer-administered questionnaire was used for data collection. A binary logistic-regression analysis was performed in all patients with ‘presence of RHT’ as the dichotomous dependent variable and other independent co-variants.2) and those who were older than 55 years were significantly higher in the RHT group than in the non-RHT group. In the binary logistic regression analysis older age (OR:1.36), longer duration of hypertension (OR:1.76), presence of diabetes mellitus (OR:1.67) and being obese (OR:1.84) were significantly associated with RHT.Mean age was 61 ± 10.3 years and 50.2% were males. The mean of average systolic and diastolic blood pressures (BP) were 133.04 ± 12.91 mmHg and 81.07 ± 6.41 mmHg respectively. Uncontrolled BP was present in 41.1% (n = 114) of patients, of which RHT was present in 19.1% (n = 53). Uncontrolled BP were due to ‘therapeutic inertia’ in 27.8% of the study population. Those with diabetes mellitus, obesity (BMI > 27.5 kg/mth of the population was suffering from RHT, which was significantly associated with the presence of obesity and diabetes mellitus. Therapeutic inertia seems to contribute significantly towards the presence of uncontrolled BP.A significant proportion of the hypertensive patients were having uncontrolled hypertension. Nearly 1/5 Hypertension is a common non-communicable disease that is prevalent worldwide; it leads to numerous disabling complications such as stroke, atherosclerosis, retinopathy, chronic kidney disease and cardiac failure . MajoritStudies have shown that older age, obesity, excessive use of alcohol, and high sodium intake are strongly correlated with poor control of hypertension ,5. Patieth of the population of Sri Lanka was suffering from hypertension and the prevalence is expected to increase further in the coming decades [Sri Lanka is a middle income developing country in the South Asian region with a population of over 20 million. In 2005, nearly 1/5 decades . Further decades . The pre decades . Further decades . Genetic decades .There are numerous studies and published guidelines from developed countries on the prevalence, risk factors and management of ‘Resistant’ hypertension. However, presently there are no studies from developing South Asian countries. The present study aims to study the prevalence of ‘Resistant’ hypertension in a hypertensive population of South Asian origin and define deferential risk factors in the same population.This descriptive cross sectional study was conducted over a period of 3 months from 1st of March 2009 to 30th of May 2009. Ethical approval for the study was obtained from the Ethics Review Committee, Faculty of Medicine, University of Colombo, Sri Lanka.st time, patients who were too ill/unable to answer the questionnaire and patients who did not consent were excluded from the study.Patients were recruited from a cohort of hypertensive patients attending follow-up clinics at the Institute of Cardiology of the National Hospital of Sri Lanka (NHSL). Situated in Colombo the NHSL is the largest tertiary care hospital in Sri Lanka. There were about 50 hypertensive patients visiting daily (excluding Sundays) for follow up to the cardiology clinic, these patients are given clinic numbers on the first come basis and they come to clinics usually once per month. In order to choose the sample for our study we used a random sampling technique. In each week we selected three random days to visit the clinic. On each day of study we first selected all the patients with hypertension from the daily clinic register. These patients were then arranged in ascending order according to their clinic number. The first patient was chosen randomly from hypertensive patients 1 to 10 and then every third patient thereafter was invited for the study. Patients who gave the informed written consent were included in the study. The patients who visited the clinic for the 1A pre-tested expert-validated interviewer administered questionnaire was used for data collection (Annexure 1). The following data were collected; socio-demographic details, duration of disease, medication history, risk factors, complications and other co morbidities. The following risk factors were evaluated; history of smoking, alcohol consumption, drugs , family history, high salt intake and presence of obesity. The antihypertensive drugs currently used by the patients were recorded according to their classes and drugs used for other co-morbidities were also documented. Patients’ compliance to treatment was also evaluated.-2). Two consecutive resting seated blood pressures were recorded 10 minutes apart, manually using mercury sphygmomanometers. Patients’ previous 3 blood pressure values were taken from their medical records in clinic books.Height was measured as the maximum distance to the uppermost position on the head from heels, with the individual standing barefoot and in full inspiration using Harpenden stadiometers  to the nearest 0.1 cm. Body weight was measured using a SALTER 920 digital weighing scale  to the nearest 0.1 kg. Body Mass Index (BMI) was calculated as weight in kilograms divided by height squared in meters . The significance of the differences between means was tested using z-test. In all analyses a p values < 0.05 was considered statistically significant. A binary logistic regression analysis was performed in all patients with ‘presence of Resistant hypertension (RHT)’ as the dichotomous dependent variable  and age, gender , duration of hypertension, current cigarette smoking , current alcohol consumption , high salt intake , diabetes mellitus , ischaemic heart disease , hyperlipidaemia , chronic kidney disease  and obesity  as the independent variables (co-variants).2. Majority of the study population (n = 245/88.4%) had one or more co morbidities and ischemic heart disease (n = 214/77.3%), hyperlipidaemia (n = 144/52.0%) and diabetes mellitus (n = 118/42.6%) were the commonest co-morbidities . Mean age was 61 ± 10.3 years (range 25–83), and 50.2% were males. Majority of the study population (75.5%) were the age of 55 years. Mean duration of hypertension was 9.2 years (range 1–38), majority of the patients were having hypertension for ≤ 9 years (n = 152/54.9%). The mean of average systolic and diastolic blood pressures of the population was 133.04 ± 12.91 mmHg and 81.07 ± 6.41 mmHg respectively and 73.3% (n = 203) of them were admitted to hospital at least once due to a complication arising from hypertension . The mean BMI in the study population was 25.02 ± 4.52 kg/mEither systolic (≥140 mmHg or >130 mmHg in diabetics) or diastolic (≥90 mmHg or >80 mmHg in diabetics) blood pressure values measured during two recent clinic visits one month apart, were high in both visit in 41.1% (n = 114) of patients. Among these 114 patients, 37 (32.4%) of them were using 3 antihypertensive drugs including a diuretic, a proportion of 13.3% when considering the entire study population. Another 5.7% (n = 16) of patients who were having normal blood pressures, were using 4 or more anti-hypertensive drugs. Hence the percentage of patients with resistant hypertension according to the definition was 19.1% (n = 53) of the entire study population. The phenomenon of doctors’ failing to intensify medication regimens at encounters with patients, who have an uncontrolled risk factor, has been described recently as ‘therapeutic inertia’ . AccordiAll the patients with resistant hypertension were compliant with their therapeutic regime and majority (93.9%) of the patients in the non-resistant hypertensive group was also compliant. Table 2) and those who were older than 55 years were significantly higher in the resistant hypertension group than in the non-resistant hypertension group  and non-resistant (63.8%) hypertension groups were obese. Obesity is recognized as the sixth most important risk factor contributing to the overall burden of disease worldwide . It is sThis epidemic of obesity and obesity-related hypertension is paralleled by an alarming increase in the incidence of diabetes mellitus and chronic kidney disease. We observed a statistically significant relationship between diabetes mellitus and resistant hypertension in the logistic regression analysis. Hypertension in diabetics interferes with the rate of development and progression of diabetic complications, which in turn aggravates the hypertensive disease. It appears to be universally accepted that the tight treatment regimes for hypertension in diabetics reduces cardiovascular risk and slows the rate of progression of diabetic complications such as diabetic nephropathy. Hypertension is usually linked with renal disease and it is both a cause and a complication of hypertension. However in our study sample the number of hypertensive’s with renal disease were minimal, probably due to the fact that there are specialized clinic for patients with renal disease at the NHSL, while we conducted the study in a specialized cardiology clinic. Furthermore, blood pressure, plasma glucose, and lipids are continuous variables that exert a dose-dependent effect on cardiovascular risk . Hence iResistant hypertension represents a different phenotype to the general population and it is reasonable to assume that genetic factors play a greater role in pathogenesis. In one of the few genetic evaluations of patients with resistant hypertension, investigators in Finland found that 2β ENaC and γENaC gene variants were significantly more prevalent in the patients with resistant hypertension than in the normotensive controls . A partiThere are a wide range of anti-hypertensives available for the treatment of hypertension. Among them diuretics play major role in blood pressure control. However most of the patients (63.5%) in our study sample were not on any diuretic, including furosemide, spiranolactone and thiazide diuretics. It has been said that combinations of the thiazide-type and potassium-sparing subclasses may be highly effective, providing nearly optimal therapy for some, and might be considered more often in the treatment of hypertension . TreatmeThere are several limitations that need to be kept in mind when drawing conclusions from the present study. The cross-sectional design of our study limits the inference of causality for the risk factors identified. Therefore, it is important to conduct prospective studies on resistant hypertension and look for causality. There was also incomplete documentation on drug-prescribing decisions and regarding the hospital admissions due to disease complications. It may have led to an underestimation of the control of disease and medication intensifications. In addition, lack of diagnostic laboratory tests may have led to under ascertainment of co-morbidities. Furthermore, it is said that the mental stress is important as an aetiological agent for resistant hypertension. However we did not evaluate the patients stress levels in the present study. In addition although risk factors such as Diabetes, Ischaemic Heart Disease and Chronic Kidney Disease were considered their severity was not evaluated .A significant proportion of the hypertensive patients were identified as having uncontrolled hypertension. Nearly one fifth of the population was suffering from RHT, which was significantly associated with the presence of obesity and diabetes mellitus. Therapeutic inertia seems to contribute significantly towards the presence of uncontrolled blood pressure and its role and causative factors needs further evaluation.The authors declare that they have no competing interests.WANK, TP, MD, PR and GRC made substantial contribution to conception and study design. TP, MD and WANK were involved in data collection. GRC, PR and TP were involved in refining the study design, statistical analysis and drafting the manuscript. TP and PR critically revised the manuscript. All authors read and approved the final manuscript.


Local regulation of vascular tone plays an important role in cardiovascular control of blood pressure. Aside from chemical or hormonal regulations, this local homeostasis is highly regulated by fluid-shear stress. It was previously unclear how vascular endothelial cells were able to sense fluid-shear stress. The cellular functions of mechanosensory cilia within vascular system have emerged recently. In particular, hypertension is insidious and remains a continuous problem that evolves during the course of polycystic kidney disease (PKD). The basic and clinical perspectives on primary cilia are discussed with regard to the pathogenesis of hypertension in PKD. The changes in blood vessel diameter serve as an important physiological regulator of blood flow. These changes, caused by contraction and relaxation of vascular smooth muscle, can be regulated centrally and locally. The central regulation of cardiovascular function is achieved through neuronal control through complex projections from central and peripheral neurons –3. The dThe mechanism involved in local regulation of blood vessels is termed autoregulation. It is required to achieve an immediate control of blood flow within a specific region in the tissue. Autoregulation is an effective and efficient way to control the amount of blood flow locally without altering the neighboring systems significantly . In an iin vivo because of the complex nature of the cardiovascular system . A . A 21]. As micro-sensory compartments, cilia have functions that depend on mechano-proteins such as polycystin-1 and polycystin-2 . Thus, tin vivo [The presence of primary cilia in vascular endothelia has been reported in human arteries –31 and hin vivo –38. Of pin vivo –44. The in vivo , 32, 33.in vivo . This fuThroughout the cardiovascular system, patterns of fluid dynamics change considerably due to continuous vascular remodeling and patterning for microadaptation purposes , 45, 46.Tg737 mouse. To further confirm that polycystin-1 and -2 are sensory proteins in cilia, endothelial cells derived from mouse and human with polycystic kidney were used. Ciliary polycystin-1 and/or -2 are absent from the primary cilia in these cells. In Tg737 endothelial cells, polycystins are concentrated in the base of the primary cilia. Functional assays were carried out by challenging these cells with various magnitudes of fluid-shear stress (0.5–50 dyne/cm2). While shear-induced cytosolic calcium increase is observed in normal endothelial cells, neither endothelial cells' isolated mutants nor diseased arteries exhibit this calcium response to shear stress [To test the hypothesis that cilia are mechanosensitive organelles, endothelial cells without cilia were isolated and generated from r stress , 24. insensitive cells or arteries could respond to other mechanical stimulation. Most important is that PKD cells and arteries fail to produce nitric oxide (NO) in response to fluid-shear stress.To validate cilia roles in fluid sensing, endothelial cells or arteries were subject to various mechanical stimulations . The speTo understand how ciliary polycystins are required to activate a biochemical cascade for NO production, various inhibitors were utilized to block the molecular functions . RemovinPolycystic kidney disease (PKD) is characterized by bilateral enlarged cystic kidneys, which have been associated with primary cilia dysfunction , 51, 52.Hypertension, in particular, has been a continual risk factor for other cardiovascular complications in PKD. Similar to cystogenesis, pathogenesis of hypertension in PKD has also been associated with primary cilia dysfunction. Within the context of clinical hypertension, there are two theories that could help describe the pathogenesis of hypertension in PKD . The firIn an observational study of 312 children with PKD, it is reported that high blood pressure promotes faster renal volume growth. PKD children with high blood pressure have faster renal growth than those with lower blood pressure. This suggests that hypertension is a risk factor independent from kidney function in PKD . ConsistOf note is that hypertension occurs at a much earlier age in patients with PKD than in the general population . The medTo examine endothelial function in PKD, the plasma concentrations of vasodilator nitric oxide were measured in PKD patients and healthy controls. In this study, the plasma concentration of nitric oxide was reduced in PKD patients, confirming an association between PKD and endothelial dysfunction . The endAlthough ciliary therapy does not exist today, it is appealing and tempting to speculate the possibility of treatment for localized blood vessel injuries such as aneurysm, atherosclerosis, dissection, edema, hemorrhage, and vascular ectasia, among others in PKD. In particular, endothelium-dependent relaxation is impaired, and endothelial nitric oxide synthase activity is decreased in patients with PKD –73. The It is believed that as renal cysts progress, the cysts will cause structural damage in the nephrons, which leads to distortion of the renal architecture . Such a Activation of the RAAS, which is well documented in the clinical course of the disease  and in PIt was also reported that the sympathetic nerve activity is increased in hypertensive patients with PKD, regardless of renal function , 97. ThiSince cardiovascular abnormalities are thought to initiate from the cystic kidneys in PKD, there has been a great interest in studying the outcomes after renal transplantation in these individuals. Interestingly, renal transplant recipients with PKD still showed an increase in cardiovascular morbidity as seen in non-PKD transplant recipients . In a diPrimary cilium dysfunction has been associated with PKD, and primary cilia have also been proposed to regulate blood pressure. We believe that because our knowledge on cilia biology is still relatively limited compared to other organelles within a cell, there are certainly many more questions than answers that we could provide at present. In order to better understand the relationship between cilia and pathogenesis of hypertension, we need to understand the physiological roles of cilia in more detail and in many other organ systems. For example, vascular endothelial cilia have recently been proposed to regulate cell division  and endoWhether or not dysfunction in primary cilia causes hypertension in PKD, there is certainly much work remaining. We are on the verge of applying our concept and understanding of PKD to better clinical practice and patient outcomes. Nonetheless, early and effective treatments of hypertension are clinically very important to decrease the morbidity and mortality of patients with PKD.


Introduction. There have been six previous cases that reported pseudopheochromocytoma in patients taking clozapine. Our case showed the direct link of clozapine to serum levels of certain markers. Case. This is a case of a 49-year-old obese Caucasian female who was referred to endocrinology for investigation of Cushing's syndrome, based on raised blood pressure and Cushingoid facies. The patient had underlying schizophrenia and was stable on clozapine. Her blood pressure was 150/99 mmHg on bendroflumethiazide and candesartan. We measured her 24-hour urinary-free cortisol, which was normal but 24-hour urinary-free noradrenaline was elevated at 835 nmol (76–561) with normal adrenaline 36 nmol (7–82) and dopamine 2679 nmol (366–2879), as the patient had history of palpitations and sweating. Two sets of 24-hour urinary-free cortisol measurements were normal and serum cortisol suppressed to <50 nmol/l after a 1 mg overnight dexamethasone. Two further 24-hour urinary-free catecholamines showed a raised level of noradrenaline. MRI demonstrated normal adrenals and MIBG scan did not show any abnormal uptake at adrenal glands. Conclusion. Pseudopheochromocytoma has been reported in patients taking clozapine. A number of different mechanisms for raised plasma noradrenaline levels with clozapine have been postulated. The above case highlights an unusual but known side effect of clozapine. Phaeochromocytoma is a very rare endocrine condition. The symptoms of phaeochromocytoma are varied and mimicked by many drugs and medical and surgical conditions. The common initial screening test is free urinary catecholamines and more specifically urinary metanephrines. Drugs can cause false positive elevation of plasma and urinary catecholamines or metanephrines.We described a case of a 49-year-old lady with hypertension and paranoid schizophrenia who was treated with clozapine with false elevation of urinary-free catecholamines and metanephrines. This case illustrates difficulty in distinguishing a true case of phaeochromocytoma from a pseudopheochromocytoma especially in a symptomatic patient who is dependent on antipsychotic medications, which can cause false positive elevation of urinary-free catecholamines and metanephrines.A 49-year-old obese Caucasian female presented to the endocrine clinic following a GP referral for the investigation of a possible diagnosis of Cushing's disease due to a raised blood pressure and Cushingoid facies. The patient had underlying long-term schizophrenia and was stable on 100 mg of clozapine. Her blood pressure control was suboptimal despite being on bendroflumethiazide and candesartan.Clinical examination demonstrated a Cushingoid habitus characterised by typical facies, a supraclavicular fat pad, and central adiposity. Her blood pressure was 150/99 mmHg and she appeared flushed. Examination of the remainder of her cardiovascular system was unremarkable and her visual fields and fundi were also normal.Her 24-hour urinary-free cortisol was normal but 24-hour urinary-free noradrenaline was elevated at 835 nmol (76–561) with normal levels of adrenaline 36 nmol (7–82) and dopamine 2679 nmol (366–2879), which were requested by the GP in light of the patient's history of palpitations and sweating. Two sets of 24-hour urinary-free cortisol measurements were normal and serum cortisol suppressed to <50 nmol/l after a 1 mg overnight dexamethasone dose. Two further 24-hour urinary-free catecholamines showed raised levels of noradrenaline. Urea and electrolytes, liver function tests, and calcium were all normal.An MRI demonstrated normal adrenals and a meta-iodobenzylguanidine (miBG) scan did not show any abnormal uptake in the adrenal glands. Based on these investigations, she was diagnosed with pesudopheochromocytoma due to clozapine, on which she was maintained at that time. She was lost to follow up and presented two years later at the hypertension clinic when she was on a different antipsychotic medication, zuclopenthixol. The repeat 24-hour urinary-free catecholamine as well as urinary normetadrenaline and metadrenaline were in the normal range. Urinary-free levels were as follows: noradrenaline 332 nmol, adrenaline 12 nmol, normetadrenaline 3.48 nmol (0.00–4.90), and metadrenaline 0.33 nmol (0.00–2.00).Using the keywords “hypertension,” “clozapine,” and “phaeochromocytoma” individually or in varying combinations, we searched a number of online databases for previous cases of pseudopheochromocytoma secondary to clozapine therapy. In all, six previous cases –3 were fPrior to initiating clozapine therapy, systolic blood pressure ranged 110–130 and diastolic blood pressure ranged 70–90. During therapy with clozapine, systolic blood pressure ranged 143–180 and diastolic blood pressure ranged 106–120. Furthermore, the heart rate during the period of elevated blood pressure ranged 100–130 and all six patients had elevated urinary catecholamines.Clozapine was stopped in four out of six of the patients. In each case, the blood pressure and the 24-hour urinary catecholamine normalised after clozapine was stopped. Two of the patients continued with clozapine, one of whose blood pressure settled spontaneously.Clozapine is a tricyclic dibenzodiazepine with complex pharmacological actions that include an affinity for a wide variety of receptors including alpha adrenergic, serotonergic, and muscarinic .A number of studies have reported increased plasma noradrenaline levels in patients on clozapine treatment –8. This There are a number of drugs besides clozapine that have been known to cause elevations in plasma and urinary catecholamines. It is therefore possible that the raised plasma noradrenaline levels identified in the cases found in our literature search may in fact be false positives for clozapine. Four patients were concurrently on antidepression medication, three patients were treated with antihypertensive medication, and two patients were also on sulpiride treatment, all of which may be implicated in raising plasma noradrenaline levels. Furthermore, sulpiride is known to block alpha-2-adrenorecepetors and an acute hypertensive episode has been described with its use . This maNevertheless, Breier et al.  comparedIn conclusion, our patient developed pseudopheochromocytoma secondary to the initiation of treatment with clozapine, which subsided on cessation of the drug. Clozapine causes an elevation of plasma noradrenaline through any one of a number of possible mechanisms working individually or in concert. Though other drugs, including other antipsychotics, may also raise plasma noradrenaline levels, it appears as if clozapine does so to a greater extent. Hypertension and tachycardia also seem to be associated with clozapine therapy , and it As hypertension has a potentially dangerous side effect with serious complications such as cardiac failure and other end-organ damage, the use of the drug must be considered carefully with the benefits outweighing any risks. Where clozapine is used, reports in the literature suggest that any resultant hypertension may be controlled with the use of appropriate medication.This case was able to demonstrate the direct link of clozapine to raise urinary noradrenaline and normetadrenaline levels as these normalised after discontinuation of clozapine.


Telehealth systems benefit from the rapid growth of mobile communication technology for measuring physiological signals. Development and validation of a tablet PC enabled noninvasive body sensor system for rural telehealth application are discussed in this paper. This system includes real time continuous collection of physiological parameters  and fall detection of a patient with the help of a body sensor unit and wireless transmission of the acquired information to a tablet PC handled by the medical staff in a Primary Health Center (PHC). Abnormal conditions are automatically identified and alert messages are given to the medical officer in real time. Clinical validation is performed in a real environment and found to be successful. Bland-Altman analysis is carried out to validate the wrist blood pressure sensor used. The system works well for all measurements. The population of elderly individuals is quickly expanding far and wide. The population of individuals of more than 65 years of age around the world will achieve 761 million by 2025, more than twofold of the 1990 figures –6.Hypertension and accidental falls are the two emerging public health problems and a barrier to active ageing . HyperteFall prevalence in India increases with age and is the highest in women and older adults . All perLatest developments in the field of wireless technology can be utilized for monitoring. Wireless body area sensor network (WBASN) is a developing technology that interconnects tiny nodes with sensing capabilities in, on, or around a human body . Recent Community Health Centers (CHC) and Primary Health Centers (PHC) are managing a heavy patient load with the shortfall of doctors as well as supporting staffs . So the This paper is organized as follows: A wearable wrist sensor worn by the patient is used in this work for real time implementation. An embedded platform is used for acquiring the biological information from the wrist sensor and transmitting to a mobile phone/tablet PC running on android platform which is monitored by a medical staff.The hypertension status of the person under test is immediately sent to the tablet PC and automatic alert facility for hypertensive patients is sent to the medical officer through short message service (SMS) facility. The proposed telehealth system architecture with remote monitoring facility is shown in The block schematic of the body sensor unit developed for this work is shown in The body sensor unit, connected to the patient at the health center, consists of the following sensor units.(a) Blood Pressure/Pulse Rate Sensor. Arterial pressure is defined as the hydrostatic pressure exerted by the blood over the arteries as a result of the heart left ventricle contraction [traction . Blood pA noninvasive blood pressure (NIBP) sensor working on oscillatory principle is connected at the wrist of the subject. Wrist sensor measures systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate (PR) of the subject under test. The proper cuff and bladder size used in the assessment of blood pressure is important for accurate measurement. The use of a cuff that is too short and narrow for a given arm results in erroneously high blood pressure measurement. Use of a cuff that is too large results in erroneously low blood pressure measures. Wrist blood pressure sensor used in this work has a cuff with a bladder that is 120 mm wide and 250 mm long.(b) Temperature Sensor. The LM35 series are precision integrated-circuit temperature sensors, whose output voltage is linearly proportional to the Celsius (Centigrade) temperature [perature . The LM3(c) Accelerometer Sensor. A wearable sensor system called Smart Wristlet, providing 24-hour fall detection service, is discussed in [x-, y-, and z-axes are experiencing free fall, 0 g pin (6th pin) will generate a high voltage which can be used to detect person fall. This signal is given to the interrupt pin of microcontroller in order to give highest priority to this event.ussed in . The aboussed in . MMA 736Embedded technology is implemented to perform a specified task. The programming of PIC 16f877A microcontroller is done using embedded C . This isBluetooth wireless communication has the advantage of higher data rate and easy interfacing with personal digital assistant such as a smart phone or a tablet PC. JYMCU HC-05 Bluetooth Module is used in this work which connects to the embedded platform for wireless transmission. Bluetooth module is connected at the software serial port of the microcontroller.Android Studio IDE is used to develop the application for tablets/smart phones with Android Operating System . AndroidA low cost high performance tablet PC (Digiflip XT 811) with Kitkat 4.4 operating system is used in this work for real time implementation. Tablet PC has the advantage of large screen size and better functionality compared to a mobile phone. The android application receives the data transmitted from the body sensor unit via bluetooth communication facility. An android application developed for tablet PC is used for the purpose of real time acquisition of data, comparison with threshold value, storage in SQL database, and alert mechanism generation using SMS facility.The android application initiates GPS services provided by the mobile phone network. While executing the subroutine for fall alert the developed android application collects location information via services given by the network provider or GPS provider. Information such as latitude, longitude, and exact address are collected by proper subroutines. This information is sent along with the text of fall alert message.The examinations have been carried out in Rural Primary Health Center in Andoorkonam, Trivandrum district of Kerala, India. The measurements were authorized by the Office of the District Medical Officer. Patients having Blood pressure variations or under medication for hypertension were directed by the medical officer for measurement. Overall 291 patients including healthy staffs in the PHC have been included.The aim of the validation of the device is to understand the reliability of the data obtained using the wrist sensor. The study also aims to get the feedback of the patients under test about the wrist sensor for blood pressure measurement. The study was conducted at a rural Primary Health Center in Trivandrum and the procedures in this study were approved by the District Medical Officer (DMO) and the medical officer, Andoorkkonam. The study was conducted in accordance with guidelines provided by the medical officer and under the supervision of two trained staff nurses. All subjects were informed and got consent for this study.291 subjects suspected to have hypertension/under medication for hypertension were suggested for BP measurement by the medical officer. 113 male subjects and 178 female subjects were first measured by the sphygmomanometric method and then by the digital wrist sensor based on oscillometric method. Hardware setup  is shown in Age frequency plot of males and females in different age groups under study are shown in The same subject was asked to take measurements using the wrist sensor also. The sensor was suitably positioned at the heart level in order to eliminate errors caused by position artifacts. The pair of data were used for validation of the wrist sensor. The statistical analysis was done for systolic blood pressure and diastolic blood pressure using Bland-Altman method.The system was tested in a practical environment and found to be most successful. The information was transmitted successfully to the tablet PC and stored in the SQL database by the developed android application. Patients with hypertension  were correctly identified and automatic alert messages were generated and sent to the medical officer by the developed android application. Low blood pressure conditions (SBP below 90 mm of Hg and DBP mm of Hg below 60) were also identified. Normal and high body temperature were identified and transmitted to the tablet PC via bluetooth module.Screen shots of outputs obtained are shown in The validations were carried out largely according to the recommendations of the Association for the Advancement of Medical Instrumentation (AAMI). AAMI recommends the inclusion of a larger patient number and a greater number of subjects in an older age group in order to test the monitors' performances over a wider range of patient characteristics. The criteria require device to observe discrepancy within 5 ± (8 s.d.) mm of Hg for mean difference and standard deviation.Bland-Altman analysis was carried out to show the agreement between the two tests. The scatter plot of difference and average of SBP and DBP taken by wrist sensor method and sphygmomanometric method of female population and male population are shown in The accuracy of wrist sensor is calculated by identifying true positives, false positives, true negatives, and false negatives. The obtained accuracy is shown in The aim of this comparison was the analysis for clinical suitability of the wrist blood pressure sensor for family and community health care application. A comparison was done with sphygmomanometric method, which served as a reference device because of its wide distribution and acceptance. The parameters under investigation were the systolic and diastolic blood pressure.The trials showed satisfactory acceptance from the patient side because of the low discomfort caused by the wrist blood pressure sensor. Bland-Altman analysis shows very good agreement between the two methods of measurement.Wrist blood pressure sensor is more suitable in subjects with obesity having large arm sizes. Wrist blood pressure sensor does not require patients to remove clothing while taking measurements and it provides less discomfort compared to arm cuff monitors during inflation.The measurement taken at any time is successfully transmitted to the tablet PC and is stored in the SQL database of the android phone/tablet by the developed application without any manual intervention. This enables the medical officer to ascertain whether a drug is effective or not. The developed system is less expensive and causes less inconvenience for the patients.The validation conducted for the oscillometric wrist technique yields good results which shows good correlation between the BP readings taken with a sphygmomanometer and oscillometric wrist sensor. Patient's opinion about wrist sensor was promising. The device passed the AAMI criteria for SBP and DBP measurement except for male systole data. This study suggests that wrist devices can produce reliable and accurate results. The principal easiness of wrist blood pressure sensor based on oscillometric methods offers the opportunity for wide spread use. This may ultimately lead to an improvement in common efforts to prevent hypertension.A modern approach of health monitoring and management is put into practice by the experiment conducted using the developed system. The ever-increasing workload of physicians can be significantly reduced by the use of such systems.


After removal of endotracheal tube and artificial ventilation, ventilatorysupport should be continued, offering oxygen supply to ensure an arterialoxygen saturation close to physiological.The aim of this study was to investigate the effects of positive-endexpiratory pressure before extubation on the oxygenation indices of patientsundergoing coronary artery bypass grafting.2O (n=32); Group B, 8 cmH2O (n=26); and GroupC, 10 cmH2O (n=20). Oxygenation index data were obtained fromarterial blood gas samples collected at 1, 3, and 6 h after extubation.Patients with chronic pulmonary disease and those who underwent off-pump,emergency, or combined surgeries were excluded. For statistical analysis, weused Shapiro-Wilk, G, Kruskal-Wallis, and analysis of variance tests and setthe level of significance at P<0.05.A randomized clinical trial with seventy-eight patients undergoing coronaryartery bypass grafting divided into three groups and ventilated withdifferent positive-end expiratory pressure levels prior to extubation: GroupA, 5 cmHGroups were homogenous with regard to demographic, clinical, and surgicalvariables. There were no statistically significant differences betweengroups in the first 6 h after extubation with regard to oxygenation indicesand oxygen therapy utilization.In this sample of patients undergoing coronary artery bypass grafting, theuse of different positive-end expiratory pressure levels before extubationdid not affect gas exchange or oxygen therapy utilization in the first 6 hafter endotracheal tube removal. Thus, pulmonary complicationsoccur in up to 60% patients undergoing CABG.Intraoperative conditions, such as general anesthesia, manual compression of the leftlower lung lobe during exposure of the posterior heart surface, manual compressionof the right lung during cannulation of the inferior vena cava, manual compressionof lungs during dissection of the internal mammary artery and apnea duringcardiopulmonary bypass (CPB) may impair pulmonary function. Typical restoration ofhemodynamic stability occurs 5–6 h after surgery in uncomplicated CABG. Thisinterval also correlates with regaining of consciousness and IMVweaning.Invasive mechanical ventilation (IMV) is essential during the first few hours afterCABG to allow recovery from anesthesia and reestablish homeostasis.The spontaneous breathing trial (SBT) is a simple method using pressure supportventilation (PSV) to determine whether a patient would tolerate IMV interruption.This ventilation mode consists of a pressure support of 7 cm H2O (theminimum level to overcome circuit resistance), positive end-expiratory pressure(PEEP) of 5-8 cm H2O , and inspiredoxygen fraction (FiO2) ≤ 40%. This trial lasts 30-120 min and is helpfulin identifying patients who are able to maintain spontaneousbreathing.When IMV is no longer required, the most appropriate method for its discontinuationmust be determined2) close to physiological levels (95%). Oxygen therapy can be offeredusing a nasal catheter, nebulization mask, or Venturi system.Following endotracheal tube and artificial ventilation removal, respiratory supportshould be provided with oxygen to ensure arterial oxygen saturation at Hospital Universitário da Universidade Federal do Maranhão, in SãoLuís, Maranhão, Brazil. We excluded patients with chronic obstructive pulmonarydisease and those undergoing emergency, off-pump, or combined surgeries. We excludedpatients who required surgical reintervention or noninvasive ventilation during thefirst 6 h after extubation.Before surgery, patients received explanations and information about the research.After surgery, data were collected from physiotherapy evaluation forms and medicalrecords. All data were registered in a form that captured preoperative,intraoperative, and postoperative periods. All included patients underwent generalanesthesia and median sternotomy.After ICU admission, mechanical ventilation was applied using an Evita 2 Dura . Patients were ventilated in volume-controlled mode,according to the routine protocol, with the following settings: a tidal volume of6–8 mL/kg, respiratory rate of 14 bpm, inspiratory flow of 8-10 times the minutevolume, inspiratory time of 1 s, and inspired oxygen fraction of 40%.During the preoperative period, patients were randomized into groups by simple draw,and this information was shared with the ICU care providers. SBT was initiated oncethe following clinical conditions were met: hemodynamic stability, absence ofbleeding or minimal bleeding, absence of vasopressor use or low and stable doses ofvasopressors, Glasgow Coma Scale ≥ 10 and strong respiratory drive.2O and FiO2 30%). The sample wasdivided into three groups: Group A, PEEP = 5 cm H2O; Group B, PEEP = 8 cmH2O; and Group C, PEEP = 10 cm H2O. Extubation wasperformed after 30–120 min with no destabilization signs. Following extubation, allpatients received additional oxygen support by Venturi mask  with an FiO2 of 31% to ensure arterial oxygen saturationclose to physiological levels (around 95%).The spontaneous breathing trial was administered using pressure support ventilation(support pressure 7 cm H2) andPaO2/FiO2 ratio.Arterial blood samples were collected before extubation and at 1, 3, and 6 h aftermechanical ventilation withdrawal. Samples were processed by an ABL 800 FLEX bloodgas analyzer , according to the routine protocol. Wethen identified the arterial oxygen partial pressure (PaO2N). Toestimate the ideal arterial oxygen partial pressure (PaO2I) for eachpatient, we used the following equation to account for age and supine position:PaO2I = 109 − (0.43 × age).Following the first arterial blood gas analysis after extubation, oxygen support wasadjusted according to the necessary inspired oxygen fraction  was required following extubation, it was applied,as per the routine protocol, according to the individual's needs. It is noteworthythat patients who used NIV during the first 6 h after extubation were excluded.Ethical approval was obtained from the local Ethics Committee (protocol Nº. 327.798),as required by Resolution 466/12 of the National Health Council. All patientsprovided written informed consent.P value was <0.05.Data were evaluated using the Stata/SE statistical software version 11.1 . To test normality, we used the Shapiro–Wilk test.Quantitative variables were described as means and standard deviations, anddifferences were determined using the Student's t, ANOVA, or Kruskal–Wallis test,depending on normality. Qualitative variables were expressed as proportions andtested by G-test and William's correction. Results were considered statisticallysignificant when 2. Groups did not differ significantly with regard todemographic, clinical, or surgical variables, as seen in Ninety patients were randomized and underwent CABG during the study period. Of these,twelve (four of each group) were excluded because of postoperative surgicalreintervention (6) and noninvasive ventilation use during the first 6 h afterextubation (6) . Therefo2O) were ventilated for 13.6±8.1 h, whereas those in Group B (PEEP 8cm H2O) were ventilated for 11.7±6 h and those in Group C (PEEP 10 cmH2O) were ventilated for 13.2±4.8 h (P=0.69). Therewere no differences in mean gas exchange values (PaO2/FiO2)between groups at 1, 3, and 6 h after extubation ,12.Therefore, we chose to evaluate oxygenation indices after extubation, because theyproperly reflect changes in pulmonary function following on-pumpsurgery.Gas exchange impairment is a significant complication during the CABG postoperativeperiod. Dongelmans et al., who compared high versusphysiological PEEP (10 vs. 5 cm H2O) after CABG, showed that the highestPEEP levels improve oxygenation and lung compliance but are associated withincreased mechanical ventilation duration. In their randomized clinical trial of 136patients undergoing CABG who were mechanically ventilated at 5, 8, or 10 cmH2O of PEEP, Borges et al. showed that the highest PEEP levels may increaserespiratory mechanics and provide better oxygenation indices in the immediatepostoperative period.To reopen collapsed lung units and improve arterial oxygenation following thoracicsurgery, different PEEP levels have been proposed, in which patients undergoing CABG andventilation with PEEP of 0, 5, or 10 cm H2O did not experience asustained arterial oxygenation benefit from higher PEEP levels.Our hypothesis that application of higher PEEP levels throughout SBT would improveoxygenation after extubation was not supported by our measurements during the first6 h after extubation. The results were consistent with those measured in therandomized clinical trial by Marvel et al.?During mechanical ventilation of adult patients, PEEP is generally set to 3–5 cmH2O, as this is considered physiological. However, our study providedsome evidence that levels between 5 and 8 cm H2O, possibly up to 10 cmH2O, may more closely mimic normal respiratory physiology for suchpatients.A question that arose during our research was what PEEP level would be consideredphysiological to avoid alveolar collapse while performing SBT, given that the"expiratory delay function" of the glottis  is removed during artificialventilation.Physical therapists play an important role in conducting patient-screening protocolsfor mechanical ventilation weaning,22. Ourresearch emphasizes identification of optimal variables during weaning asfundamental to this process so as to minimize patient complications.The knowledge of physical therapy was found to be generally applied across the entiretreatment processIn this sample of patients undergoing CABG, the use of different PEEP levels beforeextubation did not affect gas exchange or oxygen therapy utilization in the first 6h after endotracheal tube removal.