The standardized techniques of blood pressure (BP) measurement in the clinic are emphasized and it is recommended to replace the mercury sphygmomanometer by a non-mercury sphygmomanometer. Out-of-office BP measurement using home BP monitoring (HBPM) or ambulatory BP monitoring (ABPM) and even automated office BP (AOBP) are recommended to correctly measure the patient’s genuine BP. Hypertension (HTN) treatment should be individualized based on cardiovascular (CV) risk and the level of BP. Based on the recent clinical study data proving benefits of intensive BP lowering in the high risk patients, the revised guideline recommends the more intensive BP lowering in high risk patients including the elderly population. Lifestyle modifications, mostly low salt diet and weight reduction, are strongly recommended in the population with elevated BP and prehypertension and all hypertensive patients. In patients with BP higher than 160/100 mmHg or more than 20/10 mmHg above the target BP, two drugs can be prescribed in combination to maximize the antihypertensive effect and to achieve rapid BP control. Especially, single pill combination drugs have multiple benefits, including maximizing reduction of BP, minimizing adverse effects, increasing adherence, and preventing cardiovascular disease (CVD) and target organ damage. These Korean Society of Hypertension guidelines for the management of hypertension defined levels of evidence as below: A, Data derived from multiple randomized controlled trials or meta-analysis; B, Data derived from a single randomized controlled trials or non-randomized clinical trials; C, Experts’ opinion or data derived from limited evidences. Also classes f recommendations were defined as below: Class I, Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, and effective. Therefore it should be performed; Class IIa, Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure exists. However, in general, weight of evidence/opinion is in favor of usefulness/efficacy. Therefore it is reasonable to be performed; Class IIb, Usefulness/efficacy is less well established by evidence/opinion. Therefore it may be considered; Class III, Evidence or general agreement that the given treatment or procedure is not beneficial and in some cases may be harmful. Therefore it is not recommended.Accurate measurement of BP is essential for the diagnosis, treatment, and prognostication of individuals with high BP. BP varies according to the environment, body part, and clinical setting of measurement. Therefore, the measurement should be repeated and a standard method should be used Table . All aduhttp://www.dableducational.org).In the office or clinic, the auscultatory method of measuring BP using a stethoscope is the current standard measurement method. BP measuring devices used for the office BP measurement include a mercury sphygmomanometer, an aneroid sphygmomanometer, and an electronic sphygmomanometer. Electronic sphygmomanometers comprise auscultation and vibration method equipment. The mercury sphygmomanometer will be banned by 2020 because of the risk of environmental mercury pollution. Recently, the non-mercury sphygmomanometer equipped with various electronic pressure gauges has been certified and is commercially available so that BP can be measured by auscultation or by the oscillometric method instead of by mercury BP monitoring . The upper arm cuff is applied to the ankle and auscultation is performed on the dorsalis pedis or posterior tibial artery. A large cuff can be applied to the thigh, using a bladder that is 20% wider than the diameter of the thigh (15–18 cm). Auscultation is performed on the posterior tibial artery. Because the measured value varies widely in case of arrhythmia, the BP values should be averaged with more than three times of measurement . Salt reduction has many benefits, including lowering of BP and reducing the need for diuretics, which cause detrimental urinary loss of potassium and calcium. The avoidance of urinary calcium loss prevents the development of osteoporosis and renal calculi.Sensitivity to salt tends to be higher in patients who are elderly, obese, or have diabetes or family members with HTN. Greater salt sensitivity means a greater reduction in BP in response to salt restriction. Because of the high correlation with salt intake and energy intake, reducing caloric intake can reduce salt intake. Dietary habits must be modified. Some recommendations are not to put additional salt on the table during the meal and to avoid high-salt processed foodstuffs. Some frequently eaten foods, such as kimchi, stew, soup, salted fermented seafood, instant ramen, and dry bar snacks containing meat and fish, are very salty. When cooking, natural ingredients should be used instead of synthetic flavoring agents. The patient should reduce absolute salt intake but also try to consume more low-salt foods.Eating potassium-rich foods can help prevent HTN, and can lower BP in hypertensive patients. Potassium can inhibit BP rise with salt intake by excreting sodium outside the body. The higher the potassium intake, the more potent the BP-lowering effect of potassium can be achieved. However, attention should be paid to potassium intake in patients with impaired renal function.HTN is closely associated with obesity, and weight reduction decreases BP. Central obesity in particular is closely associated with HTN, dyslipidemia, diabetes, and CV death. In a patient heavier than 110% of the ideal body weight, a weight reduction of only 5 kg can decrease BP. The beneficial effects of weight reduction are higher in patients with diabetes, dyslipidemia, and LVH. The combination of weight reduction with exercise, moderation of alcohol consumption, and reduction of salt intake has synergistic effects on BP. The recommended initial goal of weight reduction is 4–5 kg, with an additional 5 kg reduction after the initial goal has been achieved.2)] varies among reports and according to nationality. A collaborative analysis reported that BMI either above or below the apparent optimum of approximately 22.5–25 kg/m2 is itself a strong predictor of overall mortality [2 and recommended a BMI of less than 25 kg/m2. Unfortunately, there are no Korean-specific data on appropriate waist circumference. A waist circumference of less than 90 cm for men and 85 cm for women is recommended for Asian individuals.The ideal BMI [weight (kg)/height , 1 glass of wine (200–300 mL), 1 glass of sake (200 mL), 2 shots of whisky (60 mL), or 2–3 glasses of soju corresponds to 30 g of alcohol.The benefits of regular exercise are lowering of BP, improvement of cardiopulmonary function, reduction of body weight, improvement of the lipid profile (including elevation of HDL-cholesterol), and reduction of emotional stress. Aerobic exercises such as brisk walking, jogging, bicycling, swimming, jumping rope, playing tennis, and aerobic dancing are recommended for patients with HTN . The appDuring smoking, the BP increases temporarily in response to nicotine. Among patients with white coat HTN, smokers maintain a higher daytime ambulatory SBP than do non-smokers with a similar office BP . BecauseBP is lower in vegetarians than in people who mainly eat meat, and maintaining a vegetarian diet can reduce BP. The BP-lowering effect results not from decreasing the intake of animal protein but from increasing the intake of vegetables and fruits in combination with decreasing the intake of saturated fatty acids. In a study in elderly people, BP decreased by 3/1 mmHg when intake of vegetables and fruits was increased alone but by 6/3 mmHg when it was combined with a decrease in fat intake –123. It Caffeine from various foods rapidly increases BP, but the effect does not progress to HTN because tolerance to caffeine develops. Emotional stress increases both BP and the risk for CVD, making the control of emotional stress important for the management and patient adherence of HTN. Further studies are required to examine the long-term effects of stress control on HTN and CVD. The effectiveness of various methods of stress management, such as relaxation and biofeedback, for the management of HTN remains uncertain. There is still no clear evidence for the effects of micronutrients, calcium, magnesium, and supplementary fiber on BP.The occurrence of CV events in patients with HTN can be decreased by reducing the BP. Currently available antihypertensive drugs are more effective than placebo for prevention of CVD. This preventive effect is relatively larger for stroke than for CAD. The extent to which CV events are reduced depends on the degree of BP reduction. All major classes of antihypertensive drugs, including beta-blockers and diuretics, are suitable for first-line treatment. However, the individual drug should be prescribed with consideration of the patient’s individual situation, including age, comorbidities, and possible adverse effects. Simplifying the medication schedule, careful monitoring of the adverse effects, and checking the BP at home are useful for improving patient adherence and making the patient an active participant in the treatment.For reducing long-term CV morbidity and mortality, it is essential to control most of the modifiable risk factors and to reduce the BP to less than 140/90 mmHg . Drug thIt is reasonable to choose drugs according to the patient’s comorbidities and clinical characteristics rather than his or her BP level. There are five available classes of first-line drugs with proven BP-lowering effects, safety, and acceptable adverse effects according to multiple studies. They are: 1) ACE inhibitors or ARBs; 2) beta-blockers; 3) calcium channel blockers; and 4) diuretics such as hydrochlorothiazide, chlorthalidone, or indapamide. All reduce BP to a similar extent when the dose has been adjusted. However, there might be individual differences in BP lowering, adverse effects, and long-term CV events, making it very important to choose the appropriate drugs according to the patient’s combined risk factors and comorbidities Table . No anti2 [Diuretics decrease BP initially by reducing reabsorption of sodium in the renal distal convoluted tubules and later by decreasing peripheral vascular resistance. High-dose thiazide-derivative diuretics can induce hypokalemia, glucose intolerance, hyperuricemia, arrhythmia, and adverse lipid metabolism, but low doses rarely have these effects. Combination of diuretics with beta-blockers is not recommended in patients with obesity or at high risk of diabetes because of adverse effects such as new-onset diabetes and adverse lipid metabolism. Thiazide-like diuretics such as chlorthalidone and indapamide have been found to be more effective than hydrochlorothiazide , 138, bu2 . SpironoSelective beta-1 blockers are recommended for patients with HTN in combination with angina pectoris, myocardial infarction, or tachycardia. Beta-blockers are also effective in younger patients who have higher heart rates . HoweverLong-acting calcium channel blockers are preferable to short-acting calcium channel blockers, which can cause tachycardia and increase cardiac workload. Because calcium channel blockers have a vasodilatory effect on the coronary artery, they are highly effective in patients with stable angina or variant angina, which is caused by coronary artery spasm. They are also effective for slowing the progression of carotid atherosclerosis and reducing cardiac hypertrophy . The nonACE inhibitors/ARBs reduce mortality in patients with heart failure and help to inhibit the progression of renal disease. They also help to prevent LVH and atherosclerosis and have little effect on blood glucose or lipid metabolism . In addiSide effects include hyperkalemia, acute renal damage in bilateral renal artery stenosis, abnormal taste, leukopenia, angioedema, and rash.Alpha-blockers can alleviate urinary symptoms in patients with prostate enlargement and also improve the metabolism of glucose and lipids. However, they can cause orthostatic hypotension and are associated with worsening of heart failure. Agents that act on the central nervous system, such as clonidine, methyldopa, and reserpine, have many side effects and are therefore not recommended as first-line drugs. Renin inhibitors have been developed and used in other countries but were not introduced in Korea. Renin inhibitors significantly reduced BP and proteinuria when used alone or in combination with diuretics. However, aliskiren has not been proven to improve the prognosis of patients with CVD. Methyldopa is still preferred for the treatment of HTN in pregnant women but is not the first choice because of its side effects. Hydralazine is a vasodilator that is relatively safe for pregnant women with HTN.More than 2/3 of patients with HTN require drugs from more than two drug classes with different mechanisms to achieve control of HTN. Combination therapy is particularly helpful for patients receiving prolonged BP treatment, high risk patients, and patients with lower target BP. If the first drug used is not effective for BP control, then a drug of another class should be tried. If the efficacy is insufficient, the dose should be increased or another drug added. However, it is recommended to combine two different drugs in smaller doses rather than to increase the dosage of one drug because such low dose combinations lower BP more effectively and improve the adherence while decreasing the adverse effects  despite treatment with more than three different classes of antihypertensive drugs, including diuretics. The prevalence of resistant HTN is reported to be 5–30% in other countries. However, considering the frequency of pseudo-resistant HTN, the prevalence of true resistant HTN is assumed to be below 10%. Patients with resistant HTN are at much higher risk for complications such as CVD and CKD .Among the wide range of causes of resistant HTN Table , non-adhTo diagnose resistant HTN, treatment adherence should be confirmed and then the home BP or ambulatory BP should be monitored in order to exclude white coat HTN. If BP cannot be controlled despite the use of effective doses of three different classes of drug, then the dose of diuretics should be increased, or thiazide diuretics changed to loop diuretics in patients with renal impairment. However, most patients with resistant HTN require a different mechanism for BP control, and the fourth drug added should be spironolactone, amiloride, or an alpha-blocker such as doxazosin –159. WheCarotid baroreceptor stimulation or renal denervation may be tried in patients with true resistant HTN since the risk of procedure-related complication is low. However, there are non-responders and a lack of evidence of long-term effects, therefore it is not currently recommended , 161.In patients whose BP has been well controlled for years, or for an extended period, it may be possible to reduce the number and/or dosage of drugs. This may particularly be the case if BP control is accompanied by healthy lifestyle changes such as weight loss, exercise habits, and a low-fat and low-salt diet, which remove environmental pressor influences. A reduction of medications should be made gradually, and the patient should be checked frequently, for example at least for three months, because reappearance of HTN can occur frequently .The goal of antihypertensive therapy is to reduce the overall CV risk in patients who have other risk factors such as diabetes, dyslipidemia, CAD, stroke, and CKD. Accordingly, these other risk factors should be treated concurrently.Aspirin administration has been shown to produce an absolute benefit for the secondary prevention of CVD in patients with HTN . HoweverLipid-lowering agents have a protective effect on high risk patients with HTN. Although there is very little Korean data, a 50% reduction in LDL-cholesterol in patients who had an LDL-cholesterol level ≥ 130 mg/dL significantly lowered the risk of CVD . LowerinThe goal of glycemic control in patients with DM is less than 6.5% of glycated hemoglobin, further lowering if there is no complication associated with early diabetes and low risk of hypoglycemia. Conversely, in patients with severe hypoglycemia, short life expectancy, advanced microvascular and macrovascular complications, and elderly people over 75 years of age, the goal of glycemic control can be individualized taking into account the risk of hypoglycemia .Patients should generally be followed up once monthly, at least until the target BP is achieved. Patients with severe HTN (grade 2) require more frequent follow-up. The serum potassium and creatinine levels should be measured at least 1–2 times yearly. If the BP is controlled and stable, then the patient should be followed up every 3–6 months. A longer follow-up interval may be associated with low adherence. Therefore, patient adherence also must be monitored as well as the regular follow up tests for blood samples. A longer follow-up interval to monitor the status of BP control can be achieved by encouraging home BP measurement.Trust between doctor and patient is the most important issue in the treatment of HTN, and the patient should therefore be encouraged to participate in the treatment plan. Many patients may have obtained information about various antihypertensive agents through various routes, so discussion may be necessary. First, identify the patient’s point of view to determine the relative importance of efficacy, cost-effectiveness, and side effects. It is necessary to reduce overall CV risk as much as possible while maintaining the patient’s adherence. Self-measurement of BP by using HBPM can improve adherence .


Cardiovascular disease (CVD) is a leading cause of death in patients with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are known as predictors of CVD in these patients. Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury. Recently, elevated NGAL levels have been reported in patients with CVD. This study aimed to evaluate the association between plasma NGAL levels and LVH/LVDD in patients with CKD.2). Two-dimensional echocardiography was performed to measure the left ventricular mass index (LVMI). Tissue Doppler imaging was used to measure early mitral inflow velocity (E) and the peak early mitral annular velocity (E'). Diastolic function was estimated using E' and the ratio of E to E' (E/E'). The associations of echocardiographic index with clinical and laboratory variables , the inferior vena cava collapse index (IVCCI) < 50%, and plasma NGAL) were investigated using univariate and multivariate analyses.This study included 332 patients with pre-dialysis CKD (estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73mIn multivariate logistic regression analysis, plasma NGAL was an independent predictor of LVH , P < 0.001). In addition, hypertension, intact PTH, and IVCCI < 50% were independent predictors of LVH. Plasma NGAL  was also an independent factor of LVDD. Furthermore, hypertension, intact PTH, and IVCCI < 50% were independent predictors of LVDD. Receiver operating characteristic curve analysis  showed the best cutoff value of plasma NGAL for identifying LVDD was ≥ 258 ng/ml with an associated sensitivity of 77.6% and a specificity of 87.6%.Plasma NGAL levels were independent predictors of LVH and LVDD in patients with pre-dialysis CKD, suggesting that plasma NGAL could be a biomarker for LVH and LVDD in these patients. Cardiovascular disease (CVD) is a leading cause of death in patients with chronic kidney disease (CKD) . Not onlNeutrophil gelatinase-associated lipocalin (NGAL) is a protein belonging to the lipocalin family, which is rapidly released in response to a variety of cellular stresses, including ischemia and inflammation . NGAL isSeveral studies have reported on the associations between NGAL and cardiac structure or function in patients with chronic heart failure (CHF) , 11, 12.−1.154 × age−0.203 × 0.742  or × 1.21 (if African-American). All adult patients (≥ 18 years old) with CKD [eGFR < 60 ml/min/1.73m2] and who were not on dialysis were included. To exclude patients with acute kidney injury and to clearly identify patients with CKD, only patients whose previous serum creatinine level was known from medical records or who were followed for at least 3 months were included. Patients with valvular heart disease, congenital heart disease, cardiomyopathy, evidence of systolic heart failure [left ventricular ejection fraction (LVEF) < 50%], known CHD , and atrial fibrillation were excluded. This study protocol was approved by the Institutional Review Board of Pusan National University Yangsan Hospital (IRB No. 05-2017-178). Informed consent was waived by the IRB due to the retrospective nature of the analysis using information contained in medical charts and records, which were anonymized.Patients who had visited the nephrology clinic in Pusan National University Yangsan Hospital between 2010 and 2016 were investigated retrospectively in this cross-sectional study. Estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease (MDRD) equation : 186 × s2. All blood variables including albumin, uric acid, calcium, phosphate, total cholesterol, hemoglobin, C-reactive protein (CRP), intact parathyroid hormone (PTH), and plasma NGAL were measured concomitantly. Plasma NGAL level was measured using Triage NGAL immunoassay  with a measurable range from 15 ng/ml to 1300 ng/ml. Intact PTH levels were measured using electrochemiluminescent immunoassay  (reference range: 10–65 pg/ml).Demographic and clinical data on age, gender, and presence of diabetes or hypertension were obtained by reviewing medical records. Diabetes was defined as the use of diabetes medication or fasting plasma glucose concentration ≥ 126 mg/dl. Hypertension was defined as the use of hypertension medication or systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg. Body mass index (BMI) was calculated by measuring the weight and height of each patient and is expressed as kg/m3 –{LV internal diameter}3] + 0.6 g). LV mass index (LVMI) was calculated by dividing LV mass with the patient’s body surface area (BSA) [LVMI = LV mass (g)/BSA (m2)] [2 in men and > 95 g/m2 in women [Transthoracic echocardiography was performed using an IE33 echo system . All echocardiographic data were measured according to the guideline of the American Society of Echocardiography . StandarSA (m2)] . LVH wasin women . The LVEin women . The infin women . Cyclic in women . Thus, tP < 0.05 were considered statistically significant. All analyses were performed using the SPSS version 21.0 statistical package  and MedCalc Statistical Software version 15.8 .Continuous variables are expressed as the mean ± standard deviation and categorical variables are presented as percentages. Differences among groups were tested with one-way ANOVA for continuous variables and with the chi-square test for categorical data. Pearson’s correlation was used to investigate the correlation associated with the LVMI, E', and E/E' ratio in the study subjects. Uni- and multivariate logistic regression analyses were performed to calculate the odds ratio (OR) with 95% confidential interval (CI) for having the LVH and LVDD in the study subjects. Receiver operating characteristic (ROC) curve analysis was employed to assess the best cut-off value of plasma NGAL for predicting the LVH and LVDD in the study subjects. Values of 2) were 42.7 ± 7.9 in CKD stage 3, 21.7 ± 4.1 in CKD stage 4, and 10.0 ± 2.5 in CKD stage 5. There were no significant differences across the three groups in sex, total cholesterol, BMI, and prevalence of DM, hypertension and glomerulonephritis. Patients with advanced CKD were more likely to be old and have elevated levels of serum phosphate (P < 0.001), uric acid (P = 0.004), CRP (P < 0.001), and intact PTH (P < 0.001), whereas they were likely to have decreased levels of serum albumin (P < 0.001), calcium (P < 0.001), and hemoglobin (P < 0.001). Patients with advanced CKD were also more likely to have volume overload as indicated by IVCCI < 50% (P = 0.048). Plasma NGAL levels were significantly higher in the advanced CKD stages (P < 0.001). In the echocardiographic parameters, patients with more advanced CKD stages had a higher LVMI (P < 0.001) and prevalence of LVH . The degree of LVDD was more severe with increasing CKD stage, which was evidenced by lower E' (P = 0.003) and higher E/E' ratio (P = 0.041). However, the prevalence of LVDD was not different across the CKD stages. There were no significant differences between the three CKD groups in LVEF.The baseline characteristics of the study population are shown in r = 0.540, P < 0.001) and E/E' . Plasma NGAL levels were negatively correlated with E' . There was a significant correlation between LVH and LVDD. The LVMI was negatively correlated with the E  and positively correlated with the E/E' .The mean interval from the plasma NGAL measurement to echocardiography was 31.4 ± 15.0 hours (range: 3–74 hours). Data of LVH and LVDD according to tertiles of plasma NGAL values are shown in To investigate the diagnostic power of plasma NGAL for predicting the presence of LVH and LVDD in patients with pre-dialysis CKD, ROC analysis was performed . The areLVH and LVDD are common and their prevalence and severity are known to increase with the progressive decline of renal function in CKD patients , 4, 16. NGAL is upregulated and secreted in kidney injury. In CKD patients, blood NGAL level is known to be elevated and is a predictor of the progression of CKD . Our stuWith regards to the association between NGAL and cardiac structure or function, previous studies showed inconsistent results. Bolignano et al. reported that serum NGAL was correlated with LV systolic function in 46 elderly patients with CHF . YndestaHow the plasma NGAL levels are associated with the LVH and LVDD in CKD patients is unclear. Ventricular remodeling in LVH and LVDD is a highly complex process that not only involves alterations in the cardiomyocyte but also alterations in the extracellular matrix, and matrix metalloproteinase (MMP) is an important mediator in this process . NGAL foIn this study, patients with advanced CKD were more likely to have higher plasma NGAL levels. This result suggests that chronic renal injury might enhance the production or reduce the clearance of NGAL . The preOur study has several limitations. First, due to the cross-sectional design of our study, it is difficult to establish temporal relationship and causality. Future prospective studies are needed to verify the potential causal relationship between plasma NGAL and the development of LVH and LVDD in CKD patients. Second, there was no investigation about the medication history at the time of study enrollment due to limited patient information. Thus, we could not rule out the possibility that antihypertensive medications such as angiotensin-converting enzyme inhibitor or angiotensin receptor blocker might have affected the association between plasma NGAL and LVH/LVDD. Third, the study subjects were highly selected. In fact, patients with normal LVEF without valvular or ischemic heart disease are not common in the setting of patients with CKD, especially advanced CKD stage. Therefore, it is unclear if our results can be extrapolated to all patients with CKD. However, we excluded patients with these confounding abnormalities to reveal the relationship between NGAL and LVH/LVDD more clearly.Despite the limitations, our study has some clinical implications. Recently, combined cardiac and renal dysfunction has gained considerable attention. The cardio-renal syndrome (CRS) comprises a broad spectrum of diseases within which both the heart and kidneys are involved, acutely or chronically . Of the In conclusion, this study demonstrates for the first time the association between plasma NGAL levels and LVH/LVDD in pre-dialysis CKD patients with preserved LV systolic function. We found that plasma NGAL levels were independently associated with LVH and LVDD in pre-dialysis CKD. We also showed the best cut-off value of plasma NGAL for predicting the presence of LVH and LVDD. Although the results of our study suggest that plasma NGAL may have a potential role as a biomarker for LVH and LVDD in pre-dialysis CKD patients, future studies are mandatory to clarify our findings.S1 File(XLSX)Click here for additional data file.


Closed loop total intravenous anesthesia is a technique in which the patient’s hemodynamic and anesthetic depth variables are monitored, and based on this information, a computer controls the infusion rate of drugs to keep them within pre-established clinical parameters.TM monitorTo describe the technical and clinical performance of a closed loop system for total intravenous anesthesia with propofol and remifentanil, using the SEDLineMulticentric prospective cohort studySurgery roomASA I-II undergoing elective surgeryTM) of the SEDLine monitor for propofol, and on hemodynamic variables for remifentanil. The measurement of clinical performance was made based on the percentage of PSITM maintenance time in the range 20–50. Precision analysis was evaluated by measuring median performance error (MDPE) can be defined as the median difference between actual and desired values, which refers to the degree of precision in which the controller is able to maintain the control variable within the objective set by the anesthesiologist; it represents the direction (over-prediction or under-prediction) of performance error (PE) rather than size of errors, which is represented by MDAPE, median absolute percentage error, Wobble index, which is used for measuring the intrasubject variability in performance error.The authors designed a closed loop system that implements a control algorithm based on anesthetic depth monitoring and the Patient State Index (PSITM maintenance time in the 20–50 range was 92% (80.7–97.0). MDPE was 10.7 (− 11.0–18.0), MDAPE 21.0 (14.2–26.8) and wobble 10.7 (7.0–16.9). No adverse surgical or anesthetic events were found.Data were obtained from 93 patients in three healthcare centers. The percentage of PSIThe closed loop total intravenous anesthesia system with SEDLine developed by the authors was used without major complication and appear to be feasible its use in clinical performance. Total intravenous anesthesia (TIVA) is a technique administered using two methods: open loop or target-controlled infusion system (TCI) through manual intravenous infusion, and closed loop control system. Closed loop is an automated control system based on the feedback principle, which calculates and administers the drug according to the target or effective-site concentrations defined by the anesthesiologist. The open loop system has been shown to be inaccurate for predicting and maintaining the desired clinical effect, since pharmacokinetic and pharmacodynamic mathematical models have little physiological correlation and great interindividual variation  monitoring is commonly used as index of the level of consciousness to guide propofol administration.  between 0 and 100, where PSITM 100 represents wakefulness and 0, with an isoelectric EEG, suppression. The PSITM between 20 and 50 is associated with an adequate level of anesthetic depth  and heart rate (HR) are used as controlled variables  IPS Universitaria, Ambulatory Headquarters (Medellín), (2) Hospital San José (Bogotá D.C.), and (3) S.E.S Hospital de Caldas , with a convenience sample of 93 patients. Written informed consent was obtained from each participant before data collection and appropriate measures were taken to minimize risks and maintain confidentiality. The protocol was summited to the Ethical and Research Institutional Board (three universities) and approved by the Bioethics Committees of each institution. The study was nor registered in any research platforms. We followed the STROBE  guidance in conducting and reporting our investigation.Inclusion criteria were age over 18 years, American Society of Anesthesiologist (ASA) physical status 1–2, planned for undergoing elective noncardiac surgery  of low or intermediate risk, under general anesthesia by closed loop TIVA technique were studied. Patients with a history of allergy to opioids or any component of propofol, pregnant, with morbid obesity (BMI > 40), who did not consent to their participation and patients requiring analgesic or anesthetic peripheral block prior to surgery were excluded from the study. The participating anesthesiologists were trained in the operation of the equipment. The eligibility criteria were verified and informed consent was completed.TM as a clinical variable for the control of propofol concentration, and HR and BP as control variables for remifentanil infusion.The authors designed a closed loop system using the PSIOn the day of surgery at the holding area, a peripheral IV line was established with an 18-gauge IV canula in the forearm and two 3-way keys were placed. In the operating room, patients were monitored with pulse oximetry and non-invasive BP using a ROOT® monitor  connected to the module and the closed loop software designed by the researchers. Standard monitoring, including 5-lead electrocardiography and capnography were attached and recorded with independent monitors.The developed control algorithm contains a patented diffuse logic control module that adjusts the dose-response effects in situ of the hypnotic (propofol) and the opioid (remifentanil) agents according to the physiological variables of the patient.TM for dose adjustment. Fuzzy logic was chosen as the best control mechanism, because its linguistic nature allows translating better the decisions of an expert anesthesiologist into equations and curves, in such a way that there are no unexpected answers or very “abrupt” answers, as may be the case with a deterministic control. In other words, for a control system like this, radical scales cannot be presumed if a patient with a PSI value of 51 is awake, but is anesthetized with a value of 50.For propofol, the algorithm took into account electromyography parameters, suppression rates, spectral edge frequencies and the PSIFuzzy logic was also used for remifentanil. Control variables are “changes in hemodynamic variables” and not their absolute values, that is to say, a universal blood pressure value is not taken into account, since a patient can be significantly over-dosed if taken to a MAP of 50 when basal MAP in the anesthetic phase is 60 and naturally resists going below that level. For this reason, the controller analyzes the patient’s sensitivity to induction doses and, during maintenance, modifies the target doses according to new changes in the HR or MAP with respect to the basal “sensitivity” found during induction. Similarly, for an automatic controller, a patient with a MAP of 50 cannot be considered normotensive and is considered hypotensive with MAP at 49.In case of requiring vasoactive agents or of having alterations in the mentioned variables, the closed loop system allows converting the system in an open one and continuing the TCI infusion in that way. This prevents the system from interpreting a bolus of ethylephrine as a nociceptive response. The system has a button through which the anesthesiologist can anticipate a painful surgical stimulus and apply a bolus of opioid prior to the stimulus without abandoning the closed loop mode, after which the system continues to analyze the hemodynamic changes and can increase even more the target concentration in case of finding disturbances.TM monitoring system , consisting of four channels, are placed in the frontal region . The PSITM, BP, pulse oximetry, and HR (monitor ROOT®) are connected to the signal processing and control unit, consisting of a computer  with the algorithm developed by the research team connected to a perfusor , with a maximum flow rate of 1200 mL/h and with capacity for two 60-mL syringes, which executes the control orders for the perfusion rates calculated by the closed loop software for propofol and remifentanil. The PSITM is reported with a delay of 20 seconds while the spectrogram and suppression rates are reported in real time , and the target concentration is selected. The program performs a simulation using the pharmacokinetic parameters according to the Schnider . The closed loop system algorithm has two moments: (a) induction and (b) maintenance, adjusting the rate and duration of propofol delivery differently at each time. During induction, the controller attempts to achieve the target concentration in a phased manner based on the initial calculation—which is in turn based on the pharmacokinetic model (continuously feeding back through the PSITM)—and during maintenance from a target value of the PSITM, but taking into account the existing PSITM (which is recorded every 10 s).During the surgical procedure, the algorithm adjusts the perfusion rate of propofol every 30 s, re-feeding based on the anesthetic depth reports of the SEDLineThe perfusion rate of remifentanil is controlled by monitoring the ANALGOSCORE designed and validated by Hemmerling et al.  and the presence or absence of intraoperative recall according to the Michigan classification.Anthropometric measurements, sociodemographic, and hemodynamic variables, baseline MAP and HR, and intraoperative data were recorded. For the purposes of this study, the researchers defined hemodynamic instability as a 20% reduction of the baseline sustained systolic BP during two consecutive doses. The variables maintenance time in the PSIIt is a descriptive study, for that reason we don’t report statistical test. Quantitative variables were reported using measures of central tendency and dispersion, after evaluating the criterion of normality through the Kolmogorov-Smirnov test. Qualitative variables were presented as proportions and frequencies. The statistical analysis was performed using SPSS version 20.0 and Excel 2013.TM was evaluated using the formulas described by Varvel et al.  is the weighted residual of the target value at any given time point; the difference between the actual values and the target value.Median performance error (MDPE) is a measure of bias and indicates whether the administration of drugs with the system is systematically above or below the target value.Median absolute performance error (MDAPE) indicates the inaccuracy of the TCI system and is a quantitative measure of how far the observed value deviates from the target; its value varies between 20 and 50%.Wobble indicates the within-subject variability of the TCI system. In this context, Wobble is a measure of variability in the patient’s PE. The clinically accepted value is 10–20%.Divergence is the slope of linear regression between the MDAPE and time. Divergence shows whether inaccuracy of the TCI system changes over time.The technical performance of the system based on the PSI Varvel, , which h Varvel,  recommenAll these measures focus on the capacity of the TCI system to achieve and maintain a specific plasma drug concentration, which are appropriate to evaluate the performance of computer-controlled infusion pumps  and the bias (MDPE) should be close to zero, and the relationship between the observed value and the anticipated value would be unity. The TCI system should also be stable over time, so that oscillation and divergence are as low as possible. PE < 20–40% and MDPE < 10–20% are considered clinically acceptable.One hundred patients were taken to closed loop TIVA; the information of 7 cases was lost due to a storage error in the system. The 93 patients analyzed were distributed as follows: 47 in institution 1, 27 in institution 2, and 19 in institution 3 . 46.3% of surgeries were plastic surgery, followed by 22.1% of general surgeries   related to disconnection of the venous line and consequently of the remifentanil and propofol infusions , with MDAPE 21.0 (14.2–26.8), and Wobble 10.7 (7.0–16.9) Table .Table 3TM, measured with the percentage of time of maintenance of the PSITM between 20 and 50, was good in all institutions, being > 70% of the anesthetic duration in 85.3% of patients, value considered adequate as reported for this type of device    .Some of the limitations of this study were the number of cases and its descriptive nature that did not allow making comparisons with the system based on monitoring with BISTM that provides the PSITM as an index of anesthetic depth, was used without major complication and appear to be feasible in its use in ASA I and II patients undergoing elective non-cardiac surgeries.This study, which used a total intravenous anesthesia administration system with propofol and remifentanil guided by a novel neuromonitoring system, the SEDLineTM vs. closed loop systems with SEDlineTM; actually, most of them focus on showing the safety of the closed system vs. administration with open system, making necessary, in our opinion, to make progress in establishing which could be the most appropriate anesthetic depth monitor to link and feedback the TCI system.It is necessary to carry out further studies to compare this technology with similar ones and demonstrate their advantages to obtain clinically relevant conclusions and continue optimizing the system. To date, there are no studies that compare closed loop systems with BIS


The prognosis of patients with recurrences from stage 4 neuroblastoma is not uniformly dismal. The evaluation of new therapies therefore needs to consider the individual risks of the treated patients. This study aims to define clinically useful risk criteria.Inclusion criteria were: first recurrence of neuroblastoma stage 4 aged ≥18 months and enrollment in first line trials between 1997 and 2016. Patients were randomized into a training set (N = 310) and an independent validation set (N = 159). The primary endpoint was secondary event‐free survival. The individual treatment elements the patients received during initial and recurrent disease were analyzed as binary and time‐dependent variables. A five‐step multiple time‐dependent Cox regression analysis was performed on the training set to identify prognostic variables adjusted for the individual frontline treatment. The selected variables resulted in a prognostic index (PI) and were used to build a risk score system. The score was validated with the validation set.Of the 469 patients, 372 were treated with curative intent and 97 with palliative intent. The PI included the variables number of recurrence organs (hazard ratio [HR] = 2.27), time to recurrence (HR = 2.03), liver metastasis at diagnosis (HR = 1.77), first recurrence at site of the primary tumor (HR = 1.55), and age (HR = 1.29). Three risk groups were built and confirmed in the validation set. The scoring system was likewise useful for the curatively or palliatively treated subgroups.A new risk score system for patients with first recurrence of stage 4 neuroblastoma aged ≥18 months at diagnosis is proposed. The prognostic index of each patient with first recurrence of stage 4 neuroblastoma aged >18 months at first diagnosis can be calculated. If a characteristic is present, use the indicated figure. If absent, use 0. The sum indicates the related risk group. For clinical scientists, reporting on phase 2/3 trials requires a comparison with equivalent risk groups. The study objective was to develop a robust score system taking into account the individual treatment the patients had received. A large data set was retrospectively analyzed, focusing on the largest and worst group, ie stage 4 neuroblastoma aged ≥18 months at initial diagnosis, including patients treated with palliative intent.22.1This is a retrospective analysis of data obtained from the national trials NB97 and NB2004 of the German Pediatric Oncology Society. The data lock was 30 April 2019. The primary endpoint for this analysis was secondary event‐free survival (secEFS), and the secondary endpoint was secondary overall survival (secOS). Table http://www.kinderkrebsregister.de). If medical care had been finished, the local registration offices were approached in accordance with the national law. Of all German neuroblastoma patients known to the German Childhood Cancer Registry, 99.3% participated in one of the two trials between 1997 and 2016.The trials were conducted in 66 pediatric oncology university and community hospitals in Germany and Switzerland. All protocols were approved by the ethics committees of the University of Cologne. Written informed consent was obtained from the parents or legal guardians before enrollment and included the follow‐up after recurrences until death. Yearly routine check‐up reports were requested by the trial office from the local institutions and/or by the German Childhood Cancer Registry (2.2The inclusion criteria were (a) neuroblastoma stage 4 according to international criteria (INSS)2.3P‐values were calculated. For all analyses, IBM SPSS statistical package version 24 and SAS version 9.4 were used.Secondary event‐free survival was defined as the time from first recurrence until second recurrence or until death of any cause or until the last examination. For simplicity, recurrences where tumors had completely disappeared as well as progressions where tumors had partially disappeared or had been stable have been comprised under the term “recurrences”. Secondary overall survival was defined as the time from first recurrence until death of any cause or until the last examination. Kaplan‐Meier estimates for secEFS and secOS were compared using the log‐rank test. For multivariable survival analyses, the Cox regression model was used. Estimated hazard ratios (HR) with 95%‐confidence intervals (95%‐CI) and Wald 2.4Continuous variables (eg age and time from diagnosis to first recurrence) were entered in continuous and in binary form (median as cut‐off) into the model. Count variables (eg number of recurrence sites) were additionally used in the binary form (one vs more than one). Missing data were treated as missing completely at random. First line therapies were included as binary variables, and therapies with curative intent after the first recurrence were included as time‐dependent variables (effective during treatment time and the following month). Palliative treatment was considered as a binary variable.2.5Patients were stratified according to the variables palliative treatment (yes/no), MYCN amplification (yes/no),2.6A multiple time‐dependent Cox regression analysis was performed on the training set to identify prognostic variables that are available at the time of first recurrence diagnosis. As some of the considered variables had missing values and regression analysis is dependent on complete information, variables were categorized into three groups: variables with a high number of missing values (≥15%), variables with some missing values (>0‐<15%) and the variables without any missing data.P‐value of score test ≤.05) and backward selection steps . The procedure is summarized in Figure A 5‐step approach for the selection of variables was used based on consecutive forward selection  contains the time‐dependent (second‐line therapy) variables. The vectors β, γ, and δ depict the corresponding vectors of estimated regression coefficients. The model fit was assessed by estimating the integrated time‐dependent area under the curve and Harrell's concordance statistic.The first two steps were used to test whether any variables with missing values showed to be significant. In the first step (forward selection), all variables were entered into the model to identify significant variables with ≥15% missing values. The second step of forward selection included variables with <15% missing values plus the variables with ≥15% missing values selected in the first step. This was done in order to have a higher number of complete cases available for analysis. The final model was built in steps three to five. In the third step, only variables without missing values plus the selected variables from the previous step were considered and again chosen through forward selection. In the fourth step, the model from the previous step was expanded by successively adding the treatments as time‐dependent covariates into the forward selection model in order to adjust for the therapy the patients received. Finally, in the fifth step the set of variables was reduced via backward selection, resulting in the final model2.7Xβ. The PI is a measure of the risk for an event independent of the received therapy. It can be calculated for each patient based on his/her characteristics regarding the prognostic variables. Based on an optimal stratification of the PI, three risk groups were built. This was done using all possible pairs of cut‐off values. Each cut‐off pair defined three risk groups and was evaluated in a Cox regression model including the risk groups plus the therapeutic variables of the final model. Finally, the cut‐off pair with the smallest P‐value in the likelihood ratio test was chosen .The parameter estimates of the selected nontherapy variables were then used to produce the prognostic index (PI), PI = The resulting risk groups defined the risk score.2.8The risk score was applied to the independent validation set in order to test the reliability to discriminate the three subgroups regarding secEFS.The overall confirmatory null hypothesis was:H0: the secEFS of patients in the lower risk group is equal to or worse than the secEFS of patients in the intermediate risk group or the secEFS of patients in the higher risk group is equal to or better than the secEFS of patients in the intermediate risk group.P‐value is calculated as P:= max where P1 [P2] is the one‐sided Wald P‐value of the variable risk group (higher [lower] risk group vs intermediate risk group) in the Cox regression model including risk group and the therapy variables from the last step of model building. The same hypotheses were exploratively evaluated for secOS. To investigate the robustness of the score, the analysis was repeated with risk group as the only explanatory variable. The results obtained were exploratively reassessed for the cohort of curatively treated patients. Additionally, the five diagnostic variables from the final model were separately analyzed in a Cox regression model including the therapy variables from the last step.The 3Four hundred and sixty nine cases with recurrences of stage 4 neuroblastoma aged ≥18 months at initial diagnosis were identified. The CONSORT diagram  was 8% (95%‐CI 6‐10), and the 5‐year secOS was 10% (95%‐CI 6‐14). The median time from the first to the second event was 5.4 months (95%‐CI 4.4‐6.4) and to death 12.6 months (95%‐CI 10.9‐14.4).χ2 test, P < .001). Patients treated with palliative intent had a shorter median secEFS time  than curatively treated patients . The median secOS times were 2.1 months (95% CI 1.6‐2.6) for palliatively treated patients and 16.1 months  for curatively treated patients. The median time from the first to second event and to death remained stable over time for the patients treated with curative intent .Twenty one percent of patients were treated with palliative intent. The frequency decreased from 32% during 1997‐2004 to 14% during 2004‐2019 , the optimal two cut‐offs were at 3.4P < .001), thus supporting the validity of the risk score. The validation set consisted of 159 cases, of which 16% were attributed to risk group 1, 38% to risk group 2, and 45% to risk group 3. The risk score reliably discriminated between the groups for secondary event‐free as well as for overall survival. The HRs of the multivariable Cox model for secEFS including the therapeutic variables were 0.82  and 1.97 . For secOS, the HRs were 0.77  and 2.07 . Figure The overall null hypotheses that secEFS is independent of risk group could be rejected at a significance level of 2.5% (P = .002) and secOS (P < .001), while intermediate vs lower risk were not discriminated . In the statistically small subgroup of patients with palliative care (n = 33), the score discriminated also higher risk vs intermediate risk (sec EFS P = .016) and lower vs intermediate risk , but not secOS higher vs intermediate risk (P = .118). Figure In the subgroup of curatively treated patients (n = 126), the score was different between higher vs intermediate risk as well for secEFS .The strengths of the study are: (a) a focus on a homogeneous group of patients with a poor prognosis (stage 4 aged ≥18 months); (b) the large number of patients analyzed (N = 469); (c) an almost complete coverage of known German patients ; (d) the inclusion of patients treated with palliative intent; (e) the adjustment for the individual treatment received before the recurrence; (f) the long period of accrual (1997‐2019); (g) and the validation of the score in an independent set of patients.The study has limitations. One is the retrospective nature of the analysis. The main information was obtained through medical reports and yearly routine queries while other structured detailed reports were only rarely available. Second, the diagnostic work‐up at the time of recurrence was not always complete. For example, bone marrow cytology was rarely performed in the event of osteomedullary metaiodobenzylguanidine accumulation or in cases of palliative treatment intent. Nonetheless, the date and the sites of recurrences used for the analysis were unambiguous. Thus, more recurrence sites were possible, but not fewer. Third, the therapeutic elements applied to treat the recurrence were comprised under one heading, eg “chemotherapy”. Specific data on drugs used, dosages, and timing were rarely available and not analyzed. Thus, only “presence” or “absence” of a therapeutic element and the time period were used for the adjustment. But even this limited information concerning consecutive treatment approaches is rarely available in most data bases. Fourth, the decision to treat a patient curatively or palliatively was up to the patient's family and the local treating team. The information about the therapeutic intent was communicated in all cases from the treating institution. It cannot be excluded that some of the palliative treatment patients may have been categorized as curative intent patients. The portion of patients treated palliatively decreased with time. Fifth, it was not our goal to analyze the effect of different treatments patients received. As the secondary treatment variables are included in the analysis as time‐dependent variables assuming a constant effect of therapy during treatment plus four weeks not considering the doses and other factors, the parameters describing the effect of the treatment must be interpreted with care and we do not suggest any therapy recommendation based on the found effects. Sixth, the designations “lower”, “intermediate”, and “higher” are relative and must be viewed in the context of the generally poor survival of this specific cohort of stage 4 patients with first recurrence. Finally, the risk score is not applicable to patients refractory to or without or with inadequate first line therapy  amplification,The combination of the individual risk factors resulting in a score to predict the individual risk is new. Through the inclusion of the therapeutic variables, the resulting parameters from the multivariable analysis yield the effect of the risk factor when corrected for the treatment the patients received. This is the important point of our study. The five described variables appear to cover the impact of The authors of this study see two implications: the estimation of the individual risk of a patient for treatment selection and the presentation of basic risk group data for comparisons with outcomes obtained by new therapeutic approaches. The gold standard to evaluate a new therapy is a randomized clinical trial. This score may help to balance the different risk categories within such a trial.In conclusion, a new risk score system for patients with first recurrences of stage 4 neuroblastoma aged ≥18 months at diagnosis is proposed.None declared. Click here for additional data file.


Introduction: Previous studies have suggested that the circulatory system was involved in the production of circulatory bubbles after diving. This study was designed to research the cardio-vascular function characteristics related to the production of high bubble grades after diving.Methods: Thirty trained divers were investigated both at baseline and after a 30-msw SCUBA dive. At baseline, the investigations included blood pressure measurement, echocardiography, and assessment of aerobic fitness using VO2 peak measurement. Blood samples were taken at rest, to measure the plasma concentration of NOx and endothelin-1. After diving, circulating bubbles were detected in the pulmonary artery by pulsed Doppler at 20-min intervals during the 90 min after surfacing. The global bubble quantity production was estimated by the KISS index.Results: Divers with a high bubble grade (KISS > 7.5) had systolic blood pressure, pulse pressure, weight, and height significantly higher than divers with a low bubble grade. By contrast, total arterial compliance, plasma NOx level, and percentage of predicted value of peak oxygen uptake were significantly lower in divers with a high bubble grade. Cardiac dimensions, left ventricular function, and plasma endothelin-1 concentration were not significantly different between groups. The multivariate analysis identified blood pressure as the main contributor of the quantity of bubble production. The model including pulse pressure, plasma NOx level, and percentage of predicted value of peak oxygen uptake has an explanatory power of 49.22%.Conclusion: The viscoelastic properties of the arterial tree appeared to be an important contributor to the circulating bubble production after a dive. During the decompression stage after a dive, circulating bubbles are commonly observed in the venous system. Since the 1970s, venous gas emboli (VGE) can be screened by ultrasonography and Doppler. To quantify the number of bubbles, it is usual to rate the number and frequency of bubbles compared with the heartbeat. Using this method, bubble grades have been proposed . PreviouAccording to the previous studies, we hypothesized that the viscoelastic properties of the circulatory system of healthy volunteers studied at baseline before a dive, differed between bubble-prone divers and bubble-resistant divers.All the procedures were conducted in accordance with the Declaration of Helsinki and were approved by the local Ethics Committee (CCPPRB 1 Aix Marseille No. 20062103). Each method and the potential risks were explained to the participants in detail, and they gave written informed consent before the experiment.–2, and body surface area 1.93 ± 0.14 m2, volunteered to participate in this experiment. All of them were regular recreational or professional SCUBA divers with 100–4,000 dives and without a past history of diving injury. Each participant underwent a physical examination and a full medical history. The subjects were non-smokers and were included if they had no hypertension, cardiovascular or kidney disease, and no medication during the study.Thirty trained male divers, aged 37 ± 7 years, weight 77 ± 8 kg, height 175 ± 8 cm, BMI 25 ± 2 kg mDuring the inclusion visit, it was verified that volunteers had a similar arterial pressure on both upper limbs.−1 with an elevation of 2%, after which the treadmill speed was increased by 1 km h−1 every 1 min until volitional fatigue was reached. The data were averaged for 20 s and the VO2 peak was defined as the highest value of oxygen uptake despite increased workload. The criteria indicating maximal exercise were as follows: plateauing of oxygen consumption, respiratory gas exchange ratio ≥1.1, and heart rate (HR) ≥95% age-predicted maximal HR. The results were reported in VO2 peak (ml kg−1 min−1) and in percent-predicted peak VO2 calculated according to the equation [weight (kg) × 56.36 − (0.413 × age)] proposed by To assess individual aerobic fitness, each volunteer performed an incremental fatigue treadmill test. Ventilatory and gas-exchange parameters were measured using a breath-by-breath system  which was calibrated before each test. The subjects spent 3 min at rest to reach a steady-state gas exchange condition. Thereafter, all participants carried out a 4-min warm-up running session at 8 km hDivers underwent the echocardiographic examinations in basal conditions 1 h before the dives. The subjects were placed in left lateral decubitus. HR was recorded by echocardiogram and the rate was averaged over 60 s. The cardiac ultrasound examinations were carried out by an experienced investigator (AB) using a commercially available echocardiograph  connected to a transducer array of 2.5–3.5 MHz. At this time, any cardiac abnormalities resulted in the exclusion of the subject from the study. Doppler recordings were performed at the end of a normal expiration in order to eliminate the effects of respiration on the parameters studied. Measurements were averaged from at least three different beats.Left atrial (LA) diameter, left ventricle (LV) end systolic and end diastolic diameters , left ventricle end systolic and end diastolic interventricular septal thickness, and left ventricle end systolic and end diastolic posterior wall thickness were measured by M-mode echocardiography from the left short and long axis views. Left ventricular mass (LVM) was assessed by M mode echocardiography and the application of Devereux’s formula . The sta−1. Peak velocity and velocity-time integral (VTI) of the initial flow (E wave), representing the early filling phase, and of the late flow (A wave), representing the atrial contraction, were measured. The peak velocities ratio (E/A) and the ratio of the A wave VTI to the total VTI  were calculated. The interval from the aortic valve closure signal to the mitral valve opening signal (IVRT) was also measured.Left ventricular filling was studied using transmitral blood flow velocities recorded by pulsed Doppler. Transmitral blood flow velocities were obtained from the apical four-chamber view, positioning the sample volume at the mitral valve leaflet tips. Doppler velocity curves were recorded at 100 mm sE) to TDI early diastolic velocity of the mitral annulus (E′) was calculated as an index of LV filling pressures (Tissue Doppler imaging (TDI) of the mitral annulus during diastole was recorded. The ratio of transmitral early diastolic velocity (ressures .Right ventricle end-diastolic diameter (RVEDD) was measured by M-mode echocardiography from the left parasternal long axis views. The measurement of the peak of the tricuspid regurgitation velocity (TRV) was performed using continuous wave Doppler.RVOT) was recorded from the parasternal short axis view. Pulmonary vascular resistance (PVR) was estimated by the formula [(TRV/ TVIRVOT × 10) + 0.16] in Wood units (WU) according to the method proposed by The RV outflow tract time-velocity integral (TVId2/4.Cardiac output (CO) was derived from the aortic blood flow. The aortic cross-sectional diameter was measured by 2D echocardiography from the left parasternal short axis view at the level of the aortic root. Aortic cross-sectional area (ACSA) was calculated as: ACSA = 3.14 × The aortic systolic flow velocity -time integral (VTI Ao) was measured using the pulsed wave Doppler profile of aortic blood flow from the apical four chamber view making it possible to calculate LV stroke volume (LV SV = VTI Ao × ACSA) and cardiac output (LV CO = LV SV × HR).Systemic vascular resistance and total arterial compliance were calculated as mean arterial pressure/CO and LV SV/pulse pressure (PP), respectively .Sphygmomanometric blood pressure measurements on the right arm were obtained using an automatic device  at the end of each echocardiographic examination. This automated device was validated by the British Hypertension Society and the Association for the Advancement of Medical Instrumentation .−1 at 4°C. Plasma was then stored at −70°C until analysis. Nitric oxide (NO) is rapidly converted in plasma; consequently to estimate NO bioavailability, the sum of stable metabolites of NO, i.e., nitrate and nitrite (NOx) was used. Plasma NOx was determined using a spectrophotometric kit . Plasma concentration of endothelin-1 was measured using a commercially available ELISA kit .Blood samples were taken before the dives. The tubes were immediately placed in iced water and centrifuged for 15 min at 4,000 rmin−1) was 30 min. At the bottom, the divers performed a regular finning action for a distance to 400 m. After 30 min, the ascent rate up to the decompression stop was 9–10 msw min−1. Decompression stop (9 min at 3 msw) was in accordance with the French Navy procedure . After the dives, they were instructed to reduce activity as much as possible.The day before the dives it was recommended that no intense physical activity was performed and a low-nitrate diet was followed. All the dives were performed 3–4 h after a light meal between 10 and 11 a.m. The volunteers were weighed both before and after the dives. The divers breathed air during the dives. They were equipped with neoprene diving wet suits, the thickness of which was in accordance with the temperature of the sea (from 15 to 20°C at the surface). The dive profile was the same for all divers. They performed the SCUBA dives in open seawater at 30 m of seawater (msw) on a regular flat bottom. The bottom time including the descent time (velocity of the descent time from 10 to 15 msw minThe duration of the transfer to the laboratory was around 25 min (the return of the boat to port and the route from the port to the laboratory); consequently, the investigations began 30 min after the end of the dive. Examiners were blinded to the results of the other investigations (previous examinations or investigations performed by the other examiners). Investigations were undertaken in a quiet room with a controlled environmental temperature (28°C).Circulating vascular bubble detections were performed by an experienced investigator (JMP) using a pulsed Doppler equipped with a 2-MHz probe . The screening tests were performed in the laboratory at 20-min intervals during the 90 min after surfacing . The subjects were in the left lateral position and rested for 1 min before the test. The Doppler probe was placed along the left edge of the sternum to record the pulmonary artery blood flow. VGE were monitored in the pericardial area with the divers at rest, during muscle contraction of the quadriceps (the patients were told to contract the quadriceps to pull the patella superiorly tightly during 10 s) and during flexion of the lower limb (hip and knee flexion to 90°). Each maneuver was repeated twice. The Spencer scale was used to quantify the bubble amount . The quaFurthermore, after diving, an echocardiographic examination has been repeated 1 h after emersion. During this examination, it was performed both the study of the cardiac function (results not reported in the present work) and the assessment of the circulating bubbles quantity.The Kisman-Masurel integrated severity score (KISS) was calculated from bubble detections performed at rest, to estimate the magnitude of the evolved gas phase induced by the decompression stress .Thereafter, the population was divided in two groups according to their bubble production:- Divers with a low bubble grade (LBG) producing few bubbles, i.e., with a maximal bubble grade ≤2 and a KISS index <7.5.- Divers with a high bubble grade (HBG) producing an important circulating bubble quantity, i.e., with a maximal bubble grade >2 and a KISS index >7.5.p < 0.05.Data are expressed as mean ± standard deviation. All the statistical analyses were performed with R statistical software . The disvia a stepwise method: the algorithm calculates the VIF score for all explanatory variables and removes the variable with the highest value, then recalculates the VIF scores on the remaining values, until there are no variables with a VIF greater than the threshold (10 here)  10 here) . On thes10 here)  of the g10 here) . This al10 here) .−2). The quality of the echocardiographic examinations was considered to be poor in two divers. These volunteers were excluded from the subsequent analysis. VO2 peak was measured as a mean of 49 ± 6 ml kg−1 min−1 .All divers had a normal left ventricular systolic and diastolic function. Left ventricular mass was measured as a mean of 198 ± 52 g (104 ± 27 g m−1. Plasma endothelin-1 concentration was 1.4 ± 0.7 pg ml−1.Plasma NOx level was 30 ± 8 μmol LNone of the divers presented any disorders suggesting a decompression accident.Significant weight loss was found after the dives (as a mean 590 ± 390 g – 0.8% of body mass).One hour after the dive, the quantity of circulating bubbles assessed by pulsed Doppler and echocardiography were closely related.n = 3), no bubbles were detected whereas in other individuals Grade 3  and divers with a low bubble grade (15 divers).The mean age of the two groups of divers with an LBG and an HBG was not significantly different .p < 0.05) and a height (179 ± 6 vs. 172 ± 7 cm – p < 0.05) significantly higher than divers with an LBG. In total, the body surface area of the divers with an HBG was larger than divers with an LBG (1.99 ± 0.1 vs. 1.86 ± 0.14 m2). BMI was not significantly different between the two groups (25 ± 1.9 vs. 24.9 ± 1.8 kg m−2).Divers with an HBG had a weight (80 ± 7 vs. 73 ± 9 kg – 2 peak was not significantly different between groups (LBG divers 50 ± 6 vs. HBG divers 48 ± 7 ml kg−1 min−1). Nevertheless, when the result was expressed as the percentage of the predicted value [according to the equation proposed by p < 0.05).The VOEchocardiographic parameters including left ventricular systolic and diastolic function and right heart study were not significantly different between the two groups  and 2.Hemodynamic data did not report differences in HR and cardiac output between groups . However−1 vs. divers with an HBG 1.7 ± 1 pg ml−1).The plasma endothelin-1 concentration was not significantly different between the two groups (divers with an LBG 1.2 ± 0.1 pg ml−1) when compared with divers with an HBG (23.3 ± 4 μmol L−1 – p < 0.05).Plasma NOx level was higher in divers with an LBG (34.5 ± 6 μmol LCorrelation result was represented in the correlogram .2 (% predicted), and plasma NOx level.The variable inflation factor step procedure kept the following variables: age, height, BMI, HR, left ventricular mass, % EF, PP, SVR, VO2 . Within this model:The generalized orthogonal pursuit algorithm selected the following model: PP, VOz = 2.38, p = 0.0171) and can be considered as large .- The effect of PP was significant  tended to be significant  and could be considered as medium .- The effect of VOz = −1.34, p = 0.1815) and could be considered as medium .- The effect of the plasma NOx level was not significant  + plasma NOx level model was the following log Lik = −19.337 (Df = −3), Chisq = 17.071, p = 0.0006833.The Likelihood ratio test result of PP + VOAs expected, both correlogram and VIF algorithm results showed that most of the hemodynamic and blood pressure variables were correlated and collinear. In the final model, we observed that plasma NOx was not significantly related to the high bubble grade state but when plasma NOx variable was dropped, the new model had a decrease of the explanatory power (from 49.2 to 38.52%).The main result of this study was that volunteers with an HBG after the dive presented both higher SBP and PP at baseline when compared with divers with an LBG. The multivariate analysis supported this finding. Indeed, the main contributor to the bubble quantity assessed by the KISS index was the blood pressure regimen.It is recognized that the determinants of systolic blood pressure are stroke volume, HR, and the distensibility of the arterial tree . In our 2 peak to divers with an LBG. Nevertheless, the percentage of predicted VO2 peak was significantly higher in divers with an LBG, suggesting that aerobic fitness was higher in this group when compared with divers with an HBG. This result was supported by the multivariate analysis. Indeed, the percentage of predicted VO2 peak was retained in the model. The impact of aerobic fitness on the production of VGE after a dive has been previously reported by some studies . None of the divers were overweight. Furthermore, most divers were middle-aged (24 out of 30 were from 30 and 45 years). A larger range for age and BMI could be more appropriate to study these factors.Lastly, in this study some factors known to impact bubble production such as age and BMI were not observed . Our stuThe mechanism explaining the impact of arterial compliance on the circulating bubbles quantity remains hypothetical. The visco-elastic properties of the arterial wall might affect the diffusion of inert gas. Indeed, it has been reported that the systemic infusion of an endogenous nitric oxide synthase inhibitor lead to an increase in vascular stiffness and a decrease in cerebral blood flow in healthy subjects . As suggIn the present study, arterial compliance appeared to be a major factor in the circulating bubble quantity after a dive. The measurement of blood pressure including pulse pressure can provide the dive medical doctors with a simple means of estimating the risk of a high quantity of circulating bubbles after diving. It is therefore important to check blood pressure regularly in professional divers. When an increase in systolic blood pressure and pulse pressure is recorded, it should be recommended that dietary changes are made and the duration of endurance exercise training increased. These recommendations can be beneficial for reducing both the cardio-vascular risk factors and the quantity of bubble production after diving.The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.All the procedures were conducted in accordance with the Declaration of Helsinki and were approved by the local Ethics Committee (CCPPRB 1 Aix Marseille No. 20062103). Each method and the potential risks were explained to the participants in detail and they gave written informed consent before the experiment.AB and JP conceived and designed the study. NV and JR assisted with the technical aspects of the protocol, recruited all the participants, and were involved in the acquisition of the data. AB and GC analyzed the data and performed the statistical analysis. AB, GC, and JP have drafted the article, while NV and JR revised it critically for important intellectual content. All the authors have given final approval of the version to be published.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Arterial oxygenation and respiratory mechanics were recorded in the supine position, and at 30 minutes and 90 minutes after placement in the prone position. The changes in partial arterial oxygen pressure (PaO2) over time did not differ between the groups. The changes in partial arterial carbon dioxide pressure over time were significantly different between the two groups (P = 0.040). The changes in mean airway pressure (Pmean) over time were significantly different between the two groups (P = 0.044). Although ERV provided a significantly higher Pmean than CRV during surgery, the changes in PaO2 did not differ between the two groups.Prolonged inspiratory to expiratory (I:E) ratio ventilation may improve arterial oxygenation or gas exchange and respiratory mechanics in patients with obesity. We performed a randomised study to compare the effects of the conventional ratio ventilation (CRV) of 1:2 and the equal ratio ventilation (ERV) of 1:1 on arterial oxygenation and respiratory mechanics during spine surgery in overweight and obese patients. Fifty adult patients with a body mass index of ≥25 kg/m This is both a concern for general healthcare and a major risk factor for related diseases and perioperative morbidity2. Several studies have revealed that obesity is related to poor postoperative outcomes, such as longer hospital stay, high incidence rates of wound infection, and pulmonary complication5.The overweight and obese population has increased sharply in recent years4. Cautious management of mechanical ventilation is necessary in patients with obesity to control these altered respiratory mechanics, which lead to impaired oxygenation and gas exchange during surgery.Obesity itself leads to abnormalities of lung mechanics and function. Thus, the obese population has a high incidence of postoperative pulmonary complications resulting from reduced lung compliance, decreased functional residual capacity, and susceptibility to atelectasis formation under general anaesthesia6. Numerous studies have focused on methods to improve oxygenation or respiratory mechanics in patients with obesity during the perioperative period10, and lung protective strategies have been employed in such patients undergoing general anaesthesia11. Conventionally, high positive end expiratory pressure (PEEP) with the recruit manoeuvre is used to manage impaired oxygenation in patients with obesity during general anaesthesia8. Prolonged inspiratory to expiratory (I:E) ratio ventilation, which is also an effective ventilatory manoeuvre in obese patients undergoing laparoscopic bariatric surgery13; this technique improves gas exchange, arterial oxygenation, and respiratory mechanics in patients with acute respiratory distress syndrome or acute lung injury. A prolonged I:E ratio sustains increased alveolar pressure and decreases dead space, consequently improving arterial oxygenation and respiratory function.Moreover, obesity correlates with an increased risk of intraoperative hypoxaemiaTherefore, we hypothesized that prolonged I:E ratio ventilation improves arterial oxygenation and respiratory mechanics in overweight and obese patients undergoing lumbar spine surgery. This randomised study compared the conventional ratio ventilation (CRV) of 1:2 with the equal ratio ventilation (ERV) of 1:1 in terms of their effect on arterial oxygenation and respiratory mechanics during posterior lumbar spine surgery in overweight and obese patients placed in the prone position.Fifty patients were enrolled in the present study; two dropped out, one in each group, because they were not subjected to the scheduled study protocol Fig. . Demogra2) over time were significantly different between the two groups (P = 0.040). However, PaCO2 was not significantly changed during surgery in either group. The two groups did not differ in terms of the changes in oxygen partial pressure (PaO2) or alveolar-to-arterial oxygen gradient (D(A-a)O2) over time, although PaO2 was significantly increased and D(A-a)O2 significantly decreased during surgery in both groups (P < 0.001 in both cases).Figure Table The haemodynamic parameters during surgery are listed in Table 13, suggests that ERV does not confer superior arterial oxygenation than CRV during posterior lumbar spine surgery in overweight and obese patients placed in the prone position under general anaesthesia. However, ERV did confer a significantly higher Pmean than CRV during surgery. This was the first study to reveal the impact of prolonged inspiratory ventilation on patients in the prone position.The current study, which was expanded from our previous study assessing the effect of prolonged inspiratory ventilation in patients undergoing laparoscopic bariatric surgery14. Consistent with a previous study15, our results showed that PaO2 was significantly higher at T30 and T90 than at Tsupine in the ERV group, and that changes in Pmean were higher in the ERV group than in the CRV group, but this latter effect did not reach statistical significance. ERV improves oxygenation by increasing Pmean and concomitantly reducing Ppeak13. Pmean is related to arterial oxygenation because it is the average alveolar pressure that opens and inflates the alveoli against the elastic recoil of the lungs and chest wall16. An elevated Pmean value induces alveolar recruitment, which improves ventilation perfusion mismatch and blood oxygenation17. Thus, a prolonged I:E ratio sustains an increased alveolar pressure, thus increasing patients’ functional residual capacity18. Although our results do not confirm that ERV is clinically superior to CRV, ERV may be feasible in overweight and obese patients with deteriorated oxygenation during general anaesthesia.Postoperative pulmonary complication is one of the main factors determining length of hospital stay and cost burden on patients. Generally, general anaesthesia using muscle paralysis generates impaired pulmonary gas exchange because of alterations in respiratory mechanics and atelectasis formation. Obesity may increase the risk of postoperative pulmonary complications2 significantly increased over time in both the ERV and CRV groups, perhaps because the patients were placed in the prone position. Numerous studies have demonstrated that the prone position can improve oxygenation in pneumonia, acute respiratory distress syndrome, and acute lung injury21. Pelosi et al. also reported that the prone position resulted in improved lung compliance, a rise of functional residual capacity, and improved oxygenation in obese patients under elective general anaesthesia22. A rise in functional residual capacity was also seen after placement of the patients in the prone position, perhaps because there was decreased cephalad pressure on the diaphragm and changes in the gravitational ventilation/perfusion gradient23. The improved oxygenation also results from movement of the diaphragm, because, compared with the supine position, the prone position leads to greater excursion in the posterior diaphragm in regions where atelectasis formation and ventilation/perfusion mismatch are most severe during general anaesthesia; furthermore, pulmonary perfusion is more uniformly distributed in the prone position24. We assumed that the prone position improves oxygenation during general anaesthesia, regardless of which mechanical ventilatory manoeuvre is used, and further study is required to confirm our results.PaO26. In contrast with some studies, our data showed that PaCO2 was increased in the intraoperative period. We permitted the study practitioners to manage the respiratory rate and maintain an end-tidal carbon dioxide tension (EtCO2) level between 33 and 36 mmHg. This may have created bias. Additional studies are needed to verify the actual impact of ERV on gas exchange.Prolonged I:E ratio ventilation and prone positioning improve ventilation/perfusion heterogeneity to produce efficient gas exchange6. Therefore, in the present study, the mean BMI of both groups may have affected arterial oxygenation during the study period. Secondly, our study group did not include morbidly obese patients whose BMI was more than 35.0 kg/m2; the purpose of the study was to investigate the effect of prolonged I:E ratio ventilation in overweight and obese patients. Hence, a supplemental study examining prolonged I:E ratio ventilation during spine surgery should be performed in morbidly obese patients.The present study had some limitations. Firstly, even though we used a randomisation plan generator, the mean body mass index (BMI) of the ERV group was higher than that of the CRV group. Despite this statistical deficiency, ERV did not confer better arterial oxygenation than CRV in patients in the prone position in the present study. In one study by Kendale and Blitz, an increase in BMI correlated with an increase in intraoperative hypoxaemia riskIn conclusion, ERV conferred lower peak inspiratory pressure and higher mean airway pressure than CRV in overweight and obese patients undergoing posterior lumbar spine surgery in the prone position under general anaesthesia. Therefore, ERV may reduce the airway pressure increase in overweight and obese patients undergoing spinal surgery in the prone position. Even though ERV did not confer better arterial oxygenation than CRV in the present study, ERV may be feasible in overweight or obese patients during general anaesthesia. Further study is needed to confirm the impact of ERV on oxygenation in patients with elevated BMI undergoing spine surgery in the prone position.2 were enrolled the study. Patients were excluded if they had severe pulmonary disease , haemodynamic instability, and/or hypovolaemia. The enrolled patients were randomly allocated according to a predetermined sequence to receive an I:E ratio of either 1:2  or 1:1 . One researcher in our institution who was not involved in the present study generated the allocation sequence without blocking using a randomisation plan generator (http://www.randomisation.com). This study was performed in accordance with relevant guidelines and regulations, including the CONSORT guidelines  and registered at the US Clinical Trials Registry (NCT02961920). After obtaining written informed consent, we assessed 54 patients scheduled for lumbar spine surgery in our institution between November 2016 and October 2018. Fifty adult patients with an ASA physical status of I or II and a BMI of ≥25 kg/m2 level between 33 and 36 mmHg during surgery, the respiratory rate was adjusted. To maintain anaesthesia, sevoflurane was used, with an end-tidal concentration of 2–2.5% by volume and a bispectral index score between 40 and 60. Rocuronium (0.2 mg/kg) was injected every hour. The inspired oxygen fraction (FiO2) was 0.4, using oxygen and air. Radial artery catheterization was conducted to allow repeated blood sampling and continuous blood pressure monitoring.To induce anaesthesia, intravenous propofol (1.5 mg/kg) and rocuronium (0.8 mg/kg) were administered. Volume-controlled mechanical ventilation was applied, with a tidal volume of 10 mL per ideal body weight (kg), an I:E ratio of 1:2 or 1:1, depending on the group allocation, and no external PEEP. To maintain the EtCO2, and peripheral oxygen saturation. We measured intraoperative respiratory mechanics, including peak airway pressure (Ppeak), mean airway pressure (Pmean), plateau airway pressure, and PEEP using the anaesthesia machine . We also measured arterial blood gas at three time-points: 10 minutes after anaesthesia induction, Tsupine, T30 and T90. We calculated Pdriving, Cdyn, and Cstatic from respiratory data, and D(A-a)O2 from arterial gas analysis data. Pdriving was defined as the difference between plateau airway pressure and PEEP. Cdyn and Cstatic were calculated using the following formulas: tidal volume/(Ppeak − PEEP) and tidal volume/Pdriving, respectively. Alveolar oxygen tension was calculated using the following formula: FiO2(PB − 47 mmHg) − (PaCO2/0.8), where PB is the barometric pressure (760 mmHg).Standard monitoring during anaesthesia included continuous electrocardiography, systemic arterial pressure, heart rate, EtCO2) was 181 (28) mmHg in obese patients after placement in the prone position22. We assumed a mean PaO2 difference of 15% between the CRV and ERV groups. With an α-value of 0.05 and a statistical power of 90%, a sample size of 23 patients was required for each group. Anticipating a 10% drop out rate, we recruited 50 patients.A previous study reported that, during CRV with an inspired oxygen fraction of 0.4, the mean value (standard deviation) of partial arterial oxygen pressure  was used for statistical analyses.Continuous variables are expressed as mean ± standard deviation, and categorical variables as number of patients (%). Continuous variables were analysed using the Student’s t-test or Mann–Whitney U test. Categorical variables were analysed using Fisher’s exact test. Serial changes in respiratory variables and haemodynamic changes were analysed using repeated measures ANOVA, followed by Bonferroni correctionNCT02961920 (Date of registration: November 11 2016) https://clinicaltrials.gov/ct2/show/NCT02961920?term=NCT02961920&rank=1.


IntroductionSixty-seven million Americans have hypertensionthat costs the nation $47.5 billion each year. The aim of this study was to determine if regular phone calls by residents helped achieve better blood pressure control.MethodsThe study was a randomized open-labeled study in a resident-run outpatient clinic in Rochester, New York. A total of 57 poorly controlled hypertensives in the clinic were divided into two groups. All the patients received scheduled phone calls once every two weeks for a total of 24 weeks. In one group, the medications were adjusted over the phone and the other group was referred to be seen in the clinic for elevated blood pressures. Both the groups were compared to the usual standard of care group.ResultsFifty-eight patients were recruited for the trial out of which 53 were used for the final data analysis. Eleven patients completed the trial and had a mean drop of systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 28 and 11 mmHg with p < 0.01 and p < 0.03, respectively. Among the patients who did not complete the trial but answered at least one phone call, the mean drop of SBP and DBP was 29 and 8 mmHg with a p < 0.001 and p < 0.008, respectively. When these were compared to the usual standard of care group, the mean drop in SBP was 28.36 (12.36-48.36), 29.85 (11.85-47.85), and 0.76 (8.04-9.56) with a p < 0.02.ConclusionsPatients enrolled in the trial had much better blood pressure control compared to the usual standard of care. Residents can take greater ownership of patients to help achieve better blood pressure control. To our knowledge this is the first such study done exclusively by residents in a resident-run clinic. Seventy-five million Americans have hypertension, which costs the nation $47.5 billion each year . StudiesThe Rapid Intervention through Telephone Encounters for Blood Pressure control (RITE-BP) trial was a prospective, randomized, open-labeled trial that was conducted in the resident-run outpatient medicine clinic at the Rochester General Hospital, Rochester, New York. The study protocol was approved by the institutional review board at our hospital.Patients were identified and recruited between March 2015 and October 2015. Patients were randomly selected and approached for enrolment when they visited the clinic for a follow up appointment. The inclusion and exclusion criteria were as outlined below.Inclusion criteria•       Systolic blood pressure (SBP) of ≥ 150 and/or diastolic blood pressure (DBP) of ≥ 90 as documented in two or more consecutive previous visits to the clinic.•       Age 25-70 years.Exclusion criteria•       If they followed with a cardiologist or a nephrologist•       If they were followed by the hypertension clinic•       Non-English speaking patients•       Did not have a working phone number•       Documented learning disabilities•       Pregnancy.Once enrolled and after consent was obtained, they were randomly assigned to Group A or Group B. Patients in both the groups received a home blood pressure monitoring kit, a dietary pyramid chart indicating the foods they should be taking to help achieve better blood pressure control, and an exercise chart listing the various aerobic exercises they should try for at least 30 minutes, five times a week. The patients were asked to check their blood pressures twice a day preferably in the morning and evening and record them in a log that was provided to them. For the next six months, patients in both groups received a phone call from one of the investigators every two weeks. During each phone call the patients were asked questions from a pre-set questionnaire. The responses were noted, and the patients’ blood pressure was averaged over a two-week period. If the averaged blood pressure was >150 systolic and or >90 diastolic in Group A, changes were made to their anti-hypertensive medication regimen after discussing with the clinic preceptor. If the averaged blood pressures were elevated in Group B, a follow up appointment was made for them with their primary care provider in the clinic. If a patient did not answer three consecutive calls over a six-week period, they were subsequently excluded from the trial. The patients in both the groups had a follow up appointment with one of the investigators at three months and at completion of the trial at six months at which time their blood pressures were measured, logs documented, and counseling provided again on diet, exercise, and medication compliance  tests, and Fischer’s exact test for data analysis. Baseline characteristics were compared between three groups of patients with ANOVA tests, Chi-square tests, and Fisher’s exact test. Continuous variables are expressed as mean (M) and standard deviation (SD). Dichotomous variables are expressed as number (n) and percentage (%). The ANOVA analysis was used to compare means for continuous variables. The Chi-square tests were used to compare proportions for categorical variables. The Fisher’s exact test was used for categorical variables when one or more values in the contingency table were below five. To evaluate the efficacy of intervention, paired t-test was performed to compare blood pressure values before and after.We used the During the recruitment period from March 2015 to October 2015 we approached 183 patients who were eligible for the trial. Of these, 58 patients agreed to be a part of the study. Five patients were excluded from the final analysis, one patient started following with cardiology and another with nephrology for their blood pressure control; three patients did not have a documented blood pressure at the end of six  months  between the groups who completed the trial, those who did not complete and control Group C, we noticed a drop of 28.36 (12.36 to 48.36), 29.85 (11.85 to 47.85), and 0.76 (-8.04 to 9.56) respectively which was statistically significant with p = 0.02  of the same groups we found a mean drop of 11.09 (-2.62 to 25.94), 11.85 (-5.81 to 47.85), and 1.19 (-14.34 to 16.43) for those who completed the trial, not completed the trial, and the control Group C, respectively, with a p = 0.051  before the trial and at the completion of the trial was 170.47 +/- 15.25 and 140.61 +/-12.89 with p = 0.018 and the mean DBP was 92.66 +/- 14.04 and 80.8 +/- 13.65 with p = 0.001, respectively. For those who completed the trial, the mean SBP (in mmHg) before and at the completion of trial was 166.18 +/- 13.49 and 137.81 +/- 14.81 with p = 0.0001 and mean DBP was 91.9 +/-13.08 and 80.81+/-12.68 with p = 0.0001, respectively (Figures One particular area that continues to be neglected is the resident-run clinics when it comes to blood pressure control. These resident clinic patients are usually from a low socio-economic background, diverse cultural group with no insurance or government-sponsored plans like Medicare and Medicaid -17. PatiThe RITE-BP trial showed that patients who enrolled in the study, irrespective of which group they belonged to had significantly better blood pressures compared to the control group at the end of six months. The patients in the control group belonged to the same population group as the study patients with similar baseline characteristics.Our study also showed that there was no statistical difference in blood pressures among the patients who had changes made to their medications over the phone and those who hadn’t. What is even more surprising was that in the medication group only one patient’s medication was changed over the phone. Over the six-month period of the study no medication changes were made by the regular primary care providers for the patients enrolled in the study. The common denominator for all the groups in our study population was the device given to measure their blood pressures and counseling on exercise and diet.We believe that providing a patient with blood pressure monitoring devices, intense coaching on diet and exercise given at the initial visit, and knowledge that a provider was closely following their blood pressures as a psychologically motivating factor were responsible for better blood pressure values in our study subjects compared to the control group. Positive affirmation and psychology have been previously shown to be strong motivating factors to help achieve better blood pressure control -24.Our study has several limitations. As medication changes were being made to the study, participants and investigators were not blinded. The study was done and data were analyzed before the results of the SPRINT trial were published, although currently the JNC VIII guidelines are still in vogue on which our study is based. Of the initial 183 patients that we approached, only 58 agreed to join our trial. One may argue that the patients who volunteered for our study were motivated enough to ensure medication, dietary, and exercise compliance which resulted in the results that we were able to achieve. Our study also had a very low number completing the trial. This is in line with generally patients having poor follow up rates at resident-run clinics and issues with compliance. The no-show rate at our clinic is around 25%-35%. Our sample size was small. We also relied on our patients to provide accurate manual blood pressure readings, which we believe our patients did provide honestly; however, there is always a chance that they could be just giving us random numbers. But we followed up with the patients at three and six months and their logs and blood pressure readings in the clinic reflected the change just as they had said. Our follow up period was short and it would be interesting to follow these patients to see if there has been any residual effect due to our trial.There are several future directions that the trial can take to further analyze this issue. The use of mobile phone apps has increased in recent years and the use of an algorithm to remind patients to check their blood pressures and take their medications could help. One would also like to analyze the economic impact of utilizing residents and the overall manpower required to help achieve better blood pressure control.In conclusion, our trial was able to show that residents were able to achieve a significant drop in systolic and diastolic blood pressures of the patients who were motivated, received regular phone calls, had a blood pressure measuring device, and received intense counseling on exercise and dietary habits compared to the usual standard of care groups. Perhaps following these steps could help us curb this ever-growing problem.