Diabetic Ketoacidosis (DKA) is a potentially life-threatening emergency that requires prompt diagnosis and treatment. In paediatric populations an end tidal capnography value greater than 36 mmHg was found to be 100 % sensitive in ruling out DKA.2 (ETCO2) cut-offs were determined.A cross sectional observational study of adults ≥ 17 years of age presenting to the emergency department between January 2014 and May 2014 with glucose > 550 mg/dL. In all patients, nasal capnography and venous blood gas analysis were performed prior to any insulin or intravenous fluid administration. The diagnosis of DKA was based on the presence of anion gap metabolic acidosis, hyperglycaemia and ketonemia. The overall diagnostic performance (area under the curve [AUC]), sensitivity, specificity and likelihood ratios at different end tidal CO2 was 0.95 with a 95 % CI of 0.91 to 0.99. Test sensitivity for DKA at ETCO2 level ≥35 mmHg was 100 % . An ETCO2 level ≤ 21 mmHg was 100 % specific  for DKA.71 patients were enrolled in the study of which 21 (30 %) met the diagnosis of DKA. The area under the curve for ETCONasal capnography exhibits favourable diagnostic performance in detecting patients with or without DKA among those who present to the emergency department with a glucometer reading > 550 mg/dL. The partial pressure of CO2 at end expiration is termed end tidal CO2 (ETCO2) [2 tension. Because ETCO2 closely approximates arterial CO2 tension, it can potentially be used to predict the presence or absence of DKA. Obtaining blood tests may be time-consuming. A rapid non-invasive sensitive screening tool that rules out DKA in patients with severe hyperglycaemia may avoid unnecessary administration of insulin infusion as part of initial therapy. Similarly, a non-invasive test with high specificity in identifying those with DKA; may expedite prompt diagnosis and treatment of DKA.Diabetes mellitus is the most common endocrine disease in the world. Acute complications of diabetes include severe hyperglycaemia, diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS). DKA is a potentially life-threatening emergency characterized by hyperglycaemia, metabolic acidosis and ketonemia along with severe electrolyte abnormalities . HHS is  (ETCO2) . In resp2 to assess patients for DKA versus severe hyperglycaemia. We hypothesized that ETCO2 exhibited at least a “fair discriminatory power”  [2 in patients with blood glucose > 550 mg/dL (30.6 mmol/L); to determine the sensitivity, specificity, likelihood ratios at different ETCO2 cut-offs; and to establish the degree of correlation of both venous pH and serum bicarbonate with ETCO2, and between venous pH and serum bicarbonate.In our emergency department, patients found to have blood glucose >550 mg/dL, regardless of clinical status, are taken to our high acuity area. This triage process often leads to overcrowding the critical area and overwhelming the medical team. For this subset of patients, we wished to investigate the diagnostic characteristics of ETCOUC <0.8)  for DKA Cross sectional observational study was conducted at a single emergency department in an urban tertiary care centre in Detroit, Michigan, between January 2014 and May 2014. Given that there was no harm or injury in applying an end tidal monitor to patients’ nasal cannula, a waiver of informed consent was granted. This study was approved by our hospital’s institutional review board (IRB #8560).As per our emergency department’s protocol, patients with a known history of diabetes, or patients presenting with specific complaints  are screened at triage with a point of care glucose measurement. Inclusion criterion included a point of care glucometer  reading of “high” on presentation which corresponds to a glucose level >550 mg/dL. Exclusion criteria consisted of receipt of intravenous fluids or insulin prior to the application of nasal capnography.2 sampling cannula placed by trained medical personnel while they were being placed on the monitor and having their initial vital signs taken. The cannula was attached to a capnograph/capnometer . A single ETCO2 value was documented when a stable waveform was recorded on the monitor . Venous blood was collected into collecting tubes for electrolytes, glucose, beta hydroxybutyrate (ßHB), and complete blood count. No time delays between the blood draws and the application of the end tidal capnography. A venous blood gas (VBG) sample was then collected in an arterial blood collection syringe, sent to the laboratory over ice and analysed by blood gas analyser . Measurements of interest were pH and CO2 obtained from the VBG sample and measured serum bicarbonate (HCO3), ßHB, and blood glucose from routine analysis of venous blood. Capnography was compared to a reference standard for diagnosing DKA defined as a triad of hyperglycaemia >250 mg/dL, high anion gap metabolic acidosis and ketonemia [Patients were approached and identified by the nursing staff in triage. Patient recruitment and enrolment occurred at all times throughout the duration of the study. All Eligible patients had nasal CO2 and other arterial blood measurements and between venous pH and serum bicarbonate. Sensitivities and specificities were calculated at different levels of ETCO2. For all analyses, P < .05 was considered significant.Statistical analysis was performed using SAS software version 9.3  and ROCs were performed using MedCalc Statistical Software version 13.2.2 . Categorical variables were presented as frequencies and percentages. Continuous variables were intentionally presented as median, interquartile range (IQR), minimum and maximum to appreciate the spread of the data. Mann Whitney rank sum test was used for group comparisons for continuous data. Categorical data comparisons were performed using chi-square test. Pearson coefficients were used to evaluate the correlation between ETCO2 values ranged between 5 and 35 mmHg in patients with DKA. Patients with DKA had higher median levels of glucose and ßHB and lower partial pressure of CO2 (pCO2), ETCO2, serum bicarbonate, and pH.Seventy-one consecutive patients were enrolled in the study. The median age was 48.0 years (IQR 39–58) and 39 (55 %) were male. All patients had a known history of diabetes. Twenty-one patients had DKA . There was a significantly higher percentage of insulin dependent diabetic patients in the DKA group (57 % versus 24 %). Patient demographics, by presence or absence of DKA are presented in Table 2 in diagnosing DKA is represented in the ROC in Fig. 2 level ≥35 mmHg was 100 %  and specificity was 68 . At an ETCO2 level less than or equal to 21 mmHg specificity was 100 %  and sensitivity was 57 % . Table 2 cut-offs.The diagnostic performance of ETCO2 and serum bicarbonate levels , coefficient of determination r2 = 0.76 , coefficient of determination r2 = 0.56 , coefficient of determination r2 = 0.70.Finally, there was a strong correlation between ETCO.56 Fig. . There wDKA is one of the few endocrine emergencies. It is characterized by hyperglycaemia, ketonemia and metabolic acidosis along with electrolyte abnormalities. It is a condition that should be readily recognized and promptly treated. The mainstay of medical treatment is intravenous fluid rehydration, insulin replenishment through an intravenous drip, electrolyte correction and identification of the cause of the ketotic state .2 in those presenting with blood sugar greater than 550 mg/dL in an attempt to identify thresholds which may help identify those with or without concomitant DKA.DKA and severe hyperglycaemia are distinct clinical entities with different treatments. Although the mainstay treatment is fluid resuscitation, patients with DKA require insulin to reverse their ketotic state. Patients with severe hyperglycaemia without ketosis require fluid resuscitation first and foremost; they may or may not need insulin, and those who do infrequently require continuous insulin infusion . We soug2 exhibited a good diagnostic performance (AUC 0.95), 95 % CI, 0.91 to 0.99. DKA was highly prevalent in patients with glucose > 550 mg/dL . At ETCO2 ≤ 21 mmHg, DKA was ruled in (specificity 100 %) At ETCO2 ≥ 35 mmhg, DKA was ruled out (sensitivity of 100 %). Furthermore, there was a strong correlation between ETCO2 and PH as well as bicarbonate, which would suggest that ETCO2 could be useful in identifying DKA patients presenting with remarkably low PH levels and would allow faster and more aggressive care.In this cohort of adult patients presenting with high glucose, ETCO2 correlated highly with arterial pH and pCO2 [R = 0.8395, P < 0.0001). Therefore, it is reasonable to replace the arterial blood gas with venous blood gas in the evaluation of a patient with DKA. Third, we used ßHB level >3 mmol/L to diagnose ketonemia. Although the American Diabetes Association (ADA) [2 and acidosis were in pediatric patients with type I diabetes [2 values less than 29 mmHg could identify DKA with a specificity of 100 and 91 %, respectively, whereas no patient with ETCO2 values > 35 mmHg had DKA (sensitivity 100 %). In contradistinction, in this study, the corresponding specificity at ETCO2 values < 29 mmHg was only 88 % , however, the sensitivity at ETCO2 values > 35 mmHg was also 100 % . The different diagnostic accuracies at the same ETCO2 cut-offs between our study and the paediatric studies may be secondary to different spectrum and distribution of acute or chronic acid base disorders in adults compared to the paediatric population or secondary to statistical variation.Our study differs from other studies in several ways. First, our cohort consisted of patients with blood glucose > 550 mg/dl measured by glucometer. Second, we used VBG pH to diagnose acidemia. Several studies have shown that venous pH and pCOand pCO2 –9. In paand pCO2 . In thison (ADA)  states ton (ADA) , 13. Foudiabetes –16. Thesdiabetes  and Gilh2 in adults as a screening tool for DKA with blood glucose > 250 mg/dL and clinical symptoms of DKA [2 had a uniquely high diagnostic accuracy (AUC 0.963) overall, and at ETCO2 cut-off of 24.5 mmHg; it was highly sensitive (90 %) and specific (90 %). The diagnostic performance of our test as measured by AUC was very high (AUC 0.95). Specificity at ETCO2 cut-off of 24.5 in our study was slightly higher (96 % vs. 90 %); however our study did not demonstrate a high sensitivity at this ETCO2 cut-off (sensitivity 57 % vs. 90 %). Several patients in our cohort had DKA at higher ETCO2 levels than 24.5 either because of chronic respiratory acidosis disorders or because of coexisting metabolic alkalosis.To our knowledge, only one study by Soleimanpour et al. has evaluated the utility of ETCOs of DKA . The stu2 and perform a cost analysis for the use of ETCO2, however, this was not the aim of this study and it is our hope that this study can stimulate future research studies. Finally, It would also have been important to provide the data on other potential confounders of ETCO2 within our patient population, however a significant amount of our patients did not have any formal diagnosis of Chronic Obstructive Pulmonary Disease (COPD) or any Pulmonary Function Tests (PFTs) in our records.Our study has some limitations. First, the results can only be applied to patients with blood glucose >550 mg/dL (30.6 mmol/L). It is important to note that patients with blood glucose level <550 mg/dL can be in DKA, however we chose not to look at this subset of population since it was studied earlier in the literature and because our main objective was to check the test characteristics of the test among patients with severe hyperglycemia . A non-iThis single centre study suggests that end tidal capnography in adults presenting to the emergency department with glucose levels > 550 mg/dL may useful in identifying and ruling out DKA. The external validity of the results should be confirmed by further prospective studies.This study was approved by Henry Ford Hospital’s institutional review board (IRB #8560). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board at our institution and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.A waiver of informed consent was granted by our IRB. The authors have obtained consent to publish data from participants.


Identifying the risk factors for diabetes mellitus related foot ulceration would save more limbs from amputation. This report focuses on the determining the burden of peripheral arterial disease and neuropathy in persons with diabetes mellitus (DM).This is a descriptive study carried out in the Diabetic Clinic of the Lagos State University Teaching Hospital in patients with DM who had no past/present history of foot ulceration. Biothesiometry was employed and ankle brachial pressure indices were measured to evaluate for neuropathy and peripheral arterial disease (PAD) respectively.A total of 225 persons living with DM who met inclusion criteria were recruited consecutively over a 3 months period. Age range was 28–87 years with the mean [61.4 (10.8)] and median (63) years respectively. Patients symptomatic for neuropathy and PAD were 37 and 40 % respectively of the study population. An older age of >60 years and poor glycaemic control were potential predictors of neuropathy. Neuropathy and PAD occurred commonly in the seventh decade of life.Given the fairly high proportions of neuropathy and PAD in our patients with DM, we recommend that they be routinely examined in persons with DM. Peripheral arterial disease, a pointer to the presence of atherosclerosis is oft reported in diabetes mellitus (DM). Potential sequelae of this finding in DM are diverse ranging from cardiovascular morbidity, the development of foot ulceration, increased risk for amputations and depending on severity, may result in death from any of the aforestated complications of DM. Neuropathy is a commonly documented complication of DM which may be asymptomatic but may lead to reduced quality of life in people who have painful neuropathy. Neuropathy is a well recognised risk factor of foot ulcers in persons with DM.In order to reduce the burden of cardiovascular and foot complications of DM it is imperative to screen persons with DM for these entities. There are a variety of screening techniques which are currently in use and these include the evaluation of vibration perception threshold (VPT) using the biothesiometer and documentation of ABI to detect PAD . In thisDiabetic peripheral neuropathy which is documented to be present in 60 % of diabetic persons confers a great risk of foot ulceration; microvascular disease and suboptimal glycemic control are also contributory. The prevalence of neuropathy was 76 % PAD was 6.3 % in patients without a prior history of foot ulceration as earlier reported in 2005 by Ogbera et al.  and 48 %People living with DM are at high risk for PAD which unfortunately is often associated with poor prognosis of foot ulceration. The determination of PAD using clinical symptoms is unreliable and the presence of neuropathy may be contributory to this scenario. Given the inconsistencies associated with the symptoms of PAD, the measurement of ankle-brachial pressure index (ABI) is an objective relatively simple, non-invasive and inexpensive technique employed in the evaluation of PAD. ABI test is widely used in the hospital setting not only to screen asymptomatic patients but also to diagnose patients with clinical symptom of PAD. In a Nigerian report on middle and elderly patients with DM, the prevalence rate of PAD was found to be 53 % . ReportsThis study was done to document the burden of PAD and neuropathy in persons with DM.This is a descriptive Study carried out at the Diabetes Clinic of the Lagos State University Teaching Hospital (LASUTH), Ikeja, Nigeria. This is a 750 bed hospital upgraded in 2001 from a General Hospital to a teaching hospital. It is located in the capital of Lagos State with highly subsidized health care costs as a result of governmental policy.Consenting patients were recruited consecutively over a 3-month period. All persons living with DM aged more than 20 years and who had no past histories of foot ulceration, were recruited into the study. Ethical approval was obtained from the Lagos State University Teaching Hospital.Demography validated interviewer administered questionnaires were used to obtain histories pertaining to clinical characteristics of DM status and complications of neuropathy and PAD, smoking, alcohol and co-morbidities such as hypertension. Long duration of DM means >10 years and older age referred to >60 years.2 (kg/m2). Waist circumference was determined by applying a tape measure to the midpoint between the inferior margin of the last rib and the crest of the ilium. The blood pressure was measured both in supine and upright positions.The anthropometric indices measured included waist circumference, height and body weight, and the body mass index (BMI) in weight/heightA biothesiometer was used to determine semi quantitatively vibration perception thresholds in a standardized manner by a single observer. The biothesiometer probe, which vibrates at an amplitude proportional to the square of the applied voltage, was applied perpendicularly to the test site with a constant and firm pressure. Subjects were initially familiarized with the sensation by holding the probe against the distal palmar surface of hand. VPT was then measured at the distal plantar surface of great toe of both the legs. The voltage was slowly increased at the rate of 1 mV/sec and the VPT value was defined as the voltage level when the subject indicated that he or she first felt the vibration sense.DM Neuropathy referred to a vibration perception threshold values of more than 15 mV with or without the presence of neuropathic symptoms .A hand held Doppler equipment with a frequency of 12 MHz was used to document the ABI. The ABI was performed by measuring the systolic blood pressure from both brachial arteries and from both the dorsalis pedis and posterior tibial arteries after the patient has been at rest in the supine position for 10 min. We used a standard blood pressure cuff at the ankle. We began recording the pressures with the right arm, then the right leg, then the left leg, and finally the left arm.The higher systolic blood pressure value was used as the numerator of the ABI in each limb. . The diagnostic criteria for PAD based on the ABI were interpreted as follows:Normal if 0.91–1.30, Mild obstruction if 0.70–0.90, Moderate obstruction if 0.40–0.69, Severe obstruction if <0.40, Poorly compressible if >1.30 .HbA1c was assayed using a fully automated Boronate Affinity assay for the determination of the percentage of hemoglobin A1C (HbA1c %) in whole blood. Poor glycaemic control consisted of glycosylated hemoglobin (Hba1c) levels of ≥7 % .Hypertension was said to be present in persons known to have a history of elevated blood.Fasting blood samples were taken for the determination of four parameters of the lipid profile viz total cholesterol (TCHOL), high density lipoprotein cholesterol (HDL-C), and triglyceride (TG). Total cholesterol assay was done using a modified method of Liebermann-Burchard, HDL-cholesterol by precipitation method and TG was estimated using a kit employing enzymatic hydrolysis of TG with lipases . LDL-C w2 was used to test for differences in proportions. A p value of ≤0.05 was deemed significant.Statistical analyses were performed with SPSS version 15. A multiple regression analysis with PAD as the dependent variable in conjunction with multiple independent variables was used to evaluate for possible predictors of PAD. Independent sample Student’s t test was used to compare quantitative data. χA total of 225 persons living with DM met the inclusion criteria. The age range was 28–87 years with the mean and median ages of the as 61.4 (10.8) and 63 years respectively. There were 163 (68 %) females giving a M: F ratio of 1:2.6. The mean age of the males was greater than that of females and the difference was statistically significant .Other clinical parameters are shown in Table Neuropathy: Neuropathy was detected in 120 (56 %) of the study population. The proportions of females and males with neuropathy were comparable . Persons with neuropathy were older than those without neuropathy and this difference was statistically significant (63.9 (9) vs 58.2 (11) years, p = 0.0001). Positive symptoms of neuropathy ranging from burning nocturnal pain, pin and needle sensation were noted in 68 patients and negative symptoms of numbness was documented in 16 patients. Poor long term glycaemic control and being elderly as shown in Table The total number of persons with PAD was 90 (40 %). The proportions of females and males PAD were comparable . The mean age of persons with PAD and those without PAD was comparable. The results of comparisons made for some clinical and biochemical parameters between persons with PAD and persons without PAD is shown in Table DM associated neuropathy and peripheral arterial disease were prominent in the seventh decade of life. These results are shown in Fig. The proportions of the Study population with elevated total cholesterol, LDL-C, TG and low HDL levels were 99 (44 %), 44 20 %), 129 (57 %) and 66 (29 %) respectively. A comparison of the distribution of abnormal lipid parameters between DM patients with PAD and DM patients with neuropathy is shown in Fig. 0 %, 129 There is a growing awareness amongst healthcare professionals on the importance of early detection of risk factors for diabetes mellitus foot ulceration especially because this complication of DM has been associated with a high disease morbidity and mortality in resource poor countries.In this report, neuropathy was a commonly documented entity and painful neuropathy its prominent symptom was noted in about half of the patients studied. Impaired vibration sense is an early sign of neuropathy, hence its assessment is an important element of the neurological examination of the patient with diabetes . We screA possible relation between glycaemic control and DM complications has being pointed out by findings from the UK Prospective Diabetes Study (UKPDS)  and not There is a dearth of Reports on detection on PAD using ABI from Africa. In a recent study from Uganda , the autBarring the limitations of occasional high ABI indices that may be suggestive of incompressibility of the vessels, calculating the ABI for screening purposes is of benefit in detecting PAD even in the absence of foot ulcers. However it is imperative to note that the handheld Dopplers equipment does not give waveform pattern as and such, may fail to detect the PAD when Monckebergs sclerosis is present. We excluded persons with high ABI because of the potential of misleadingly high figures in detected PAD.. Hitherto, apart for research purposes, screening for PAD is not carried out routinely for persons living with DM in the hospital setting in hospitals in Lagos. Of interest also are our findings of comparable clinical and biochemical parameters between patients with PAD and patients without PAD. In this Report, PAD, was diagnosed albeit in a few persons even in persons who were aged less than 40 years. Hypertension and dyslipidaemia, though of fairly high prevalence rate, their role in the possible development of PAD and neuropathy could not be ascertained in this report.We did not document waveform patterns whilst examining for PAD.The burden of Peripheral neuropathy and peripheral arterial disease is high and may go undetected if not screened for. We recommend that PAD and neuropathy be screened for in diabetic clinics.


Patients with severe acute exacerbations of asthma often receive inappropriate antibiotic treatment. We aimed to determine whether serum procalcitonin (PCT) levels can effectively and safely reduce antibiotic exposure in patients experiencing exacerbations of asthma.In this randomized controlled trial, a total of 216 patients requiring hospitalization for severe acute exacerbations of asthma were screened for eligibility to participate and 169 completed the 12-month follow-up visit. Patients were randomized to either PCT-guided (PCT group) or standard (control group) antimicrobial therapy. In the control group, patients received antibiotics according to the attending physician’s discretion; in the PCT group, patients received antibiotics according to an algorithm based on serum PCT levels. The primary end point was antibiotic exposure; secondary end points were clinical recovery, length of hospital stay, clinical and laboratory parameters, spirometry, number of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma.P < 0.001) and antibiotic exposure  compared to standard therapy. There were no significant differences in clinical recovery, length of hospital stay or clinical, laboratory and spirometry outcomes in both groups. Number of asthma exacerbations, emergency room visits, hospitalizations and need for corticosteroid use due to asthma were similar during the 12-month follow-up period.PCT guidance reduced antibiotic prescription Chinese Clinical Trial Register  Asthma is a problem worldwide, with an estimated incidence of 300 million affected individuals and 250,000 annual deaths from asthma . Acute eBecause most exacerbations of asthma are associated with viral respiratory tract infection (RTI) and bacterial infection seems to play only a minor role, global asthma management guidelines do not recommend routine use of antibiotics . HoweverAs many as 75% of all antibiotic doses are prescribed for RTIs, such as acute bronchitis, community-acquired pneumonia (CAP), acute exacerbations of asthma or chronic obstructive pulmonary disease (COPD), despite their mainly viral cause . This inIn our previous study, we demonstrated that PCT can be used accurately and effectively to determine whether acute asthma patients have bacterial infections and to guide the use of antibiotics in the treatment of acute exacerbation of mild to moderate asthma . HoweverThis was a randomized controlled trial. The study was approved by the Shanghai Fifth People’s Hospital Research Ethics Committee, and all patients or their legally authorized representatives provided written informed consent.From January 2009 to December 2011, consecutive patients ages 18 to 65 years who were hospitalized in the Fifth People’s Hospital of Shanghai with severe acute exacerbations of asthma were eligible for enrollment in the study. Asthma was defined according to the guidelines of the Global Initiative for Asthma . A severBaseline assessment included asthma and medical history, vital signs, physical examination, routine blood tests, chest radiography, spirometry and clinical events related to asthma within the previous year, including asthma exacerbations, need for systemic corticosteroids, ED visits and hospitalizations for asthma. Spontaneously expectorated sputum samples were obtained to identify potential pathogenic microorganisms.Serum PCT was measured using the B.R.A.H.M.S. PCT sensitive Kryptor , a rapid sensitive assay with a functional sensitivity of 0.06 μg/L and a lower detection limit of 0.02 μg/L with an assay time of less than 30 minutes.Eligible patients were randomized to either PCT-guided (PCT group) or standard antimicrobial therapy (control group). Allocation to either intervention was conducted according to computer-generated random numbers produced by an independent statistician. After randomization, an opaque, sealed, sequentially numbered envelope containing the PCT or control protocol was prepared for each subject according to group assignment. The control group received antibiotic according to the discretion of the treating physician, who was unaware of the patient’s PCT levels. PCT levels of patients in the PCT group were provided to their attending physicians. Patients in the PCT group were treated with antibiotics on the basis of a PCT algorithm validated in previous studies ,10,12–16The primary end point was antibiotic use, expressed as rate of antibiotic prescriptions in percentage and relative risk of antibiotic exposure. Secondary end points included measures of treatment success; length of hospital stay; clinical, laboratory and spirometry outcomes at discharge; and results of spirometry at the 12-month follow-up examination, as well as the results of the Asthma Control Test (ACT) , the resThe ACT was used to determine the level of disease control. The overall ACT score varies from 5 (very poor asthma control) to 25 (full asthma control), with scores ranging from 20 to 24 defining controlled asthma, scores ranging from 16 to 19 partly indicating controlled asthma and scores ≤15 identifying uncontrolled asthma. The AQLQ was used to evaluate quality of life. The AQLQ consists of 32 items covering asthma-related symptoms and limitations during the 2 weeks preceding administration of the questionnaire, and responses are scored on a scale of 1 to 7, with higher numbers indicating a better quality of life. The validity and reliability of the ACT and the AQLQ have been evaluated for use in Chinese patients with asthma ,22.2 test, two-sampled t-test and/or Mann-Whitney U test as appropriate. Relative risk (RR) was calculated with 95% confidence interval (CI). P < 0.05 was defined as statistically significant.Discrete variables are expressed as percentages and continuous variables as mean ± standard deviation (SD) for variables normally distributed and as median with interquartile range (IQR) for nonnormally distributed data. Comparability of groups was analyzed by χAssuming 90% of the patients in the control group would use antibiotics and anticipating a 15% decrease in antibiotic usage in the PCT group, a sample size of 158 patients (79 patients per group) was necessary to detect a significant difference in antibiotic prescription rate between the groups with 80% power and an α error of 0.05. To account for possible loss of patients to follow-up, we planned to enroll 180 patients.The time to the first occurrence of asthma-related clinical events  was analyzed using Kaplan-Meier survival curves and by the logrank test. For outcomes during the follow-up period, we performed per-protocol analyses. Data were analyzed using SPSS version 16 for Windows statistical software .n = 90) or the control group (n = 90); of these 180 patients, 169 completed the 12-month follow-up visit, and 5 patients in the PCT group and 6 patients in the control group were lost to follow-up , fluoroquinolones , aminopenicillin , cephalosporins . A single antibiotic was used in 108 patients , and combination therapy with two or more antibiotics was administered in 15 patients .All patients received any one or a combination of the following medications for treatment of the exacerbation: theophylline, corticosteroids, βChlamydophila pneumoniae , followed by rhinovirus  , and 24 causative microorganisms were isolated . The most frequently detected pathogens were P = 0.145).The median PCT concentration was 0.113 μg/L , and 74 patients (41.1%) had PCT levels <0.1 μg/L, 30 (16.7%) had PCT levels between 0.1 and 0.25 μg/L and 76 (42.2%) had PCT levels >0.25 μg/L. PCT levels did not differ significantly between patients with sputum samples  and those without  (n = 3), patient’s request (n = 1) and purulent sputum (n = 2). Four patients in the PCT group from whom antibiotics were initially withheld (those with a PCT level <0.25 μg/L) received an antibiotic based on a PCT level >0.25 μg/L at the second measurement during reevaluation after 6 to 24 hours. Overall, antibiotic exposure was lower in patients for whom antibiotics were prescribed according to the algorithm based on PCT levels compared to standard therapy  . Thus, in spite of overruling, the PCT algorithm permitted a 44.3% reduction in antibiotic use.In the PCT group, 38 patients received antibiotics according to the PCT algorithm. Overruling was observed in six patients with PCT <0.25 μg/L. The reasons for overruling included receiving mechanical ventilation (P = 0.518). The median of antibiotic duration in the PCT group  was similar to that in the control group  (P = 0.198). There were no significant differences between groups in laboratory measures, length of hospital stay or spirometry at discharge  in the PCT group and eleven (12.2%) in the control group received mechanical ventilation treatment (P = 0.698), and systemic corticosteroids for ≥3 days were needed in 89 cases . There were no significant differences in the exacerbation rate  or in the hospitalization rate for exacerbations of asthma  (Table Clinical and laboratory measures of outcome, spirometry and ACT and AQLQ scores were similar at the 12-month follow-up visit in both groups Table . During We observed a significant reduction in antibiotic use in patients hospitalized with severe acute exacerbations of asthma for whom a decision could be made on the basis of an algorithm of PCT measurements. Importantly, withholding antibiotic treatment did not cause apparent harm according to clinical and laboratory outcomes at discharge and during the 12-month follow-up period.Mycoplasma pneumoniae and Chlamydophila pneumoniae may play a role in its pathogenesis [Exacerbation of asthma is often precipitated by a viral respiratory infection, and atypical bacteria such as ogenesis –25. Antiogenesis , a totalogenesis , Graham ogenesis , 55 patiUnder realistic clinical practice conditions, the challenge for physicians is to identify asthma patients with bacterial RTI for whom antimicrobial treatment is likely to be beneficial. Patients are often prescribed antibiotics despite clinical practice guideline recommendations against the empiric use of antibiotics in acute exacerbations of asthma –7. CliniCirculating levels of PCT are elevated in patients with systemic bacterial infections, but they remain relatively low in patients with viral infections or inflammatory diseases ,34. HencOnly a few asthma patients were included in two previous trials of PCT-guided therapy, ,13. In oHowever, some limitations of the present study should be recognized. First, we excluded patients older than 65 years of age, which may limit the application of our findings to older patients. Second, we did not conduct a formal cost–benefit study. To evaluate if a PCT-based strategy is cost-efficient under real-life conditions, cost aspects should be carefully considered. Third, this study was performed in a single center with a high baseline use of antibiotics for the treatment of asthma. Reductions in antibiotic use by means of PCT therapy guidance will be less in centers that already use antibiotics for asthma less often. Fourth, because of its relatively small sample size, our study has limited power to prove the safety of the PCT strategy, and we cannot exclude a potential harm of reducing antibiotic therapy on the basis of PCT guidance. Taking into account the limited population size in the study, a multicenter trial that includes a large number of patients with severe exacerbation of asthma is desirable to validate our data. We emphasize that any infection is too complex to be reduced to a single cutoff of a surrogate marker, and biomarkers should complement rather than replace good clinical practice. Certainly, results from the use of biomarkers should be considered in light of the pretest probability of disease presence.The results of our study support the concept that PCT guidance reduces antibiotic exposure in patients with severe acute exacerbation of asthma without apparent harm. Given the prevalence of asthma and the duration of illness, a reduction in antibiotic prescriptions for the treatment of exacerbations could result in fewer side effects, lower costs and, in the long term, lead to diminishing drug resistance, particularly in countries such as China, where patients are suffering from the overuse of antibiotics ,43.Antibiotic overuse in China is normal, and patients with severe acute exacerbations of asthma often receive inappropriate antibiotic treatment.The results of this single-center study show that a significant reduction in antibiotic use in patients hospitalized with severe acute exacerbations of asthma for whom a decision could be made on the basis of an algorithm of PCT measurements.Withholding antibiotic treatment on the basis of PCT guidance did not cause apparent harm for up to 12 months.Additional larger multicenter studies are needed to confirm the usefulness of PCT guidance during treatment of severe asthma exacerbation.


To determine the use of information technology (IT) & electronic media for improving compliance rate to doctors’ advice in hypertensive patients in Karachi.Total 400 persons  were randomly selected in six districts of Karachi. Data was collected through a pretested questionnaire. Following was sample criteria: age above 15 years, living in Karachi and ambulatory. Persons admitted in a hospital, individuals who were doing some physical activity during survey e.g. exercise, labor work etc., individual in stressed condition, non-cooperative individuals – not willing to get BP checked and fill questionnaire, and pregnant women were excluded. Those who did not sign the consent form were also excluded. SPSS was used for data analysis and descriptive statistics was employed for sensitivity analysis. For healthcare awareness, people look for health programs on radio and TV channels. Short Message Service (SMS) and phone are highly appreciated by patients for reminders. To increase compliance to doctors’ advice, less educated people prefer phone calls over SMS whereas educated individuals favor SMS. Although price of medicine has not emerged as a major contributing factor for non-compliance, discount on medicinal products is highly appreciated by the patients.The study concludes that there is a widespread awareness of high blood pressure in the sample population of Karachi e.g. 72.5%. People consider reminder message system i.e. Calls and Short Messaging Service (SMS) would help them in improving compliance to doctors’ advice. Juxtaposing these facts, a large number of cases of stroke, and other cardiovascular events could be projected. Hence disease load of high blood pressure would be significantly high in future. In one study, the factors of non-compliance reported included dose missed due to forgetfulness (56.8%), intentionally dose missed (12.7%), unable to take medicine due to too many tablets (11.6%), poor counseling by doctors (4.6%), and cost issues (3.8%). Other reasons for non-adherence or non-compliance were age, poor awareness and symptomatic treatment.2In Pakistan, around 18million people of 15 years and above age are estimated sufferers of high blood pressure. Seventy percent (70%) of them are not aware of this disease. Out of those who are taking medication, only 3% achieve blood pressure control.3 In a clinical trial, hypertension short message service (SMS) was used as tool for the desired blood pressure control. It was reported that its efficacy rate went up to 85% in the trial as compared to 20% in routine practice. It was thought that the success was due to increased communication between patient and physician through SMS.4Cell phone can play its role in improving patient compliance and disease management.5In the present era, the channels of mass communication have been increased and innovative techniques of knowledge sharing have become more common in the society. Communication channels have become more useful for information sharing and knowledge spreading through different media that focus on the improvement of personal health. Furthermore, efforts towards changing the attitude and behavior, people have become more communicative and effective by the usage and widespread of social marketing methods and techniques. Social marketing is basically the application of marketing practices for the non-profitable social purposes, as Philips Kotler and Gerald Zaltman described it as “the arrangement and implementation of social change by using a potentially strong framework”.6In the public health sector, adoption of the social marketing techniques worldwide has been increasing day by day but there are still many misconceptions and confusion prevalent in the minds of the health professionals. These are basically due to lack of understanding and knowledge about the benefits and influence of social marketing methods.7The recent technological advancements in the field of internet and mobile technology have offered great opportunities for improvement in the public health sector. However, an important aspect of these advancements is still not fully exploited for the benefit of society. Further, these technological developments could also be helpful in improving physician-patient relationship and the follow-up.The objective of this study was to determine the elements of communication which could improve compliance to physician instructions in a targeted population and help achieve blood pressure control in hypertensive patients. The study also aimed to find effectiveness of current communication modes for improving patient’s compliance.The population of Karachi is approximately 18 Million and is increasing continually and thought it has surpassed 20 million but still the official figures show around 14.5 million.For the purpose of sample selection, the study established inclusion and exclusion criteria. Inclusion criterion included (1) above 15 years of age, (2) Karachi resident; and (3) ambulatory patients. Whereas, exclusion criteria excluded (1) persons admitted in healthcare facilities e.g. medical centers or hospitals, (2) individuals who were doing some physical activity during the survey e.g. exercise, labor work etc., which can change their blood pressure,(3) individual observed to be in stressed condition, (4) who are not willing to cooperate for blood pressure check and fill questionnaire, (5) who do not want to sign survey consent form; and (6) pregnant women.10-13 Statistical Package for Social Sciences (SPSS) was used for data analysis and descriptive statistics used for analyzing the data regarding sensitivity analysis, frequency of hypertensive, and normotensive and awareness level between the hypertensive and normotensive.For the purpose of data collection, a survey was performed using a questionnaire developed in light of the literature review Descriptive statistics was summarized in terms of frequencies and percentages for qualitative/categorical variables . Total sample size comprised 400 of which 200 were males and 200 females. The sensitivity analysis of the data  & IV shoAbout 83 (20.8%) of the selected individuals self-reported to be hypertensive of which 43 were (51.8%) males and 40 (48.2%) were females, which means hypertension was prevalent almost equally in both the genders. The sensitivity analysis reveals that either control is established in 9 (2.9%) including 7 (77.8%) males and 2 (22.2%) females, or those people who thought they had hypertension but did not have. Of those reporting to be non-hypertensive, 12 (14%) were found hypertensive which meant they were not aware of their hypertensive silent killer condition or thought they were healthy but were at risk of hypertension. These (14%) included 5 (41.7%) male and 7 (58.3%) female.The probability tree of survey for determining awareness and prevalence of hypertension applied to the population is presented in A probability of 0.1850 of being afflicted with hypertension and acknowledging positive (a true positive result)A probability of 0.0300 of being afflicted with hypertension and acknowledging negative  A probability of 0.0225 of not being afflicted with hypertension and acknowledging positive  A probability of 0.7625 of not being afflicted with hypertension and acknowledging negative (a true negative result) The The positive predictive value (PPV) is 0.8916, whereas the negative predictive value (NPV) is 0.9621. Thus it might be expected that only about 89% of subjects who say they have high blood pressure are actually hypertensive. However, a subject who denies suffering from high blood pressure may be hypertension free (at least 96% of the time) in this population.The data in a) Mobile Phones are common and available to almost everyone, whereas internet is not accessible to every person.b) Phone calls are more convenient than e-mails.c) Elderly people have difficulty in reading SMS and accessing their e-mails.d) Less educated people also prefer phone calls as they have difficulty in following the messages sent through SMS.e) The subjects look for a chance to discuss their concerns.f) They gain more confidence through two-way communications.g) Personal touch of phone call that has greater impact than that of SMS or e-mail.Significantly high number of subjects asked for increasing air time of health and disease related programs on television and radio for improving disease awareness of general public. For improving adherence rate to doctors’ advice and thus control of blood pressure, discount on medicine and regular B.P. monitoring could be used. Discount on medicine was more emphasized by the patients as it would help in improving compliance. Other suggestions included increased discussion session and social support to the patients. By social support they meant establishment of hypertensive care centers, call centers for answering queries and educating patients, and continuous public education lectures on hypertension.The study concludes that there is a widespread awareness of hypertension not only among hypertensive patients but also among normotensive as well, in both genders in Karachi. However, rate of control of hypertension is just 24.4%; 98.8% do not receive any reminder for improving drug intake, where as 1.2% do receive reminder message for medical checkup. For improving disease awareness, most of the subjects prefer health awareness programs on television and radio. 87.5% of subjects prefer phone calls alone (64.6%), with SMS (19.5%), and with SMS & e-mail (2.4%). SMS is preferred by 8.5% subjects only. This shows that phone calls could be beneficial for better rate of control of high blood pressure. It is recommended that a structured study should be designed to find out how this mode could be used effectively to improve patients’ adherence to doctors’ advice.MIH: conceived, designed, prepared manuscript, statistical analysis of data, and statistical inference. BSN, MIH & NA: Collected data.NA: Referencing and arranged data.IA: Design modification.BSN: Reviewed and final approval of manuscript.MIH: Takes responsibility and accountable for all aspects of the work in ensuring.


Children with type 1 diabetes (T1D) are at higher risk of early adult-onset cardiovascular disease. We assessed cardiovascular structure and function in adolescents with T1D compared with healthy controls and the relationships between peripheral vascular function and myocardial parameters.199 T1D  and 178 controls (14.4 ± 2.1 years) completed endothelial function by flow mediated vasodilatation (FMD), arterial stiffness using pulse wave velocity (PWV) along with M-mode, pulse wave and tissue Doppler, and myocardial deformation echocardiographic imaging. Systolic  and diastolic  blood pressures, carotid femoral PWV and endothelial dysfunction measurements were increased in T1D compared with controls. Systolic and diastolic left ventricular dimensions and function by M-mode and pulse wave Doppler assessment were not significantly different. Mitral valve lateral e’  and a’  myocardial velocities were decreased and E/e’  increased in T1D. Left ventricular mid circumferential strain  was higher, whereas global longitudinal strain was lower (−19.0 ± 1.9 vs. −19.8 ± 1.5 % p < 0.001) in T1D.Adolescents with T1D exhibit early changes in blood pressure, peripheral vascular function and left ventricular myocardial deformation indices with a shift from longitudinal to circumferential shortening. Longitudinal follow-up of these changes in ongoing prospective trials may allow detection of those most at risk for cardiovascular abnormalities including hypertension that could preferentially benefit from early therapeutic interventions. The development of abnormal ventricular function in diabetes is multifactorial and has been attributed to metabolic disturbances, renal impairment, myocardial fibrosis, small vessel disease, cardiac autonomic neuropathy, and insulin resistance , 2. In aDiabetes has long been known to be a major risk factor for the development of cardiovascular disease . ConsequAccordingly, our aim was to evaluate cardiovascular structure and function in adolescents with T1D compared with healthy controls and to assess the relationships between these peripheral vascular and myocardial parameters with clinical parameters in patients with T1D.http://www.clinicaltrials.gov/ct2/show/NCT01581476), which was designed to examine the effect of angiotensin converting enzyme inhibitors and statins on renal, retinal and cardiovascular endpoints. Our study did not include participants involved in the intervention trial; however, as an ancillary component of non-randomized low-risk arm of AdDIT we also included high-risk subjects who chose not to enter the AdDIT intervention study. All analyses in this manuscript were performed using biological specimens and data collected from subjects enrolled in the observational and ancillary arm of AdDIT, specifically baseline data from the study obtained at Greater Toronto Area sites.Patients were recruited from the longitudinal, observational, non-interventional arm of the adolescent type 1 diabetes cardio-renal intervention trial (AdDIT) from clinical sites in the Greater Toronto Area. In brief, the non-randomized low-risk arm of AdDIT is a 4-year observational/natural history study, following adolescents at low and middle risk of developing microalbuminuria (EudraCT Number: 2007-001039-72) . High-riPatients with uncomplicated T1D were recruited from endocrinology clinics at The Hospital for Sick Children, Credit Valley Hospital and Markham–Stouffville in the Greater Toronto Area , and inclusion/exclusion criteria have been described elsewhere . HealthyControl subjects were recruited as similar aged healthy volunteers, who were not on any vasoactive medications, had no previous history of familial hyperlipidemia, diabetes, obesity, hypertension, or any other significant cardiac, renal or systemic disease and normal cardiac anatomy and function by screening echocardiogram .® sphygmomanometer . Systolic and diastolic blood pressures were also converted to z-scores for age, sex and height  with all 178 healthy control subjects. These groups were well matched for sex, age and height . For arterial stiffness, carotid-radial PWV was significantly higher in T1D vs. healthy controls . Similar trends were seen for carotid-femoral PWV, although differences did not reach significance .Male gender was the only variable that explained a proportion of the difference in FMD, between the T1D and control groups . For carotid-radial PWV, the variables that explained differences between the T1D and control groups were diastolic blood pressure  and male gender .Echocardiographic assessment adjusted for sex, age and BSA to accommodate for any differences in body proportions between the groups are presented in Table As shown in Table During childhood, patients with T1D generally do not have clinical cardiovascular symptoms as there is a delay between the diagnosis of T1D and cardiovascular events which could be used for therapeutic interventions slowing down the progression of CV disease , 29, 30.Our first major observation was that we found increased systolic and diastolic blood pressures in adolescents with T1D compared with controls. Previous studies have consistently shown similar differences in blood pressure in children and young adults with T1D compared with controls , 32, 33.From a physiologic perspective, it seems unlikely that higher blood pressure in the T1D group was due to primary changes in cardiac function, since between group differences in mean heart rate, LV stroke volume and ejection fraction or cardiac output were very small. Instead, based on abnormalities described below, it seems more plausible that the higher blood pressure values may therefore have been due to an increase in peripheral vascular resistance, thereby leading to secondary echocardiographic changes. An increase in peripheral vascular resistance as the primary cause of early increases in blood pressure in T1D, rather than an increase in cardiac output, would be in contrast with early blood pressure changes in young, non-diabetic patients with essential hypertension. In this non-diabetic setting, increased cardiac output has been reported as the earliest hemodynamic change that precedes a rise in peripheral vascular resistance . FortunaIn addition to measuring blood pressure, to more fully evaluate the peripheral vasculature, we evaluated endothelial function with FMD and arterial stiffness using PWV , since pOur third major finding relates to changes in LV systolic and diastolic function in adolescents with T1D. Increased measures of LV systolic function by M-mode, such as shortening and ejection fraction as we found in our cohort, suggest that LV systolic function at rest is increased in adolescents with T1D. These observations have been suggested by others in a small (n = 39) adolescent cohort that only included boys, although the mechanism is not well understood . Early cIn addition to these changes in M-mode echocardiography, we observed early changes in LV myocardial velocities and strain in adolescents with T1D compared with controls. We speculate again that the higher blood pressure values observed in this T1D cohort, although still within the “normal” range, may in part explain this ventricular remodeling. Alteration of LV longitudinal deformation with decreased global longitudinal strain, similar to what we found in our cohort, has been previously reported in children and adults with T1D , 55. LV Our observations have potential clinical implications for the early identification of patients with T1D who are at high risk of future complications, and for earlier therapeutic interventions. FMD and arterial stiffness measures have been shown to predict future cardiovascular events in high risk groups, although the clinical utility of these parameters in early T1D has yet to be determined , 44. TheOur work has important limitations. Our adolescents with T1D were well matched in comparison to our controls, except for being heavier with consequent larger BSA and BMI. To account for these differences, we additionally reported models adjusted for sex, age and BSA. BSA was chosen, given that echocardiographic parameters are routinely indexed to this rather than BMI. Second, despite our relatively large sample size, we found only carotid-radial PWV and not carotid–femoral PWV differed between the two groups. Since carotid-femoral PWV is thought to reflect larger arteries compared to carotid-radial PWV, it is possible that early changes in arterial stiffness in adolescents with T1D are primarily limited to smaller arteries. Given the cross sectional design of this analysis, we were not able to determine the long term clinical significance of this and other statistically significant between group differences. Longitudinal data is being collected in this cohort as part of the AdDIT Observational Study and will help to clarify the relationships between these physiological measures and clinical outcomes. Finally, this study in adolescents was not designed to elucidate physiological mechanisms responsible for between group differences in cardiovascular function, such as early changes in nitric oxide bioavailability, autonomic tone, vitamin D levels or inflammatory biomarkers –63. ThesIn conclusion, adolescents with T1D exhibit early changes in blood pressure, peripheral vascular function and left ventricular myocardial deformation indices with a shift from longitudinal to circumferential shortening. Longitudinal follow-up of these changes may allow early detection of those most at risk of early adult-onset cardiac disease that would preferentially benefit from preventive therapeutic interventions. Additional studies are also required to better elucidate subgroups of patients with early T1D with the most deleterious cardiovascular profiles, who may, as a consequence, be at the highest risk of future clinical disease.


Anemia is a common complication among patients with chronic kidney disease (CKD), and it is associated with unfavorable clinical outcomes in patients with CKD independent of the estimated glomerular filtration rate (eGFR). We assessed the association of the urinary albumin-to-creatinine ratio (ACR) and eGFR with anemia in CKD patients.We conducted a cross-sectional study using baseline data from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD). Multiple regression analysis was performed to identify the independent association of albuminuria with anemia. Furthermore, odds ratios for anemia were calculated by cross-categorization of ACR and eGFR.2 and 853.2 ± 1,330.3 mg/g, respectively. Anemia was present in 644 patients (40.5%). Multivariate analysis showed that the odds ratio of anemia increased according to ACR levels, after adjusting for age, sex, eGFR, body mass index, pulse pressure, cause of CKD, use of erythropoiesis stimulating agents, serum calcium and ferritin  = 1.43, 95% confidence interval (CI) = 0.88–2.33; ≥300 mg/g, adjusted OR = 1.86, 95% CI = 1.12–3.10). In addition, graded associations were observed in cross-categorized groups of a higher ACR and eGFR compared to the reference group with an ACR <30 mg/g and eGFR ≥60 mL/min per 1.73 m2.Among 1,456 patients, the mean age was 53.5 ± 12.4 years, and the mean eGFR and ACR were 51.9 ± 30.5 mL/min per 1.73 mThe present study demonstrated that albuminuria was a significant risk factor for anemia in CKD patients independent of the eGFR. The incidence and prevalence of chronic kidney disease (CKD) have rapidly increased worldwide, and CKD is recognized as a risk factor for all-cause mortality and cardiovascular mortality . Anemia Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of CKD recommended that CKD is classified based on the cause of CKD and the estimated glomerular filtration rate (eGFR) category, and the albuminuria category (CGA) . To dateThe study protocol was approved by the institutional review board at each participating clinical center including the Seoul National University Hospital, Severance Hospital, Kangbuk Samsung Medical Center, Seoul St. Mary’s Hospital, Gil Hospital, Eulji General Hospital, Chonnam National University Hospital and Pusan Paik Hospital in 2011. All participating patients provided written informed consent.We used baseline data of the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD), a nationwide prospective cohort including CKD stage 1–5 non-dialysis patients from February 2011 to July 2014. The study aimed to explore the risk factors for renal or cardiovascular outcomes in Korean CKD populations. The detailed design and methods of the KNOW-CKD have been previously published . Among 1Baseline demographics, and clinical and laboratory values were extracted from the electronic data management system (PhactaX). Blood samples were analyzed at each hospital laboratory of the participating centers. Ten mL of whole blood was obtained by using the serum separation tube (SST) and centrifuged within 1 hour for serum separation before being sent to the central laboratory (Lab Genomics) for creatinine measurement. Serum creatinine was measured by an IDMS-traceable method and the eGFR was estimated using the CKD Epidemiology Collaboration equation using age, sex, race, and the serum creatinine level . Another2) and albuminuria . Generalized additive models were computed using the R Statistical package software (version 2.15.3), and SPSS software, version 19.0 (SPSS Inc.) was used to perform the remaining statistical analyses. Tests were considered statistically significant at P < 0.05.Continuous variables were expressed as mean ± standard deviation and categorical variables as a number (percentage). The ACR was analyzed as a categorical variable and as a natural log-transformed variable (Ln ACR) to approximate a normal distribution. To compare baseline characteristics according to the ACR groups, analysis of variance and chi-square tests were used for continuous variables and categorical variables, respectively. Spearman’s correlation analysis was used to determine the association between hemoglobin and Ln ACR. We performed univariate logistic regression analysis to determine the association between anemia and other variables including demographics and various laboratory data. Multivariate logistic regression analysis was applied to calculate adjusted odds ratio (OR) by stepwise backward selection with adjustment for covariate effects to those variables that were significantly associated with anemia in univariate analysis. Missing variables were replaced using the linear interpolation imputation method. Moreover, ORs were ascertained by model approaches for covariate adjustment as follows: model 1 = adjusted for age and sex; model 2 = model 1 + eGFR; and mode 3 = model 2 + cause of CKD, BMI, use of an erythropoiesis stimulating agent (ESA), pulse pressure, serum calcium, and ferritin. Graphical illustrations of the relationship of the ACR and eGFR with anemia were also obtained by generalized additive models. Additionally, we evaluated multiplicative interaction based on categories of the combination of eGFR and ACR. We compared the risk in nine categories of the eGFR  was the most common cause of CKD, followed by diabetic nephropathy (21.6%), hypertensive nephropathy (20.2%), and polycystic kidney disease (17.4%). Two hundred twenty two patients (15.2%) had an eGFR ≥90 mL/min per 1.73 m2, 268 (18.4%) had an eGFR of 60–89 mL/min per 1.73 m2, 227 (15.6%) had an eGFR of 45–59 mL/min per 1.73 m2, 316 (21.7%) had an eGFR of 30–44 mL/min per 1.73 m2, 317 (21.8%) had an eGFR of 15–29 mL/min per 1.73 m2, and 106 (7.3%) had an eGFR <15 mL/min per 1.73 m2. A2 (ACR 30–299 mg/g) and A3 (ACR ≥300 mg/g) were present in 455 (31.3%) and 774 (53.2%) patients, respectively. The mean hemoglobin levels were 12.8 ± 1.9 g/dL, and 644 patients (44.2%) had anemia at baseline. One hundred-twenty seven patients (8.7%) were taking ESA therapy. Baseline clinical characteristics stratified by categories of ACR are presented in Among 1,456 patients, the mean age was 53.5 ± 12.4 years, and 896 patients (61.5%) were male. The mean eGFR and ACR were 51.9 ± 30.5 mL/min per 1.73 mPearson’s correlation analysis showed that hemoglobin levels were inversely related with Ln ACR levels  . Univari2 for fully adjusted model was 0.387). Otherwise, microalbuminuria failed to show a significant increase in the prevalence of anemia compared with the reference group. When patients using an ESA were regarded as those with anemia or were excluded in multivariate analysis, the value of OR for anemia was not noticeably changed  compared with normoalbuminuria (ACR < 30 mg/g) in every eGFR category.2) in a general population of 30,528 people[2) and macroalbuminuria . In another cross-sectional study that included 820 patients with diabetes, the prevalence of anemia were stratified according to the albumin excretion rate  and eGFR . Subjects with macroalbuminuria were more likely to have anemia at all the eGFR categories [Anemia is a common manifestation of CKD and the prevalence of anemia increases as the eGFR declines . Anemia 28 people. Howevertegories . Unlike The increased prevalence of anemia in diabetic patients with albuminuria cannot be explained by reduced renal function , 9. SomeIn our study, serum ferritin and TSAT levels, as measures of the iron deficiency status, were feasible in most of the study subjects. The lowest TSAT quintile, and the lowest and highest serum ferritin quintiles showed a high OR for anemia. Measuring TSAT and the serum ferritin are well-established tests for assessing iron status. However, since serum ferritin is an acute-phase reactant, high ferritin concentrations should be interpreted with caution. In the present study, there was a correlation between serum ferritin levels and the Ln C-reactive protein level . A U-shaped relationship between the serum ferritin level and anemia was also observed. Although serum ferritin levels were included in multivariable analysis, the association between anemia and albuminuria remained significant. Compared to previous studies, reliable data and adjusting the iron deficiency status could be the strengths of this study. Meanwhile, considering the association between anemia and albuminuria, it can be hypothesized that recognizing of patients with albuminuria and the use of interventions such as angiotensin converting enzyme inhibitors (ACEI) or an angiotensin receptor blocker (ARB) may lead to the improvement of anemia. However, ACEI has been suggested as causing anemia in several studies rather than improving anemia , 32. In 2, patients with eGFR ≥60 mL/min per 1.73 m2 were not further categorized into >90 and 60–89 mL/min per 1.73 m2 group according to CKD staging recommendations in multiplicative categorization between the eGFR and albuminuria [2) and normoalbuminuria was small, groups with eGFR <45 mL/min per 1.73 m2 were not further categorized into CKD stages 3b, 4, and 5. Notwithstanding these limitations, the simultaneous measurement of the ACR and creatinine in a central laboratory and the enrollment of CKD patients with a preserved eGFR are the major strengths of this study.There are several limitations of this study. First, only a single ACR measurement was available at baseline. ACR level may be high due to extremely low levels of creatinine as well as high levels of albuminuria. However, the 24-hour urine collection was obtained from most of the study population, and the protein excretion rate was measured, showing excellent correlation with the ACR. Although timed urine collection  remains the gold standard assessment of proteinuria, measurement of the ACR is more convenient, and it showed superiority in predicting renal events . Second,uminuria , 21. LikIn conclusion, the present study demonstrated that albuminuria was significantly associated with an increased prevalence of anemia, independently of eGFR, in patients with CKD.S1 TableAbbreviations: ACR, albumin to creatinine ratio; ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; BMI, body mass index; CI, confidence interval; CKD, chronic kidney disease; DN, diabetic nephropathy; eGFR, estimated glomerular filtration rate; ESA, erythropoiesis-stimulating agent; GN, glomerulonephritis; HTN, hypertension; LVMI, left ventricular mass index; OR, Odds ratio; PCR, protein to creatinine ratio; PKD, polycystic kidney disease; PTH, parathyroid hormone; SBP, systolic blood pressure; TSAT, transferrin saturation.(DOCX)Click here for additional data file.S2 TableAbbreviations: ACR, albumin to creatinine ratio; ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; BMI, body mass index; CI, confidence interval; CKD, chronic kidney disease; DN, diabetic nephropathy; eGFR, estimated glomerular filtration rate; ESA, erythropoiesis-stimulating agent; GN, glomerulonephritis; HTN, hypertension; LVMI, left ventricular mass index; OR, Odds ratio; PCR, protein to creatinine ratio; PKD, polycystic kidney disease; PTH, parathyroid hormone; SBP, systolic blood pressure; TSAT, transferrin saturation.(DOCX)Click here for additional data file.S3 TableAbbreviations: ACR, albumin creatinine ratio; eGFR, estimated GFR; CI, confidence interval; BMI, body mass index; ESA, erythropoiesis stimulating agent; CKD, chronic kidney disease.Anemia . Model 1: adjusted for age and sex. Model 2: adjusted for age, sex, and the eGFR. Model 3: adjusted for age, sex, the eGFR, serum calcium level, BMI, use of an ESA, smoking, the cause of CKD, and ferritin level. (DOCX)Click here for additional data file.S4 Table. Model 2: adjusted for age, sex, and the eGFR.Model 3: adjusted for age, sex, the eGFR, serum calcium level, BMI, use of an ESA, smoking, the cause of CKD, and ferritin level.Abbreviations: ACR, albumin creatinine ratio; eGFR, estimated GFR; CI, confidence interval; BMI, body mass index; ESA, erythropoiesis stimulating agent; CKD, chronic kidney disease.Anemia . Model 1: adjusted for age and sex(DOCX)Click here for additional data file.S5 TableAbbreviations: ACR, albumin to creatinine ratio; BMI, body mass index; CI, confidence interval; CKD, chronic kidney disease; DN, diabetic nephropathy; eGFR, estimated glomerular filtration rate; ESA, erythropoiesis-stimulating agent; GN, glomerulonephritis; HTN, hypertension; OR, Odds ratio; PCR, protein to creatinine ratio; PKD, polycystic kidney disease.(DOCX)Click here for additional data file.


Blood pressure is a major cause of cardiovascular disease (CVD) and both may increase as outdoor temperatures fall. However, there are still limited data about seasonal variation in blood pressure and CVD mortality among patients with prior-CVD.We analysed data on 23 000 individuals with prior-CVD who were recruited from 10 diverse regions into the China Kadoorie Biobank during 2004–8. After 7 years of follow-up, 1484 CVD deaths were recorded. Baseline survey data were used to assess seasonal variation in systolic blood pressure (SBP) and its association with outdoor temperature. Cox regression was used to examine the association of usual SBP with subsequent CVD mortality, and seasonal variation in CVD mortality was assessed by Poisson regression. All analyses were adjusted for age, sex, and region.P < 0.001), especially among those without central heating. Above 5°C, each 10°C lower outdoor temperature was associated with 6.2 mmHg higher SBP. Systolic blood pressure predicted subsequent CVD mortality, with each 10 mmHg higher usual SBP associated with 21%  increased risk. Cardiovascular disease mortality varied by season, with 41% (21–63%) higher risk in winter compared with summer.Mean SBP was significantly higher in winter than in summer (145 vs. 136 mmHg, Among adult Chinese with prior-CVD, there is both increased blood pressure and CVD mortality in winter. Careful monitoring and more aggressive blood pressure lowering treatment in the cold months are needed to help reduce the winter excess CVD mortality in high-risk individuals. See page 1152 for the editorial comment on this article (doi:10.1093/eurheartj/ehv024)1 Over 80% of CVD deaths now occur in low- and middle-income countries such as China,2 and the burden of disease from CVD is projected to increase further over the next few decades in these countries.3Cardiovascular disease (CVD) is a leading cause of mortality and morbidity, with an estimated 17 million deaths in 2008.6 and is known to be associated with lifestyle and environmental factors. There is evidence that outdoor temperature affects blood pressure,9 with particularly large effects in China.8 Exposure to cold temperatures can lead to vasoconstriction and tachycardia, both of which contribute to increased blood pressure and cardiac load.10 Excess CVD mortality has been reported during the cold seasons,15 part of which may be driven by temperature-related increases in blood pressure. Individuals who are already suffering from CVD may be at, particularly, increased risk when exposed to cold temperatures. However, limited large-scale data exist about seasonal variation in blood pressure and CVD mortality among people with prior-CVD, especially in China where few people have access to central heating in winter and where few people with prior-CVD are properly managed.16Increased blood pressure is one of the most important modifiable causes of CVD,We report data from the China Kadoorie Biobank (CKB) study of over 500 000 adults aged 30–79 years who were recruited from 10 diverse regions in China during 2004–8 and followed up ever since for mortality and morbidity to 31 December 2013. The present study is of 23 000 participants who reported at the baseline visit having a physician diagnosed CVD and aims (a) to examine the association of outdoor temperature with blood pressure measured at recruitment, both overall and in different population subgroups, (b) to investigate the association between usual blood pressure and subsequent CVD mortality, and (c) to assess any seasonal variation in CVD mortality rates and then compare it with predicted risk based on seasonal changes in blood pressure.17 Briefly, the baseline survey took place between 2004 and 2008 in 10 geographically defined areas in China . At the baseline survey, detailed information about general demographic and socio-economic status, dietary and other lifestyle habits , indoor air pollution, medical history, and current medication were collected using an interviewer-administered laptop-based questionnaire. Participants were asked whether they had ever been diagnosed by a physician with a range of chronic diseases  . This provides indirect evidence that self-reports of prior-CVD in our study were generally reliable. Occlusive and haemorrhagic CVD may involve different pathophysiological mechanisms.37 Although the present study included a sufficiently large number of CVD deaths to assess the overall effect of season on CVD mortality, the statistical power to separately examine the seasonal patterns of subtype of CVD mortality is rather limited. The isolated clinic BP measurements used in our study are unable to provide as reliable an assessment of blood pressure as ambulatory blood pressure monitoring, and may lead us to underestimate any patterns or associations. However, the high comparability of baseline characteristics between participants enrolled at different seasons or months, as reported previously,8 suggests that seasonal variation in blood pressure is likely to be driven primarily by changes in outdoor temperature rather than by other lifestyle factors.There are some limitations to our study. Although it was explicit that all reported prior disease history should be based on physician diagnosis, it was not possible with such a large cohort to adjudicate all the self-reported cases retrospectively. However, there is an evidence from other studies of similar nature in China that self-reported history of CVD showed a good consistency with hospital records.Our study findings suggest that seasonal variation in CVD mortality rates in people with prior-CVD result, at least partly, from seasonal variation of blood pressure. Given the high prevalence of CVD in the Chinese population, especially of stroke, even moderate increases in CVD mortality rates during the winter months, as shown in this study, must account for large excess numbers of CVD deaths. The results from the present analyses suggest that seasonal changes in blood pressure should be taken into account in the diagnosis and treatment of hypertension and CVD. For patients with prior-CVD or other high-risk individuals, more intensive anti-hypertensive treatment and more frequent blood pressure monitoring may be required in winter to achieve the same blood pressure control as in other seasons. Longer follow-up of this large cohort study and the use of well-characterized non-fatal CVD events may allow for more detailed analyses of seasonal variation separately in the main components of CVD, namely IHD, ischaemic, and haemorrhagic stroke.European Heart Journal onlineSupplementary material is available at .Wellcome Trust in the UK (088158/Z/09/Z) and the Chinese Ministry of Science and Technology. The UK Medical Research Council, the British Heart Foundation and Cancer Research UK also provide core funding to the Clinical Trial Service Unit and Epidemiological Studies Unit at Oxford University for the project. Funding to pay the Open Access publication charges for this article was provided by Welcome Trust.The baseline survey and the first re-survey were supported by a research grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term continuation of the project during 2009–2014 is supported by program grants from the Conflict of interest: none declared.


Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function. To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis).ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3,074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated ( Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD. Renal function declines with age and according to the burden of vascular risk factors, while serum creatinine and proteinuria have been associated with late life incident all-cause dementia ACE gene with the most significant effects for higher activity of the angiotensin-converting enzyme are rs1800764 and rs4291 ACE in 17q23, while rs4291 is at ∼3.8 kb from the same site Genetic effects account for most of the variance in serum levels of the angiotensin-converting enzyme AT1R gene may increase the anti-hypertensive effect of Benazepril An earlier study had already demonstrated that the A1166C polymorphism of the Consecutive outpatients with dementia due to Alzheimer disease according to National Institute on Aging - Alzheimer's Association criteria After diagnostic confirmation, all patients had at least three yearly consultations, and were assessed for age, gender, arterial hypertension, and use of angiotensin-converting enzyme inhibitors. For statistics, only the first and the last evaluations were taken into account, the last evaluation one year apart from the first one. Fasting urea and creatinine levels were measured from venous blood samples at the beginning and at the end of the follow-up after one year. Blood pressure was measured in every evaluation after the participant sat resting for 5 min in a warm and quiet room, while the diagnosis of arterial hypertension followed the JNC 7 report ACE genotypes or haplotypes. In secondary analyses, the impacts of systolic and diastolic blood pressure variations in one year over variations in levels of urea and creatinine were assessed.The primary outcome measure was the variation in one year of levels of urea and creatinine, taking the following independent variables into account: use of an angiotensin-converting enzyme inhibitor and ACE genotypes of rs1800764 or rs4291, or their represented haplotypes, was correlated with anti-hypertensive treatment using angiotensin-converting enzyme inhibitors. All genotyping procedures were carried out only after clinical data were collected from all patients.After blood samples were collected from all patients in tubes with ethylenediaminetetraacetic acid 0.1%, genomic DNA was extracted using a standard salting-out procedure. Genotyping was undertaken by way of Real-Time Polymerase Chain Reactions using TaqManENT#174; SNP Genotyping Assays on the Applied Biosystems 7500 Fast Real-Time PCR System , following the standard protocols of the manufacturer. Presence of ACE genotypes was estimated by way of the Chi-square test. Multiple linear regressions were employed for comparisons within each patient group concerning variations of urea and creatinine in one year, with two degrees of freedom: ACE genotypes or haplotypes, and use or not of an angiotensin-converting enzyme inhibitor. Simple linear regressions were used for correlations between yearly variations in urea and creatinine, and yearly variations in systolic and diastolic blood pressure, so that genetically mediated effects of angiotensin-converting enzyme inhibitors over urea and creatinine variations could be evaluated independently of their blood pressure lowering properties. The threshold of significance was set at p= <0.05.One-way analysis of variance with post-hoc Tukey test was employed for variations of blood pressure, urea and creatinine in one year, taking initial and final values into account. The Hardy-Weinberg equilibrium for This study is part of the research project 1067/10 (CAAE 0540.0.174.000-10) approved by the Ethics Committee of our university hospital in August 2010. Procedures of the study were in accordance with the Declaration of Helsinki. All invited patients and their legal representatives agreed to participate on the research and signed the Informed Consent Form before the evaluation.A total of 217 patients were included in this study. During follow-up, 14 patients (6.5%) passed away, 11 patients (5.1%) abandoned the study, and 2 patients (0.9%) were excluded due to incomplete clinical data, resulting in a final sample of 190 patients.ACE haplotypes, six were represented in the sample.ACE polymorphisms and the use or not of angiotensin-converting enzyme inhibitors. No significant impacts over urea or creatinine variations were found regarding any independent genotypes of rs1800764. The presence of each A allele of rs4291 led to an yearly urea increase of 3,074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of angiotensin-converting enzyme inhibitors was protective regarding creatinine variations. With regard to creatinine variations for all studied haplotypes, the use of angiotensin-converting enzyme inhibitors was protective for carriers of rs1800764 CT / rs4291 AA, while carriers of rs1800764 CT / rs4291 AT had steeper reductions in blood creatinine levels, particularly when they were treated with angiotensin-converting enzyme inhibitors.p= 0.212) or diastolic blood pressure (p= 0.098) in one year. Likewise, no correlations were found between creatinine variations and variations in systolic blood pressure (p= 0.767) or diastolic blood pressure (p= 0.713) in one year. Nevertheless, variations of urea and creatinine in one year were positively correlated with each other (p= <0.0001).Overall, no correlations were found between urea variations and variations in systolic blood pressure  over earlier dementia onsetOverall, 80% of our patients with dementia due to Alzheimer disease had arterial hypertension, confirming the burden of this risk factor over cardiovascular health in older people. Though we conveniently employed a cohort of patients who had dementia due to Alzheimer disease, the neurological diagnosis probably had little effect over the cardiovascular burden of our population. Nonetheless, earlier studies had confirmed the combined effect of cerebrovascular risk factors (arterial hypertension, diabetes Limitations of this study include the fact that it was conducted in a single centre, with a short follow-up and no randomization, and lacking measurements of serum levels of the angiotensin-converting enzyme or urinary creatinine clearance, as well as an evaluation of sarcopenia. Also, it is unknown whether the pharmacogenetic effects of angiotensin-converting enzyme inhibitors over urea and creatinine variations are either dose-dependent or more significant when starting treatment or at any time during anti-hypertensive therapy, due to the fact that many patients were already under treatment when they were included in the study. We tried to minimize these limitations by keeping observers blinded to genetic data during the evaluations. Nevertheless, to the best of our knowledge, this is the first study to evaluate the pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea and creatinine variations.We conclude that the effects of anti-hypertensive therapy with angiotensin-converting enzyme inhibitors over creatinine variations are genetically mediated and independent of systolic or diastolic blood pressure variations. Future studies should assess pharmacogenetic effects of angiotensin-converting enzyme inhibitors regarding variations in urinary creatinine clearance, and consider serum levels of the angiotensin-converting enzyme as a variable.


Patients with resistant hypertension are subjected to a higher risk of getting stroke, myocardial infarction, congestive heart failure and renal failure. However, the exact prevalence of resistant hypertension in treated hypertensive patients in Malaysia is not known. This paper examines the prevalence and determinants of resistant hypertension in a sample of hypertensive patients.We examined the control of blood pressure in a randomly selected sample of patients with hypertension in a primary care clinic. Demographic data, blood pressure and anti-hypertensive drug use were captured from patient records at the end of 2007. Resistant hypertension is defined as failure to achieve target blood pressure of < 140/90 mmHg while on full doses of an appropriate three-drug regimen that includes a diuretic. Multivariate logistic regression was used for the analysis.A total of 1217 patients with hypertension were entered into the analysis. Mean age of the patients was 66.8 ± 9.7 years and 64.4% were female. More than half of the subjects (56.9%) had diabetes mellitus. Median BP was 130/80 mmHg. Overall prevalence of resistant hypertension was 8.8% (N = 107/1217). In multivariate logistic regression analysis, presence of chronic kidney disease is more likely to be associated with resistant hypertension . On the other hand, increase per year of age is associated with lower odds of resistant hypertension in this population .Resistant hypertension is present in nearly one in ten hypertensive patients on treatment. Hypertensive patients who have underlying chronic kidney disease are associated with higher odds of having resistant hypertension. Hence, in managing patients with hypertension, primary care physicians should be more alert and identify patients with chronic kidney disease as such patients are more likely to develop resistant hypertension. By doing that, these patients can be treated more aggressively earlier in order to achieve blood pressure target and thus reduce cardiovascular events. Resistant hypertension is an important medical condition as uncontrolled blood pressure (BP) is associated with a fourfold risk of cardiovascular events compared with hypertensive patients achieving BP targets ,2. The dStudies also show that resistant hypertension is associated with increasing age, female gender, black race, presence of diabetes, obesity, chronic kidney disease and left ventricular hypertrophy -14. EarlStrokes are more common in Asia than in developed countries while the reverse is true for coronary artery disease . ElevateWe examined the control of blood pressure in a randomly selected sample of patients in an urban primary care clinic. Random numbers was generated by computer based on the patient registration number with the clinic. This selected sample consists of adult patients aged 30 years and older with hypertension who were treated and on long term follow-up in our primary care clinic. The study was conducted in an outpatient clinic of the University Malaya Medical Centre, a teaching hospital in Kuala Lumpur, the capital city of Malaysia. This clinic is run by 14 family medicine specialists, 30 vocational trainees in family medicine and other medical officers. This tertiary hospital including its primary care clinic serves a multi-ethnic population of 450,000 in the surrounding area.People in the community can choose their own source of care. This teaching hospital functions on an open access basis to the community. A full range of services are offered at this clinic. Those who attend our clinic are mainly those requiring long term care of chronic conditions like hypertension, diabetes, dyslipidaemia in addition to the usual short term primary care illnesses.Care is provided free for public sector service employees and their dependents while all others are required to pay an equivalent of US$8.50 for both the consultation and a month’s supply of medication. Our study population consists of three main ethnic groups, namely the Malays, Chinese and Indians .Ethics approval for this study was obtained from the Ethics Committee of the University of Malaya Medical Centre.All patients with underlying hypertension were eligible for this study. Hypertension was defined as those who had a documented diagnosis of hypertension [i.e. BP ≥ 140/90 mmHg] or those on anti-hypertensive agents.This sample was randomly selected using a computer generated number based on the patient’s unique registration number with the clinic. All patient records were in paper form. We extracted the patients’ information based on the last entry in 2007 from their records manually according to a predetermined proforma  which included the patient’s socio demographic, blood pressure, weight, height, biochemical profile and use of anti-hypertensive agents. This was then entered into an electronic Excel spreadsheet and then converted to a SPSS format for analysis using SPSS version 21.The data was captured by a trained and experienced abstractor and accuracy of data entry was checked by the investigators themselves.Patients’ blood pressure which was measured by the attending doctors as part of daily routine care were also captured from the medical records. Patients recruited into our study were those who had been diagnosed to have hypertension or were on antihypertensive medications. Diagnosis of hypertension in our clinics is made in accordance with standard recommendations i.e. based on at least 2 BP measurements at least 2 weeks apart . Height 2.We used the Cockcroft-Gault formula to calculate the estimated glomerular filtration rate (GFR) as a measure of renal function. The presence of chronic kidney disease (CKD) was defined as estimated GFR < 60 mL/min per 1.73 mAnti-hypertensive drug use was also captured from medical records and classified into the following classes: renin-angiotensin-system (RAS) inhibitors encompassing angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB); beta-blockers, calcium-channel blocker (CCB), diuretics and alpha-blockers N.Resistant hypertension in this study is defined as office BP ≥140 and/or 90 mmHg despite the use of at least three antihypertensive drugs, one of which is a diuretic. Diabetes mellitus (DM) was based on the doctors’ diagnosis or the use of hypoglycemic agents or both as stated in the medical records. Smokers were defined as current if they were still smoking; non smokers for those who never smoked or currently not smoking, regardless of when they had stopped smoking as indicated in the patient records.All statistical analysis was done using the Statistical Package for Social Sciences (SPSS version 21). Continuous data are described as mean and standard deviation if the distribution is normal. When the data was a skewed distribution, median, minimum and maximum value were used to describe the data. Categorical data are reported as proportions (percentage). Chi-square test or Fisher exact tests were used for the categorical or dichotomous variables. Multivariate logistic regression analysis was used to look for the predictors of resistant hypertension. All variables with the p-value of less than 0.25 in the univariate analyses as well as clinically significant variables were entered into the multivariate logistic regression. The dependent variable was resistant hypertension (yes or no). The independent variables were age, gender, ethnicity, BMI, presence of diabetes, chronic kidney disease, dyslipidaemia and smoking status. All analyses were done with 95% confidence intervals (CI), and the level of significance was set at p < 0.05.A total of 1222 hypertensive patients were eligible for this study. Out of this, 1217 (99.6%) patients had complete drug therapy data and were entered into the analysis.2 and a third (34.9%) of the patients had underlying CKD.Table The mean number of anti-hypertensive agents used was 2.0 ± 1.0. The control rate of those on 2 drugs was 52.3% while it was 48.0% for those on 3 drugs. Three fifths (60.9%) of the diabetics and two fifths (41.3%) of the patients with CKD were on 3 antihypertensive agents. Calcium-channel blockers were the most commonly prescribed drug (53.2%) followed by angiotensin converting enzyme inhibitors or angiotensin receptor blockers (51.0%), beta-blockers (44.5%), diuretics (32.5%) and alpha-blockers (3.5%). For those patients who were on at least three drugs, 70.2% (n = 181) were on diuretics and 29.8% (n = 77) were not on diuretics. Among those patients who were on at least 3-antihypertensive agents including diuretics, 40.9% (n = 74) achieved blood pressure target while 59.1% (n = 107) had resistant hypertension. On the other hand, of those on at least 3 antihypertensive drugs which did not include a diuretic 96.1%, (n = 74) were controlled and 3.9% (n = 3) were not controlled.Overall prevalence of resistant hypertension was 8.8% (N = 107) with 95% confidence interval (CI) 7.21-10.39. Table Table The prevalence of resistant hypertension in this primary care setting is 8.8%. This is lower than that reported in secondary care ,33 but iOur findings also show that hypertensive patients with CKD had 2.9 odds of having resistant hypertension compared to those without CKD. This is consistent with findings in other studies ,14. One Our study sample is made up of older patients as seen from the mean age of 66.9 years. That resistant hypertension is negatively associated with age could be due to the survival effect of fitter patients, whereby those with resistant hypertension had already succumbed to the complications of uncontrolled or resistant hypertension.2 versus 26.3 kg/m2).Previous studies have shown obesity to be associated with resistant hypertension , althougFurthermore studies have shown diabetes to be associated with resistant hypertension ,8,12 butMany studies have shown that most patients with hypertension need 2 or more drugs to achieve target BP -38. Not In our study, it is possible that interaction between some of the factors of interest may explain the stronger associations evident in the multivariate compared with univariate regressions, particularly for CKD. However, this was not evident when interaction terms were included between CKD and BMI (p = 0.79) but significant interaction found between CKD and age (p < 0.001).Our present study has several strengths and some limitations. The strength of our study is that it is done in the primary care setting where the prevalence of resistant hypertension is different from that in secondary care. Secondly, our sample size is large enough to give us a better picture of the prevalence of resistant hypertension in primary care.A limitation of our study is that adherence to medication was not available from the patient records. If adherence is taken into account, the “true” resistant hypertension may be lower as many studies have shown that “resistant hypertension” is frequently due to non-adherence. However doctors in routine daily clinical practice are not accurate in assessing adherence and even if adherence is assessed, this information is seldom recorded. Pill counting or use of electronic devices is indicated to confirm adherence, but this may not be practical in a real clinical setting -41.The prevalence of resistant hypertension in this primary care population of patients with hypertension is relatively low. Nevertheless every effort is still needed to recognize it early. The presence of CKD is associated with higher odds of having resistant hypertension. On the other hand, increase in one year of age is associated with lower odds of having resistant hypertension in this population. These results indicate that clinicians should recognize resistant hypertension earlier, especially in those who have CKD so that early referral or intensifying therapy can be put in place.BP: Blood pressure; DM: Diabetes mellitus; BMI: Body mass index; Kg/m2: Kilograms per square meter; eGFR: Estimated glomerular filtration rate; N: Number; CKD: Chronic kidney disease; CI: Confidence intervals; OR: Odds ratio; RAS: Renin-angiotensin-system.The authors declare that they have no competing interests.CYC contributed in the conceptualization of the paper, data entry and writing of the manuscript while CSM contributed in data analysis and writing of the manuscript. CYC is the corresponding author. Both the authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/15/131/prepub