IntroductionDapagliflozin is a member of a novel class of drugs (sodium-glucose cotransporter-2 inhibitors) used to treat type 2 diabetes mellitus and licensed in Pakistan in 2017. This retrospective observational study evaluated the effects of dapagliflozin on glycated hemoglobin (HbA1c) concentrations in patients treated at endocrinology clinics in Islamabad, Pakistan. The secondary objectives included assessing the effects of dapagliflozin on weight reduction and blood pressure control and to determining its safety.MethodologyPatients with type 2 diabetes who were treated with dapagliflozin were identified by screening the electronic medical records at tertiary care hospitals in Islamabad. Data were collected at the first visit and at follow-up. Categorical variables were recorded as frequencies and percentages and compared by McNemar’s tests, and continuous variables were recorded as means and standard deviations and compared by paired sample t-tests.ResultsMean HbA1C concentration was significantly lower at follow-up than at the first visit . Bodyweight  and diastolic blood pressure  were also significantly lower at follow-up than at the first visit, whereas systolic pressure showed a marginally significant reduction .ConclusionThis first observational study of patients in Pakistan treated with dapagliflozin found that HbA1c concentration, weight, and blood pressure were reduced after initiation of dapagliflozin treatment. Pakistan currently ranks fourth in the world in the percentage of people with diabetes mellitus, with an estimated prevalence of 26.3% . EffectiSeveral studies have evaluated and confirmed the safety and efficacy of dapagliflozin in real-life clinical settings. Pakistani populations differ in genetic characteristics, as well as in demographic, cultural, and lifestyle characteristics, from the populations of Western countries -10. This2, or a history of recurrent genitourinary tract infections. Patients were also excluded if they were taking this drug for weight loss, or if data were missing from their medical records.This retrospective observational study involved patients evaluated at endocrinology clinics of Shifa International Hospital and Umar Diabetes and Foot Care Centre in Islamabad, Pakistan. The study was conducted after approval by Ethical Review Committee. All patients with type 2 diabetes, who were treated with dapagliflozin, were identified by screening electronic medical records at these hospitals. Patients were included if they had been diagnosed with type 2 diabetes for at least six months and were treated with dapagliflozin as monotherapy or combined with one or two other oral agents or insulin. Patients were excluded if they had type 1 diabetes, a glomerular filtration rate (GFR) <45 ml / min / 1.73 mData were collected at the first visit and at follow-up. The date of the first prescription of dapagliflozin was defined as the medication index date. The baseline period was defined as two to three months before the medication index date. Based on available information, follow-up data were retrieved three to six months after the medication index date.2, neuropathy based on symptoms), dyslipidemia, and urinary albumin:creatinine ratio. Details about other antidiabetic drugs, antihypertensive agents, and lipid-lowering medications were also recorded at baseline and follow-up, as were clinical parameters, including weight, systolic blood pressure, diastolic blood pressure, glycated hemoglobin (HbA1c), and serum creatinine concentrations. For laboratory parameters, the last available measurement during follow-up (three to six months after medication index date) was compared with baseline measurements.Patient information was collected using a predesigned data collection form. Demographic characteristics included age and gender, and disease-related characteristics at the first visit included duration of diabetes, number of comorbidities, microvascular complications . Categorical variables were recorded as frequencies and percentages for each category and compared by McNemar’s tests, and continuous variables were recorded as means and standard deviations and compared by paired t-tests. Predictors of post-dapagliflozin HbA1c (%) reduction and weight loss (dependent variable) were evaluated using a multivariate linear regression model. Results are expressed as odds ratios (ORs) and 95% confidence intervals (CIs). A p-value <0.05 was considered statistically significant.The study cohort consisted of 412 patients with type 2 diabetes  at baseline to only 5.58% (n=23) at follow-up. These findings indicated that dapagliflozin-associated improvement was greater among patients with poor glycemic control, despite the study cohort being younger and having a longer duration of diabetes than other study cohorts.One of the benefits of SGLT2 inhibitor treatment in patients with type 2 diabetes mellitus is the weight loss associated with this class of drugs, a study showed weight loss change versus placebo was -1.3 to -2.0 kg . In the Although 27% of the patients in this study experienced side effects of dapagliflozin, only a small percentage had urinary tract infections and genital infection. This may have been due to the use of wet hygiene practices in Pakistani populations, resulting in lower rates of urinary tract and genital infections than those observed in other clinical studies of dapagliflozin . Also, oThis study had several limitations, mainly concerning the source of the data. For example, the interval between HbA1c measurements was not constant. Also, patient records did not mention whether insulin doses were reduced after they started taking dapagliflozin. Because this study analyzed patients treated with dapagliflozin for three to six months, it was not possible to predict therapeutic persistence. Large-scale real-life studies are needed to determine whether treated with SGLT2is or hygiene practices were responsible for the reduced rates of urinary tract and genital infections in Pakistani populations. An ongoing open-label randomized controlled trial is testing the safety and efficacy of another SGLT2i, empagliflozin, in a Pakistani Muslim population (SAFE-PAK Study).This retrospective, real-life observational study evaluated the effectiveness and safety of dapagliflozin in Pakistani patients. Our findings indicate that the SGLT2i dapagliflozin is an effective agent in treating patients with type 2 diabetes, with good efficacy and safety profiles. Dapagliflozin use in patients with diabetes is associated with improved glycemic control by controlled excretion of glucose through the urine and weight loss as a secondary, additional benefit. Furthermore, it had a positive impact on the cardiovascular dynamics by maintaining blood pressure. However, dapagliflozin use is associated with a mild risk of urinary tract infection, albeit lower than what has been previously reported. Dapagliflozin is a useful treatment option for patients in this cohort with type 2 diabetes.


It is associated with several complications including an altered blood picture and damage in multiple organs, including the kidneys. Kidney disease is seen in most patients with SCA and may affect glomerular and/or tubular function, thereby putting these patients at risk of urinary tract infections. However, there is a paucity of data on the prevalence of urinary tract infections (UTIs) among SCA patients in Zambia. This study aimed to determine the prevalence of UTIs and haematological and kidney function profiles among SCA patients at the University Teaching Hospitals, Lusaka, Zambia. This was a cross-sectional study conducted between April and July 2019 involving 78 SCA patients who presented at the UTH. Blood and midstream urine samples were collected from each participant using the standard specimen collection procedures. Full blood counts and kidney function tests were determined using Sysmex XT-4000i haematology analyser and the Pentra C200 by Horiba, respectively. Bacterial profiles of the urine samples were determined using conventional microbiological methods. We found that all the measured patients' haemoglobin (Hb) levels fell below the WHO-recommended reference range with a minimum of 5 g/dl, a maximum of 10.5 g/dl, and a mean of 8 ± 1 g/dl. Fifty percent of the participants had moderate anaemia, while the other 50% had severe anaemia. The minimum WBC count of the participants was 0.02 × 109/L with a maximum of 23.36 × 109/L and a mean of 13.48 ± 3.87 × 109/L. Using the one-way analysis of variance test, we found no significant difference in mean WBC count and Hb concentration across various age-group categories that we defined. Bacteriuria was found in 25% of participants. The most common bacterial isolates were Staphylococcus aureus (32%) and coagulase-negative Staphylococci (32%). Klebsiella pneumoniae was 16%. We found no significant association between bacterial isolates and white blood cell count, age groups, sex, and anaemia severity p = 0.41. None of the participants were diagnosed with kidney disease. There was a high prevalence of asymptomatic UTIs among SCA patients at UTH, which, when coupled with the marked leukocytosis and anaemia, may negatively impact the clinical outcome of the patients. Therefore, we recommend close monitoring of sickle cell patients in Zambia for such conditions to improve patients' outcomes.Sickle cell anaemia (SCA) is an inherited disease resulting from mutations in the  In SCA, red blood cells deform into a sickle shape and damage cell membranes [Sickle cell anaemia (SCA) is an inherited disease resulting from mutations in the embranes . The disembranes –3. It isembranes , 5. Estiembranes . Althougembranes . The funembranes –9.The disease is associated with various complications ranging from an altered blood picture to complications such as leukocytosis, increased platelets, and decreased hematocrit and haemoglobin  and multHowever, there is a paucity of data on the prevalence of both symptomatic and asymptomatic urinary tract infections among SCA patients in Zambia. Therefore, this study aimed to determine the prevalence of UTIs and haematological and kidney function profiles among SCA patients at the University Teaching Hospitals, Lusaka, Zambia.The study was a cross-sectional study conducted at the University Teaching Hospital (UTH) in Lusaka, Zambia.The study included both male and female participants of all age groups with sickle cell anaemia who visited the UTH sickle cell clinic between April and July 2019. All patients with a history suggestive of recurrent UTI were excluded from the study.A qualified or trained clinical personnel collected blood samples via a vein puncture from each patient for blood cell counts and kidney function tests. Each patient was asked to submit midstream urine in sterile containers for urine culture after being given instructions on how to collect the sample by the attending health personnel. The urine samples were cultured within 2 hours upon receipt. Otherwise, they would be stored at 4°C in a refrigerator for up to 24 hours maximum before culture.Sickle cell anaemia was diagnosed by first running the haemoglobin solubility test. Specimens that showed precipitation in high-molarity-buffered phosphate solution in this test were then confirmed for sickle cell anaemia using gel haemoglobin electrophoresis on the Helena SAS-1 plus and Helena SAS-2 Auto-stainer .The Sysmex XT-4000i  haematology analyser was used to carry out haematological analysis while kidney function was assessed by determining the serum creatinine levels using the Pentra C200 by Horiba . We used creatinine to assess kidney function because studies have shown that serum creatinine above specific cutoff points reliably identifies patients with acute kidney injury or chronic kidney disease –17. All μL was dipped in a vertical position in the urine sample, and the loop was used to inoculate the plates using the streak plate method. The urine sample was streaked onto the agar plates by holding the loop at 45° angle to the agar plate. The agar plates were then incubated at 37°C for 24 hrs. The plates of blood agar were incubated in 5–10% CO2 atmosphere. After 48 hrs of incubation, the urine cultures were classified as negative , positive , and contaminated . The samples were classified as contaminated when polymorphic bacterial growth was observed and as insignificant when bacterial growth was lower than 103 colony-forming unit (CFU)/mL and significant when monomorphic bacterial growth was higher than 105 CFU/mL [Enterobacteriaceae were differentiated using triple sugar iron, Simmon's citrate, urease, lysine iron , motility, and indole tests. Pure colonies were used for the inoculation of test media and were incubated for 18 to 24 hours at 37°C. For Gram-positive isolates, the catalase test was used to distinguish Staphylococcus species from Streptococcus species. Furthermore, the coagulase test  was used to differentiate Staphylococcus aureus from the other Staphylococci.The urine samples were inoculated on blood and Cysteine Lactose Electrolyte Deficient (CLED) agars. Briefly, a well-calibrated loop of 1 5 CFU/mL . Biochemp value of <0.05 was used to indicate statistical significance.Data were entered in Excel and analysed using Python 3.7 for Mac. Age characteristics, anaemia prevalence and severity, WBC count categories, and UTI prevalence were analysed using descriptive statistics and presented as means, frequencies, percentages, and graphs. Data were checked for normality using the Shapiro–Wilk test and log-transformed to a nearly normal distribution. A one-way analysis of variance (ANOVA) was used to compare the mean difference of haematological parameters across our defined age group categories. Logistic regression analysis was used to examine the relationship between bacteria isolation and age groups, sex, anaemia severity, and white blood cell categories, and a Ethical approval for the study was obtained from the University of Zambia Health Sciences Research Ethics Committee (UNZAHSREC) (Protocol ID: 20190217067). Informed consent was obtained from the adults while assent for the children to take part in the study was obtained from their guardians.The study consisted of 78 participants out of which 45 (58%) were females and 33 (42%) were males. The minimum age was 2 years old and the maximum age was 28 years old, with a mean age of 11.4 ± 6.1 years. Participants were divided into age group categories, as shown in μmol/l and maximum 75 μmol/l with the mean of 38.23 ± 12.3 μmol/l. All participants had creatinine levels below 110 μmol/l.Minimum creatinine concentration of the participants was 19 All patients had Hb levels below the WHO-recommended reference range   with a mF (4.67) = 1.316, p = 0.273. The minimum WBC count of the participants was 0.02 × 109/L with a maximum of 23.36 × 109/L and a mean of 13.48 ± 3.87 × 109/L. Ninety percent (90%) had high WBC count (10 × 109/L), 7% normal count (between 4 × 109/L and 10 × 109/L), and 3% had low WBC count (below 4 × 109/L F (4.67) = 0.19, p=0.466.Using ANOVA, we showed that there was no significant difference in mean Hb concentration across age groups, Staphylococcus aureus (32%) and coagulase-negative Staphylococci (32%). Klebsiella pneumoniae was 16%, Enterococcus 5%, Streptococcus 5%, Pseudomonas species 5%, and Proteus mirabilis were 5%.Out of 72 urine specimens cultured, we found growth of bacteria in 18 (25%) specimens, whereas the other 54 (75%) specimens had no growth . The mosp=0.41) relationship between bacterial isolation and all the variables.We performed logistic regression analysis to examine the relationship between bacterial isolation and white blood cell count categories using age groups, sex, and anaemia severity as possible confounders. Here, our results revealed a nonstatistically significant  that we found was higher than those reported in Nigeria (6%);  and in JKlebsiella spp, Staphylococcus aureus, Streptococci, Enterococcus spp, Pseudomonas, Proteus mirabilis, and E. coli which are the major causes of UTIs worldwide. Additionally, organisms such as Staphylococcus aureus, Streptococcus, and Proteus have a broad representation as causative agents of UTIs in developing countries due to poor environment and personal hygiene [Staphylococcus aureus (24%), Streptococcus (4%), and Proteus (4%) in the urine of SCA patients. Furthermore, impairment of the immune system in SCA also contributes towards the presence of asymptomatic bacteriuria, including infections with Proteus and Staphylococcus species [We found that the aetiologic pathogens associated with UTIs in our study included  hygiene . Therefo species . With al species . The intThere is a possibility that some participants have early kidney malfunction, which may not be detected by the use of serum creatinine . Serum cThere is a need for close monitoring of sickle cell patients in Zambia as there is a high prevalence (25%) of asymptomatic UTIs, and the majority of them (90%) has a high WBC count which impacts negatively on the clinical outcome of the patients. Also, we recommend the introduction of newborn screening for SCA so that the patients can receive the right treatment from the time they are still young.


Among older patients, ISH was correlated with higher LVMI (+8.8 g/m2), lower eGFR (−0.2 log units), and higher ACR (+1.0 log units), whereas IDH was not associated with these renal/cardiovascular parameters. In conclusion, ISH was associated with a relatively high risk of target organ damage irrespective of age, whereas IDH was only correlated with renal injury in younger CKD patients.The aim of this study was to investigate associations between age-dependent variations in isolated systolic/diastolic hypertension (ISH/IDH) with target organ damage in chronic kidney disease (CKD). A cross-sectional study was conducted among 2,459 CKD patients with ambulatory blood pressure monitoring. Blood pressure was categorized into four groups: normotension, ISH, IDH, and systolic-diastolic hypertension. The outcome measurements were left ventricular mass index (LVMI), estimated glomerular filtration rate(eGFR), and urinary albumin creatinine ratio (ACR). Older patients (≥60-years-old) had a higher prevalence of ISH and a lower prevalence of IDH than younger patients (<60-years-old). In multivariate analysis, compared with the normotension group, younger patients with ISH were associated with higher LVMI (+14.4 g/m Chronic kidney disease (CKD) is a major global public health problem. Even in the early stage, CKD patients have a higher risk of cardiovascular disease (CVD) , 2. AlthTo the best of our knowledge, data on the correlation of ISH or IDH with subclinical cardiac damage in different age groups of CKD patients are scarce. Limited research  has been2. The prevalence of normotension (NM), ISH, IDH, and SDH among all patients were 38.3%, 7.6%, 15.7%, and 38.4%, respectively. P<0.01). The eGFR levels were significantly lower in elderly patients compared with younger patients, except in the ISH and SDH groups.A total of 2459 patients were included in this study. The mean age of participants was 46.8±14.9-years-old, and 1091 patients (44.4%) were women. The mean eGFR was 58.2 mL/min/1.73 mThe prevalence of hypertensive subtypes in different stages of CKD is shown in 2) and lower eGFR (−0.3 log units) and lower ACR (−0.3 log units) than younger patients. To further adjust for other confounding risk factors (Model 3 in P<0.05).In univariate analyses, ISH, IDH, and SDH were correlated with higher LVMI and ACR, and lower eGFR . SDH was also significantly associated with higher LVMI in both younger and older patients . There was no relationship between IDH and LVMI in either age group . SDH was also significantly associated with lower eGFR in both younger and older patients . IDH was only negatively associated with eGFR among younger patients   .P<0.05). SDH was also significantly associated with higher ACR in both younger and older patients . IDH was only positively correlated with ACR among young patients   .In this cross-sectional study, we studied associations between distinct types of ambulatory hypertension and several markers of subclinical target organ damage in CKD patients of different ages. The two most clinically important findings of our study were as follows: (1) in younger patients, using NM as a reference, ISH and SDH had higher LVMI and ACR, and lower eGFR, while only IDH correlated with renal damage; (2) in older patients, only ISH and SDH were correlated with these renal/cardiovascular parameters. These data suggest that age plays a role in the target organ damage from ISH and IDH in CKD patients, and therefore special but different attention should be paid to CKD patients with isolated hypertension in different ages.Based on the current pathophysiological understanding, the hypertension subtypes are manifested by singular elevations in SBP or DBP, which may reflect unique biological processes that are closely related to age, because aging causes structural changes to blood vessels . The mecHere, we enrolled 2459 CKD patients with ABPM and first explored associations between target organ damage and isolated systolic or diastolic hypertension in different age groups. We found that ISH and SDH had higher risks of target organ damage irrespective of age or target organ, whereas IDH was only associated with renal damage in younger patients. These results suggest that age should be taken into account when assessing the cardiovascular risk of isolated hypertension in non-dialysis CKD patients.Among the markers of cardiac damage, LVMI is a powerful and well-established predictor of CVD in CKD patients  that hasIn addition to heart damage, both aging and hypertension are associated with decreased renal function , 30. OurThis study has several strengths. First, to the best of our knowledge, this is the first study to investigate the impact of age on correlations between isolated hypertension and target organ damage in non-dialysis CKD patients in China. Identifying non-benign BP types and further optimizing the cardiovascular risk assessment for CKD patients are particularly important. Second, all included patients had comprehensive assessments, and the cohort size was large. Third, we measured BP by 24-h ambulatory monitoring, given that ABPM is now considered a keystone in hypertension management . ISH andIn conclusion, our findings highlight the age-specific effects of different isolated hypertension types on cardiac and renal damage in CKD patients and have potential clinical implications. ISH was generally related to cardiac and renal damage without age modifications, while IDH was only harmful to renal function, and then mainly in younger patients. Considering that ISH and IDH, as intermediate phenotypes with unpredictable development, have a high probability of transitioning to SDH , 38, theThe study protocol was approved by the ethics committee of our hospitals, and was approved by the Institutional Review Board. All patients gave their written informed consent to the use of data for scientific purposes.A total of 2850 CKD inpatients aged 18 to 75 years and completed ABPM for this cross-sectional study. We excluded 391 participants according to the following criteria: dialysis or transplant, changes in the estimated glomerular filtration rate (eGFR) >30% in the previous 3 months; pregnancy; atrial fibrillation; inadequate ABPM readings; night work or shift-work employment; inability to communicate and comply with all of the study requirements. Finally, a total of 2459 CKD patients were included into the current analysis. In terms of causes of renal disease, 1509 patients had primary glomerulonephritis; 252 cases had diabetic nephropathy; 124 subjects had hypertensive nephropathy; and 574 patients had other causes of renal disease.Ambulatory blood pressure monitoring was performed with the automated measurements programmed at 15-minute intervals during the daytime and 30-minute intervals at night as previously , 40. TheUsing mean 24-hour ambulatory thresholds , regardlEchocardiography was performed by two trained cardiologists, according to the recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging . DetailsAn isotope dilution mass spectrometry–traceable methodology was utilized to determine serum creatinine, and eGFR was estimated using the CKD-EPI (CKD–Epidemiology Collaboration) formula. According to Kidney Disease Improving Global Outcomes (KDIGO) , based oAs recommended in KDIGO guidelines, we preferred urine albumin creatinine ratio (ACR) as the measure of albuminuria. A first morning urine sample was collected on the day of ambulatory blood pressure measurement, and the concentration of urinary albumin and creatinine were measured by immunoturbidimetry in the central laboratory.Patient data including sociodemographic and clinical characteristics, medical history, and current therapy were obtained from interviews and physical examinations at the initial study visit and from clinical records. Body mass index was weight in kilograms divided by the height in meters squared. The definitions of Diabetes mellitus, Hyperlipidemia, CVD history have been previously reported . In addiP values <0.05 were considered statistically significant. All statistical analyses were performed using SPSS version 25  and R Version 3.6.0. Graphs were generated with GraphPad Prism 8 .Data were tested for normal distribution using the Kolmogorov–Smirnov test. Descriptive statistics are presented as the mean ± standard deviation (SD) for normally distributed variables and as the median (interquartile range) for non-normally distributed variables. Frequency and percentage were used for categorical variables. Comparisons among the BP groups were performed using ANOVA or nonparametric tests for continuous variables and the χ2 test for categorical variables. The Bonferroni method was used for post hoc pairwise comparisons. A multiple linear regression model was used to analyze the cross-sectional association of age and BP types with parameters of subclinical target organ damage  before and after adjusting for other significant variables from the univariate linear regression analyses. Associations between age and the BP types were analyzed in the multivariate adjusted model. After stratification for age (<60- versus ≥60-years-old), multiple linear regression models were employed to study correlations between BP types and subclinical target organ damage parameters in the different age groups. In the graphs, the non-standardized coefficient beta-values  are given, which correspond to the quantitative difference between each BP group and NM as the reference group. Supplementary Table 1


Participants were randomly assigned to the following groups: Group LMA , or Group ETT . Intraoperative hemodynamic and respiratory variables including mean blood pressure (MBP), heart rate (HR), and peak inspiratory pressure (PIP) were compared. Postoperative sore throat, hoarseness, postoperative nausea and vomiting (PONV), and pulmonary aspiration were recorded. The PaCO2_2h were equally effective between two groups . The intraoperative change in MBP, HR, and PIP were differed over time between two groups . There were no differences of the incidence of postoperative complications at 24 h following LLDH . No case showed pulmonary aspiration in both groups. Compared with endotracheal tube, second-generation LMA is equally efficient during LLDH. The second-generation LMA can be considered as the effective airway devices for securing airway in patients undergoing prolonged laparoscopic surgery.The second-generation laryngeal mask airway (LMA) provides a higher sealing pressure than classical LMA and can insert the gastric drainage tube. We investigated the difference in respiratory variables according to the use of second-generation LMA and endotracheal tube (ETT) in laparoscopic living liver donor hepatectomy (LLDH). In this single-blind randomized controlled trial, intraoperative arterial carbon dioxide partial pressure at 2 h after the airway devices insertion . Endotracheal tube (ETT) is widely used for airway maintenance. Since laryngeal mask airway (LMA) was developed in 1980s2. However, due to the structural limitation of LMA, it might not provide proper seal and there are possibility of inadequate ventilation, hypoxia, and pulmonary aspiration compared to ETT4. Thus, LMA use has been limited to the surgery of short duration. In addition, obesity, laparoscopic surgery, and gastroesophageal reflux disease (GERD) have been considered as relative contraindications of LMA5.LMA has several advantages over ETT including ease of insertion, lower risk of trauma to the trachea, reduced postoperative sore throat, dysphagia, and dysphonia, and improved hemodynamic and respiratory stability during device insertion and anesthetic emergence6. In our institute, second-generation LMA has been used during laparoscopic liver resection since 2017. Moreover, we reported a case of successful application of second-generation LMA during laparoscopic living donor right hepatectomy7. Although the second-generation LMA with modified design is known to provide higher sealing pressure and reduces the risk of pulmonary aspiration, there is a lack of prospective research investigating the suitability of LMA in prolonged laparoscopic surgery.Previous study has shown that both classic LMA and second-generation LMA did not increase the risk of gastric distension compared to ETT in gynecologic laparoscopy performed within 42 minDonor safety is a major concern of living-donor liver transplantation. Anesthesia and related complications, as well as short- to long-term morbidity and mortality, are issues to be addressed in terms of donor safety. The aim of present study was to evaluate the suitability of second-generation LMA in donors underwent laparoscopic living liver donor hepatectomy (LLDH).https://cris.nih.go.kr/cris/ CRiS No. KCT0003711, date of registration: 03/04/2019, principal investigator: Gaab Soo Kim,). In addition, we followed to the declaration of Helsinki.This single center, single-blinded, randomized controlled equivalance trial was approved by the Institutional Ethics Committee  and written informed consent was obtained from all participants. It registered at Clinical Research Information Service  physical status ≥ III, body mass index (BMI) > 30 kg/mvs group ETT. Random allocation was performed under 1:1 ratio with six blocking combination (4 numbers per block) using computer-generated program and the results were concealed to participants until each participant’s enrollment. Randomization was also maintained until opening a sealed opaque envelope immediately before surgery by one anesthesiologist (GSK). GSK, has extensive experience for second-generation LMA, performed management from anesthetic induction to removal of airway device and was not involved in data collection. LLDH was performed by two surgeons  blinded to the airway device. Although the attending anesthesiologist could not keep masked due to the nature of our trial, participants were masked until the completion of the study.Participants were randomly assigned to one of two study groups according to the use of airway device: group LMA 8. In the group ETT, tracheal intubation was performed using conventional laryngoscopy. The cuff pressure was maintained at 25 cmH2O in group ETT. The cuff was inflated with air, and the cuff pressure was measured by a cuff pressure gauge in both groups . Effective ventilation after the airway device insertion was defined as meeting the following criteria: (1) typical square wave capnography, (2) symmetric thoracic expansion (3) absence of audible leak (4) peak inspiratory pressure < 30 mmHg9. If the aforementioned criteria were not met, the position of LMA was modified up to 3 times. If the effective ventilation was not achieved, LMA was removed and ETT was intubated with the exclusion of participant from the study. Arterial line was placed in the right radial artery and used it to monitor mean arterial pressure and perform arterial blood gas analysis every 2 h. During surgery, fraction of inspired oxygen (FiO2) 0.5, a tidal volume of 8 mL/ideal body weight, and positive end expiratory pressure (PEEP) 6 cmH2O were applied in both groups. The respiratory rate was adjusted to maintain the end-tidal carbon dioxide (ETCO2) as 35–40 mmHg. After confirming the effective ventilation, a gastric drainage tube was inserted through the gastric access hole of the LMA. When ineffective ventilation was detected during surgery, it planned to remove LMA and replace by ETT. Anesthesia was maintained with isoflurane and continuous remifentanil infusion (up to 0.2 mcg/kg/min) and the intra-abdominal pressure was adjusted at 12 mmHg during laparoscopic procedure. At the end of the surgery, muscle relaxation was reversed with neostigmine 1.5 mg and glycopyrrolate 0.4 mg. The amount of gastric drainage were measured in group LMA. After the airway device was removed, the patient was transferred to the post-anesthetic care unit (PACU).In the operating room, standard monitors were applied including electrocardiogram, pulse oximetry, and non-invasive blood pressure. Before anesthetic induction, midazolam 2 mg was injected and morphine sulfate 400 mcg was intrathecally given for postoperative analgesia. After preoxygenation for 3 min. anesthesia was induced with thiopental 5 mg/kg, vecuronium 1 mg/kg, remifentanil 0.2 mcg/kg/min, and isoflurane 2 vol%. Second generation LMA  or ETT  was placed according to the assigned study groups. The size of LMA was chosen according to the manufacturer’s recommendation and the size of ETT was chosen based on the gender . In the group LMA, the head of participant was in a sniffing position and the anesthesiologist secured jaw thrust and mouth opening with the left hand. LMA was advanced through the palate-pharyngeal curve with fully deflated status. LMA cuff was inflated and maintained within green zone and oropharyngeal leak pressure (OLP) was measured. OLP was assessed at the equilibrium airway pressure measured after applying a closed valve system with 4 L/min of oxygen with gas leakage occurred into mouth2 less than 92%) was investigated. In the general ward, the degree of sore throat and hoarseness using 4-grade scales  were assessed at 6 and 24 h following surgery. Both postoperative nausea and vomiting (PONV) during postoperative day (POD) 1 were recorded as yes or no. Pulmonary aspiration was identified by the radiographic finding with related signs and symptoms including vomiting and dyspnea within POD 3. The grade was recorded as follows: 0 = no pulmonary aspiration, 1 = pulmonary aspiration.During anesthetic emergence, the restlessness score  was recorded and desaturation . Minute ventilation 2 h after the insertion of airway device (MV_2h) was additionally assessed to minimize the possibility of bias related to the maintenance of predetermined level of ETCO2 as 35–40 mmHg. The secondary outcomes were the comparison of hemodynamic parameters  and respiratory parameters  over time, and postoperative outcomes , and the incidence of pulmonary aspiration between two groups.The primary outcome was the difference in arterial carbon dioxide partial pressure 2 h after the insertion of airway devices (P2 39.25 (standard deviation [SD] 3.89) mmHg and the ETT group showed the average PaCO2 39.64 (SD 3.60) mmHg. Two-sided design was used to test equivalence between groups. To analyze the equivalence (margin 3) under power 80%, 82 subjects, 41 subjects per group, were required. Considering a 10% potential failure to complete the protocol, 92 subjects were included.The sample size was calculated to detect equivalence between the use of second-generation LMA and ETT. Based on our pilot data , the patients using second-generation LMA showed the average of PaCOaCO2_2h and ETCO2 between two study groups. Generalized Estimating Equation was applied to repeated measurements of parameters including PaCO2, ETCO2, PIP, Ppl, MBP, HR, and QTc. Ordinal data such as postoperative sore throat and hoarseness were compared using Cochran-Armitage trend test. Continuous variables were compared using Student’s t-test or the Mann–Whitney U test, as appropriate. Shapiro–Wilk test was used to test normality. Categorical variables were analyzed using Chi-squared test or Fisher’s exact test as appropriate. Data are presented as mean (90% confidence limits [CL] or SD) or median (interquartile range [IQR]) as appropriate for continuous variables; and as number (with percentages) for categorical variables.Schuirmann’s two one-sided tests approach was used to test equivalence of PP-values were computed and an effect was considered statistically significant at the level of P = 0.05.All statistical analyses were performed using SAS version 9.4 . Two-sided 16th congress of the Asian Society of Transplantation 2019, 29th, September, 2019.Eighty-eight participants were recruited and two cases were subsequently excluded in this trial: one who had switched to insert ETT due to poor LMA fitting despite repeated attempts and one who had converted to laparotomy. Since there were fewer dropouts, a total of 86 participants completed present trial and finished the study earlier than expected Fig. . ParticiaCO2_2h showed that LMA and ETT were equally effective . There was no statistical difference in MV_2h between two groups (group LMA: mean (SD) 5.23 (1.20) L/min vs group ETT: mean (SD) 4.97 (0.84) L/min, P = 0.253). The 90% CL of mean difference in ETCO2_2h was within equivalence margin . The change in MBP, HR, and PIP were different over time between two groups . In particular, group ETT showed significantly elevated intraoperative PIP than group LMA. Aforementioned variables showed smaller changes in group LMA compared to group ETT .The P2O and the amount of drained gastric contents were 10.10 (15.73) mL. No adverse events were observed in both groups during study period.Intraoperative and emergence variables were not statistically different between both groups Table . In addiOur results demonstrated that second-generation LMA was equivalent to ETT in donors underwent LLDH on intraoperative respiratory, hemodynamic variables, and early postoperative outcomes.10, most previous human studies reported the mean time of airway device application was about 70–80 min and it did not exceed 100 min13. Airway devices were maintained approximately 280–290 min in this study. Moreover, unlike previous clinical trials investigated postoperative airway complications including sore throat, dysphagia, and dysphonia after using second-generation LMA and ETT, we compared intraoperative variables in prolonged laparoscopic surgery14. This is another strength of our research.To our knowledge, this is the first randomized controlled trial demonstrated the suitability of second-generation LMA during long-lasting laparoscopic surgery. Although one experimental research investigated the degree of upper airway injury after long-term use (three to 24 h) of second-generation LMA in pigsaCO2, which was selected as a marker of the suitability of ventilation, showed that second-generation LMA has an equivalent effect to ETT during LLDH. In addition, our results indicated that ETCO2 and Ppl were stable with second-generation LMA. These indicated that both devices might be efficiently used in long-term laparoscopic surgery.The most common concerns related to using LMA during laparoscopic surgery are inadequate ventilation, gastric distension, and pulmonary aspiration of gastric contents. Since gastric access port of the second-generation LMA can manage problems related to the gastric distension, improper ventilation may be more important issue in long lasting surgery. Therefore, we focused especially in intraoperative respiratory parameters. As a result, P18. We found that MBP and HR were elevated especially from baseline to 1 min after airway device insertion in the current study. It demonstrated that ETT insertion is more irritating than LMA insertion and cause hemodynamic instability. This result is consistent with previous researches demonstrated that the insertion and removal of the LMA was less invasive and induces fewer stress responses than with ETT20. Thus, we suggested that second-generation LMA will be more suitable for patients requiring hemodynamic stability.Endotracheal intubation using laryngoscopy is a stressful condition that results in tachycardia and hypertension caused by catecholamine release22. We considered that narrower inner diameter of ETT than that of LMA was related to the increased airway resistance.In the current study, group ETT showed more increased PIP than group LMA during surgery. This is in line with previous studies comparing the airway pressure of LMA and ETT2, the primary outcome, it is insufficient to determine difference of pulmonary aspiration between two groups. Further research is needed on the risk of pulmonary aspiration associated with the use of second-generation LMA. Third, the investigator and clinicians in the operating room were not blinded to the assigned group. Since our protocol did not fit for double-blinded, it may cause observer bias. To minimize possible biases, the investigator and clinicians in the operating room decided not to be involved in this trial any more than to fill out information in the operating room. Fourth, since gastric drainage tube was inserted only in group LMA, we did not evaluate the degree of gastric distension between two study groups. There may be a difference because gastric drainage tube was not inserted in group ETT. For accurate comparisons, gastric drainage tube should be inserted in both groups.We acknowledge several limitations in this study. First, we conducted the trial on liver donors, not patients with certain diseases. Because liver donors are considered to be providing the comparable conditions as healthy volunteers, our results may be different from the diseased patients and may not be applicable to other surgeries. Therefore, we suggest that care should be taken when using LMA for long lasting laparoscopic surgery in patients with various diseases. Second, although there were no cases of pulmonary aspiration in this study, we could not confirm the effectiveness of second-generation LMA on pulmonary complications. Since the number of subjects required in our study was based on PaCOIn conclusion, second-generation LMA provides appropriate ventilation and stable hemodynamics during LLDH. Second-generation LMA with gastric drainage tube can be selected as one of the effective alternative to ETT for securing airway in patients undergoing prolonged laparoscopic surgery.


Canagliflozin reduces hospitalizations for heart failure (HF) in type 2 diabetes mellitus (T2DM). Its effect on cardiorespiratory fitness and cardiac function in patients with established HF with reduced ejection fraction (HFrEF) is unknown.2) and minute ventilation/carbon dioxide production (VE/VCO2) slope (co‐primary endpoints for repeated measure ANOVA time_x_group interaction), lean peak VO2, ventilatory anaerobic threshold (VAT), cardiac function and quality of life , at baseline and 12‐week follow‐up.We conducted a double‐blind randomized controlled trial of canagliflozin 100 mg or sitagliptin 100 mg daily for 12 weeks in 88 patients, and measured peak oxygen consumption . Canagliflozin improved lean peak VO2 , VAT  and VO2 matched for respiratory exchange ratio  compared to sitagliptin. Canagliflozin also reduced MLHFQ score .The study was terminated early due to the new guidelines recommending canagliflozin over sitagliptin in HF: 17 patients were assigned to canagliflozin and 19 to sitagliptin, total of 36 patients. There were no significant changes in peak VO2 or VE/VCO2 slope compared to sitagliptin, while showing favourable trends observed on several additional surrogate endpoints such as lean peak VO2, VAT and quality of life.In this small and short‐term study of patients with T2DM and HFrEF, interrupted early after only 36 patients, canagliflozin did not improve the primary endpoints of peak VO Dapagliflozin reduced the risk of worsening HF or death from cardiovascular causes in established HFrEF patients and improved quality of life (QoL) in patients with and without T2DM.2) during cardiopulmonary exercise testing (CPX) and largely responsible for the reduced QoL in HF.2 is a strong prognostic factor in HFrEF, and its improvements have been associated with long‐term reduction of clinical events, making it a strong surrogate outcome measure.Exercise intolerance is a hallmark consequence of HF, typically defined as a reduction in cardiorespiratory fitness (CRF) measured as a reduced peak oxygen consumption 4 inhibitor with proven cardiovascular safety with glucose‐lowering efficacy similar to SGLT2 inhibitors.We investigated whether canagliflozin improved peak VO22.1The CANA‐HF study was a double blind, randomized, controlled study investigating the effects of canagliflozin 100 mg daily compared to sitagliptin 100 mg daily for 12 weeks in 88 patients with T2DM and stable chronic HFrEF on CRF started on September 2016. On 22 October 2018, due to the new guidelines released by the American Diabetes Association2.2Briefly, stable patients with symptomatic HF (New York Heart Association [NYHA] class II‐III) with a left ventricular ejection fraction (LVEF) ≤40%, T2DM and reduced CRF were enrolled  to calculate the slope via least squares linear regression.2 slope is a marker of HF severity defined as minute ventilation/carbon dioxide production (VE/VCO2) slope.At baseline and 12 weeks subjects underwent a symptom‐limited CPX, using a metabolic cart interfaced with a treadmill utilizing a conservative ramping protocol wherein the speed and grade increased approximately 0.6 estimated metabolic equivalents every minute, as previously described.2.4DT).At baseline and at 12 weeks we performed resting transthoracic Doppler echocardiography.2.5We measured QoL at baseline and 12 weeks using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The MLHFQ is a 21‐item graded questionnaire used to assess the impairments in QoL in HF, higher scores reflect a greater HF symptom burden.2.62 using dual‐energy X‐Ray Absorptiometry (DEXA) We measured body weight and height to calculate body mass index (BMI) and waist circumference at baseline and at 12 weeks.2.7We measured non‐fasting biomarkers: HbA1c, N‐terminal pro‐brain natriuretic peptide (NTproBNP) and glomerular filtration rate (GFR), at baseline and 12 weeks.2.8Because canagliflozin increases glucose and sodium urinary excretion resulting in a modest daily caloric deficit, we also assessed dietary caloric and sodium intake: the research dietitian performed a standardized 5‐pass 24‐hour dietary recall.2.92 and the VE/VCO2 slope after 12 weeks of treatment with canagliflozin 100 mg daily or sitagliptin 100 mg daily. We measured QoL using the MLHFQ and additional CRF variable: ventilatory anaerobic threshold (VAT), and DEXA‐measured lean peak VO2.2 has been proposed to be superior to peak VO2 in determining prognosis in patients with HFrEF, especially in patients with obesity, in which peak VO2 may underestimate the overall level of CRF.2 after 12 weeks, using the VO2 values corresponding to the lowest RER achieved between baseline and follow‐up. Such analysis allowed for correction of differences in RER between baseline and follow‐up. Additional exploratory analyses included measures of resting cardiac function, anthropometrics, body water and blood pressure.The co‐primary endpoints for the study were changes from baseline in peak VO2.10P‐values were reported throughout, with statistical significance set at the two‐tailed .025 level for the co‐primary endpoints and .05 for the additional analyses. Missing data were omitted and not imputed and the cases excluded from the related analysis. A sample size of 40 patients per group provided sufficient power to detect a MD in the interval change in peak VO2 of 1.50 ± 1.76 mL kg−1 min−1 expected with canagliflozin compared to sitagliptin, which we predicted to have no significant effects on peak VO2 .2 of 1.50 ± 1.76 mL kg−1 min−1 with canagliflozin compared to sitagliptin .Statistical analyses were performed with SPSS 24.0 package . Continuous data are reported as means and standard deviations for normally distributed variables or median and interquartile range for potential deviation from the Gaussian distribution, and discrete variables were reported as N and %. We used the nonparametric Wilcoxon signed‐rank test for repeated measures to assess the within‐group related changes compared to baseline. The differences in interval changes between the two groups were compared using a random‐effect analysis of variance model for repeated measures to analyse the effects of time and group allocation. Unadjusted 33.1No statistically significant differences were found between the two groups at baseline, except for peak RER, which was significantly lower in the sitagliptin group compared to canagliflozin Table . Patient3.22: from 16.2 ± 3.4 to 16.9 ± 4.0 mL kg−1 min−1, P = .23; VE/VCO2 slope: from 34.1 ± 6.1 to 33.8 ± 4.2, P = .66) and sitagliptin groups , nor between‐group differences . Therefore, we calculated the RER‐matched VO2, allowing for a VO2 comparison at similar levels of exercise effort. Canagliflozin showed a significant improvement in RER‐matched VO2 , however, there was no significant time_x_group interaction . No significant changes for NTproBNP were found at time_x_group interaction . No significant changes in estimated GFR were observed at time_x_group interaction analysis .Glycemic control  did not differ between canagliflozin and sitagliptin (3.6P = .15) . Sodium intake was not significantly affected by either intervention at time_x_group interaction .We did not observe any significant changes in reported daily caloric intake . We did not observe a significant difference in waist circumference between groups .Neither canagliflozin nor sitagliptin significantly affected blood pressure or fluid status .In the current study, we have shown that 12‐week treatment with an SGLT2 inhibitor, canagliflozin, was well‐tolerated and did not improve the primary endpoints of peak VO2, such as lean peak VO2 and VAT.Canagliflozin was associated with a significant improvement in QoL and additional CPX variables that have been found to consistently predict prognosis in patients with HF, and have proven to be more sensitive than peak VO2 may be a stronger prognosticator than peak VO2, particularly in individuals with obesity, in which peak VO2 adjusted by total body mass may result in an underestimate of CRF.2) and 100% had either overweight or obesity. VAT allows the quantification of the ability to sustain submaximal physical activity for prolonged periods, which approximates levels associated with activities of daily living in individuals with HF, who rarely perform higher intensity activities.2. Of note, an assessment of peak VO2 adjusted per RER showed a significant improvement with canagliflozin. It is unclear as to why subjects in the canagliflozin group exercised to a lower peak RER post‐intervention. This may be related to the imbalance in RER at baseline, with higher values in the canagliflozin group, but it could be related to other factors such as improved cardiac function allowing the individuals to reach the same or higher effort level while maintaining a greater cardiac reserve. It is indeed noteworthy that although canagliflozin patients tended to have lower RER at follow‐up this did not negatively affect the peak VO2, as it is was not reduced from baseline. It is possible that in this cohort of HFrEF patients with obesity and deconditioning, a treatment that improves cardiac function may fall short in improving peak VO2 due to supervening secondary limitation to maximal aerobic capacity.In patients with HF, lean peak VO2 slope, an effort‐independent CPX variable, was not affected by either treatment. Of note, while peak VO2 was clearly reduced in the investigated population (64% ± 12% of predicted), offering room for significant improvements, the mean VE/VCO2 slope was only mildly elevated (33.3 ± 7), with 11 subjects (31%) presenting with a normal VE/VCO2 slope (<30), potentially minimizing the ability to detect significant changes with the intervention.On the other hand, the VE/VCOCanagliflozin was associated with greater LVEF at 12 weeks compared to baseline, while sitagliptin had neutral effects, however, the time_x_group analysis was not statistically significant. Importantly, prior studies have shown favourable changes in systolic function  in preclinical models of HF.These effects appear to be independent of glycemic control, which did not differ between the two groups. We did not observe significant changes in biomarkers of myocardial wall stress and renal function, such as NTproBNP and GFR, respectively. The lack of changes may be related to the study being underpowered to detect significant changes in such variables and/or short duration of treatment.No changes in blood pressure and fluid status were found. While this may appear surprising, the baseline blood pressure and fluid status were within normal ranges, likely due to the fact that patients were required to be on maximally tolerated optimal medical therapy and stable without evidence of fluid overload prior to enrolment. We cannot exclude the possibility, however, that in this population, the blood pressure lowering effects of SGLT2 inhibitors2 when patients where concomitantly treated with loop diuretics. Empagliflozin has also been associated with improved peak VO2 in other non‐randomized studies in patients with established HF.2, like we attempted to do in our trial. Peak VO2 is a more sensitive parameter of exercise capacity than 6‐minute walk test distance, which instead estimates functional capacity and does not provide insights on the determinants of reduced CRF.2, while we hope that ongoing clinical trials, such as the EMPA‐TROPISM will provide a final answer, also in patients without T2DM.Canagliflozin and other SGLT2 inhibitors have been shown to reduce hospitalizations for HF and renal eventsThe mechanisms responsible for such effects are largely unknown. The hearts of patients with HF present with metabolic dysregulation resulting in reduced ability to utilize carbohydrates as an energetic substrate, with a resulting compensatory increased utilization of fatty acids and ketone bodies. By increasing fatty acid oxidation, ultimately increasing the production of ketone bodies, SGLT2 inhibitors, may increase the availability and utilization of these newly preferred energetic substrates in the setting of HF.Sitagliptin was neutral on CRF, QoL, cardiac function and biomarkers, confirming its safety profile explored in a large cardiovascular outcome trial.The study is not without limitations. In addition to the early termination, there were some differences in the baseline characteristics of the patients, which could have potentially affected the overall results of the study. Moreover, the small sample size of the study does not allow to definitely confirm the lack of differences of the safety profile of the two agents in the investigated population.52 and VE/VCO2, we report for the first time that in patients with T2DM and HFrEF canagliflozin was associated with improvements in several measures of CRF such as lean peak VO2, VAT and RER‐matched VO2, and an improvement in the MLHFQ score reflecting a reduced HF symptom burden compared to sitagliptin, despite no significant differences in glycemic and hemodynamic control.Despite the early interruption in enrolment and the failure to show differences in the primary endpoints of peak VO Dr Abbate has served as consultant to Janssen. Dr Carbone is supported by a Career Development Award 19CDA34660318 from the American Heart Association. The other authors have nothing to disclose.Supplemental Figure S1 Effects of treatments on blood pressure and body fluid. Canagliflozin nor sitagliptin were associated with significant changes in resting systolic blood pressure (BP) and diastolic BP . Neither intervention affected body fluids, assessed with bioelectrical impedance analysis, including total body water (TBW) in litres (L) and percent (%) of body weight , intracellular water (ICW) in L and % of TBW , and extracellular water (ECW) in L and % of TBW . All p values>0.05. Data are presented as mean ± SD.Click here for additional data file.


Chronic kidney disease (CKD) affects drug elimination and patients with CKD require appropriate adjustment of renally cleared medications to ensure safe and effective pharmacotherapy. The main objective of this study was to determine the extent of potentially inappropriate prescribing  of renally-cleared medications commonly prescribed in Australian primary care, based on two measures of kidney function. A secondary aim was to assess agreement between the two measures.2, and/or two urinary albumin/creatinine ratios ≥3.5 mg/mmol in females  at least 90 days apart. PIP was assessed for 49 commonly prescribed medications using the Cockcroft-Gault (CG) equation/eGFR as per the instructions in the Australian Medicines Handbook.Retrospective analysis of routinely collected de-identified Australian general practice patient data . All adults (aged ≥18 years) with CKD presenting to general practices across Australia were included in the analysis. Patients were considered to have CKD if they had two or more estimated glomerular filtration rate (eGFR) recorded values < 60 mL/min/1.73mn = 9926) of these patients had at least one PIP based on either the Cockcroft-Gault (CG) equation or eGFR . There was good agreement between CG and eGFR while determining the appropriateness of medications, with approximately 97% of the medications classified as appropriate by eGFR also being considered appropriate by the CG equation.A total of 48,731 patients met the Kidney Health Australia (KHA) definition for CKD and had prescriptions recorded within 90 days of measuring serum creatinine (SCr)/estimated glomerular filtration rate (eGFR). Overall, 28,729 patients were prescribed one or more of the 49 medications of interest. Approximately 35% (This study highlights that PIP commonly occurs in primary care patients with CKD and the need for further research to understand why and how this can be minimised. The findings also show that the eGFR provides clinicians a potential alternative to the CG formula when estimating kidney function to guide drug appropriateness and dosing. The prevalence of chronic kidney disease (CKD) is rapidly increasing worldwide, alongside its complications –3. Most Previous studies have reported potentially inappropriate prescribing (PIP) of medications in CKD (defined as the use of a contraindicated medication or inappropriately high dose according to the kidney function) ranging from 13 to 80%, with most of the medications being initiated in the community setting , 4. In AThe automated reporting of estimated glomerular filtration rate (eGFR) calculated from the modification of diet in renal disease (MDRD) or CKD epidemiology collaboration equation (CKD-EPI) is now routinely provided by laboratories whenever a serum creatinine (SCr) value is measured, as a tool to enhance the identification and classification of CKD . Most ofGiven this background, the main objective of this study was to determine the extent of PIP of renally-cleared medications commonly prescribed in Australian primary care, based on two separate estimates of kidney function (CG and CKD-EPI).This retrospective study included data collected by MedicineInsight, developed and managed by NPS MedicineWise. MedicineInsight is a large-scale national data program in Australia to extract and collate longitudinal, whole-of-practice data from the clinical information systems of consenting general practices. De-identified patient data collected include demographics, encounters (not including progress notes), diagnoses, prescriptions and pathology tests. As of July 2017, MedicineInsight had recruited 650 general practices with data pertaining to 3.6 million patients . The Ins2, and/or two urinary albumin/creatinine ratios (ACR) ≥ 3.5 mg/mmol in females or ≥ 2.5 mg/mmol in males, at least 90 days apart)  followed by medications for diabetes  and beta-blockers . Vildagliptin  followed by fenofibrate  were the most commonly prescribed medications at an inappropriate dose, whilst dapagliflozin  followed by alendronate  had the highest rates of use when contraindicated either by CG CrCl or eGFR  when determining the appropriateness of medications. Approximately 97% of medications that were classified as appropriate by eGFR were considered to be appropriate by the CG equation, while 88.1 and 61.1% of the medications considered to be contraindicated and inappropriately dosed by eGFR, were considered to be contraindicated and inappropriately dosed by the CG equation, respectively Fig. . The topThe results demonstrate that Australian general practice patients with CKD are frequently prescribed PIP. Approximately 35% of the patients were prescribed at least one PIP. The findings have corroborated the high rate of potentially contraindicated medications and inappropriate dosing found in international studies, including a systematic review that reported rates of PIP between 13 to 80% , 4. ThesThe extent of PIP in our study and the previous literature highlights the complexity of prescribing in CKD and could be due to the contribution of several factors. Firstly, in Australia there is a lack of up-to-date accessible guidelines on drug dose adjustments in patients with impaired kidney function. Another important aspect to consider is the inconsistencies with dosage adjustment recommendations between different drug information sources, as well as the product information of different brands of the same drug , 15. It 2 debate on the definition and staging of CKD exists as to whether CKD may be over diagnosed. However, these values are a sign of impaired kidney function that could affect the clearance of drugs. Hence, it is essential to consider renal function when prescribing renally-cleared medications as the PIP may lead to adverse outcomes.The nature of the electronic health record (eHR) may also be a potential factor for PIP. The current eHR may not alert prescribers to appropriately adjust dosages of medications cleared by the kidney unless the patient has CKD recorded as a diagnosis. Only 20% of the patients included had a formal diagnosis of CKD documented whilst all patients had laboratory evidence of CKD and this lack of coding of CKD as a condition may have had a role in the PIP findings , 8. WhilThe agreement between the two equations (CG and CKD-EPI) was excellent, with 97% of the medications rated as appropriate by eGFR being also rated as appropriate by the CG equation. Previous studies comparing drug doses derived from eGFR equations and CG have commonly reported discordance rates between 10 and 40% , 20. TheMost of the medications with PIP were consistent with previous studies . AntidiaIt is important to note that for some medications commonly prescribed in the study  clinical markers, such as heart rate and blood pressure, are often more important than kidney function in guiding dosage adjustment. Additionally, some medications do not have adequate published data in patients with renal impairment and may have been conservatively recommended as to be avoided rather than having an increased potential for toxic effects .Our study also showed that PIP was common across all stages of CKD. Although stages 1, 2 and 3a CKD seldom impact on the prescribing of renally cleared medications, several common medications such as metformin, gliptins and SGLT2 inhibitors do have specific recommendations in patients with early stages of CKD. Previous studies in patients with advanced CKD have shown contrasting results. Some studies have reported that in patients with advanced CKD the likelihood of PIP is less due to more vigilant monitoring and nephrology consultations, while other studies have shown an increased number of problems –26. FurtThe major strength of the current study is that it assessed prescriptions in primary care in a large cohort of patients. Previous Australian studies of inappropriate drug prescriptions in CKD have focussed on older people in the community and aged care settings, or when patients were admitted to the hospital . HoweverOur study highlights that PIP is common in Australian general practice, underlining the complexity of prescribing for patients with CKD. Understanding situations where prescribing is truly inappropriate would assist in the design of interventions to improve safe medication prescribing in patients with CKD. Our study also shows that although CrCl using the CG formula has been the most common method of estimating kidney function for drug dosing purposes for over 40 years, the widespread availability and extensive clinical use of eGFR now provides clinicians with a potential alternative. However, careful consideration of the risk-benefit ratio of individual drugs and doses within each patient is warranted.Additional file 1. Examples of renally cleared medications and dosage recommendations from the AMH.Additional file 2.


Isolated night-time hypertension (INH) was diagnosed in 11.9% (n = 3256). Untreated subjects had MH relatively more often than treated subjects . Females had higher relative risk (RR) of having WCH than males . Whereas, males had higher RR of MH than females . INH subjects had lower average systolic and diastolic dipping percentages  than those without INH. In conclusion, for diagnosis of hypertension there was a contradiction between OBPM and ABPM in approximately one-third of all patients, and a substantial number of patients had INH. Using ABPM in routine hypertension management can lead to a reduction in burden and associated costs for Indian healthcare.The present paper reports differences between office blood pressure (BP) measurement (OBPM) and ambulatory blood pressure measurement (ABPM) in a large multi-centre Indian all comers’ population visiting primary care physicians. ABPM and OBPM data from 27,472 subjects  were analysed and compared. Patients were classified based on the following hypertension thresholds: systolic BP (SBP) ≥ 140 and/or diastolic BP (DBP) ≥90 mmHg for OBPM, and SBP ≥ 130 and/or DBP ≥ 80 mmHg for 24-h ABPM, and SBP ≥ 120 and/or DBP ≥ 70 mmHg for night-time ABPM and SBP ≥ 135 and/or DBP ≥ 85 mmHg for daytime ABPM, all together. White coat hypertension (WCH) was seen in 12.0% ( In India, cardiovascular disease (CVD) is the number one cause of mortality, causing over 2 million deaths covering more than a quarter of all deaths in 2015  and is cA total of 32,808 patients attending 574 primary care clinics for routine management of hypertension spread throughout the whole of India participated in the present study. All patients were included between January 2017 and November 2018. OBPM was performed as usual in clinical practice without further instructions to the treating physician. Patients were referred for ABPM because their physician considered this necessary. As ABPM service was not available in the hospitals, it was made available by the sponsor Eris Lifesciences Ltd.  who had no further interference than providing the service. Healthcare workers visited the patient at home to connect the 24-h ABPM device to the patient and picked up the device the following day. Subsequently, The ABPM report was emailed to the treating physician. ABPM was performed according to standard instructions using validated 24-h ABPM devices  sustained normotension (SNT) normal OBPM + normal 24-h + normal daytime +  night-time BP; (2) sustained hypertension (SHT): elevated OBPM + elevated 24-h or elevated daytime or elevated night-time BP; (3) White-coat hypertension (WCH): elevated OBPM + normal 24-h + normal daytime + normal night-time BP; and (4) masked hypertension (MH): normal OBPM + elevated 24-h or elevated daytime or elevated night-time BP. Isolated night-time hypertension (INH) was defined as elevated night-time ABPM and normal daytime ABPM. Isolated daytime hypertension as normal night-time ABPM and elevated daytime ABPM.Information about the subject’s age, gender, height, body weight and family history for cardiovascular diseases were collected. Also personal clinical history for cardiovascular diseases , presence and treatment of arterial hypertension, diabetes mellitus and dyslipidaemia were recorded. Patients were included if OBPM was performed and ABPM contained 70% or more successful readings with averages for both day and night ABPM available.n) and relative (%) frequency in case of categorical variables. Differences across groups were evaluated by multi-analysis of variance (MANOVA) by entering in the analysis BP classification  as independent and the parameters as represented in Table t-tests were used to compare OBPM and ABPM values in the same participant for the full sample and within subgroups. To analyse BP values related to age, patients were divided in six age groups of equal numbers (ranks). Binary logistic regression analysis was used to determine the relative risk of gender to either masked or white coat hypertension. Results were presented in p-values. A p-value of <0.01 was considered significant. Data analysis was performed using IBM SPSS Statistics version 26 for Windows.Data analysis was performed by grouping the patients according to one of the four BP categories . Given the observational nature of the study, no sample size estimation was done. All subjects included for analysis provided valid data and thus no methodology for replacing missing data was implemented. Main demographic and clinical data of the two subgroups were summarised by calculating the mean (±SD) in case of continuous variables, and the absolute  or patients had <70% successful ABPM readings . Patients with <70% successful ABPM readings were relatively more often female (37% vs 32%), more often obese (25% vs. 22%) were less often taking medication (42% vs. 46%), had higher night-time SBP (126 vs. 124 mmHg) but lower night-time DBP (71 vs. 72 mmHg) [all p < 0.001]. Of the excluded patients, 3340 (65% of the excluded) had >50% but <70% successful ABPM readings  of the 32,808 subjects completed 24-h ABPM with enough successful readings (>70%) and were included for the analysis. Reasons for exclusion were because there was no OBPM value available . OBPM values were significantly higher than daytime ABPM, 24-h ABPM and night-time ABPM, respectively, both for SBP and DBP , but there was no difference in WCH prevalence .Figure p < 0.0001.In 5266 subjects (35.2%) of the untreated population, there was a contradiction in outcome between OBPM and the combination of 24-h daytime and night-time ABPM. For the treated population this contradiction was seen in 3331 subjects (26.7%), p < 0.0001) but lower DBP (85.2 ± 12.4 vs. 87.0 ± 12.0 p < 0.0001) thus a higher pulse pressure  than males (44.5% treated), but for 24-h ABPM they had similar SBP  and lower DBP . Females had a higher white coat effect (OBPM-24h ABPM) than males for SBP  and DBP . This resulted in a higher relative risk (RR) of having WCH for females as compared to males . Whereas, males had a higher risk of MH as compared to females .For OBPM females (47.6% treated) had an average higher SBP  and mean daytime and 24 h ambulatory SBP than females , and a similar night-time ambulatory SBP  without significant differences for DBP  and for office SBP . For both men and women, average night-time SBP increased more with age than the average daytime ABPM value.Figure DBP Fig. . For theFigure p = 0.60). Women had relatively more often INH than men . However, men showed isolated daytime hypertension more often than women .Table p < 0.001), thus a low dipping percentage  and were on average older  than those without INH.Patients with INH had similar night-time (123.7 ± 8.9/ 70.4 ± 6.5 vs. 124.4 ± 18.9/ 72.3 ± 11.5) but lower daytime ABPM SBP and DBP values . The high number of patients with MH (n = 3439 (23.0%)) in the untreated group is concerning, as these patients would not receive anti-hypertensive treatment if only OBPM were performed, whereas their cardiovascular risk is similar to the patients with hypertension [To the best of our knowledge, this is the first large population study demonstrating the importance of 24-ABPM for hypertension management in general healthcare in India. Considering that 24-h ABPM is superior to OBPM for diagnosing hypertension, the present study showed that from the 27,472 patients, 8597 patients (31.3%) would have been wrongly diagnosed if only  OBPM was considered as common in current Indian primary care practice. For patients without treatment, this misclassification percentage was higher than in those who were treated . This higher male prevalence may have had some influence on the outcome due to significant differences related to gender such as, e.g., the higher prevalence of INH and a higher systolic white coat effect in women as was found in the present study. In addition, treating physicians were not instructed how to perform OBPM but they performed the procedure according to routine practice. This means that there probably were differences in OBPM performance regarding the device (brand) that was used, technique  and number of measurements. On the other hand, this represents general clinical practice and how clinic BP measurement is performed in India and it may possibly reveal the limitations of this standard procedure. The prevalence of WCH and MH of the present study is based on a single OBPM visit, which could lead to erroneous diagnosis in real practice in case of different outcome as compared to ABPM. However, possibly some physicians, who normally do not use ABPM, base their diagnosis and/or treatment on more than one OBPM per visit and/or on more than one clinical visit. This most likely gives a better estimation of the patient’s BP and would lead to a lower rate of erroneous diagnosis. Taking the average BP from multiple clinical visits is more in line with hypertension management guidelines, but obviously these seem to have a low adherence rate in clinical practice in India . The subThe prevalence of white coat and masked hypertension together of 31% is similar to another large ABPM data registry that contains ABPM and OBPM data of >14,000 adult patients around the globe . AlthougThe present data show a male to female ratio of 2:1. As the data are obtained from clinical practice, this suggests that females are less likely to visit a doctor and those who visit a doctor are on average 2 years older than males. Although the present study showed that females were relatively more often sustained normotensive (14.8% vs. 12.5%) and less often sustained hypertensive than males (53.8% vs. 56.3%), it is unlikely that the lower cardiovascular risk (cardiovascular events in India) justifies these large differences. Although women have lower BP at younger age, this rapidly changes after menopause. Considering the fact that women have a higher life expectancy than men in India  one woulThe definition of WCH and MH is often based on OBPM and (awake) daytime ABPM  althoughSome studies found typical patient characteristics linked to either WCH  and masked hypertension (MH).Ambulatory blood pressure measurement is superior to office blood pressure measurement and therefore recommended for hypertension management.Night-time blood pressure measurement is an important cardiovascular risk predictor.This is the first largescale study performed comparing OBPM and ABPM in the whole of India. Certain parameters can be specific for certain populations but also the hypertension management method can be country specific.WCH was seen in 12% of the population and 19% had MH. Females had higher risks of WCH and men were at higher risk of having MH.Isolated night-time hypertension was diagnosed in 12% of the study subjects and provide an extra reason to perform ABPM in Indian healthcare in order to improve overall hypertension management.Supplement 1Supplement 2Supplement 3Supplement 4


Background: Previous studies have indicated an association between hypertension and intestinal barrier dysfunction in mice models. The present study aims to investigate the association between hypertension and intestinal barrier impairment in humans and identify the novel potential risk factors for hypertension.Methods: Medical data from consecutive inpatients were retrospectively pooled from patient records. We compared intestinal barrier serum markers  between those patients with and without hypertension. Moreover, the associations between intestinal barrier markers and cardiovascular risk, hypertension history, blood pressure control, hypertensive complications, and antihypertensive medication history were also analyzed.Results: Overall, 106 hypertensive and 251 normotensive subjects were included. Patients with hypertension had a higher level of DAO  and LPS . In hypertensive patients, multivariate logistic regression analyses showed that long hypertension history (≥20 years), poor control of diastolic blood pressure, cardiac and renal complications, and use of multiple antihypertensive medications were risk factors for elevated DAO, while the use of multiple antihypertensive medications was a risk factor for elevated D-lactate (P < 0.05).Conclusions: Hypertension is associated with impairment of intestinal barrier, especially in patients with long duration, poor blood pressure control, cardiac and renal complications, and use of multiple antihypertensive medications. The current study indicates that intestinal barrier dysfunction might be a potential predictor of hypertension. Hypertension is a significant public health issue worldwide, which is the strongest modifiable factor related to cardiovascular disease and strokes, causing high morbidity and mortality , 2. The The association between the gut and cardiovascular disease has begun to draw our attention in recent years , 5. The D-lactate  , 14, lip-lactate , 18 are Currently, the correlation between hypertension and intestinal barrier impairment is far from known. The present study aims to investigate the role of typical serum markers of intestinal barrier function in hypertensive patients and to find novel potential risk factors for predicting and treating hypertension.Helicobacter pylori; and (vii) secondary hypertension caused by renal parenchymal, adrenal, renovascular, or thyroid disease. Patients hospitalized more than once during the study period were recorded only once. A total of 1372 patients were detected with the three serum biomarkers in the department of gastroenterology in 2017, and a final 357 subjects were included in the present study.In this retrospective study, we reviewed the medical data of all inpatients in the Department of Gastroenterology of the First Affiliated Hospital of Guangdong Pharmaceutical University treated from January to December 2017. The exclusion criteria were as follows: (i) carcinoma; (ii) severe heart, lung, liver, or kidney disease, except hypertensive cardiac or renal complications; (iii) non-steroidal anti-inflammatory drug use in the previous month; (iv) intestinal diseases such as ulcerative colitis, Crohn's disease, or intestinal obstruction; (v) history of gastrointestinal surgery; (vi) bacterial infection, except This study was performed in accordance with the Declaration of Helsinki and with the approval of the Ethical Committee of the First Affiliated Hospital of Guangdong Pharmaceutical University. Given that this was a retrospective study, informed consent from the research subjects was waived.We collected data from patient records on demographics (age and gender), height, and weight [to calculate the body mass index (BMI)]. We also collected data on hypertension-related factors including hypertension status, cardiovascular risk, duration, BP control, complications, and antihypertensive medication use. Diagnosis of hypertension was based on the classic criteria: systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg . SubjectH. pylori status, and three intestinal barrier markers. Smokers were defined as patients who had smoked at any stage in their life. Alcohol consumption was defined as drinking >140 g of alcohol per week. Hypercholesterolemia was defined as serum cholesterol >5.2 mmol/L , history of diabetes, cholesterol level, 2 mmol/L . H. pyloU-tests for medians. To identify risk factors for elevated intestinal barrier markers, we performed logistic regression analyses with a backward stepwise approach. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. P < 0.05 (two-sided) was considered statistically significant.IBM SPSS software version 22  was used to perform statistical analyses. Categorical variables are presented as frequencies and proportions. Non-normally distributed continuous variables are presented as medians and interquartile ranges. The statistical significance levels of differences between the hypertensive and normotensive subjects were tested using Chi-square or Fisher's exact tests for categorical variables and Mann–Whitney In total, 357 patients (251 without hypertension and 106 with hypertension) were included, but specific subsets were used in different analyses (detailed below) due to patients having missing data for some variables. The demographics and clinical characteristics of the included patients were shown in D-lactate. P = 0.044) and elevated LPS  but not D-lactate . After adjustment for gender, age, BMI, smoking, alcohol consumption, liver disease, diabetes, and H. pylori infection, the logistic regression analysis showed that hypertension was a risk factor for elevated DAO  and elevated LPS . In addition, representative images of capsule endoscopy showed that edema, hyperemia, and mucosal lesions were frequently detected in the small intestine of patients with hypertension, whereas they were rarely observed in those participants without hypertension  , poor DBP control , cardiac complication , renal complication , and use of multiple antihypertensive medication  were risk factors for elevated DAO   .P = 0.068, The association between blood pressure control and the intestinal barrier biomarker was further determined. Compared with patients with good DBP control, those with poor control showed a trend toward a higher prevalence of elevated DAO, although there is no significant difference (43.48 vs. 24.10%, Our findings show that hypertensive patients had higher prevalence rates of elevated DAO and LPS than normotensive subjects, which indicates that hypertension is associated with serious intestinal barrier impairment, including small intestinal epithelium injury and endotoxin translocation. These important findings might improve early diagnosis and potential therapeutic target for hypertension-related intestinal damage in hypertensive patients. To the best of our knowledge, this is the first study to assess the association between hypertension and intestinal barrier integrity in humans.These clinical findings  are consKlebsiella spp. and Streptococcus spp. (Several mechanisms might explain why hypertensive patients have intestinal barrier impairments. First, hypertension can cause decreased intestinal blood flow , 12. Onecus spp. , 26. Thecus spp. , 28. Fincus spp. . Inflammcus spp. .Vice versa, intestinal barrier dysfunction plays an important role in the etiology of hypertension. Gut microbiota is considered as a composition and regulator of the intestinal barrier, which plays a critical role in the metabolism and maturation of the immune system . A leakyThe enzyme DAO is mainly expressed in intestinal mucosa and usually has a low presence in blood. The amount of DAO is positively associated with the permeability of the intestinal barrier . PreviouOur results show that impaired intestinal barrier is associated with multiple hypertension-related factors and complications . IntestiIn conclusion, the present study indicates that hypertension is associated with biomarkers of intestinal barrier impairment, especially in patients with long hypertension duration, poor BP control, cardiac and renal complications, and the use of multiple antihypertensive medications. Further studies are required to determine the precise mechanism of the intestinal barrier, serum biomarkers, and the gut microbiome in hypertension and, finally, to gain insights into diagnosis or therapy for hypertensive patients.There are several limitations to the present study. First, the results were generated from a single-center study. Second, due to the retrospective nature of our study, some confirmatory examinations, such as endoscopic and mucosal pathologic examinations, were not available for most patients. Serum markers only indirectly reflect intestinal barrier function. Finally, more cases of participants as well as mechanism studies are required to generate a confirmatory conclusion.All datasets generated for this study are included in the article/This study was performed in accordance with the Declaration of Helsinki and with the approval of the Ethical Committee of the First Affiliated Hospital of Guangdong Pharmaceutical University. Given that this was a retrospective study, informed consent from the research subjects was waived.CL, DL, and PX designed the study and carried out the data collection. H-JZ and X-XH designed the study. All authors wrote the paper, read, and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


High blood pressure (HBP) among children and adolescents has been associated with elevated risk of cardiovascular diseases later in life. The aim of this study was to determine the relationship between body composition and blood pressure among Polokwane private school children. Mean body fat % was significantly (P < 0.05) higher in girls (23.74) than the boys (16.77). There was a significant (P < 0.05) association between systolic blood pressure (BP) and waist circumference (WC) unadjusted (OR = 1.125) and adjusted (OR = 1.097) for age and gender. This study included a total of 1665 children and adolescents (846 boys and 819 girls) aged 5 to 15 years old. Anthropometric measurements including weight, height, hip circumference (HC) and waist circumference (WC) were taken according to standard procedures. Descriptive statistics were done to determine the prevalence of hypertension and mean of all the variables. Pearson correlation, linear regression and logistic regression were all done to determine the association between blood pressure (BP) and the anthropometric measurements. All statistical analysis were done using SPSS. There was a significant association between body composition and blood pressure among Polokwane Private School children. Lowering the risk factors of high BP in children and adolescents will lower their risk of cardiovascular diseases in adulthood. High blood pressure (HBP) among children and adolescents has been associated with elevated risk of cardiovascular diseases later in life . It has Anthropometric measurements including BMI, waist circumference (WC), and skinfold thickness, are a noninvasive and affordable technique to evaluate children’s nutritional status and have been recommended for wide use in clinical practice . There aNumerous studies have reported the prevalence of HBP among children in developed areas in and out of South Africa ,13 whichThis study included a total of 1665 children aged 5 to 15 years from Polokwane Private School . Most of the participants were black children (99.77%) and 0.2% were white; 0.01% were colored and 0.02% were Indians, which resulted in their exclusion from the analysis. The study took part in Polokwane, a city in Limpopo Province, South Africa. Children who were available at the schools during the days of the survey participated in the study.The ethics committee of the University of Limpopo granted ethical approval prior to the study . Written informed consent was attained from parents and guardians of the children.All participants undertook a sequence of anthropometric measurements of waist circumference (WC), weight and height following standard procedures of the International Society for the Advancement of Kinanthropometry . TrainedBoys  body fat % = 1.21 (triceps + subscapular)−0.008 × (triceps +subscapular) 2 +1.7  Girls  body fat %: 1.33 × (triceps + subscapular)−0.013 × (triceps + subscapular) 2 − 2.5For participants with a sum of triceps and subscapular <35 mm.Percentage body fat was based on the sum of triceps and subscapular skinfolds using the equation below ,16:Boys Boys  body fat % = 0.783 (triceps + subscapular) + 1.6Girls  body fat %=0.546 (triceps + subscapular) + 9.7Then the following equation was used: Using an electronic Micronta monitoring kit, at least three readings of systolic blood pressure (SBP) and diastolic pressure (DBP) were taken at an interval of five minutes apart after the participants had been seated for 5 minutes or longer , the aveBlood pressure measurements were categorised according to SBP and/or DBP percentiles as follows: normal BP—average SBP and/or average DBP <90th percentile; prehypertension—average SBP and/or average DBP ≥90th percentile but <95th percentile; and hypertension—average SBP and/or average DBP ≥95th percentile .Descriptive statistics (mean and standard deviation) were done for age, blood pressure and all the body composition variables , while descriptive frequencies were done for blood pressure only. Pearson correlation coefficients were performed to determine the relationship between blood pressure and the body composition variables by gender. Linear regression was also performed to determine the relationship between blood pressure and the body composition variables by gender. Logistic regression was performed to further determine the relationship between blood pressure and the body composition variables. All statistical analysis was done using SPSS version 25 and the P value was set at P < 0.05.The aim of this study was to determine the relationship between body composition and blood pressure among Polokwane Private School children. The current study found several significant correlations between both SBP and DBP with age, weight, height, BMI, WC, HC, WHR, tricep skinfold thickness, subscapular skinfold thickness and body fat % among Polokwane Private School children (girls and boys) aged 5 to 15 years. A study by Mushengezi and Chillo  found siAs indicated on the findings of the current study, among other anthropometric body composition variables, BMI and height were consistently significantly associated with SBP in correlation, linear regression and logistic regression. A study by Kuciene and Dulskiene  reportedThe prevalence of high SBP was 5.7% and 4.8% in girls and boys, respectively, while high DBP was 6.1% and 5.1% in girls and boys, respectively. The prevalence of overall hypertension was 5.3%. A similar study reported the prevalence of high SBP in girls of 5.6% and 4.8% for boys. The findings were similar to those when DBP was used . In bothThe limitations of this study are that the BP readings were recorded as the average of three measurements, which were taken after 5 minutes apart according to standard procedures, measurements were only taken on one occasion. Therefore, the possibility of bias cannot be excluded in the results. The current study did not have the resources to assess body composition using more direct indicators of body composition  such as Bioelectrical Impedance, Hydrostatic Weighing and DEXA , among others. The strengths of the study were the large sample size and the different analytical methods used to determine the same association.There was a significant association between body composition and blood pressure among Polokwane Private School children. There was an inconsistent association between blood pressure and waist-to-hip ratio. There was an overall low prevalence of high BP in the current study, however girls were more at risk than boys. Since the children are young and dependent on their parents/guardians, schools should regularly have educational programs to teach parents about healthy living  and the dangers associated with unhealthy habits. Therefore, the parents can make better choices and teach the children. This will lower the children’s risk of cardiovascular diseases in adulthood.