This study evaluates the actual blood pressure control rate and its estimation by general practitioners, the use of single-pill or free combinations, and the attitude towards single-pill combinations in primary care.Cross-sectional observational survey in primary care between January 2015 and September 2016 in Belgium and Luxembourg. The participating general practitioners enrolled hypertensive patients taking at least 2 antihypertensive molecules (as fixed or free associations).742 general practitioners included a total of 8,006 patients, with a mean age of 66 ± 12 years. Systolic blood pressure and diastolic blood pressure were respectively 141 ± 17 mmHg and 82 ± 10 mmHg (means ± SD). These patients had a blood pressure control rate of 45%, whereas it was estimated by general practitioners to be 60%. General practitioners with 11–25 years’ experience performed better than general practitioners with 36–51 years’ experience in the evaluation of blood pressure control. Combinations used were free in 39%, single-pill in 34% and mixed in 27% of the patients. Patients receiving single-pill combinations were younger than those treated with free combinations , with fewer comorbidities . In patients treated solely with free pill associations, 66% of patient cases, general practitioners were willing to switch to a single-pill combination. The main reasons were improved adherence (76%) and better blood pressure control (64%).In patients requiring at least two antihypertensive drugs, blood pressure control rate remains low and is overestimated by general practitioners. Free combinations remain largely used although many general practitioners seem willing to shift to single-pill combinations. Treatment simplification could improve adherence and blood pressure control rate, which has been shown to lead to reduced morbidity and mortality. Arterial hypertension is one of the main modifiable risk factors for cardiovascular diseases worldwide , 2. On tDespite available treatments, control of arterial hypertension remains suboptimal , which iWhen combination therapy is used, the use of single-pill drug combinations (SPCs), also known as fixed-dose combinations, is favoured by guidelines , becauseIn Belgium and Luxembourg, epidemiological data on the use of antihypertensive drug combinations in primary care are scarce. The current study was conducted in these 2 countries in a sample of patients to whom at least 2 antihypertensive agents were prescribed. The objectives of this study were to evaluate actual blood pressure control, its estimation by general practitioners (GPs), the type of drug combinations used and the GPs’ attitude towards the prescription of SPCs.dx.doi.org/10.17504/protocols.io.tkwekxeThe complete study protocol can be found on For this observational cross-sectional survey, a random sample of 840 primary care physicians throughout Belgium and Luxembourg were contacted to participate. From January 2015 to September 2016, each physician included 12 consecutive hypertensive patients treated with at least 2 antihypertensive drugs, in order to obtain a planned study sample of 10,000 patients. In total 742 GPs (88% of the intended sample) included 8,006 (80% of the intended sample) patients treated with at least 2 antihypertensive drugs, resulting in a capture rate of on average 10.8 included patients per participating GP.Paper case report forms were filled out manually with existing patient data recently registered in the medical file of the participating GPs as part of their routine clinical practice. The following data were collected for each patient: demographics (age and sex), current office systolic and diastolic blood pressure, doctors’ judgement about blood pressure control, presence of comorbidities , type of prescribed antihypertensive drugs , and GPs willingness to switch to SPCs.No specific recommendations were given regarding the BP measurements and the definitions of co-morbidities were left to the discretion of the GPs.Systolic blood pressure and diastolic blood pressure cut-off values were based on the 2013 ESH-ESC guidelines [Given the retrospective observational design of the study, no ethics committee approval was requested, in accordance with the Belgian law on experiments involving human subjects (7 May 2004). The study was conducted according to the quality standards for non-interventional studies outlined in the prevailing Code of Deontology of the Belgian pharmaceutical industry association (pharma.be).All data collected in the case report forms were entered in an Excel table. In order to verify the quality of the data entry, a quality control was performed on the concordance of the data of 5% of the patients, randomly selected by a computer algorithm, between the Excel table and the original case report forms. In this 5% subsample of the dataset, 0% errors in data entry were identified. The statistical analysis was subsequently performed in this controlled dataset using Stata software v. 14. All statistical tests were two-sided using a significance level of 0.001. Data is are presented as mean ± standard deviation or as proportions (%). Student’s t-test and one-way ANOVA were applied to compare means and Chi-squared test was used to compare proportions.Of the 840 GPs contacted for this study, a total of 742 GPs enrolled 8,006 hypertensive patients treated with at least 2 antihypertensive drugs. The mean age was 66 ± 12 years and 54% of the patients were male. Mean systolic and diastolic blood pressure were 141 ± 17 mm Hg and 82 ± 10 mm Hg, respectively. No difference in mean blood pressure were observed in the different subgroups of patients. Comorbidities were observed in 64% of the patients. Among the patients with comorbidities, 49% had diabetes mellitus, 50% had a previous cardiovascular event, 16% had renal insufficiency and 19% had other comorbidities. Patients were treated with either two (57%), three (31%) or more than three (12%) antihypertensive drugs. Combinations were free in 39%, single-pill in 34% and mixed in 27% of the patients. There was no significant difference observed in use of SPCs between Belgium and Luxembourg.SPCs were exclusively used in only 34% of patients, while in the remaining 66% of patients the combinations used were either free (39%) or comprised both SPC and free components (27%). Patients taking SPCs were younger, were more often men and had a lower prevalence of comorbidities .Control of both systolic and diastolic blood pressure based on the 2013 ESH-ESC guidelines was observed in 45% of the patients. Systolic blood pressure was controlled in 47% and diastolic blood pressure in 70% of the patients .The blood pressure control rate was estimated by the GPs to be 60%. When a patient was considered by the GPs as having controlled blood pressure, this patient was truly controlled in 72% of the cases . On the other hand, when a patient was estimated to have his blood pressure uncontrolled, this statement was correct in 97% of the cases  .When both systolic and diastolic blood pressure were uncontrolled (28% of the study population), GPs wrongly considered the blood pressure to be controlled in 10% of the cases. When only systolic blood pressure was not controlled (25% of the study population), 47% of the patients were erroneously estimated to be controlled. When only diastolic blood pressure was not controlled (2% of the study population), 78% of the patients were wrongly estimated to be controlled .Best concordance between the measured blood pressure control rate based on Guidelines and the blood pressure control rate evaluated by the GP was observed in GPs with 11–25 years’ experience  and worst in older GPs with 36–51 years’ experience .In the population of patients solely treated with free pill associations , doctors were willing to switch to a SPC in 66% of the cases. Of these cases when doctors were willing to switch to a SPC, in 55% of the cases the preferred switch was to a SPC concerned two-drug combination, in 37% of the cases a SPC concerned three-drug combinations and in 8% either single pill, two-drug or three-drug therapies.The main reasons for which GPs considered shifting to SPCs were improved adherence (76%) and better blood pressure control (64%) .In our study population, 1,263 (16%) of the patients were aged 80 years or more, with more women (58%) than men. Octogenarians had more comorbidities than patients aged less than 80 years. The most prevalent comorbidities in octogenarians in comparison with patients under 80 years were renal insufficiency and prior cardiovascular event, whereas diabetes and other comorbidities were less frequent. Octogenarians were more often treated with free drug combinations than younger patients .Based on the 2013 ESH-ESC criteria (systolic blood pressure < 150 mmHg and diastolic blood pressure < 90 mmHg), the actual blood pressure control rate in octogenarians was 71%. When blood pressure control rate was defined as a blood pressure < 140/90 mmHg, it was 50% in octogenarians compared to 44% in patients aged less than 80 years (P < 0.001). In octogenarians, GPs considered blood pressure as controlled in 68% of the patients. When an octogenarian was judged by the GP as having controlled blood pressure, this patient was truly controlled in only 72% of the cases, and when an octogenarian was judged as having uncontrolled blood pressure, this statement was correct in 96% of the cases (no significant difference compared to patients aged < 80 years).In this large and specific population of hypertensive patients taking at least 2 antihypertensive drugs and followed in primary care, we observed a blood pressure control rate of 45%, which was overestimated by the GPs. Although the exclusive use of SPCs is relatively low compared to the use of combination treatment with at least one free component, a majority of GPs considered switching the therapy to SPCs in order to increase therapeutic adherence and blood pressure control.Few studies have examined the blood pressure control rate in hypertensive patients in Belgium. Comparing two large epidemiological studies, blood pressure control rates of 25% and 33% were reported in treated hypertensive patients . In 3,76The large Prospective Urban Epidemiology (PURE) study examined hypertension prevalence, awareness, treatment and control in adult subjects from countries with different economic levels. Data were collected from January 2003 to December 2009. Among the patients treated for high blood pressure, 32.5%  had their blood pressure controlled . Control rate was 40.7% in high-income countries, and, specifically in Europe and North America, it was 38.5% . In an eAs previously described, diastolic blood pressure is more often controlled than systolic blood pressure , 14. OveSPCs were exclusively used in only 34% of patients, while in the remaining 66% of patients the combinations used were either free (39%) or comprised both SPC and free components 27%). The use of SPCs, as compared to their free-drug counterparts, has been shown to be associated with a significant higher adherence rate to treatment –22 and l%. The usAlthough the methodology of this study was not designed to identify the motivations of drug prescriptions by the GPs, we can speculate on several reasons. First, fixed dosages of the components into the SPC could limit adaptation of the dosages of the components, although, at least in Belgium and in Luxembourg, most SPC are launched with all dosages of the individual components. Second, until recently, European guidelines have recommended an antihypertensive strategy based on an initial monotherapy, followed, if BP target is not achieved, by the addition of other drugs . Once thSeveral initiatives have been proposed to improve BP control rate, including a more generalized prescription of SPC . Based oThe inclusion of 1,263 patients aged ≥ 80 years allows us to describe, for the first time to our knowledge, the use of antihypertensive drug combinations in octogenarians. Expectedly, octogenarians were more often women and had more comorbidities than patients aged < 80 years. Octogenarians received more often free drug combinations. It is possible that GPs want to keep dosage adjustment flexibility in these more vulnerable patients with a high prevalence of kidney disease. On the other hand, SPC were more often used in younger patients with less comorbidities, presumably because GPs could believe that these patients require less “fine-tuning” of the dosages of the components in the SPC. Results from a recently published study from Germany are in accordance with this latter observation . An analThis study has several limitations. Physicians participated to the study on a voluntary basis, which may reflect a particular interest in the management of high blood pressure. Therefore, they could be unrepresentative of the general GP population and their patients may not fully reflect the general population of hypertensive patients in Belgium and Luxembourg. No specific definitions were given for diabetes mellitus, previous cardiovascular events, renal insufficiency and other comorbidities, and given the retrospective nature of the study no specific recommendations were given for blood pressure measurement. Thresholds for blood pressure control were not recalled: overestimation of blood pressure control by GPs could reflect their lack of knowledge of the most recent guidelines. Results are based on treatment prescribed by the GPs, and it is inherent to the observational study design that we could not check whether the patients actually take the antihypertensive therapy which might have an influence as adherence to antihypertensive therapy is known to be low in hypertensive patients . FinallyIn conclusion, in this large-scale study conducted in hypertensive patients treated with drug combinations, we observed a blood pressure control rate of 45%. The blood pressure control rate was overestimated by GPs, which could prevent treatment intensification in many patients (i.e. therapeutic inertia). Although the use of SPCs, free and mixed combinations was balanced in the study population, many GPs planned to substitute free combinations for SPC, which could lead to improved adherence, blood pressure control rate and hopefully better cardiovascular prognosis.S1 FileOriginal scientific protocol of the ACHIEVE study.(PDF)Click here for additional data file.S2 Filend inclusion wave of patients.Investigateur. Amendment to the ACHIEVE protocol justifying the 2(PDF)Click here for additional data file.S3 FileScientific protocol and CRF of the ACIEVE study in english.(PDF)Click here for additional data file.S4 FileTREND statement checklist.(PDF)Click here for additional data file.S1 DatasetThe anonymized dataset of the ACHIEVE study.(ZIP)Click here for additional data file.


We aimed to study arterial stiffness variables in patients with rheumatoid arthritis (RA), specifically considering their associations with path model mediation analysis. We examined arterial stiffness expressed by the pulse wave velocity (PVW), augmentation index (AIx), distensibility, and clinical and biochemical characteristics in a cohort of 214 RA patients. Variable associations were analysed using multivariate linear regression analysis. We also used path model mediation analysis for PWV variable. Our results indicate that age, systolic blood pressure (SBP), and body mass index (BMI) were significantly associated with PWV, and collectively accounted for 32% of PWV variability. The parallel mediation analysis showed that SBP and BMI accounted for 21% and 7%  of the total effect of age on PWV, respectively, indicating a partial mediation effect. The associated variables with AIx were age and tender joint count, while those with distensibility were BMI and sex, overall accounting for 16.5% and 4.7% of the variation in AIx and distensibility, respectively. We observed no associations of arterial stiffness with inflammatory variables, disease activity and duration, or cholesterol levels. In conclusion, in our population of RA patients, age is the most important variable that determines the increase in PWV. We have also shown that a significant proportion of the negative effects of age on PWV occurs through increases in SBP and BMI. In our study, lipid and inflammation variables were not associated with an increase in arterial stiffness. The chronic inflammation that acts as an independent risk factor for CV3 seems to increase the morbidity and CV mortality of these patients5.The increase in cardiovascular risk (CV) is currently one of the most important causes of comorbidities in patients with rheumatoid arthritis (RA)6 and the measurement of pulse wave velocity (PWV) is widely accepted as a precise and non-invasive method to assess arterial stiffness in humans7. While the PWV directly measures the arterial elasticity of the great vessels8, the augmentation index (AIx) is a more complex parameter that depends on both vascular elasticity and peripheral resistance.Increased arterial stiffness is one of the earliest stages of atherosclerosis9. These indices are frequently used as surrogate CVD endpoints in clinical studies since they provide non invasive measures that reflect early effects of several stimuli on the arterial wall10.An additional parameter used to measure arterial stiffness is carotid distensibility, which measures the ability of the artery to expand and contract during cardiac pulsation and relaxation13. In these studies, associations with variables that are characteristic of the disease such as disease duration15, inflammatory variables19, and disease activity22 have been demonstrated, although arterial stiffness has also been correlated with age24 and SBP25. There are few published studies that have evaluated distensibility as a marker of arterial stiffness in RA26, and the results of these studies are similar to those obtained for PWV and AIx. However, these findings were in contrast to those of other publications, which demonstrates the need for additional studies and meta-analyses to provide information about these associations27. Furthermore, others and we have evaluated subclinical atherosclerosis in RA30 but the relationship of arterial stiffness parameters in individuals with subclinical atherosclerosis has shown differing results32.In recent years, there has been a growing interest in the relationship between PWV, Alx, and RA due to reports that an increase in these markers of arterial stiffness suggests endothelial dysfunction. Some case-control studies reported increased arterial stiffness in RA patientsThe aim of this study was to describe the association between arterial stiffness as measured by PWV, AIx, and carotid distensibility by specifically considering the relationship between the characteristics of the disease and lipid profiles within a population of RA patients, as well as mediating variables that might affect that relationship. Additionally, we sought to determine if there was a relationship between arterial stiffness, cIMT, and carotid plaque presence in RA patients.30. Briefly, the 1987 American College of Rheumatology criteria for RA diagnosis were used to select patients who attended the University Hospital Sant Joan de Reus via external consultation. 214 patients between 20 and 80 years of age were included in the study. The clinical research Ethics Committee of the University Hospital Sant Joan approved the study and we executed the investigation in accordance with our Institution’s guidelines and the Helsinki Declaration.The AR population of the present study has been described in a previous paperWe informed patients about the research nature of the study and they provided written informed consent prior to participation. Patients were included from September 2011 to November 2014 and on the same day of the visit, fasted blood extraction and carotid ultrasound were carried out.Fasting venous blood samples were obtained in EDTA tubes from 214 patients. Analytical variables including hemogram, general biochemistry, glycated haemoglobin, thyrotropin, albumin, and lipid profile  were determined by enzymatic methods. Measurement of apolipoproteins A1 and B were carried out by immunonephelometry and lipoprotein (a) by an enzyme-linked immunosorbent assay. Standard laboratory methods were used to quantify rheumatoid factor (RF), citrullinated anti-cyclic peptide antibodies (ACPA), antinuclear antibodies, and inflammatory markers . RF positive (RF+) was defined by values of RF >20 and positive ACPA (ACPA+) was defined by ACPA values >1. Dyslipemia was defined as having HDLc <50 mg/dL for women or <40 mg/dL for men, or TG >150 mg/dL, or LDLc >100 mg/dL or in treatment with statins or other hypocholesterolemic drugs.We obtained information about the classical CV risk factors , the use of hypolipidaemic, hypoglycaemic, or antiplatelet drugs, and history of CV events. Additionally, we performed measurements of body weight, height, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), and joint physical examinations of RA. The disease activity score (DAS28) calculated according to the ESR was obtained as a measure of disease activity. Determination of swollen and tender joint counts were also obtained . The 0–10 visual analogue scale and the health assessment questionnaire (HAQ) index were used as a measure of pain and disability, respectively.in vivo by the Quality Arterial Stiffness (QAS©) radiofrequency software . Radiofrequency (RF) Signal-based Vascular Ultrasound from Esaote employs RF signal-based technology and includes QAS measurement. The RF signal is a reflected ultrasound signal that is captured by the transducer and converted in an electric signal preserving all the characteristics of the acoustic wave in terms of amplitude and phase. Local arterial stiffness is estimated as systo-diastolic changes in arterial diameter/area over systo-diastolic changes in distending pressure (pulse pressure). Maximum and minimum carotid diameters were acquired using the attained distension curves, and vascular stiffness parameters were calculated after calibration for blood pressure34. Carotid distensibility was the change in diameter of the carotid artery secondary to intravascular volume expansion caused by the left ventricle systole. The pulse wave velocity was obtained from brachial blood pressure and the accurate measurements of diameter and change in diameter of carotid arteries. Augmentation index was measured by the pulse wave analyses and local pressure. Final values were the median measurements of the right and left carotid arteries36.Arterial stiffness expressed by the pulse wave velocity, carotid distensibility and augmentation index was measured directly at both common carotid arteries using the ultrasound linear probe (5–12 MHz) as a tonometer and analysed in vivo at the predefined points using the QIMT© radiofrequency image processing software . We defined pathological cIMT as the 75th percentile of cIMT values in the general population banded with respect to age and sex, and plaque as a focal structure encroaching into the arterial lumen by at least 0.5 mm or 50% of the surrounding IMT value, or a thickness >1.5 mm. A single operator obtained and measured the images in order to reduce variabilityCarotid intima-media thickness (cIMT) was measured with a My Lab 50X-Vision sonographer  with a linear array ultrasound probe small parts broadband transducer (5–12 MHz). The far wall of the common carotid artery , the bifurcation, and the internal carotid artery of the left and right carotid arteries were identified. We measured cIMT 37. Specifically, we used a parallel mediation model (model number 4 in Hayes macro) to examine total, direct, and indirect effects of age on PWV  represent the effect of age on PWV through SBP or BMI, respectively. If the indirect effects path is statistically significant, it can be concluded that mediation has occurred. The significance of indirect effects are tested by bootstrapped 95% confidence intervals (CI). Process macro produces bootstrap estimates and bias-corrected 95% confidence intervals (CIs) for the indirect effect, and a 95% CI that does not cross zero indicates a statistically significant indirect. The effect size for mediation analysis was measured with percent mediation (PM) interpreted as the percent of the total effect (path c) accounted for by the indirect effects (path a1b1 or path a2b2). For the other tests, a p-value of <0.05 was considered statistically significant.Statistical software SPSS, version 23 was use to analysed all data. Continuous variables are presented as the mean (standard deviation), and categorical variables are presented as the percentage . Bivariate correlations were estimated using the Pearson correlation coefficient “r”. Multiple linear regression with univariate and multivariate models were used to estimate PWV, AIx, and distensibility variables. We initially selected clinically relevant variables and known confounders for inclusion in the multivariable regression analysis, and the iterative process of variable selection was performed using stepwise logistic regression analysis. Data for AIx was only available for 128 RA patients. The effect of disease activity degree was assessed by interaction analyses. Interaction terms of the four levels of DAS28  with the variables to be tested were added in the linear regression models. The interaction terms were considered significant when significantly improved the variability of the dependent variable explained by the model. Mediation analysis was used to further understand the association between age and PWV through the use of the Hayes macro-application “PROCESS” for SPSSThe study was approved by the clinical research Ethics Committee of the University Hospital Sant Joan and it was carried out in accordance with our Institution’s guidelines and the Helsinki Declaration. Patients were informed of the research nature of the study and provided written informed consent prior to participationWe included 214 patients with RA in the study. Table Disease-modifying antirheumatic drugs were administered to 75% of the patients which included 20% of patients receiving biological drugs, 57% receiving non-steroidal anti-inflammatory drugs, and/or 51% receiving corticosteroids.2 = 0.32; p < 0.0001). No other variable was associated with PWV. Then we tested the heterogeneity in disease activity degree of our population by interaction analyses between DAS28 and age, SBP, and BMI. When we added the different interaction terms in the model, we observed no significant effects of those terms on the variability of PWV explained by the model  and by BMI (a2b2 indirect pathway). Thus, age was positively associated with SBP (path a1) and with BMI (path a2). Additionally, SBP was also positively associated with PWV (path b1), while BMI was positively associated with PWV (path b2). Bootstrapping analysis revealed a significant indirect effect of age on PWV through SBP ) and through BMI ) as the 95% CI did not cross zero. The total indirect effect ((a1b1) + (a2b2)) was 0.0268,  with a stronger contribution from SBP than from BMI. Combined, both mediators accounted for approximately 28% of the total effect of age (PM = 0.279), with SBP accounting for 21% of the total effect (PM = 0.212) and BMI accounting for 6.7% of the total effect (PM = 0.067). The model also showed a significant direct effect (path c’) of age on PWV indicating that the cumulative mediating effect of SBP and BMI was only partial , as the total effect of age on PWV was reduced (β coefficient changed from 0.096 to 0.069) but remained significant.To further explore the relationships between age, SBP, and BMI with PWV, we performed a parallel mediation analysis Fig. ; Table 32 = 0.056; p < 0.003). Furthermore, stepwise multivariable linear regression analysis showed that age  and TJC  were significantly associated with AIx, accounting for 16.5% of overall AIx variability . No interaction effect of DAS28 on distensibility neither AIx was observed  and sex  were significantly associated with distensibility, accounting for 5.6% of overall distensibility variability  and BMI (7%), while the remaining 72% of the total effect can be attributed exclusively to age. The cumulative mediating effect of these variables is only partial, as the total effect of age on PWV is reduced but remained significant. It is plausible that the negative effect of age on PWV is mediated by increased SBP and BMI as these variables have been shown to independently affect PWV.39. However, the effect of age on PWV, mediated by SBP and BMI, has not been previously described. On the other hand, distensibility is not as well-studied as a marker of arterial stiffness in RA patients26, and the association between BMI and sex observed in our study has not been previously published.As seen in this study, age, SBP, and BMI have been previously identified as independent predictors of arterial stiffness in RA patients42. In any case, in our study, when “NSAIDs treatment” or “corticoids treatment” variables were introduced into the models, there was no significant association with PWV, AIx, or distensibility. Even so, the fact that corticosteroids promote endothelial dysfunction and increase the production of reactive oxygen species42 does not rule out corticosteroids as possible negative effectors of arterial stiffness. Studies designed with this objective would be necessary to better evaluate the effect of these treatments on arterial stiffness.Treatment with NSAIDs or corticoids to which our patients are subjected, may affect the associations found in our study. In fact, it has been previously described that NSAIDs and corticosteroids are associated with arterial stiffness45 but in contrast with others22. These discrepancies might be attributed to the different levels of inflammatory biomarkers profiled and to the relatively short mean disease duration of nine years within our cohort.Additionally, we observed no significant association between inflammatory variables , disease activity or disease duration and arterial stiffness . This is in agreement with previous studies39, but in our study as in others19, no association was found with lipid profiles. Therefore, static measurements of classical lipid values might not be sufficient to generate clinically useful information until more advanced measures are utilized .High cholesterol levels have been associated with reduced arterial elasticity30, we showed that age was associated with cIMT and plaque presence. In the same way, age has been the variable more associated with arterial stiffness in the present study showing the importance of this variable in the development of atherosclerotic process. On the other hand, in our previous study, we also observed an age-gender interaction effect on cIMT, which has not been observed in the present study on arterial stiffness. Furthermore, in the previous report, DAS28 was associated with an increase in cIMT in women but in the present study, we did not find any association of arterial stiffness with RA disease severity. These differences show that although cIMT and PWV are markers of early arterial wall alteration, the remodeling process of the arterial wall is still incompletely understood in RA patients. Furthermore, PWV and AIx have been independently associated with cIMT and plaque presence in RA patients31, an observation that has not been detected in the present study. Moreover, other studies failed to find this association, and the question of whether arterial stiffness augments cardiovascular risk by increasing atherosclerosis remains unclear32.In a previous study with this populationOur study has some limitations: its cross-sectional nature do not allow us to draw any conclusion about the causal relation between PWV, distensibility, and AIx and atherosclerosis. Furthermore, the selection of our RA patients are regional focus, so the results might be too population-specific and difficult to generalize across other populations. Thus, larger series with measures of atherosclerosis and with follow-up would be needed to confirm a clinical relevance of an increase in PWV and AIx regarding CV risk in our RA patients.In conclusion, the results of this study demonstrate that in patients with RA, age is the most important variable for determining the increase in PWV. We also found that a significant proportion of the negative effect of age on PWV occurs through an increase in SBP and BMI. Finally, we found no association between lipid or inflammation variables with an increase in arterial stiffness.Supplemental information


Dexmedetomidine infusion improves oxygenation and lung mechanics in patients with chronic obstructive lung disease; however, its effect in patients with restrictive lung disease has not been thoroughly investigated yet. The aim of this work was to evaluate the effects of dexmedetomidine infusion on oxygenation and lung mechanics in morbidly obese patients with restrictive lung disease.2/fraction of inspired oxygen (FiO2)}, lung compliance, dead space, plateau pressure, blood pressure, and heart rate.Forty-two morbidly obese patients scheduled for bariatric surgery were included in the study. Patients were randomized to receive either dexmedetomidine infusion at a bolus dose of 1mcg/Kg followed by infusion at 1 mcg/Kg/hour for 90 min (Dexmedetomidine group), or normal saline infusion (Control group). Both groups were compared with regard to: oxygenation {P/F ratio: PaO2/FiO2 ratio, and higher lung compliance compared to control group by the end of drug infusion. Dexmedetomidine group demonstrated decreased dead space, plateau pressure, blood pressure, and heart rate compared to control group by the end of drug infusion.Dexmedetomidine group showed significant improvement of the PaOA 90-min dexmedetomidine infusion resulted in moderate improvement in oxygenation and lung mechanics in morbidly obese patients with restrictive lung disease.clinicaltrials.gov: NCT02843698 on 20 July 2016. Dexmedetomidine is a selective α − 2 agonist with various clinical uses in both anesthesia and intensive care unit. In addition to its sedative and cardiovascular effects, dexmedetomidine has favourable respiratory effects in animals , 2, and In restrictive lung disease, the possible effect of dexmedetomidine was not well investigated in humans. In an animal model of experimental obesity, dexmedetomidine administration showed better morphological and functional lung characteristics compared to propofol ; thus, wtrials.gov registry system on 20 July 2016 (NCT02843698). A written informed consent was obtained from participants before recruitment. Patients were randomized according to an online random number generator. Concealment was achieved using sealed opaque envelopes.A randomized controlled double-blinded study was conducted in Cairo university hospital after institutional board review approval (N − 12-2016) on 24 December 2016. The study was registered at clinical.2} with restrictive lung disease {diagnosed by pulmonary function tests: forced vital capacity (FVC) < 70%}, scheduled for laparoscopic sleeve gastrectomy. Exclusion criteria were: heart failure, arrhythmias, severe liver or kidney impairment. Patients with forced expiratory volume in 1 sec (FEV1)/FVC < 70% were also excluded.The study included 42 morbidly obese patients {with body mass index (BMI) above 40 Kg/m2}, {Women: (1.07 weight) - (148 (weight/height)2} [2 of 40%. Intravenous paracetamol (2 g) and Ketorolac (40 mg) was administered before the end of surgery.Upon arrival at the operating room, patients were pre-medicated with metoclopramide (10 mg) and ranitidine (50 mg). Basic monitors were applied {electrocardiogram (ECG), non-invasive blood pressure monitor, capnography and pulse oximetry}. Drug dosing was calculated using lean body weight for all drugs except neostigmine  . LBW waseight)2} . Anesthe2O, and respiratory rate adopted to maintain end-tidal CO2 between 30 and 35 mmHg [Patients were mechanically ventilated using Maquet (Flow-i) anesthesia machine. Our ventilatory management included: volume controlled ventilation, low tidal volume (6-8 ml/Kg LBW), positive end expiratory pressure (PEEP) 8–10 mmH 35 mmHg . No recrn = 21): received dexmedetomidine  in a dose of (1μg/Kg LBW) bolus 15-min after endotracheal intubation, followed by 0.5μg/Kg/hour continuous infusion for 90 min. 2- Control group (n = 21): received 1 mL normal saline followed by continuous normal saline infusion for 90 min. The study drug was prepared and the infusion rate was calculated by a research assistant to ensure blinding of the investigator.Patients were randomly allocated into our double-blinded study using computer generated sequence into two groups: 1- Dexmedetomidine group  and atropine (0.02 mg/Kg), then patient was extubated. In the post anesthesia care unit (PACU), patient was monitored by basic monitors . Patients with oxygen saturation less than 88% on 6-l oxygen mask were admitted to the intensive care unit.2–EtCO2)/PaCO2–0.005.Dynamic lung compliance was calculated using Maquet anesthesia machine as: tidal volume/ (peak airway pressure - PEEP). Static lung compliance was calculated as: Tidal volume/ (plateau pressure - PEEP). Plateau pressure was calculated by increasing the end-inspiratory pause to 30–40%. Physiological dead space was calculated by Hardman & Aitkenhead equation : Vd/Vt =2/Fraction of inspired oxygen).Oxygenation by the end study drug infusion .Intraoperative oxygenation, lung compliance (static and dynamic), dead space (Vd/VT), and PaCOHeart rate, Systolic blood pressure (SBP), diastolic blood pressure (DBP), and plateau airway pressure .Demographic data (age – gender - BMI – smoking – comorbidities), operative data , the need for postoperative ICU, the need for postoperative mechanical ventilation, postoperative complications, and Pasero opioid-induced sedation scale .The change in each of P/F ratio and dynamic lung compliance Δ dead space (%): dead space by the end of the study drug infusion – dead space at the baseline/dead space by the end of the study drug infusion %).In a pilot study on 10 patients, we reported an intraoperative P/F ratio of 310 ± 32 in morbidly obese patients undergoing bariatric operations. Using MedCalc Software version 14.10.2 , we calculated a conservative sample size that could detect 10% difference in P/F ratio (i.e. 31) between the two study groups. A minimum number of 36 patients (18 patients per group) was calculated to have a study power of 80% and alpha error of 0.05. The number was increased to 41 patients (21 patients per group) to compensate for possible drop-outs.P value less than 0.05 was considered statistically significant.Statistical package for social science (SPSS) software, version 15 for Microsoft Windows  was used for data analysis. Categorical data (incidences of complications and comorbidities) were presented as frequency (%) and analysed by chi square test. Continuous data were checked for normality using Shapiro-Wilk test and was presented as mean (standard deviation) or median (interquartile range) as appropriate. Continuous data  were analysed using unpaired t test or Mann Whitney as appropriate. Repeated measures  were analysed using analysis of variance (ANOVA) for repeated measures with post-hoc pairwise comparisons using the Boneferroni test. A P = 0.046)  Table .Fig. 1Pa2O− 1 Vs 34.6 (5) mL cmH2O− 1, P = 0.004}, and 90 min {44.5 (9) mL cmH2O− 1 Vs 34.5 (6) mL cmH2O− 1, P < 0.001}, in addition to higher Δ dynamic lung compliance {4 (4) mL cmH2O− 1 versus − 1 (4) mL cmH2O− 1, P = 0 < 0.001} (Table 2O− 1 Vs 45 (11) mL cmH2O− 1, P = 0.01}; whilst, both groups showed comparable static lung compliance at other time points  mL cmHP = 0.01}  experienced postoperative hypoxia in the PACU that needed ICU admission. Although there was no significant difference between both study groups regarding postoperative ICU need, we could not generalize this finding because our study was not powered enough to judge it.Our study had some limitations. First: we used only one dose of dexmedetomidine for 90 min. This was because we considered our study as an exploratory study for the effect of dexmedetomidine in this population. Based on our results, we recommend more studies to investigate whether these effects could differ with different doses and with longer infusion duration. Second: the use of Hardman & Aitkenhead equation for calculation of physiological dead space; this was because volumetric capnography was not available in our unit. Third: We did not use lung recruitment manoeuvres; this was based what Defresne et al. had reported in morbidly obese patients during laparoscopic gastric bypass surgery .A 90-min dexmedetomidine infusion resulted in moderate improvement in oxygenation and lung mechanics in morbidly obese patients with restrictive lung disease.


Background: As much as 20% of all cases of hypertension are associated with kidney malfunctions. We have previously demonstrated in animals and in pediatric patients that hydronephrosis causes hypertension, which was attenuated by surgical relief of the ureteropelvic junction (UPJ) obstruction. This retrospective cohort study aimed to investigate: (1) the proposed link between hydronephrosis, due to UPJ obstruction, and elevated arterial pressure in adults; and (2) if elevated blood pressure in patients with hydronephrosis might be another indication for surgery.Materials and methods: Medical records of 212 patients undergoing surgical management of hydronephrosis, due to UPJ obstruction, between 2000 and 2016 were assessed. After excluding patients with confounding conditions and treatments, paired arterial pressures (i.e. before/after surgery) were compared in 49 patients . Split renal function was evaluated by using mercaptoacetyltriglycine (MAG3) renography before surgical management of the hydronephrotic kidney.Results: Systolic , diastolic , and mean arterial  pressures were significantly reduced after relief of the obstruction (p < 0.001). Split renal function of the hydronephrotic kidney was 39% (95% CI 37–41). No correlations were found between MAG3 and blood pressure level before surgery or between MAG3 and the reduction of blood pressure after surgical management of the UPJ obstruction.Conclusions: In adults with hydronephrosis, blood pressure was reduced following relief of the obstruction. Our findings suggest that elevated arterial pressure should be taken into account as an indication to surgically correct hydronephrosis. Cardiovascular disease, including hypertension ≥140/90 mmHg) is a major health problem, associated with increased morbidity and mortality. Secondary forms of hypertension are found in 5–20% of the hypertensive population, and most of these cases can be linked to renal abnormalities ,4.0/90 mmHgThe treatment of symptomatic ureteropelvic junction (UPJ) obstruction is surgical. It has been shown that the function of the hydronephrotic kidney is rather well preserved in young children . Based oPrevious experimental studies in animals have demonstrated that hydronephrosis, due to chronic partial unilateral ureteral obstruction, is linked to the development of renal injuries and hypertension . MoreoveWe studied the medical records and hospital charts of 212 patients with hydronephrosis, due to congenital UPJ, who were operated between 2000 and 2016 at the Urology Department of Uppsala University Hospital . All patn = 37; 76%), and to a lesser extent it was due to inflammation and fibrosis  and pelviureteral junction stricture . We included those blood pressure measurements when the patients were not in an acute situation nor in pain for any reason, even before temporary treatment with nephropyelostomy catheter or double J-stent. The same method of blood pressure monitoring (i.e. office) was used for all patients, and it was consistent in terms of location and time of the day (i.e. daytime). The procedure for all included patients was office blood pressure measurements during non-stressed situations and in the absence of any acute pain. We performed previously a similar study in which we included two control groups, i.e. one healthy not operated group and one healthy operated group and found no effects of preoperative stress on the blood pressure in patients with hydronephrosis , who were not treated with antihypertensive drugs, and with available arterial pressure values before and after surgical management of the hydronephrosis , Table 2ephrosis . MoreoveTwenty-five (52%) of these patients had right side hydronephrosis. Thirty-eight patients were operated by laparoscopic pyeloplasty, while nine patients were operated by robot-assisted pyeloplasty, and one patient underwent open surgery. The patients’ age at the time of surgery ranged from 16 to 71 years, and 24 (49%) of them were males.Renal obstruction was relieved temporarily before pyeloplasty with a double J-stent and/or percutaneous nephropyelostomy in 40 patients. The duration of this preoperative relief of obstruction ranged between two weeks and one year. Nephrostomy was performed preoperatively due to acute pain during the period the patient was waiting for the pyeloplastic surgery. Pre-relief arterial pressure was measured one day to one year before temporary relief of obstruction in these 40 patients, while pre-relief arterial pressure for the rest of patients was measured one day before pyeloplastic surgery. Post-relief arterial pressures were measured between two weeks to two years after relief of obstruction.Seven (14.3%) of the investigated 49 patients had recurrent UPJ obstruction after pyeloplasty, but in the total population the recurrence frequency was 6.6% (14 of 212 patients). Three of these had undergone robotic pyeloplasty, while four relapses occurred after laparoscopic pyeloplasty . Four ofAs a part of the routine management, preoperative evaluations of bilateral renal function were carried out using mercaptoacetyltriglycine (MAG3) renography with forced diuresis. This examination was performed in a standardized fashion. In nine patients the preoperative MAG3 renography was substituted with computed tomography (CT) urography, which has been proven an accurate and useful non-invasive imaging technique for the surgical planning (treatment) of UPJ obstruction .p values are indicated, and p < 0.05 denotes statistical significance.Non-parametric Kruskal–Wallis test, followed by Dunn’s test, was used for multiple comparisons among groups. Matched blood pressure values (before and after relief) were analyzed by non-parametric Wilcoxon test (i.e. matched-pairs signed rank test). Linear regression analysis (least squares ordinary fit) was used to compare age-grouped populations . Computed p values <0.001 for all variables)  were higher before surgical management of UPJ . After eriables) .n = 5), pre and post relief, showed significant reduction of systolic  and MAP , whereas diastolic pressure was not significantly reduced .As mentioned above, seven patients had recurrence of UPJ stenosis 2–4 months after surgical management of the hydronephrosis and were thus re-operated . AnalysiP = 0.08)  .Finally, a long follow-up period before reassessing blood pressure after surgery may influence the interpretation of the surgical intervention. In our study the shortest duration before obtaining post-relief values was 0.5 month, and the longest duration was 30 months. We stratified the blood pressure data based on the duration of the follow-up period. Linear regression analysis did not show any significant correlation between the length of the postoperative period and the change in arterial pressure . When seSupplementary Figure S1(A–C), available online). In addition, there was no correlation between the changes in systolic, diastolic, or MAP following surgery and MAG3 , available online). Further analysis, following separation by age groups (≤30 and >30 years of age) at the time of surgical management did also not reveal any significant correlations between reduction of blood pressure and MAG3 , available online).Linear regression analysis did not reveal any correlation between systolic, diastolic, or MAP before surgery and the split renal function of the hydronephrotic kidney (MAG3) , there are currently only three clinical studies that have investigated the effects of surgical relief of the obstruction on arterial pressure. The first study by de Waard et al. was a retrospective investigation that suggested reduction of arterial pressure after surgical management of dilated or obstructed upper urinary tracts . The secn = 212) that were operated in Uppsala University Hospital between 2000 and 2016, but in the final analysis only those patients with unilateral hydronephrosis due to UPJ obstruction that were not previously on antihypertensive therapy and had no underlying chronic disease were included. The exclusion of patients already on medication was made since the relationship (if any) between hydronephrosis and hypertension in such patients is difficult to evaluate. Moreover, it is very difficult to evaluate the short-term effect of obstruction relief on blood pressure if the patients are already on continuous antihypertensive treatment. We find it unlikely that this exclusion biases the results in a way that invalidates the conclusions made in this study. Of note, none of the patients included in this study initiated antihypertensive treatment after surgery or developed any other diseases before post-relief values were obtained. Life style questionnaires do not exist so we cannot exclude changes in their dietary habits or physical activity. However, no changes in BMI were observed between the pre- and post-relief examination.In the current study, we scrutinized all hydronephrotic patients , and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


The aim of this report is to describe a new device that can validate, by automated auscultation, individual blood pressure (BP) readings taken by automated sphygmomanometers.The Accutension Stetho utilizes a smartphone application in conjunction with a specially designed stethoscope that interfaces directly into the smartphone via the earphone jack. The Korotkoff sounds are recorded by the application and are analyzed by the operator on the screen of the smartphone simultaneously with the images from the sphygmomanometer screen during BP estimation. Current auscultatory validation standards require at least 85 subjects and strict statistical criteria for passage. A device that passes can make no guarantee of accuracy on individual patients. The Accutension Stetho is an inexpensive smartphone/stethoscope kit combination that estimates precise BP values by auscultation to confirm the accuracy of an automated sphygmomanometer’s readings on individual patients. This should be of great value for both professional and, in certain circumstances, self-measurement BP. Patients will avoid both unnecessary treatment and errors of underestimation of BP, in which the patient requires therapy. The Stetho’s software has been validated in an independent ANSI/AAMI/ISO standard study. The Stetho has been shown to perform without difficulty in multiple deflation-based devices by many manufacturers. Data from the Centers for Disease Control demonstrate that at least 67 million American adults have high blood pressure (BP) . The diaThe Accutension Stetho is a novel device that operates by use of a smartphone application and an inexpensive (<$30 U.S.) kit containing a specially designed stethoscope and required connectors. This report will describe the design and operation of this device.The Accutension Stetho comes as a kit for the automated auscultatory calibration of automated sphygmomanometer (BPM) readings. The initial step is to download the “Accutension Stetho” app to a smartphone. The app contains detailed instructions/diagrams for ease of use.Figure Figure Figure The BPM reading for an individual cycle is then compared to the reading estimated by the Accutension Stetho software. Because the Accutension detection system is by auscultation, the value will be virtually identical to the value that would have been recorded by a trained observer performing the ANSI/AAMI/ISO validation procedure . A shortA recent publication by Chu et al.  reportedA possible limitation of the Accutension Stetho is whether it will function accurately with automated BPMs currently marketed. Table Automated sphygmomanometers most commonly utilize oscillometric technology. By passing the ANSI/AAMI/ISO Standard testing  the deviThe Accutension Stetho cannot, of course, correct for errors made by the medical personnel or the patient with respect to factors such as cuff size, failure to rest prior to initiating a reading, lack of arm and/or back support, etc.The routine use of the Stetho device to ensure the accuracy of automated sphygmomanometers will improve clinical care in two ways: (1) avoiding treatment, and its possible side effects, in patients whose BP is incorrectly estimated by an automated device to be elevated, when, in fact, it is normal; (2) giving needed treatment to patients in whom the BP is incorrectly estimated by an automated device to be normal, when, in fact, it is elevated.Automated blood pressure estimation now the most commonly used methodologyIndividual blood pressure devices validated to be accurate on large populationsProprietary algorithms in use do not ensure accuracy for individual patientsNew smartphone app with digital stethoscope available to do automated auscultation to validate blood pressure monitor readings on individual patientsNew device critical in both clinical care for diagnosis and therapy and in research populationsDevice inexpensive and can be used by patients themselvesstetho.mp4


Breathing retraining techniques have received increased attention in the management of asthma, because there is growing evidence of the usefulness of such methods in improving quality of life, reducing symptoms and reducing bronchodilator use. Our study investigated the effect of anthroposophic therapeutic speech (ATS), which uses sounds and syllabic rhythm to improve articulation, breathing and cardiorespiratory interaction, in patients with asthma in a real-life outpatient setting.In a randomised controlled crossover trial, patients with asthma in three centres in Switzerland and Germany were randomised to either receive 11 ATS sessions or to wait. Subsequently, patients changed either to wait or to receive ATS. Primary outcomes were changes from the beginning to the end of each phase in the Asthma Quality of Life Questionnaire (AQLQ) and spirometry parameters. Secondary outcomes were changes in inhaled glucocorticoids, the Asthma Control Test (ACT), peak flow and asthma exacerbations.d = 0.86, p = 0.001) and the domain scores for symptoms, activity limitation and emotional function as well as ACT score . No significant differences were observed in spirometry parameters, inhaled glucocorticoids, peak flow and days without asthma exacerbation per week. No serious adverse events occurred during ATS sessions.Altogether, 63 patients were randomised, of which 56 were enrolled and 49 completed the study. Statistically significant differences between the ATS groups and waiting control groups were found for the overall AQLQ score  contains supplementary material, which is available to authorized users. Breathing retraining techniques have received increased attention in the management of asthma, because there is growing evidence for the safety and usefulness of such methods. The Global Initiative for Asthma (GINA) reports evidence level B for the breathing techniques adjuvant to pharmacotherapy , and the2, breathing rate and predicted forced expiratory volume for the experimental group versus no additional treatment. The effects continued for 5 months, during which time patients practised the breathing behaviour learned in the training programme [Physiotherapist-guided breathing programmes such as the Papworth method and the Buteyko method are the most systematically investigated and also yield the best evidence for effectiveness. The breathing programmes aim to reduce hyperventilation, strengthen nasal and diaphragmatic breathing, and reduce respiratory rate and minute volume . The mosrogramme , 6, 7.Active breathing modulation techniques are frequently considered to be complementary medicine (CM) . Even ifAmong holistic CM systems, anthroposophically extended medicine (AEM) is a well-integrated approach practised in both inpatient and outpatient settings by medical doctors and certified therapists. Currently, an AEM service is available in more than 50 countries . AEM proOur study is the first to investigate the effects of ATS in patients with asthma in real-life outpatient settings. Based on our clinical experience, we assumed that 3 months of ATS including weekly training with a therapist and practising at home, would improve quality of life, asthma control and lung function. In particular, the following hypotheses were tested: (i) ATS improves asthma control and quality of life in patients with asthma, (ii) ATS improves relevant parameters of pulmonary function in patients with asthma and (iii) ATS reduces the application of reliever medications (used as needed) in patients with asthma.clinicaltrials.gov (NCT02501824), because when the trial was planned, the registration of non-pharmacological trials was not required in Switzerland. A Consolidated Standards of Reporting Trials (CONSORT) checklist is included in Additional file The study was carried out as a randomised controlled multi-centre two-period crossover exploratory clinical trial conducted at three centres in Switzerland and Germany between October 2010 and August 2014. The trial was approved by the relevant ethical committees . It was registered post-interventions on 8 July 2015 on Participants were randomly assigned in a 1:1 allocation ratio to either receive 11 ATS sessions (one per week intended) or to wait (control). The patients were diagnosed and informed about the trial by the participating pneumologists. Patients interested in participating were referred to the study therapist, to receive and discuss an information sheet prior to providing written informed consent. The original study protocol included 11 conversation sessions with the same therapist as a control intervention. The protocol had to be modified after the third patient, as the patients were not complying with the 11 sessions of the control intervention, i.e. the conversations with the therapist. The conversation sessions were replaced by a waiting phase after approval from the ethical committee.Blinding of the patients, therapists and physicians was not possible due to the nature of the intervention. Blinding of the statistician, who was part of the study team and had access to the primary data, was not attempted.2 agonist more than once per week and signed an informed consent form (or signed by a parent for a minor) prior to the beginning of the interventions. The diagnosis of asthma was made according to the current American Thoracic Society/European Respiratory Society recommendations [Inclusion criteria were: 12 years or older, bronchial asthma for at least 1 year, inhaled a βndations . Asthma Exclusion criteria were: severe systemic illness, coronary heart disease, severe chronic obstructive pulmonary disease, insufficient general condition to participate in an active therapy, pregnancy and current use of oral corticosteroids.Interventions were administered in an outpatient centre  and in the pneumology units of two clinics for mainstream medicine and AEM . Each participant was seen one-to-one by the same certified therapist for all training sessions and asked to practise for at least three times a week. ATS therapists have received full-time training in speech, drama and ATS for 4 years.The training programme for each patient consisted of 10 frequently applied ATS exercises, which comprise spoken sound combinations of syllables (e.g. “Wwwwww-T” / “OM”) and rhyme (e.g. six lines of hexameter in German), adapted to the patient’s individual needs.The primary outcome measures were changes in AQLQ scores  and spirSecondary outcomes were changes in inhaled glucocorticoids (in μg) per week, ACT score , peak flTo calculate changes in the outcome parameters, baseline values  were subtracted from the values at the end of each phase. This was justified by the high correlation (>0.5) between baseline and outcome values .d = 0.5), and set a power of 0.8 and α = 0.05. For paired data, n = 34 would be sufficient to detect a significant difference. Allowing for dropouts, we determined a sample size of 50 patients to finally reach n ≥ 34 for data analysis.No study on ATS in asthma patients was available as a basis to determine the sample size. We assumed a median effect size . The random allocation sequence was generated by the statistician and managed by one therapist. Eligible patients were assigned to the two groups prior to the first information session with the therapist at which the informed consent had to be signed. The therapists enrolled the patients.p < 0.05 was considered statistically significant, and since this was an exploratory study, no adjustment for multiple comparisons was calculated. All tests were two-tailed. When within-patient differences were normally distributed (as for most primary endpoints), the dependent t-test was used to compare the two phases. For non-normally distributed endpoints, the Wilcoxon signed-rank test was applied. Missing data were not estimated.Analyses were performed using IBM SPSS Statistics for Windows, Version 23.0 . Normality of within-patient differences was verified using the Shapiro–Wilk test. Additionally, the same analysis was performed including only patients for which all data were available and whose medication intake was in accordance with the study protocol .Altogether, 63 patients with asthma were randomised, of which 56 were enrolled  and 49 (87.5%) completed the study Fig. . The basTable p = 0.015, p = 0.007 and p = 0.025, respectively). No significant changes were found in spirometry parameters (p(FEV1) = 0.631, p(FVC) = 0.961 and p(FEV1/FVC) = 0.889). The changes in the ACT score were no longer significant (p = 0.121).In addition, a per protocol analysis with 24 patients was performed, with similar results as in the intention-to-treat analysis. Statistically significant differences between the two phases were observed for the overall AQLQ score, activity limitation and emotional function  (e.g. “I can’t practise when my partner is there”), worsening of condition during the waiting phase (5), high effort required to participate in the study (2), ATS phase too short to profit from the therapy (2), difficulty in connecting with the German language (1), hoarseness (1), headache (1), and cramping in the abdomen during one exercise (1). The therapists noted 20 minor adverse events in 14 patients. These included difficulties in performing the exercises (8), coughing (5) or a tickle in the throat (4), and hoarseness (3).Of our three hypotheses, one was confirmed: ATS significantly improved asthma control and quality of life in patients with asthma. The AQLQ score rose by 0.56 points, 0.5 points being considered the minimal clinically important difference . The ACTThe baseline median ACT score of 18 points (<19) in our population as well as the median FEV1/FVC of 69% (<75%) indicated that asthma was not well controlled by our participants . After AAll patients were regularly seen by a pneumologist and took conventional medication. However, we observed a low adherence to medication in some patients. These patients were excluded in a subsequent per protocol analysis, which gave similar results as the primary analysis. Low adherence has been observed in other investigations, too . A populIt is known that objective measures in the treatment of asthma only weakly to moderately correlate with how patients actually feel and are able to function in daily life. Thus, improvements in health-related quality of life may be rated more important than spirometry values, and they may be complementary outcomes .The systematic review by Burgess et al.  identifiWhether ATS improves lung function remains to be shown. ATS uses elements of language readily available to every speaking person and modifies the depth, rhythm and duration of exhalation by means of sound and syllable combinations. The awareness of patients during therapy is shifted from respiration to voice and articulation. Asthma impairs perceptual voice quality, maximum phonation time, frequency and amplitude perturbation parameters . Thus, iKeeping in mind that we performed a total of 539 individual therapy sessions in the trial, side effects occurred only rarely. The physical symptoms seen, e.g. coughing, may occur in all voice therapies and could be dealt with accordingly. Adverse events during the waiting phase were not systematically recorded, and thus a comparison between the two phases was not possible.Some patients’ asthma symptoms increased during spring due to the higher pollen count or during winter due to infections of the upper respiratory tract. We recruited patients during all seasons to distribute these influences evenly.In planning this real-life study, we faced several methodological issues. Blinding of the patients was not possible, since ATS requires the active participation of the patients, which is a limitation of this study. Many patients were reluctant to be randomly assigned to a control group without receiving the test therapy, i.e. speech therapy. Thus, a parallel-group design with sufficient power was not feasible. Performing a crossover trial allowed all participants to receive therapy, though dropouts, trends and carryover effects would represent general difficulties in the analysis. In this trial, dropouts only occurred in the ATS phase, mostly due to reasons unrelated to the therapy . Context and meaning effects (e.g. patients’ expectations and monitoring of peak flow and medication intake) may have contributed to this finding. However, the study design does not allow us to discern if this effect continued during the second phase. In the group performing ATS first, AQLQ scores did not drop significantly during the subsequent waiting phase Fig. , suggestOn average, the patients participating in the trial experienced a positive outcome in asthma-related quality of life and asthma control, which continued after the crossover to the waiting phase. However, this carryover effect hampered our statistical analysis of the trial and reduced the practical advantages of the crossover study design. Thus, compliance and trial-design conflicts should be considered carefully in future studies of ATS. Researchers may also consider a longer treatment period and more intense regular practice at home.Breathing exercises are the most commonly used CM method for patients with asthma. In this randomised controlled crossover trial, we were able to demonstrate that ATS significantly improves asthma control and quality of life in patients with poorly controlled asthma. The side effects of ATS were only minor and occurred rarely. Whether ATS also improves lung function remains to be shown. In future trials, a longer treatment period and more intense regular practice at home may be considered.Additional file 1:CONSORT 2010 checklist of information to include when reporting a randomised trial. (PDF 57 kb)


Breast cancer is the most frequently diagnosed malignancy in women, and comorbidities like hypertension and obesity diminish their quality of life and negatively affect their response to chemotherapy. Furthermore, inulin supplementation is associated with the reduction of cardiovascular diseases (CVD) risk. To determine whether inulin supplementation prevents the elevation of blood pressure in women with breast cancer undergoing neoadjuvant therapy with cyclophosphamide and doxorubicin. This was a randomized, double-blind placebo controlled trial which included women with early-stage breast cancer undergoing neoadjuvant therapy (n=38). Patients were randomly assigned to participate in two different groups to receive either 15 g of inulin or 15 g of placebo  for 21 days. Body composition and blood pressure were evaluated before and after the supplementation period. p<0.001). However, SBP increased in the placebo supplemented group. Diastolic blood pressure (DBP) nonsignificantly decreased in the inulin group. Inulin supplementation also increased BMI (p<0.001) but reduced BFP (p=0.288). Furthermore, confounding variables, such as BMI, baseline fasting glucose, age, menopause status, vomiting, constipation, and chronic medication did not have a statistical influence over the inulin effect on SBP. Women in the inulin group showed a lower systolic blood pressure (SBP) after the supplementation (-4.21 mmHg, Inulin supplementation reduces SBP and prevents increases in DBP in women with breast cancer. This could be an innovative nutraceutical approach to prevent hypertension present in women with this type of cancer at an early stage and may improve the quality of life of the patients and their prognostic development through chemotherapy.ACTRN12616001532493. This trial is registered with  Hypertension is the comorbidity associated with breast cancer with the highest prevalence 21.8%), which is followed by chronic pulmonary obstruction (19.9%) and diabetes mellitus 16.7%) .8%, whic. The use2 , 5. In a.7% .8%, The origin of hypertension in patients with cancer is not clear; it could appear before cancer diagnosis or after that. For instance, women who used antihypertensive medications have an increased risk of breast cancer . Also, cDiet components can play a regulatory role in the development of hypertension as well. Particularly, some vegetables contain fiber and prebiotics that modulate blood pressure, preventing the appearance of hypertension . For insPrebiotics provide a variety of health benefits like the ability to increase concentrations of vitamin B and plasma glutamine, which could improve immune function . In part2/ 60mg/m2), by infusion, as part of the medical scheme established in the State Cancer Center. Patients were randomly assigned to participate in two different groups to receive 15 g of powdered agave inulin  or 15 g of maltodextrin  as a placebo. Both products were supplied in sealed packages and previously codified by trained personnel in the Molecular Biology Laboratory of the Medical Sciences Research Center (CICMED) in Toluca, State of Mexico. Once participants were assigned to one of the two groups, they were provided with 21 packages according to their respective group. After that, patients from both groups were asked to dissolve the contents of an envelope in 240 mL of drinking water, to be consumed during the breakfast. Patients initiated the ingestion of the supplement on the same day that the first cycle of chemotherapy started, and they kept taking the respective supplement for 21 days. The study was conducted in accordance with the Declaration of Helsinki and the Mexican Legislation on Scientific Research in Humans; also, the study was registered in the Australian New Zealand Clinical Trials Registry with number ACTRN12616001532493, on November 7, 2016. The protocol was approved by the Ethics Committees of the ISSEMYM State Oncology Center and the School of Medicine of the Autonomous University of the State of Mexico. Written informed consent from each participant was obtained once every patient accepted to be included in the study.A randomized, double-blind trial was conducted, involving women (n=38) diagnosed with breast cancer at early stage, beneficiaries of the State Oncology Center of the Social Security Institute of the State of Mexico and Municipalities (ISSEMYM). The inclusion criteria were women aged >18 years and planned to receive neoadjuvant chemotherapy with doxorubicin and cyclophosphamide for the first time. The participants received a standard chemotherapeutic treatment, with cyclophosphamide and doxorubicin . This analysis included body weight, body mass index (BMI), body fat percentage (BFP), lean body mass (LBM), and skeletal muscle mass (SMM), and it was conducted three hours after eating or drinking. To perform the measurement, patients were barefoot and stood on a platform at a 90° position facing ahead, holding both handles of the apparatus until the impedance scan finished and the analysis results were printed. Moreover, blood pressure was measured before and after supplementation (at the end of the 21 days). The procedure to measure blood pressure was performed according to the Official Mexican Norm for prevention, detection, diagnosis, treatment, and control of systemic arterial hypertension (NOM-030-SSA2-2009). Once systolic blood pressure (SBP), diastolic blood pressure (DBP), arterial mean pressure (MAP), and hear rate (HR) were measured, the results were compared between both study groups, before and after the supplementation period. HR was computed as the number of beats in 15 seconds by four, and it was expressed as beats per minute (bpm). The classification of patients according to blood pressure recordings was performed using the criteria established by the American College of Cardiology and the American Association of Hypertension. BMI and BFP classification was conducted according to the criteria established by World Health Organization (WHO) and to Bray G, et al. .Diet information and clinical data of renal function (urea and creatinine concentrations) were extracted from medical records in the State Oncology Center; the data corresponded to results from laboratory tests that were performed prior the beginning of the chemotherapy cycles. Furthermore, it is important to point out that, before starting chemotherapy, adequate renal and hepatic functions were verified in all participants. Regarding that, creatinine clearance was calculated with the Cockcroft-Gault equation. Dietary data were collected by the nutrition department, through an institutional questionnaire of habitual diet; the consumption was reported in equivalent measures according to the Mexican System of Equivalent Foods . In addiThe normality of SBP, DPB, MAP, HR, BMI, and BFP was assessed by the Kolmogorov-Smirnov test. Chi-square test was used to compare frequencies of blood pressure and body composition categories before and after supplementation between placebo and inulin groups. Measures of central tendency were obtained, and the effect size for each variable by group was computed as follows: (mean before supplementation - mean after supplementation)/ standard deviation. To identify significant mean differences between placebo and inulin groups a Student t-test was performed. Also, Mantel-Haenszel test was used to rule out the effect of confounders factors on blood pressure. All tests were performed in the statistical software SPSS 21, considering a significance level of 0.05.p=0.646).The original sample  included (p=0.123). There were 3 women with ductal carcinoma and DBP >90 mmHg, but there were no women with lobular carcinoma and this level of DBP. Women with ductal carcinoma (n=10) presented a higher frequency of elevated MAP (>102.2) than those with lobular carcinoma (n=3). Nonetheless, only one patient with ductal carcinoma presented with an elevated HR (>100.1 BPM). In addition, patients were classified according to their BMI; they were grouped into the following categories: underweight (n=2), overweight (n=15), and obesity (n=11) in both study groups. Most of the participants showed a high BFP . The frequency was higher in the ductal carcinoma group.Moreover, the frequencies of women under placebo and inulin supplementation with high or low blood pressure, HR, BMI, and BFP are shown in  p<0.001), DBP , MAP , and HR  increased significantly, but BMI  and BFP decreased  after supplementation. Nonetheless, in the inulin group, SBP  and HR  decreased significantly. DBP in the inulin supplemented group increased as that in the placebo group did , but the increase in MAP  was not as high as the placebo group. Cohen's d values were lower in the inulin group than the placebo group for SBP (-0.27), DBP (0.18), MAP (0.11), and HR (-0.01). Effect size was determined by Cohen's d test and it revealed that inulin supplementation generated a small effect size (d<0.5) in SBP, DBP, MAP, HR, BMI, BFP, LBM, and SMM; nonetheless, supplementation in the placebo group exerted a medium size effect (d=0.75). Furthermore, inulin supplementation produced a significant increase in BMI  with a nonsignificant loss of BFP . There was also an increase in LBM  and a minimum change in SMM  after 21 days of inulin supplementation, but they were not statistically significant.In p=0.336), BMI (p=0.910), BFP (p=0.054), menopause status (p=0.280), tobacco use (p=0.456), general use of chronic medication (p=0.520), use of antihypertensive medications (p=0.874), vomiting presence (p=0.511), and constipation (p=0.483).In addition, the Mantel-Haenszel test was applied to assess whether confounding variables could influence inulin supplementation net effect. The analysis showed that any of the following variables had a significant influence on the reduction of blood pressure by inulin supplementation: age  of the patients had a normal energy intake, 24.1% (n=7) had a low intake, and 31.0% (n=9) had a high intake; however, this is not a direct indicator of quality of the diet. Moreover, the presence of nausea and vomiting in the placebo group was 13.2% (n=5) at baseline and 23.7% (n=9) after the supplementation period. In the inulin group, the frequencies were 10.5% (n=4) and 13.2 % (n=5), respectively. Finally, the presence of constipation in the placebo group was 21.1% (n=8) at baseline and 23.7% (n=9) after supplementation and in the inulin group 26.3% (n=10) and 10.5% (n=4), respectively. Despite the fact that the presence of these events was lower in the inulin group, it was not significantly different from the placebo group.In this double-blind placebo controlled trial, we found that supplementation with inulin reduces SBP and attenuates increases in DBP and MAP in women with breast cancer under neoadjuvant therapy. Similar to our findings, some trials have shown that supplementation with dietary fiber promotes the reduction of blood pressure although there are some differences associated with the time of supplementation and the change in blood pressure. For instance, fiber intake for 8 weeks nonsignificantly reduces SBP (-1.15 mmHg) and significantly reduces DBP (-1.65 mmHg) . In contOne of the main findings in this study is that the effect of inulin supplementation on SBP is more pronounced than the one on DBP. This is consistent with experimental studies where SBP, systolic volume, and left ventricular diameter in systole were lower in rats fed with a high-fat diet and supplemented with inulin than in unsupplemented rats fed only with the high-fat diet . TherefoSupplementation with 10 and 20 g of inulin for 3 weeks has been linked to decreases in triacylglycerols and hypercholesterolemia in men , 39. In It is important to mention that there is any statistical influence from other confounding variables such as changes in BMI, glucose concentrations, age, menopause status, vomiting, constipation, and use of antihypertensive drugs. This suggests that the decrease in SBP in the group supplemented with inulin is due to the supplementation itself. Furthermore, creatinine clearance  and hepa p value was greater than 0.05 in the group supplemented with inulin, but it was lower in the placebo group. This also suggests that BMI and BFP may not exert an influence on blood pressure after inulin supplementation. Increases in BFP are usually associated with hypertension and breast cancer metastasis [Another interesting finding is the contrasting effect of inulin on BMI and BFP. At the beginning of our study, 68.4% of the patients were overweight and obese, 89.4% had a high BFP, and 34.2% had a MAP above 120 mmHg. However, the frequency of women with overweight or obesity is nonsignificantly different after 21 days of supplementation between both groups . Also, Btastasis –47, but tastasis . In our Hypertension and breast cancer are multifactorial diseases that involve complex molecular and physiological mechanisms. Besides that, there is little evidence about the effects of prebiotics on these two diseases and particularly in women with breast cancer under neoadjuvant therapy. This is the first double-blind placebo controlled clinical trial in women where the supplementation with inulin elicits a reduction in SBP and HR and prevents increases in DBP. Furthermore, inulin supplementation nonsignificantly reduces BFP and increases BMI. Therefore, this might be a novel nutraceutical approach to improve the quality of life and cardiovascular health of women who are at early stages of breast cancer and who are under this type of therapy. Consequently, supplementation with inulin might help to improve the prognosis of women with breast cancer and CVD risk. For future experimental or clinical trials, it would be interesting to consider the assessment of variables  that could further help to explain the physiological mechanisms by which inulin elicits beneficial responses as well as to increase the supplementation period and sample size.


Laparoscopic pylorus-preserving pancreaticoduodenectomy is being performed more frequently because of improved surgical techniques. Although several studies have demonstrated safety and favourable outcomes of laparoscopic pylorus-preserving pancreaticoduodenectomy compared to open pylorus-preserving pancreaticoduodenectomy, few studies have focused on the development of postoperative acute kidney injury. This retrospective study compared the prevalence and risk factors of acute kidney injury following laparoscopic and open pylorus-preserving pancreaticoduodenectomy. Data from 809 patients who underwent pylorus-preserving pancreaticoduodenectomy between February 2012 and September 2016 were analysed. Patients were divided into two groups according to the surgical procedure (open pylorus-preserving pancreaticoduodenectomy [n = 632] vs laparoscopic pylorus-preserving pancreaticoduodenectomy [n = 177]). The Kidney Disease: Improving Global Outcomes criteria were used to define postoperative acute kidney injury and risk factors were investigated using multivariable logistic regression analysis with propensity score matching analysis and standardized mortality ratio weighting to compare outcomes. No significant differences were found in the occurrence of postoperative acute kidney injury and incidence of postoperative ICU admission between open and laparoscopic pylorus-preserving pancreaticoduodenectomy groups after propensity score matching . Hospital stay was significantly shorter in the laparoscopic pylorus-preserving pancreaticoduodenectomy group . There was no significant difference in postoperative acute kidney injury incidence between both groups. Laparoscopic pylorus-preserving pancreaticoduodenectomy is promising with comparable postoperative outcomes to open pylorus-preserving pancreaticoduodenectomy and has the advantage of shorter hospital stay. With the improvement of surgical techniques, the scope of minimally invasive surgery has also expanded. Laparoscopic pylorus-preserving pancreaticoduodenectomy (LPPPD) has been reported to be safe and feasible with acceptable outcomes despite its technical difficulties , 2. StudAcute kidney injury (AKI) is known to be associated with poor postoperative outcomes including short-term and long-term mortality –7. AKI iIn laparoscopic surgery, relatively less surgical trauma and systemic inflammatory responses may influence the incidence of AKI , 14. HowThis study was approved by our institutional review board. . The informed consent was waived by the institutional review board because of the minimal risk of this retrospective study. We retrospectively collected the data of patients who underwent LPPPD or OPPPD at our centre from February 2012 to September 2016. Patients with incomplete data or including missing sCr values were excluded .All data including baseline characteristics, laboratory values, intraoperative information, and outcome data of study patients were collected using a computerized patient data recording system . Sex, age, height, weight, body mass index (BMI), underlying disease such as diabetes mellitus, hypertension, and cerebrovascular disease, and current medications including angiotensin-converting enzyme inhibitors, calcium channel blockers, beta blockers, and statin, were included in the baseline characteristics. Laboratory data included determination of levels of hemoglobin, platelets, aspartate transaminase, alanine transaminase, total bilirubin, total protein, albumin, serum creatinine, glucose, and sodium in addition to prothrombin time. Intraoperative data included administered fluid volumes such as crystalloid, synthetic colloid, albumin, and transfused blood products such as packed red blood cell (RBC) and fresh-frozen plasma, total urine output, lowest mean arterial pressure (MAP) recorded during the operation, and infusion of inotropes or vasopressors.-1) and rocuronium (0.6–1.2 mg.kg-1) and maintained with sevoflurane (1–3 vol%) and target-controlled infusion of remifentanil (2–5 ng.ml-1). After induction, arterial catheterisation was performed for continuous blood pressure monitoring and the central venous catheter was inserted into the internal jugular vein to infuse fluid and monitor central venous pressure. Crystalloids including Ringer’s lactate or PlasmaLyte were infused as maintenance fluid and synthetic colloids such as Voluven  or 5% albumin were administered for volume replacement at the discretion of the anesthesiologist. Appropriate packed RBC was transfused to maintain target hemoglobin level ≥ 80 g.l-1 in patients without history of ischemic heart disease and cerebrovascular disease, and at ≥ 100 g.l-1 in patients with history of ischemic heart disease or cerebrovascular disease. Inotropes or vasopressors were administered if the MAP was <65 mmHg.Anesthesia was performed according to our routine protocols. No premedication was given to the patients. Electrocardiography, pulse oximetry, capnography, and noninvasive blood pressure were monitored from the induction of anesthesia to the end of surgery. General anesthesia was induced with propofol  criteria; an increase of ≥ 0.3 mg.dlven days . Other ot-test or Mann-Whitney U test. Categorical variables are reported as frequencies and proportions and were analysed using the Chi-square test or the Fisher’s exact test, as appropriate. Multiple logistic regression analysis was used to detect factors associated with AKI and all variables with p<0.1 in univariate analysis were included in the multivariable analysis. Stepwise regression analysis was done to select variables accepted in the multivariate model.Continuous variables were expressed as the mean [SD] or median [IQR]. Continuous variables were compared using Student 2 = 8.6581, DF = 8, p = 0.372). PS matching was performed by Greedy matching using a caliper of 0.25 SDs of the logit of the PS. After PS matching, baseline variables were compared between the two groups. Categorical variables were compared using the McNemar test, and continuous variables were compared using the paired t-test or Wilcoxon signed-rank test as appropriate. In addition, we performed a weighted PS analysis using standardized mortality ratio (SMR) weighting. In terms of the average treatment effect on the treated (ATT), the weights for the OPPPD group were PS/(1—PS), and weights for patients receiving LPPPD were 1. The absolute standardized differences were used to diagnose the balance after propensity analysis. All absolute standardized differences after matching were less than 0.1. In the PS matched cohort, the risks of each outcome were compared with logistic regression using Generalized Estimating Equations that accounted for the clustering of matched pairs. Additionally, the outcomes were evaluated using weighted regression models with PS matching and SMR weighting.The propensity score (PS) was estimated with groups as the dependent variables by multiple logistic regression analysis. A full non-parsimonious model including demographics and preoperative variables in Of the 846 patients enrolled, 37 patients were excluded due to incomplete data; thus, a total of 809 patients were included in this study . Of thesAfter 1:1 PS analysis, all absolute standardized differences in demographics or preoperative laboratory variables after matching were less than 0.1 between the OPPPD (n = 173) and LPPPD groups (n = 173) . After PIn the multivariable analysis, LPPPD was not significantly associated with the development of postoperative AKI . Conversely, hypertension , preoperative albumin level , and synthetic colloids infusion  were significantly associated with AKI after surgery .Comparing the outcomes of the OPPPD and LPPPD group, there were no significant differences in the occurrence of postoperative AKI  and postoperative ICU admission  between the two groups . The perIn the present study, we demonstrated that there was no significant difference in the incidence of postoperative AKI between the OPPPD group and the LPPPD group. In addition, we showed that no difference was found in the incidence of AKI after PS matching and SMR weighted analysis. However, patients who underwent LPPPD had a shorter period of hospital stay than those who received OPPPD. In multivariable analysis, hypertension, preoperative albumin level, and intraoperative synthetic colloid infusion were associated with the incidence of postoperative AKI.Studies have shown conflicting results regarding the effects of laparoscopic surgery on postoperative AKI. It has been reported that increased intra-abdominal pressure may cause renal dysfunction by alterations in renal blood flow and ischemia-reperfusion-related oxidative stress during laparoscopic surgery –20. GlomLess bleeding and less requirement for RBC transfusion may be the possible causes of the similar incidence of postoperative AKI between the two groups in this study, despite prolonged pneumoperitoneum. Hemodilution and transfusion have been reported to be associated with renal dysfunction and AKI , 25, 26.-1.1.73 m-2 or above [Rather than the type of surgery, variables including history of hypertension, preoperative albumin level, and synthetic colloid infusion were associated with the occurrence of postoperative AKI. Hypertension is a known risk factor of AKI in patients undergoing general surgery , 28. In or above . This re-1 was revealed to be independently associated with the occurrence of AKI and longer hospital stay [Lower serum albumin levels are also reported to be associated with perioperative complications including AKI –31. In atal stay . The res® was used for the administration of synthetic colloids. The main component of Voluven® is hydroxyethyl starch (HES), which is reported to be associated with AKI. In a prospective randomized controlled trial performed by Myburgh et al. [In our study, Voluvenh et al.  which enh et al. –36. Therh et al. . AlthougPatients who received LPPPD had shorter hospital stays because of the smaller incision, which allowed the patient to recover quickly and enabled daily life with less pain medication . This caThere are some limitations to our study. As a retrospective study, unexpected biases cannot be excluded. The two groups have differences in their characteristics such as sex, age, underlying diseases and diagnosis. Additionally, patients in the OPPPD group were administered more fluids and had greater transfusions of packed RBCs, which means that a patient in the OPPPD group had a greater likelihood of experiencing volume overload. These could act as confounding factors and affect outcomes of our analysis. Therefore, we attempted to minimize the effects of the confounding factors using PS analysis. The diagnosis for the surgery was not considered as a dependent variable in PS matching and multivariable analysis. Features of the disease including tumour size, lymph node invasion, and differentiation also were not considered in our present study, which may have possibly caused a bias in this study. Moreover, malignancy can be a risk factor for AKI because of various reasons, including prerenal condition, sepsis, nephrotoxins, cytokines, and paraneoplastic conditions , 39. AlsWe demonstrated that there were no significant differences in postoperative AKI incidence between LPPPD and OPPPD groups in this study. In addition, the LPPPD is not a factor associated with AKI. Therefore, compared with OPPPD, LPPPD may be a promising approach with comparable postoperative outcomes in addition to the advantage of shorter hospital stay.S1 File(CSV)Click here for additional data file.