National Institute for Health and Care Excellence 2021 guidelines on chronic kidney disease (CKD) recommend the use of the Kidney Failure Risk Equation (KFRE), which includes measurement of albuminuria. The equation to calculate estimated glomerular filtration rate (eGFR) has also been updated.2) in primary care and potential referrals to nephrology.To investigate the impact of the use of KFRE and the updated eGFR equation on CKD diagnosis (eGFR <60 mL/min/1.73 mPrimary care database (Secure Anonymised Information Linkage Databank [SAIL]) and prospective cohort study (UK Biobank) using data available between 2013 and 2020.2 the following groups were identified: those with annual albuminuria testing and those who met nephrology referral criteria because of: a) accelerated eGFR decline or significant albuminuria; b) eGFR decline <30 mL/ min/1.73 m2 only; and c) KFRE >5% only. Analyses were stratified by ethnicity in UK Biobank.CKD diagnosis rates were assessed when using the updated eGFR equation. Among people with eGFR 30–59 mL/min/1.73 mUsing the updated eGFR equation resulted in a 1.2-fold fall in new CKD diagnoses in the predominantly White population in SAIL, whereas CKD prevalence rose by 1.9-fold among Black participants in UK Biobank. Rates of albuminuria testing have been consistently below 30% since 2015. In 2019, using KFRE >5% identified 182/61 721 (0.3%) patients at high risk of CKD progression before their eGFR declined and 361/61 721 (0.6%) low-risk patients who were no longer eligible for referral. Ethnic groups ‘Asian’ and ‘other’ had disproportionately raised KFREs.Application of KFRE criteria in primary care will lead to referral of more patients at elevated risk of kidney failure (particularly among minority ethnic groups) and fewer low-risk patients. Albuminuria testing needs to be expanded to enable wider KFRE implementation. The KFRE equation takes account of four variables:age;sex;eGFR; andurine albumin-to-creatinine ratio (uACR).In 2021, National Institute for Health and Care Excellence (NICE) guidelines made two recommendations that influence CKD diagnosis and referral to nephrology.GPs are advised to refer to nephrology if the 5-year risk of kidney failure is >5%.7The NICE guidelines also recommend that laboratories use eGFR equations that do not include ethnicity. The inclusion of ethnicity in these equations has been debated for several years, with many concerned that ethnicity is a social construct rather than a biological one.8 shortly after the updated NICE guideline recommended that such equations be used. A nationally representative primary care cohort followed by a prospective research cohort were studied to assess the potential impact of these guideline changes on diagnosis of CKD in primary care, potential referral rates to nephrology, and whether there was a differential impact in ethnic groups.The updated equation for eGFR calculation (which does not include ethnicity) was released in 2021,9The Secure Anonymised Information Linkage Databank (SAIL) is an electronic health records repository that holds primary care data for 79% of the population of Wales.10 Creatinine, uACR values, and diagnoses of CKD, diabetes mellitus, and hypertension were taken from GP Read codes, as previously described.11 Ethnicity is not consistently recorded in these records, so it was not used.Patients aged >18 years with serum creatinine values available between 1 January 2013 and 31 December 2020 are included in this study. Values before 2013 were not included because non-validated laboratory analysers may have been in use.12,13 Sociodemographic and medical information were self-reported and blood and urine samples were taken at baseline.13 The sampling process has been described previously.14–16UK Biobank is a research cohort that enrolled volunteer participants between 2006 and 2010 as previously described.In brief, serum and spot urine samples were collected and analysed at an accredited central laboratory. Creatinine was measured using a Beckman Coulter AU5800 analyser and the assay was externally quality controlled. Of 502 536 participants initially recruited, in this study 76 were excluded as they withdrew ongoing consent for follow- up, as well as 33 144 participants with missing creatinine values at baseline, 2205 with unknown ethnicity, and 550 with kidney failure requiring replacement therapy at baseline.8 30–59 mL/ min/1.73 m2 ≥3 months apart with no values >60 mL/min/1.73 m2.17From SAIL data, for this study, patients were identified with prevalent CKD stage G3A/G3B, that is, two eGFR values2-tests for categorical variables and analysis of variance tests for continuous variables.Prevalence of CKD stage G3A/G3B was described by calendar year from 2013 to 2020. Rates of annual uACR testing were established for these patients. This included patients with previously identified CKD, so long as they were alive throughout the year. uACR testing was stratified by age, sex, eGFR, diabetes mellitus, and hypertension, and whether CKD was coded in their medical records. Tested and untested groups were compared using χ2.From UK Biobank data, participants were labelled with CKD stage G3A/G3B if the single baseline eGFR available was 30–59 mL/min/1.73 mAccelerated eGFR decline or albuminuria: eGFR decline by ≥25% or ≥15 mL/min/1.73 m2 within 12 months, sustained for ≥3 months with no values rising above the threshold; or uACR ≥70 mg/mmol. Two sensitivity analyses were performed: a) patients with known diabetic nephropathy are not to be referred with this albuminuria threshold. The authors of the current study therefore studied whether patients with diabetes would only be referred if they had heavy to nephrotic-range proteinuria (uACR >200 mg/mmol); and b) haematuria criteria were not included because information on haematuria was not available. The authors of the current study therefore studied the impact on referrals when using a lower uACR threshold of 30 mg/mmol instead of 70 mg/mmol, which would warrant nephrology referral if accompanied by haematuria.eGFR < 30 only : incident eGFR <30 mL/ min/1.73 m2 sustained for ≥3 months with no values rising above 30.KFRE > 5% only : 5-year KFRE of >5%.5,6,19 For patients with several measurements of eGFR and uACR, the highest KFRE result was selected, given GPs are likely to act on an elevated result when it becomes available.From the group of patients with CKD stage G3A/G3B, those eligible for nephrology referral were identified using three criteria.2-tests for sex (excluding those eligible by both criteria).Those currently or previously under nephrology follow-up were discounted, assuming that patients discharged back to primary care had already been assessed. The patients eligible for referral based on eGFR <30 only and KFRE >5% only were compared using analysis of variance tests for age and χFrom UK Biobank data, participants with 5-year KFRE >5% were identified and the results stratified, first by ethnicity and then by ethnicity and diabetes mellitus status.CKD prevalence in SAIL was estimated using different eGFR equations and stratified by ethnicity in UK Biobank. The approach is detailed in the Supplementary Appendix S1. Statistical analyses were conducted using R (version 4.1.3).In total, 1 845 040 patients in SAIL and 466 561 participants in UK Biobank were studied . SupplemIn SAIL, the prevalence of CKD stage G3A/G3B among those with a creatinine measurement was 55 193/752 517 (7.3%) in 2013 and 61 721/850 394 (7.3%) in 2019 . In 2020Among patients with prevalent CKD stage G3A/G3B in SAIL, the rate of annual uACR testing fell from 46.3% in 2013 to 25.3% in 2019 . eGFR an2) G3A/G3B  76–88) were similar to patients with biochemical CKD but not coded . Of the patients with CKD G3A/G3B at any time, factors associated with higher rates of uACR testing were male sex, young age (the tested group were a median of 2 years younger), coded CKD, diabetes mellitus, hypertension, and low eGFR .The demographics of patients with coded and biochemical CKD .In SAIL, KFRE consistently identified a substantial number of patients who should be referred to nephrology who did not meet other criteria . In 20192 had a 5-year KFRE >5%. The proportion of participants with KFRE >5% was highest in those of Asian and other ethnicity  participants with eGFR 30–59 mL/ min/1.73 mthnicity . In bothMDRD) and highest using the 2021 version of the Chronic Kidney Disease Epidemiology Collaboration (eGFR2021) equation . Among patients in SAIL with CKD G3–5, a switch to using eGFR2021 from eGFRMDRD would be associated with an average increase in reported eGFR of 2.7 mL/min/1.73 m2 (IQI 1.2–4.5).eGFR was lowest using the Modification of Diet in Renal Disease equation .In practice, this change to laboratory reporting from eGFRequation . In gene2021 instead of eGFRMDRD, the number of non-Black participants meeting criteria for CKD G3–5 diagnosis would increase from 124 to 237 (a 1.9-fold increase). This would be offset by 3463/10 225 (33.9%) fewer non-Black participants classified as having CKD G3–5 if making this same reporting change. If eGFR2021 was used to calculate KFRE instead of eGFRMDRD, the number of Black participants with a KFRE >5% would increase from three to four individuals.In UK Biobank, the changes in eGFR values and thus categorisation of CKD using different equations were similar among non-Black participants . If laboratories reported eGFR2. This will be offset by reductions in referrals for patients with slow declines in their eGFR. Regular uACR testing is required for all patients with CKD for KFRE calculation, but annual uACR testing is not consistently performed in all people with CKD. Optimal referrals to nephrology will therefore depend on increases in uACR testing and awareness among GPs of KFRE.Implementation of KFRE in primary care can help GPs identify a small proportion of additional patients with previously unrecognised elevated risk who could then be referred to nephrology before their eGFR declines below 30 mL/min/1.73 m6,20 and is now recommended as a tool to guide risk assessment and nephrology referral, and to aid with risk reduction strategies. Second, the lack of ethnicity data in SAIL means this key information could not be reported. Although ethnicity differences in KFRE could be reported for the UK Biobank, diagnosis of CKD here was based on a single baseline measure of kidney function, and it was not possible to use two confirmatory measurements at least 3 months apart, as recommended in clinical guidelines.17 Given the relatively healthy and predominantly White population in UK Biobank,21 and lower rate of CKD and heavy albuminuria observed than in the general population, it is likely that use of the KFRE underestimated risk of kidney failure in the general population.This study has some limitations. First, the rates of observed kidney failure events are not reported. Neither SAIL nor UK Biobank are linked to national renal registry records, which most accurately record kidney failure events. However, KFRE has already been validated extensively,22 it would have been preferable if uPCR data had been available to identify patients with nephrotic- range proteinuria.23Finally, a uACR of >200 mg/mmol was used as an equivalent to nephrotic-range proteinuria . Although uACR 200 mg/mmol is approximately equivalent to uPCR 300 mg/mmol,24 The incentivisation of annual uACR testing for people with diabetes mellitus was removed from the GP contract in April 2014.25Reduced rates of laboratory testing in primary care in the UK have been reported before in association with changes in the Quality and Outcomes Framework.26 In 2017 in the current study the rate was 25.5%, which may have been lower because the CKD audit reports on stages G3–5, whereas this study was limited to stage G3A/G3B. In keeping with the findings of the National CKD Audit, the current study suggests that improvements in albuminuria testing particularly need to be targeted in patients with non-diabetic CKD.The 2017 National CKD Audit in England and Wales reported that 31.1% of people with CKD had an annual uACR test.27,28 and provide earlier opportunities for primary prevention interventions such as statins and sodium- glucose co-transporter-2 inhibitors.29,30By improving uACR testing and using KFRE, GPs will identify patients at high risk of kidney failure at a younger age and an earlier stage of CKD. The lifetime risk of kidney failure is higher at a younger age and patients are more likely to live long enough to require dialysis or kidney transplantation compared with older adults (such as those over the age of 80 years). However, CKD is associated with broader risks, primarily cardiovascular disease. Greater recognition of patients at risk of progressive CKD will also identify people at higher risk of cardiovascular disease2 would would lead to more patients at elevated risk of kidney failure being followed up in secondary care and more low-risk patients being monitored in primary care.31A study using 5-year KFRE >3% to guide nephrology referrals similarly found that using KFRE to guide referrals instead of an eGFR threshold of 30 mL/min/1.73 m32 The current study did not find high rates of elevated KFRE in Black participants, which may reflect low levels of albuminuria, predominance of White participants, and healthy volunteer bias in UK Biobank.21Importantly, KFRE was more likely to be elevated in ethnic groups other than White, in keeping with the previous literature suggesting that Black and minority ethnic groups are at the greatest risk of CKD progression.2021 using the 2021 CKD-EPI 2021 equation.Nevertheless, the current study shows that implementation of KFRE can identify those at the highest risk and may go some way to attenuating healthcare inequalities in CKD management in Black and minority ethnic groups. Although the UK population is predominantly White, the current study confirms that among people of Black and minority ethnicity, the rates of CKD will rise significantly if laboratories start to report eGFRAt stage G3A/G3B CKD, only a small proportion of patients are at high risk of CKD progression. These patients can be readily identified using KFRE; however, KFRE will only report elevated 5-year risk of kidney failure if there is at least moderate detected albuminuria .2 and in those with uACR >3 mg/mmol.17 The current study may therefore have overestimated the proportion of individuals with albuminuria testing appropriate for their stage of CKD.Low uACR testing rates (consistently <30%) were observed in primary care from 2015 onwards, and particularly low rates in 2020, probably because much routine disease monitoring stopped during the COVID-19 pandemic. Annual albuminuria testing rates are reported in the current study, although Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend more frequent testing: 4- or 6-monthly in those with eGFR 30–44 mL/ min/1.73 m33,34), perhaps because most of them are asymptomatic. By raising patient awareness of CKD and the importance of albuminuria testing patients may engage better with CKD management, for example, by encouraging home blood pressure monitoring and proactively providing urine samples for albuminuria testing.Several factors may explain the suboptimal rates of albuminuria testing seen in these populations with CKD in this study. Many people with CKD are unaware of the diagnosis (10%–59%35Higher rates of albuminuria testing in this study were found in people with coded compared with biochemical CKD. As clinical and laboratory records are predominantly electronic, there may be a role for automating KFRE calculation or indeed entry onto CKD registers, which has been associated with improved albuminuria testing.2 with no markers of elevated risk. However, KFRE use will be dependent on universal and regular uACR testing, particularly among older adults and those without diabetes mellitus. Overall, updated eGFR equations, if used by UK laboratories, will reduce the numbers of patients categorised as having CKD.In summary, use of KFRE in general practice will identify more patients with CKD at risk of kidney failure and needing nephrology referral, particularly among minority ethnic groups. Fewer patients will be referred with eGFR declining slowly to <30 mL/min/1.73 m


The aim of this study was to evaluate the impact on perinatal outcomes related to placental insufficiency with the application of the new 2017 ACC/AHA guidelines to a group of chronic hypertensive pregnancies during their first-trimester assessment.rd percentile.This retrospective cohort study included pregnancies with preconceptional hypertension and known perinatal outcomes. In the first trimester, a combined screening for preterm preeclampsia (p-PE) was performed, including blood pressure (BP), mean uterine artery Doppler, and maternal characteristics. Patients were divided, according to the 2017 ACC/AHA consensus, into the following groups: elevated or less, Stage 1, and Stage 2. For adverse perinatal outcome assessment, univariate and multivariate regression analyses were performed, considering the “elevated or less” group as a reference. Odds ratios (OR) were compared with linear trend analysis. The main outcomes measured were preterm PE and FGR < 3rd percentile according to the BP stage. The best multivariate predictive model for p-PE included a previous PE background (OR = 15) and mean arterial pressure in mmHg (OR = 1.1).Of the 130 included patients, 59 (45.4%) were classified as elevated or less, 47 (36.2%) as Stage 1, and 24 (18.4%) as Stage 2. p-PE showed a significant increase according to BP range ; trend p = 0.02, for elevated or less, Stage 1, and Stage 2, respectively. There was a non-significant increased trend of FGR < 3The use of the 2017 ACC/AHA consensus in pregnancies with chronic hypertension identifies an intermediate risk group for placental-mediated diseases. Preeclampsia (PE) affects 5% of pregnancies worldwide , accountIn 2017, the American Heart Association (AHA) and the American College of Cardiology (ACC) published practice guidelines that changed the definition of stage 1 hypertension, lowering the systolic blood pressure (SBP) and diastolic blood pressure (DBP) values . The newNonetheless, the implications of this newly diagnosed stage 1 hypertension were unclear for the obstetric practice. There are only few studies regarding whether pregnant women with stage 1 hypertension had a higher risk of maternal and perinatal complications. In 2018, a cohort study was published, which observed higher rates of complications for women with the new stage 1 hypertension . HoweverTherefore, the objective of this study was to evaluate the impact on perinatal outcomes associated with placental insufficiency, by the application of the new 2017 ACC/AHA guidelines to a group of chronic hypertensive pregnant women during their assessment of the first trimester of pregnancy.®.This retrospective cohort study was conducted at the Fetal Medicine Unit Hospital Clínico Universidad de Chile from November 2011 to June 2020. Before the 11–14 week screening scan, all patients were asked to complete a demographic questionnaire that included chronic disease background , family history of PE, and pregnancy background . When a chronic disease was reported, treatment was asked for and stored in the dedicated database Astraiaet al. . Briefly, maternal history was combined with mean uterine artery pulsatility index (UtA-PI) and mean arterial pressure (MAP), both expressed as a multiple of the median (MoM)  and height (centimeters) were obtained. Blood pressure was measured according to the Seventh Report of the Joint National Committee (JNC-7) using a validated digital sphygmomanometer, Omron HEM-7113 . Blood pressure was measured simultaneously in both arms and stored. For preterm PE (p-PE) screening, the multivariable algorithm of O′Gorman et al.  was usedan (MoM) , 17. A han (MoM) .via phone to obtain perinatal data. First-trimester screening assessment and perinatal data were stored in the software Astraia® and exported to an excel sheet for depuration before analysis.Perinatal outcomes were obtained from a local electronic medical chart or delivery registries. Aspirin use during pregnancy, and gestational age at the onset of PE was obtained from the electronic medical chart. In the case of delivery in another institution, patients were contacted For this study, all singleton pregnancies with known pregestational chronic hypertension during the study period were included. All patients used oral antihypertensives before conception. Withdrawal or treatment modification was performed at the first pregnancy control by an OB&GYN or maternal-fetal medicine specialist. Newborns with major birth defects or aneuploidies were excluded from the analysis. Patients without a blood pressure measurement at the first-trimester screening ultrasound and/or without a known perinatal outcome were also excluded.For this study, the following definitions according to the ACC/AHA guidelines  were useMean arterial pressure was estimated using the following formula: MAP = DBP + [(SBP-DBP)/3], where DBP was the mean diastolic blood pressure of both arms and SBP was the mean systolic blood pressure of both arms.rd centile  was used. Continuous variables were explored using the Shapiro-Wilk test to determine variable distribution. Parametric and non-parametric variables were compared using ANOVA or Kruskal-Wallis tests and expressed as mean ± standard deviation or median (interquartile range), respectively. Post hoc comparisons between pairs of groups were performed using Bonferroni or Mann-Whitney tests as appropriate. Categorical variables were compared with chi  algorithm, including blood pressure assessment. Of these, 133 (3.8%) were considered pregestational hypertension, based on a demographic questionnaire before the ultrasound. Three pregnancies were excluded because of a congenital birth defect .2. Previous PE was reported in 34/91 (37.4%) parous patients. The median gestational age at assessment was 12.7 (12.1–13.1) weeks. Notably, eighty-two (63%) patients were using the oral antihypertensive treatment and 73 (57%) patients started aspirin before 16 weeks of gestation. At first trimester assessment, blood pressure was stratified as elevated BP or less , Stage 1 , and Stage 2 . Maternal demographic characteristics and first-trimester ultrasound assessment according to blood pressure range are described in Of the 130 included pregnancies in the final analysis, maternal age at the first-trimester assessment was 35.6 (31.6–38.2) years, with a body mass index (BMI) of 30.1 (25.7–34.5) kg/m2 in the elevated or less group and 31.7 kg/m2 in the Stage 2 group, respectively (p < 0.01). There was no association between first-trimester UtA Doppler PI and blood pressure , with a median PI of 1.54, 1.63, and 1.47 for elevated or less, Stage 1, and Stage 2, respectively . PE was observed in 29 (22.3%) patients, with a significant increasing trend regarding blood pressure range in the first trimester  were also higher when blood pressure was higher, with an almost 3-fold and 4-fold higher risk for the Stage 1 and Stage 2 groups compared to the elevated or less group, respectively (There were 3 (2.3%) fetal losses  and <34 weeks  were also higher in the Stage 1 and Stage 2 groups, compared to the elevated or less group (p = 0.08). Furthermore, the rate of FGR showed an increase related to blood pressure range , although this trend was not significant , MAP in mmHg (OR = 1.1), and maternal age in years (OR = 1.4)  and MAP in mmHg (OR = 1.1). For FGR below the 3R = 1.4) .Our study demonstrated that the first-trimester blood pressure range in patients with pregestational hypertension is directly associated with adverse perinatal outcomes, mainly those related to placental-mediated diseases. Moreover, the new 2017 ACC/AHA classification identifies a moderate subgroup of pregnancies who could benefit from closer follow-up until delivery. Furthermore, the development of p-PE and FGR in these pregestational hypertensive pregnancies was also associated with the previous history of PE and uterine artery Doppler and maternal age, respectively.et al. performed a longitudinal assessment of BP and vascular function parameters in 97 pregestational hypertensive pregnancies. They demonstrated that those who subsequently developed superimposed PE and SGA, SBP and DBP were significantly higher from the first trimester to delivery  and a 4-fold higher risk of indicated preterm delivery (OR = 3.83 [1.30–11.31]) .In terms of predicting p-PE and FGR, we found out that MAP was an independent predictive factor for both diseases, whereas the previous history of PE was a predictor of the former, the maternal age and uterine artery Doppler were of the latter. These results could be of interest considering the current use of multivariate predictive models, such as the FMF proposal . This moet al. could help to answer this question, considering a therapeutic goal of < 140/90 mmHg as the best range to reduce adverse perinatal outcomes  was associated with less severe hypertension during pregnancy and no increase in SGA at delivery . Therefoet al.  demonstrOur study demonstrated that the use of the new ACC/AHA classification of chronic hypertension in the first trimester has an impact on identifying a subgroup of patients with a moderate adverse perinatal outcome that potentially requires closer follow-up and strict management during pregnancy.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.AS-M co-designed the study, performed the database depuration, performed all statistical analyses, and co-wrote the document. TC co-obtained perinatal outcomes and co-wrote the document. RG and JG co-obtained perinatal outcomes. ML and MP-C co-designed the study, reviewed, and approved the final draft. All authors contributed to the article and approved the submitted version.


The effects of topical negative pressure therapy (TNP) have been a subject of research for many years. In this study, we investigated new imaging devices to detect clinical changes that TNP causes on healthy tissue and identified differences in microcirculation created by different pressure levels. We used near-infrared spectroscopy (NIS), thermography, and a vein illuminator to measure the differences in oxygen saturation, tissue temperature, and vein pattern. A control group (−125 mmHg) and three comparison groups with only TNP dressing (Group 1), −25 mmHg (Group 2), and −175 mmHg (Group 3) were established. Thirty minutes of TNP on intact skin was followed by 30 min of resting. A total of 24 participants were measured by all imaging devices at predetermined time points. Oxygen saturation and skin temperature increased by 8.07% and 1.67 °C for the control group, 4.00% and 1.65 °C for Group 2, and 8.45% and 1.68 °C for Group 3. Group 1 showed a slight increase in oxygen saturation and a 2.7 °C increase in skin temperature. Over the 30 min following removal of TNP, oxygen saturation and temperature decreased gradually for all groups. The vein illuminator did not show significant differences in the venous pattern or flow. Our study showed that higher negative pressure values resulted in higher oxygen saturation and higher tissue temperature. In modern wound treatment, negative pressure wound therapy (NPWT) has evolved to be a standard option, especially for wound bed preparation. It is widely used for different indications such as chronic or infected wounds or as a temporary wound closure for defect coverage following trauma or tumor operations, and it is increasingly applied in the form of vacuum wound therapy with instillation ,2,3,4,5.The debate about the exact mechanisms of NPWT is still ongoing, although different effects have been well assessed. Especially, the influence of NPWT on wound bed or tissue perfusion regarding the subatmospheric pressure used is not yet fully understood.In the late 1990s, Morykwas et al. presented the first results of vacuum-assisted wound therapy, which reported an increase in tissue perfusion using NPWT in a swine model. Moreover, they assessed different levels of negative pressure in their model and observed favorable results using a subatmospheric pressure of −125 mmHg. Since then, a plethora of studies have investigated different effects of NPWT in the context of tissue perfusion, pressure distribution, or bacterial burden, as well as in the application of various wound situations ,11.Recent developments in technologies used for the analysis of tissue perfusion provided motivation to assess different pressure levels of NPWT in a clinical skin model. Both oxygen saturation and tissue temperature are important parameters in wound healing. The involvement of the parameters is undisputable but not fully understood for the various processes involved ,13,14,15A total of 27 healthy subjects participated in the study and provided written informed consent. Three female participants were not able to complete the study for technical reasons and were therefore excluded from the data analysis. Participants reported no relevant comorbidities and were randomly assigned to the different groups while keeping the female-to-male ratio similar. A positive ethical vote from the institutional ethics committee is registered (registration number 310_19 B).®; KENT Imaging Inc., Calgary, AB, Canada) and thermographic imaging  were used for the measurement of the oxygenation and the temperature of the affected skin, respectively. The techniques have been explained in detail elsewhere [Near-infrared spectroscopy  was used to find out if additional information about the venous flow pattern could be gained. The device uses near-infrared (NIR) imaging and was originally developed to visualize blood vessels in order to support venipuncture. It emits infrared light with a wavelength of 785 nm. After capturing the reflected light from the participant’s body, the resulting image is projected onto the participant’s skin, creating a real-time reproduction of the subcutaneous vein pattern. Because infrared light is absorbed by the hemoglobin, blood-filled structures such as the veins appear as dark lines compared to the adjacent tissue that reflects the green light. The device offers an inverted mode where the veins are seen as luminous green lines on a dark background. The implemented lasers together provide an image of the subcutaneous vascular structure up to 10 mm depth.The different imaging modalities were applied to reflect various possible dimensions of tissue perfusion. In contrast to spectroscopy, thermography relies on thermal heat readings, which are supposed to represent an entire surface or regions of interests within it as well as the location of potential perforating blood vessels .Standardized distances and five identical regions of interests at the thigh of the participants with a single diameter of 9 mm were defined and applied to all participants in the same way for the near-infrared spectroscopy (NIS) and the thermography. Average values out of the regions of interest were calculated and used for further statistical analysis. We performed visual comparisons of the pictures taken from the vein finder. All measurements were done by the same person to ensure there were no differences in measuring techniques.Study measurements were all done at room temperature. Participants were asked to undress, and the area was determined by measuring the middle point from the lateral superior patella to the anterior superior iliac spine . The area was carefully shaved to prevent any image disruptions. Participants were then asked to rest for 10 min. After resting, t0 images were captured. In total, 3 Groups were defined . For eveFor the left leg at the same anatomical area, different pressure levels were used to compare the effects of different TNPA levels on the tissue oxygen saturation, skin temperature, and changes in vein imaging, while keeping the other settings of TNPA the same. For Group 1, the TNPA was put on the left leg, but no negative pressure was established, to see the effect caused by the dressing itself on the skin area. For group 2, −25 mmHg TNPA was applied, and for Group 3, −175 mmHg TNPA was applied. After the TNPA was removed, t1 (30 min) images were captured. Final images were captured 30 min following the removal of TNPA (t6). Participants stayed rested and were not allowed to move or cover the area throughout the study duration.For NIS, images were captured at different time intervals (measured in min) t0 (0’), t1 (30’), t2 (35’), t3 (40’), t4 (45’), t5 (50’), and t6 (60’) . The devFor thermal imaging, images were captured at t0, t1, and t6.  The imagFor the vein illuminator, images were captured 50 cm away from the object to cover the entire anterolateral thigh region. Images of the displayed vein patterns were captured using a Canon digital camera, as the device itself provides real-time images only and does not have a built-in camera for recording. Both devices were directed at the area from the same distance, and images were captured at t0, t1, t3, t5, and t6 . BecauseThe Wilcoxon signed-rank test was used for the comparison of the nonparametric, related samples. Statistical analyses were compiled in IBM SPSS Statistics 23.0 , and graphics were created using Microsoft Excel 2021 .2 .We investigated 16 male and 8 female participants with a mean age of 31.3 years  and a mean body mass index (BMI) of 26 kg/mp < 0.01). In the following 30 min after TNPA removal, oxygen saturation decreased by 5.32% to 66.50%  at t6 (p < 0.01). Overall, a 2.75% increase was observed between t0 images and t6  (p = 0.063)  at t0 to 71.82%  at t1 (= 0.063)  Table 2p < 0.01.p ≤ 0.214). At t6, it reached 68.77%  (p = 0.678). Overall, an increase of 3.55% was observed between t0 and t6 (p = 0.086)  to 67.77% at t1  (= 0.086)  Table 2p ≤ 0.214p = 0.074). Thirty minutes after the removal of TNPA, oxygen saturation decreased to 65.62%  at t6 (p = 0.28). Overall, an increase of 1.22% was observed between t0 and t6 (p = 0.395)  at t0 to 68.40%  at t1 (= 0.395)  Table 2p = 0.074p = 0.012). Thirty minutes after the removal of TNPA, oxygen saturation decreased to 65.82%  at t6 (p = 0.012). Overall, an increase of 4.37% was observed between t0 and t6 (p = 0.183)  at t0 to 69.90%  at t1 (= 0.183) . An overp < 0.01). In the following 30 min, the temperature decreased to 31.23 °C  at t6 (p < 0.01). Overall, an increase of 0.63 °C was observed between t0 and t6  (p = 0.407)  at t0 to 32.27 °C  at t1 (= 0.407)   .p < 0.01). In the following 30 min, the temperature decreased to 31.22 °C  at t6 (p = 0.011). Overall, an increase of 1.18 °C increase was observed between t0 and t6 (p = 0.0154)  at t0 to 32.75 °C  at t1 ( 0.0154)   .p = 0.028). In the following 30 min, the temperature decreased to 31.84 °C  at t6 (p = 0.018). Overall, an increase of 0.02 °C was observed between t0 and t6 (p = 0.866)  at t0 to 33.4 °C  at t1 (= 0.866)   .p = 0.012). In the following 30 min, the temperature decreased to 32.75 °C  at t6 (p = 0.036). Overall, an increase of 1.2 °C was observed between t0 and t6 (p = 0.036)  at t0 to 33.23 °C  at t1 (= 0.036)   .Due to the design of the device, the vein illuminator is not capable of delivering quantitative measurements. It produces optical images of the venous blood flow pattern. The instrument creates live images, which were then captured using another digital camera. Comparing the images of the vein finder captured throughout the examination time, no significant differences could be detected between t0, t1, and t6 in the venous pattern, but the veins seemed to vary slightly in terms of thickness or vessel diameter, as shown in There are numerous studies researching the effects of topical negative pressure application on tissue, and different measurement methods have been used ,7,18. MuIn line with the studies by Müller-Seubert et al., the initial increase of oxygen saturation directly following the removal of TNPA (control group: −125 mmHg) showed a similar increase, even though the drop of oxygen saturation along the course was higher in this study . PreviouAt the 30 min mark after TNPA removal, Group 3 (−175 mmHg) still presented a higher level of oxygen saturation compared to the control group (−125 mmHg). However, at the same time point, the values of the control group showed higher levels than those of Group 2 (−25 mmHg). Higher levels of negative pressure up to −175 mmHg resulted in higher levels of tissue oxygen both directly after TNPA removal as well as during the progression leading up to 30 min following removal of TNPA . This coThis is in line with the results by Sogorski et al. in 2018. They found the tissue oxygen saturation increased between TNPA sessions and following the removal of TNPA for a short period of time . The effConcerning the thermography analysis, we found similar developments to those of the oxygen saturation for the initial phase, with an increase of temperature in all groups. Regardless of the negative pressure levels used, the skin temperature showed minimal differences at this point. As for the oxygen saturation values, the relative drop of skin temperature after TNPA removal depended on the pressure level initially set and revealed a higher decrease in the lower pressure levels. Hence, there is a prolonged positive effect on tissue perfusion due to TNPA. It is not able to sufficiently explain the high increase of the skin temperature in Group 1 (0 mmHg), as this might potentially be due to the aforementioned effects on the venous and arterial capillaries. This difference could be due to a lack of depression of veins as a result of no pressure combined with the physiological effect of warming under the dressing causing veins to enlarge, therefore resulting in higher temperature compared to those during TNPA. Due to a potential depression of certain vessels, TNPA could prevent the tissue from warming up over a certain level ,23,24; hFrom generally known physiological effects—as seen in exsanguination procedures in extremity surgery for instance—post occlusive reactive hyperemia effects could explain why the tissue remained at a higher temperature level under higher pressure. In an animal model, when the skin was resected and intravital microscopy was applied, Ichioka et al. found that applying a negative pressure of −125 mmHg significantly increased wound bed blood flow immediately after pressure application, and this was maintained for 1 min after the pressure was released. Whereas, in the −500 mmHg group, the blood flow decreased with time and reached a statistically significant level 5 min after the application of the pressure. This finding is of interest but is not directly applicable to our human direct skin blood flow measurements .One of the aims of our study was to evaluate any additional information that could potentially be gained using a vein illuminator to find out if referable changes in veins can be detected in the focus area. We could see a trend by macroscopic observation; however, due to technical limitations of the device with no built-in clear objective documentation system, we had to rely on the observation of the images we captured macroscopically and subjectively. These observations did not yield additional significant information regarding the exact vein diameters or other structural changes in the venous flow pattern. Nevertheless, it contested that the venous flow pattern remained stable throughout the observation time and was not occluded or significantly altered.The data of this study are of relevance as, for example, the duration of TNP application over closed incisions has been derived from clinical experiences with the vacuum wound therapy only, while exact data of skin perfusion have been limited so far. From our data, it can be drawn that future studies could aim at a longer time period after the removal of TNPA to see how much time passes for each group to reach baseline and if TNPA for several days shows prolonged effects for an even longer period.The results are not exactly transferable to an open wound situation. The test should be repeated on open wounds, rather than on healthy participants and intact skin, with TNPA treatment or appropriate animal models to better evaluate the measuring devices. Therefore, we can only evaluate the superficial effects of TNPA. Extended research can better evaluate how useful the devices are for clinical use, possibly showing the effects TNPA has on deeper tissues. Repeating the test with more participants and with a wider range of negative pressures will provide more data about the usefulness of the new devices. Although authors have investigated different pressure settings during TNPA, the basic knowledge relies on the fundamental data initially described by Morykwas et al. . These dStudies such as those presented might therefore help to better determine the effects of TNPA on skin microcirculation under various pressures and cycles, albeit the ideal pressure remains yet to be found. For our control group, we chose −125 mmHg negative pressure in accordance with the standard clinical practice and due to it being described by Morykwas et al. as the ideal pressure to induce granulation tissue in full-thickness wounds . To see Our investigations underline the efficacy of near-infrared imaging as an appropriate tool to determine changes in microcirculatory skin blood flow patterns under various topical negative pressures delivered via an open cell polyurethan foam. In addition, changes in thermography readings parallel to the values of negative pressures were detectable in the course after TNPA removal. The addition of a new device with near-infrared imaging that was originally developed to visualize venous vessels for the purpose of venipuncture shows a permanent venous blood flow pattern. Despite the initial hypothesis of an inverse relation between pressure exertion and blood flow, we noted that in this study higher levels of negative pressure resulted in higher levels of tissue oxygenation and skin temperature at the end point of 30 min following TNPA. This underlines the potential positive effects of TNPA on tissue perfusion on intact skin or over closed incisions as has been postulated previously from clinical observations.The results that are presented underline the efficacy of near-infrared imaging and thermography as appropriate tools to determine the changes in microcirculatory blood flow patterns of the skin under various negative pressure levels used during TNPA. The new device used for venous blood analysis showed a permanent venous blood flow pattern and needs further evaluation. For increasing pressure levels, we were able to support the hypothesis that there exists a positive influence of negative pressure wound therapy on skin perfusion. Especially for clinical applications of TNPA on skin, this could influence therapeutic regimes with the need for blood flow alterations. Future research is needed to assess the transferability of the presented results to human wounds.


TM). Logistic regression was fitted to identify significant associations between the SNPs and blood pressure control with amlodipine. Results: The majority of the participants were females (76.6%), older than 45 years (89.1%) and had uncontrolled hypertension (52.3%). Of the 13 SNPs genotyped, five SNPs, rs1042713 , rs10494366 , rs2239050 , rs2246709  and rs4291 , were detected among the Xhosa participants, while none were detected among the Swati and Zulu tribal groups. Variants rs1042713 and rs10494366 demonstrated an expression frequency of 97.5% and 79.5%, respectively. Variant TA genotype of rs4291 was significantly associated with uncontrolled hypertension. No association was established between blood pressure response to amlodipine and the remaining four SNPs. Conclusions: This study reports the discovery of five SNPs in amlodipine genes  among the indigenous Xhosa-speaking tribe of South Africa. In addition, the TA genotype of rs4291 was associated with blood pressure control in this cohort. These findings might open doors for more pharmacogenomic studies, which could inform innovations to personalised anti-hypertensive treatment in the ethnically diverse population of South Africa.Objective: This study describes the single nucleotide polymorphisms (SNPs) in amlodipine-associated genes and assesses their correlation with blood pressure control among South African adults with hypertension. Methods: In total, 304 hypertensive patients on amlodipine treatment belonging to the indigenous Swati, Xhosa and Zulu population groups of South Africa were recruited between June 2017 and June 2019. Participants were categorized into: controlled (blood pressure < 140/90 mmHg) and uncontrolled (blood pressure ≥ 140/90 mmHg) hypertension. Thirteen SNPs in amlodipine pharmacogenes with a high PharmGKB evidence base were selected and genotyped using MassArray (Agena Bioscience Hypertension is one of the most potent cardiovascular risk factors that affects over a billion people worldwide . The 201Amlodipine is a long-acting third-generation calcium channel blocker (CCB) that has been shown to effectively lower blood pressure and reduce cardiovascular disease risk among hypertensive patients ,12. HoweIn addition, SNPs that are harbored by genes that are indirectly implicated in the pharmacokinetics of the anti-hypertensive effect of amlodipine, such as angiotensin converting enzyme (ACE) and angiotensinogen (AGT), have been examined ,13. BothThe discovery of SNPs facilitated patient stratification for many diseases, including hypertension, and allowed physicians to adopt pharmacogenomics-based approaches in the selection of anti-hypertensive drugs to improve drug efficacy among patients . AlthougThe study protocol was approved by the Senate Research Committee of the University of the Western Cape . Permission to implement the study protocol was granted by the clinical governance of the respective hospitals in the Eastern Cape and Mpumalanga Provinces. Participants were issued with a research information sheet detailing the purpose and process of the study; it was made available in various indigenous languages . Each participant signed an informed consent form as evidence of voluntary participation in the study. Participants’ rights to privacy and confidentiality of medical information were respected during and after the study.In total, 304 patients with hypertension belonging to the indigenous Nguni  population groups of South Africa were recruited from Cecilia Makiwane Hospital , Piet Retief Hospital, Thandukukhanya Community Health Center and Mkhondo Town Clinic  between June 2017 and June 2019. Participants were eligible if they were 18 years or older and were on continuous anti-hypertensive therapy treatment for at least a year. Individuals who were bedridden, pregnant and clinically unstable were excluded from the study.A trained research nurse measured the blood pressure (BP) of each participant using a validated automated digital blood pressure monitor (Macrolife BP A 100 Plus model) according to standard protocols. The BP was recorded in triplicate and the average was used for analysis. Patients were categorized as: controlled (blood pressure < 140/90 mmHg) and uncontrolled (blood pressure ≥ 140/90 mmHg). DNA samples were collected in the form of buccal swabs and stored at −20 °C.2) and was categorized based on WHO criteria as underweight, normal, overweight and obese (30 or greater kg/m2). The age, ethnicity, smoking status and salt intake were self-reported by each participant and documented in a proforma designed for this study. Prescribed drugs for each participant were retrieved from their medical records. Physical activity was categorised as active if participants engaged in exercise leading to an increase in heart and respiratory rate, such as gardening (1–3 times per week), or inactive if they did not engage in any physical activity. Smoking status was categorised as never smoked or ever smoked (current smokers or have a history of tobacco use). Salt intake was determined by the survey question do you add salt on the table while eating or on purchased take-away food? Participants who answered “yes” were placed in the increased salt intake category; participants who answered “no” were placed in the low–moderate salt intake category. Prescribed anti-hypertensive drugs included amlodipine alone or in combination with hydrochlorothiazide, enalapril and atenolol.In addition, the nurse also measured the weight of each participant to the nearest 0.1 kg using a digital scale  and height to the nearest of 0.1 cm using a mounted stadiometer. Participants wore minimal clothing and no shoes. Body Mass Index (BMI) was estimated as weight (kg) divided by height in squared meters  of Cecilia Makiwane, Piet Retief and Ermelo Provincial hospitals in accordance with standard protocols and categorised according to the guidelines of The Society for Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA) .Genomic DNA was extracted from buccal swab samples using a standard salt-lysis procedure . BrieflyThirteen single nucleotide polymorphisms associated with blood pressure response to amlodipine were selected using the Pharmacogenomics knowledge base , EnsemblTM) were designed and optimised by Inqaba Biotechnical Industries  and used for the genotyping of the selected SNPs. The genotyping assay is based on a locus-specific PCR reaction that is followed by a single base extension using the mass-modified dideoxynucleotide terminators of an oligonucleotide primer, which anneals immediately upstream of the site of mutation. The SNP of interest is identified using MALDI-TOF mass spectrometry.Two multiplex MassARRAY systems  and adjusted odds ratios (AORs) for the adjusted logistic regression model analysis. A p-value less than 0.05 was considered statistically significant. Bonferroni corrected p-values were set at 0.025. Minor allele frequency (MAF) and Hardy–Weinberg equilibrium (HWE) tests were calculated for all the SNPs using Genetic Analysis in Excel (GenAIEx) Version 6.5. .Statistical analyses were performed using Medcalc version 2.2.0.0. The general characteristics of the participants were summarised by using simple descriptive statistics. Associations between alleles, genotypes and blood pressure response to amlodipine were measured using unadjusted and adjusted odds ratios (ORs), 95% confidence interval (95% CI) and n = 71) were males and 76.6% (n = 233) were females. Most of the study participants were older than 45 years (n = 271), 85.1% (n = 259) had never smoked, 78.0% (n = 237) had low–moderate salt intake and 53.3% (n = 159) had blood pressure ≥ 140/90 mmHg. Overall, 4.28% (n = 13) of the participants were on amlodipine monotherapy . rs1042713 was observed among 79.5% (n = 97) of Xhosa participants, of whom 76.8% (n = 63) were females and 78.2% (n = 43) were aged between 55 and 65 years. Further, rs10494366 was detected among 97.6% (n = 119) of the Xhosa participants, 97.6% (n = 80) were females and 98.2% (n = 54) aged between 55 and 65 years . Out of thirteen SNPs, only five were detected among the Xhosa tribe. However, the variant alleles of the five SNPs were not detected among Swati and Zulu participants. rs2239050, rs2246709 and rs4291 were observed among all Xhosa participants , rs10494366 (35.3%) and rs2239050 (28.7%) showed lower minor allele frequency in the Xhosa population in comparison to all selected populations. Variant rs2246709 showed a slightly higher minor allele frequency in the Xhosa population (51.6%) when compared to selected world populations. In comparison to the Yoruba (22.7%) and Luhya people (23.2%), the Xhosa population (34.4%) showed a higher minor allele frequency; however, this was lower than British (41.4%), Mexican (44.0%) and South Asian (38.4%) populations .p-value = 0.014 (In the multivariate (crude) logistic regression model analysis, the genotype TA (rs4291) was independently and significantly associated with uncontrolled hypertension with amlodipine treatment. After adjusting for other factors in the logistic regression model analysis, the magnitude and direction of the association remained unchanged. Individuals with genotype TA (rs4291) had lower odds of achieving blood pressure control in comparison with genotype AA (rs4291). However, the genotype GG (rs2239050) initially demonstrated an independent and significant association with controlled hypertension in response to amlodipine treatment in the crude logistic regression model analysis. After adjusting for confounding factors (drug regime), the effect was lost. After Bonferroni correction, TA (rs4291) remained significant with a  = 0.014 .There is a paucity of existing literature on the ethnically and genetically diverse population of South Africa in relation to pharmacogenomics-based anti-hypertensive therapy. In the current study, we describe SNPs in amlodipine-associated genes and assess their correlation with blood pressure control among South African adults with hypertension.The current study examined thirteen SNPs associated with amlodipine in 304 hypertensive individuals belonging to the indigenous Nguni tribe  of South Africa. Out of thirteen, only five SNPs  were detected among the Xhosa population. This may be due to the small number of participants that were included in the study. This is not surprising as studies with a larger sample size demonstrate high statistical power and can detect smaller associations. Furthermore, the variant alleles of these SNPs were not detected among the Zulu and Swati tribal groups. Of note, the Swati tribal group is a minority in South Africa. However, failure to detect the selected SNPs among the Zulus is surprising, as the ratio of Xhosas to Zulus in the country is 1:1. The differences observed in the SNPs detected highlights the genetic differences that exist between the two indigenous tribes that might have been brought by demographic and evolutionary events, including admixture. The minor allele frequencies displayed by the Xhosa population were different from those observed in other African and global populations, including the Luhya (Kenya), the Yoruba (Nigeria and Benin), African American (United States of America), British (Great Britain), South Asian and Mexican  people . AfricanWe found no association between blood pressure response to amlodipine and the genotypes or the alleles of rs1042713 (ADRB2) and rs2246706 (CYP3A5). In contrast, the G allele of rs1042713 (ADRB2) was significantly higher among Northern Han Chines individuals with essential hypertension . It was We found no association between genotypes and the alleles of NOS1AP rs10494366 and CACNA1C rs2239050 with blood pressure response to amlodipine. These findings are surprisingly different from previous reports. For instance, a study conducted among Caucasian patients showed that the GG genotype of rs2239050 was independently associated with an improved amlodipine treatment outcome rate of 52% . SimilarXhosa carriers of the TA genotype of ACE rs4291 were less likely to exhibit controlled blood pressure in response to amlodipine therapy. There is no record of the direct association of this polymorphism with blood pressure response to Amlodipine in the literature. However, the TA genotype was previously associated with decreased fasting plasma glucose levels among hypertensive patients undergoing amlodipine treatment . This poThis is the first study to detect SNPs associated with amlodipine among indigenous South African ethnic groups. In addition, this study reports an association between the TA genotype of rs4291 and blood pressure control with amlodipine among the Xhosa tribe of a South African cohort. However, some limitations of the study cannot be ignored, including the small sample size, lack of information on the dosing of anti-hypertensive drugs and adherence to treatment and other lifestyle measures. These factors could have impacted on the extent of blood pressure control in the cohort. Further, the authors acknowledge the fewer samples of individuals on amlodipine monotherapy. This is largely due the standard of hypertension treatment in South Africa, where patients are initiated on thiazide diuretics upon diagnosis and other anti-hypertensive drugs are introduced as add-on drugs for patients who do not respond adequately to thiazide monotherapy . Thus, wThis study reports the detection of five SNPs in amlodipine-associated genes  among the indigenous Xhosa-speaking ethnic group of South Africa. In addition, the TA genotype of rs4291 was associated with blood pressure response to amlodipine treatment among the Xhosa cohort. Findings of the study highlight the relevance of comprehensively characterizing highly diverse populations, particularly those of African origin, to facilitate pharmacogenomics-based anti-hypertensive treatment. Additionally, these findings might open doors for more pharmacogenomics studies, which could inform innovations to personalized anti-hypertensive treatment in the ethnically diverse population of South Africa. Furthermore, our findings laid a foundation for building an African-specific panel of SNPs that could be used to identify responders and non-responders to amlodipine as well as other anti-hypertensive drugs, thus, providing the right treatment to the right patient at the right time.


Hypertension is a common physical condition with high blood pressure for a prolonged period. Long risk factors like age, overweight, high dietary salt intake, smoking, sedentary lifestyle, and term hypertension might lead to various cardiovascular diseases. The normal blood pressure, systolic, is 90-119 mm Hg and diastolic 60-79 mm Hg. The objective of this study is to find out the prevalence of hypertension among current cigarette smokers patients in an outpatient department of a tertiary care centre.A descriptive cross-sectional study was done on 385 outpatient department patients in a tertiary care centre from September, 2021 to February, 2022. The sample was collected by a convenience after approval from the Institutional Review Committee (Reference number: 0505202105). Outpatient department patients who had past history of smoking cigarette>100 cigarettes and who is still smoking were included in the study. Data were analysed by using the Statistical Package for the Social Science software version 16.0. Point estimate at 95% Confidence Interval was calculated along with frequency and percentage for binary data and mean with standard deviation for continuous data.Among 385 patients, 209 (54.28%)  were hypertensive patients. One hundred fifty-six (40.51%) males and 53 (13.76%) females were hypertensive.The prevalence of hypertension was higher when compared to other studies done in similar settings. For patients 1859 years without comorbidities and ≥60 years with comorbidities, <140/90 mm Hg is normal.2Hypertension is a major public health issue in the world. Prolonged period of increase in blood pressure is hypertension. Normal systolic pressure is <120 mm of Hg, elevated is 120-129, stage 1 is 130-139, stage 2 is >140 and 180 is the stage of the crisis. The normal diastolic pressure is <80, stage 1 is 80-89, stage 2 is >90 and the stage of the crisis is 120.3 Hypertension is the major risk factor for cardiovascular disease.4 Smoking is the main factor for elevated blood pressure.5High blood pressure, smoking, and air pollution from household fuels are main risk factors for global disease burden.The aim of this study is to find the prevalence of hypertension among current cigarette smokers in an outpatient department of a tertiary care centre.A descriptive cross-sectional study was carried out among Out Patient Department (OPD) patients of Kathmandu Medical College, Duwakot, Bhaktapur. The study was started from September, 2021 to February, 2022 with the approval of the Institutional Review Committee (IRC) of Kathmandu Medical College and Teaching Hospital (Reference number: 0505202105). Patients who had past history of smoking >100 cigarettes and currently smoking were included in the study. Patients who are known case of hypertension and with normal blood pressure but under medication were considered hypertensive. The sample was collected by a convenience sampling. The sample size was calculated by using the following formula:2 × p × q) / e2n = (Z2 × 0.5 × 0.5) / 0.052  = p = prevalence taken as 50% for maximumq = 1-pe = margin of error, 5%The minimum samples size of 385 was taken. Data were analysed by using the Statistical Package for the Social Science (SPSS) software version 16.0. Point estimate at 95% Confidence Interval was calculated along with frequency and percentage for binary data and mean with standard deviation for continuous data.Out of 385 patients, 209 (54.28%)  were hypertensive patients and the mean age was 52.76±13.24 .In total, hypertensive males were 156 (40.51%) and females were 53 (13.76%) respectively .6 The current study had a markedly higher frequency than a study that showed 19.8% in 1000 population.7 Similar findings were seen in a study done in a similar setting.8In our findings, the prevalence of hypertension was 54.28% in the total sample. The prevalence was much higher in rate than in the Nepal Demographic and Health Survey (NDHS) 2016. NDHS showed no significant association with hypertension in smokers.9 An epidemiologic study showed higher blood pressure among nonsmokers and ex-smokers than current smokers.10 One of the studies showed about 38%,11 Two other studies showed significantly raised blood pressure in smokers.13 On the other hand, one of the studies showed modest relation of hypertension in smokers.14In contrast to the current study, a study was done showed diastolic and mean arterial pressure in current smokers were lower than in non-smokers.This current study has some limitations, the sample size was relatively small and data was taken from only one tertiary care centre. The larger sample size in different sites might have greater values. The females and young subjects were hesitant to disclose their smoking habits due to social norms. So, there were higher chances of error in gender and age groups findings. In addition, different age groups, habits like exercise, alcohol intake, body mass index, and ethnicity might have greater and more significant values.The prevalence of hypertension among current cigarette smokers was higher when compared to other studies done in similar settings. Most of the males were hypertensive.


Albuminuria is a risk factor for microvascular and macrovascular complications in the diabetic population. However, few studies have correlated poor glycemic control and albuminuria prevalence in Hispanic populations.To evaluate the association between glycemic control and albuminuria among Peruvian adults with type 2 diabetes mellitus (T2DM).Cross-sectional analytical study among adults with T2DM in Lima, Peru.We included adults over 18 years old who were in a clinical follow-up program at a private clinic in Lima in 2018. Poor glycemic control was defined as a serum value of glycosylated hemoglobin A1C (HbA1C) ≥ 7%. Albuminuria was defined as albumin values > 30 mg/dl in the first morning urine. We generated generalized linear regression models from the Poisson family with robust variance. We calculated the crude and adjusted prevalence ratios (PRs) with their 95% confidence interval (CI).We analyzed 907 participants of median age 58 years , and 62.8% were males. The prevalence of poor glycemic control was 39.8%, and the prevalence of albuminuria was 22.7%. The prevalences of albuminuria in groups with poor glycemic control and adequate glycemic control were 32.7% and 16.1%, respectively. In the adjusted regression analysis, we found a statistically significant association between poor glycemic control and albuminuria .The prevalence of poor glycemic control and albuminuria was high in our study population. Moreover, Peruvian T2DM adults with poor glycemic control were more likely to have albuminuria. The prevalence of T2DM in 2017 was 451 million cases worldwide, and according to the estimate of the International Diabetes Federation for the year 2045, this figure will rise to 693 million people. Around the world, almost 50% of T2DM cases have not yet been diagnosed.Type 2 diabetes mellitus (T2DM) is a worldwide public health problem. In another study on ambulatory T2DM patients at a public hospital in Lima, almost seven out of ten patients had abnormal glycemic control. At the primary care level, one study found that 20 to 30% of diabetic patients who knew about their disease were not following any type of treatment and had had a late diagnosis, given that 68% of the cases knew that their diagnosis had only been made because of the complications of T2DM.In Peru, diabetes treatment and control are poor. Regarding management, a study on rural, rural-to-urban migrant and urban participants showed that the proportions of diabetes awareness, treatment and control were 71.1%, 40.6% and 7.7%, respectively. However, there are structural problems in the Peruvian healthcare system that limit adequate care for diabetes patients. In addition to the poor quality of clinical practice guidelines for diabetes, there is also a lack of diagnostic methods and medications in primary care centers for managing these patients.In this context, complications relating to T2DM among Peruvian adults, such as retinopathy, cardiovascular disease, neuropathy and kidney disease, are an important target for public health strategies. There are several risk factors for albuminuria, such as duration of diabetes, male gender, creatinine levels and poor glycemic control, among other variables. Glycosylated hemoglobin A1C (HbA1c) is a glycemic control marker. This marker has a positive correlation with blood glucose levels during the previous six to ten weeks. Higher levels are associated with an increased risk of developing microangiopathy among diabetics.Albuminuria, along with a decreased glomerular filtration rate, is a component of diabetic kidney disease and is a risk factor for mortality and cardiac and ocular complications among diabetic people. In another study in a primary care center, the prevalence of albuminuria was 17.9% among diabetes patients and 10.8% among hypertension patients.In Peru, the prevalence of albuminuria is high in the population at risk. A study in a screening campaign in 23 nephrology centers nationwide found that the frequency of microalbuminuria was 53.45%, and that 8.96% of the patients had microalbuminuria > 100 mg/dl. while intensive glucose control reduces the risk of albuminuria. However, although studies have been conducted in different ethnic groups, few studies have included any significant proportion of Hispanic patients, despite the evidence that there are ethnic variations in albuminuria prevalence among diabetic patients. Some studies have found that Hispanic patients have greater probability of albuminuria or the initial stages of diabetic kidney disease than other ethnic groups. Considering the burden of diabetic kidney disease in the Hispanic population, and that studies that have included the Hispanic population have been conducted in the United States and not in Latin America, under the conditions of a different healthcare system that could condition different health outcomes, studies on this disease in this ethnic group are needed.Poor glycemic control has been correlated with albuminuria in various studies using HbA1C,Thus, we aimed to evaluate the association between glycemic control and albuminuria among Peruvian adults with T2DM.We conducted a study with an analytical cross-sectional design. We included adults over 18 years of age with T2DM who attended a healthcare program called “Take Care” at a private clinic in Lima, Peru, in 2018.“Take Care” is a healthcare program among chronic patients previously diagnosed with T2DM, arterial hypertension, dyslipidemia or asthma, with comprehensive monthly follow-up controls. The program offered by each patient’s insurance policy covers laboratory tests, procedures and medical consultations, according to that patient’s comorbidities. In addition, the clinical staff register all the patient’s information in the database of the program in order to carry out personalized follow-up and provide adequate treatment.We excluded patients whose data were incomplete or poorly recorded in the database and patients with a history of arterial hypertension and chronic kidney disease. In addition, in that study, the prevalence of microalbuminuria among participants with poor glycemic control was 57%, while the prevalence of microalbuminuria was 28% among participants with adequate glycemic control. With these values and using a 95% confidence level and statistical power of 80%, we calculated a sample size of 110 patients. However, because we had access to the “Take Care” program database, we decided to analyze all participants who met our eligibility criteria during 2018.To calculate the sample size, we used a study in which albuminuria and HbA1C among type 2 diabetic patients was evaluated. This showed that the prevalence of poor glycemic control was 70%. We considered the following as potential confounding variables: age, sex, systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHg), fasting glucose (mg/dl), uric acid (mg/dl), creatinine (mg/dl), waist circumference (cm) and body mass index (BMI) (kg/m2).Our exposure variable was glycemic control. A serum value for glycosylated HbA1C ≥ 7% was defined as indicative of poor glycemic control. Our outcome variable was the presence of albuminuria, defined as its presence in the first morning urine, considering values > 30 mg/dl as positive results.In the “Take care” healthcare program, the anamnesis and physical examination were carried out and recorded in the electronic medical record during the consultation with the physician. Subsequently, the clinical staff grouped the electronic medical records and laboratory tests in the healthcare program database.We requested the database of the patients with T2DM who had undergone a check-up within the “Take care” healthcare program in 2018. These patients had attended at least one annual check-up; for this purpose, laboratory tests were performed two days before they saw the physician.We reviewed the database and eliminated patients whose data were incomplete. We considered the HbA1C data that coincided with the date on which the participants underwent the albuminuria test. Moreover, we considered only the first annual measurement of both of these variables. In the same way, other laboratory tests were conducted on the same date on which the participants underwent an albuminuria test. The laboratory method for measuring glycosylated hemoglobin consisted of high-resolution chromatography, and the immunoturbidimetric method was used for albuminuria.The Institutional Review Board of the Universidad Peruana de Ciencias Aplicadas approved the research protocol on March 31, 2020 (PI 113-18). This study did not have identification codes for the participants, which thus maintained the confidentiality of patient information. The information used in this study was handled solely and exclusively by the authors of this study. Similarly, permission for collection of information from the database of the private clinic was obtained from the ethics committee of the private clinic, which approved the handling of data and its publication (letter no. 006-TI-UDID-CI-2019).We used the mean and standard deviation to describe the numerical variables with normal distribution. For variables with skewed distribution, we used the median and interquartile range (IQR). We used absolute and relative frequencies for categorical variables.We used Student’s t test to compare numerical variables with normal distribution, and for numerical variables with skewed distribution, we performed the Mann-Whitney U test. We used the chi-square test to compare categorical variables and correlated numerical variables using the Pearson coefficient. Additionally, we evaluated collinearity between the variables before entering them into the multivariable model.We generated crude and adjusted generalized linear models from the Poisson family with robust variance to assess the association between poor glycemic control and albuminuria. We reported the prevalence ratio (PR) as an association measurement, with the respective 95% confidence interval (CI). As described in the literature, we entered potential confounding variables into the multivariable model using an epidemiological approach.We carried out all analyses in the STATA statistical package , version 14.0.2 (IQR 26.6 to 32.3). The median HbA1C was 6.6% (IQR 6 to 7.9) and the median albuminuria was 12.9 mg/dl (IQR 6.02 to 26.1). The prevalence of poor glycemic control was 39.8% (n = 361) . The participants’ median age was 58 years (IQR 49 to 66) and their median BMI was 29.05 kg/mn = 361) .The median albuminuria was higher among individuals with poor glycemic control  than among those with adequate glycemic control , and this difference was statistically significant (P < 0.01). The logarithms of the albuminuria and glycosylated hemoglobin levels showed a positive and statistically significant correlation  . Also, wThe prevalence of albuminuria was 22.7% and was higher among men . In addition, there was higher median fasting glucose, abdominal circumference and SBP in the group with albuminuria than in the group without albuminuria (P < 0.01). The prevalences of albuminuria in the groups with poor glycemic control and adequate glycemic control were 32.7% and 18.1% (P < 0.01), respectively. The crude regression analysis showed an association between poor glycemic control and albuminuria . After adjusting for age, sex, SBP, DBP, fasting glucose, uric acid, BMI and creatinine in the multivariable analysis, the association with poor glycemic control remained statistically significant  .The main finding from our study was an association between poor glycemic control and albuminuria in our population. Additionally, almost one third of the sample studied had poor glycemic control or albuminuria. In a multicenter study on diabetic patients who attended their first nephrological consultation in four hospitals in Lima, 69.3% of them had albuminuria greater than 30 mg/24 hours. The prevalence of albuminuria in our study was higher than in high-income countries, probably because fewer T2DM patients achieve control over their disease through healthcare services.Two out of every ten patients with DM had albuminuria. In a previous study in Peru, the prevalence of albuminuria was 13.4%, in hospitals in Arequipa. Also, the prevalence of albuminuria was found to be 13.4% in China, 16.8% in Saudi Arabia and 24.9% in the United Kingdom. The differences found are likely to have been due to the sample size, sampling and sample characteristics or, especially, the albuminuria measurement method. For example, while albuminuria was measured with using the first morning urine in our study, the study by Herrera et al., also conducted in Lima, used 24-hour urine. Thus, our findings may have been underestimates.The prevalence of albuminuria has been found to vary significantly in other countries. Rates of 19.8% to 36.3% were found in southern India and 25.5% in northern India. Iran, Nigeria and Pakistan. In contrast, although a cross-sectional study conducted in Nepal in 2015 showed a positive correlation between albuminuria and HbA1c, this was not statistically significant; the difference in results was likely to have been due to the limited sample size, as the authors of that study acknowledged.Our results regarding the association between poor glycemic control and albuminuria were similar to those reported in recent studies conducted in India, In another study that used NHANES, it was found that among individuals without diabetes, blacks had 2.18-fold and Mexican Americans had 1.81-fold greater odds of having albuminuria than whites, after adjustment for potential confounding factors. Although the reasons for this variation are not entirely clear, they may be related to the reasons why diabetes and its complications are more frequent in the Hispanic population. These include biological factors, such as predisposition to insulin resistance, augmented insulin secretion and abdominal obesity, as well as complex socioeconomic and cultural factors.No specific studies have evaluated this association in the Hispanic population, to the best of our knowledge, although there is evidence suggesting ethnic variation in the prevalence of albuminuria. For example, a study using the National Health and Nutrition Examination Survey (NHANES), on 2,310 diabetic patients, found that the prevalence of early chronic kidney disease (CKD) was greater among Hispanics and African Americans than among whites, and Hispanics had higher albuminuria. In diabetic kidney disease, the glomerular basement membrane loses negative ionic charges and both endothelial and podocyte lesions increase the size of the pores, which thus causes loss of selectivity of glomerular filtration and produces albuminuria.Among patients with poor glycemic control, hemodynamic and metabolic changes to the glomerulus occur, which damage endothelial cells and podocytes and alter the glomerular basement membrane properties, thus contributing to alteration of the physical-chemical characteristics of the glomerular filtration barrier. Combining interventions such as medication compliance, increased physical activity and healthy nutritional habits can reduce microvascular complications and improve the quality of life of patients with T2DM. Clinicians need to seek periodic measurement of albuminuria levels, especially among patients with poor glycemic control.Clinicians need to emphasize the importance of correct glycemic control among patients with T2DM. The Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group recommends an individualized HbA1c target ranging from < 6.5% to < 8.0% among patients with diabetic kidney disease that is not being treated with dialysis, in order to reduce the risk of microvascular and macrovascular complications. Similar findings have been obtained in other countries such as Russia, China, Myanmar and Angola, where the diabetes control rates were 58.5%, 16.9%, 35.2% and 2.7%, respectively.Despite this recommendation, glycemic control is not always achieved. In some studies in Peru, it was found that in diabetic patients treated in city hospitals, between 40% and 70% had an HbA1C level greater than 7%.A systematic review found two key healthcare system barriers to effective T2DM care and management: financial constraints faced by the patient and limited access to healthcare services and medication. It also found three healthcare system factors that facilitated effective T2DM care and management: use of innovative care models, increased pharmacist involvement in care delivery and education programs led by healthcare professionals. Lastly, we could not be sure that all the conditions for adequate albuminuria measurement were observed, which might have produced false positives in our sample.Our study had some limitations. First, it had a cross-sectional design, which therefore did not allow assessment of causal relationships between the variables. Second, information bias was possible; however, we performed rigorous quality control on the data collected. Third, we did not have any information on some other potential confounding variables, such as the number of years for which the patients had been suffering from T2DM, their physical activity levels, their dietary habits, the length of time since their inclusion in the program and whether they were previously seen at another institution. Similarly, we did not have information on patients’ adherence to the program, or whether they were visiting other doctors outside the program or were hospitalized during the follow-up. Fourth, we unable to use the gold standard for measuring albuminuria (24-hour urine test), which could have caused misclassification of outcomes. However, initial screening of albuminuria using a urine sample collected early in the morning, as was done in our study, has good sensitivity compared with the 24-hour urine test.There was an association between poor glycemic control and higher prevalence of albuminuria among Peruvian patients with T2DM. Therefore, we recommend further research on cost-effective glycemic control interventions, in order to reduce the risk of microvascular and macrovascular complications in the Hispanic population.


Lung function improved, achieving a significant improvement in %FEV1 (p < 0.001), as well as asthma control, with a significant increase in asthma control test (ACT) scores in both therapies. The markers associated with the corticosteroid-saving effect were the low doses of oral corticosteroids and absence of exacerbations for mepolizumab, and higher blood eosinophilia, absence of chronic obstructive pulmonary disease (COPD), and reduction in oral corticosteroid cycles for benralizumab. The greatest improvement in lung function in both therapies was linked to lower previous FEV1 levels and absence of other respiratory diseases. The reduction in exacerbations was associated with absence of exacerbations the previous year for mepolizumab and never smokers for benralizumab. The results of this real-life study confirm the clinical benefit obtained after the introduction of an anti-IL5 biological therapy and the possible predictive biomarkers of response to treatment.Severe Uncontrolled Asthma (SUA) counts for more than 25% of cases of severe asthma. The main factors that impair the quality of life of these patients are high doses of oral corticosteroids, the presence of exacerbations, and reduced lung function. The objective of this study was to evaluate, in real life, the clinical improvement of patients with SUA treated with anti-interleukin 5 (IL5) therapies: mepolizumab and benralizumab, together with the search for biomarkers associated with the response. We conducted a retrospective observational cohort study that included patients with severe uncontrolled eosinophilic asthma in a tertiary hospital receiving biological therapies. Three types of response were evaluated: improvement in lung function, reduction in exacerbations, and decrease in the use of oral corticosteroids. After 12 months of treatment, significant reductions were found in the number of exacerbations, the use of oral corticosteroids, and blood eosinophil levels for both biological therapies ( Asthma is a chronic and heterogeneous inflammatory disease of the airways, in which various cells and inflammatory mediators are involved, partly determined by genetic factors, resulting in bronchial hyperreactivity and restriction of airflow, which give rise to recurrent episodes of wheezing, dyspnea, and exacerbations ,2.It is one of the main non-transmissible diseases affecting children and adults. The most recent World Health Organization (WHO) estimates indicate that in 2019, 262 million people were affected by asthma worldwide and 461,000 deaths due to lack of diagnosis and/or treatment were recorded that year . As it iAccording to the European Respiratory Society (ERS) and the American Thoracic Society (ATS), severe uncontrolled asthma (SUA) represents between 5% and 10% of asthma cases, making it a constant challenge to maintain this control . Data reBetween 30% and 40% of patients with severe asthma also require regular use of oral corticosteroids (OCS) to control their asthma ,7,8, whiThe Global Strategy for the Management and Prevention of Asthma (GINA) defines asthmatic exacerbation as episodes characterized by a progressive increase in symptoms of shortness of breath, cough, wheezing or chest tightness, and a progressive decrease in lung function, i.e., they represent a change from the patient’s usual status that is sufficient to require a change in treatment . ExacerbLack of prevention and/or treatment of exacerbations, together with the presence of potentiating risk factors, such as deficient treatment adherence, incorrect inhaler technique, comorbidities, exposure to toxins or allergens, and reduced lung function, represent a major problem in the clinical management of asthma, associated with increased morbidity and risk of death, which could as much as triple healthcare costs due to increased medication requirements, need for visits to emergency departments, and in many cases, hospitalization ,20,21,22The development of new anti-interleukin-5 (IL5) biological therapies, such as mepolizumab and benralizumab, for managing asthma represents a major advance in addressing it. Mepolizumab and benralizumab are humanized monoclonal antibodies, which respectively act against IL5 and its receptor (IL5R), selectively and effectively inhibiting the eosinophilic cascade ,25,26,27A total of 89 patients receiving mepolizumab treatment were included in the study. Their clinical and demographic characteristics are shown in During the previous year, all the patients had required ICS, with a median of 500 [500–1000] µg/day, 73.9% (65/89) needed bursts of OCS, with a median of 2 [0–4] cycles, and 6.7% (6/89) required maintenance OCS. Mean %FEV1 was 71.1 ± 23.7, a median baseline blood eosinophil count of 655 [330–905] cells/μL was recorded, and a baseline IgE of 122.55 [30.25–179.75] IU/mL. There were 60.2% (53/89) who suffered at least one exacerbation during the year before the treatment and the median ACT score was 12.5 [9–15.8] points. During the year before treatment with benralizumab, all patients had received ICS, with a median of 1000 [500–1000] µg/day, 87.7% (50/57) had required bursts of OCS, with a median of 2 [1–4] cycles, and 8.8% (5/57) required maintenance OCS. Mean %FEV1 was 71.7 ± 22.52, a median baseline blood eosinophil count of 410 [230–570] cells/μL was recorded, and a baseline IgE of 137.7 [50–758] IU/mL. There were 45.6% (26/57) who suffered at least one exacerbation during the year before the treatment and the median ACT score was 13 [9.5–15.5] points. p = 0.039). No significant differences between the baseline and post-treatment doses were found in the mepolizumab group. The results of the comparative analysis are shown in After 12 months of biological therapy, daily doses of ICS showed significant reductions of 50% for the benralizumab group  of the patients and 22.5% (20/89) did not require cycles of OCS. In addition, 93.3% (83/89) did not require maintenance OCS and 4.5% (4/89) achieved a reduction of 50% or more in the maintenance dose. A total of 48.1% (38/79) of the patients responded satisfactorily, with an increase of at least 10% in FEV1, and 67.9% (55/81) obtained FEV1 values higher than 80%. The rate of exacerbations was reduced by at least 50% in 47.2% (42/89) of cases and 41.6% (37/89) suffered no exacerbation during the follow-up period. The results are shown in Use of benralizumab for 12 months resulted in a reduction in OCS bursts of 50% or more in 50.9% (29/57) of cases and 10.5% (6/57) did not need cycles of OCS. In addition, 85.9% (49/57) did not require maintenance OCS and 5.3% (3/57) achieved a reduction of 50% or more in the maintenance dose. FEV1 (%) increased by at least 10% in 52.1% (25/48) of the patients and 71.4% (35/49) achieved values of more than 80%. The rate of exacerbations showed a reduction of at least 50% in 42.1% (24/57) of the patients and 52.6% suffered no exacerbation requiring emergency department treatment and/or hospitalization. The results are shown in The bivariate analysis showed a satisfactory response associated with lower initial ICS values, absence of OCS bursts during the year prior to mepolizumab, and lower number or absence of exacerbations , respectively [p = 0.03) [p < 0.001 and p = 0.0012, respectively) in OCS bursts; reductions of 55% (p < 0.001) in exacerbations requiring emergency or hospitalization. The 73% (p = 0.004) and 83%  showed reductions in the rate of exacerbations requiring hospitalization; 27% to 84% had discontinued maintenance OCS and from 32% to 100% had reduced the initial maintenance dose (p < 0.001); lung function improved by 3% to 8% (p < 0.05); reductions in blood eosinophilic counts from 69% to 92% (p < 0.05); and changes in ACT from 5 to 8 points [In this study, we found that mepolizumab treatment in severe uncontrolled asthma was very effective, significantly reducing OCS bursts per year, maintenance OCS, blood eosinophil levels, IgE, and annual rate of exacerbations requiring emergency department treatment and/or hospitalization. The reduction in IgE levels was significant, however, as expected, it was not a biomarker of response for this anti-IL5 therapy. A significant improvement in asthma control occurred, with increases in ACT questionnaire scores and FEV1. The MENSA and MUSCA clinical trials showed a clinically significant reduction in exacerbation rates by 53% and 58%  . The res = 0.03) ,45,46,47 = 0.03) . Consist8 points . HoweverThe markers significantly associated with the corticosteroid-saving effect were the absence of exacerbations and lower ICS levels; the improvement in lung function was related to low initial FEV1 percentages and absence of SAHS, and the absence of exacerbations during the year prior to treatment was associated with a positive response to the reduction in exacerbations. Previous studies relate high eosinophil levels to a greater treatment response with mepolizumab ,49; thesp < 0.001), respectively. Clearly, the reduction is greater in our study, which may be due to the greater severity of the patients included in the randomized trials. Our results reflect a 77% reduction in the rate of exacerbations, similar to the ZONDA study where reductions of 70% (p < 0.001) are reflected. Real-life studies in recent years are in line with our investigation [After 12 months of treatment with benralizumab, very promising results were reported, with substantial reductions in OCS bursts, blood eosinophils, and number of exacerbations requiring emergency care or hospitalization. Moreover, lung function and ACT score experienced significant improvements. The results presented are in accordance with the RCTs: ZONDA, SIROCO, and CALIMA. In our study, a significant reduction of exacerbations requiring emergency or hospitalization of 77% was observed, while the SIROCCO and CALIMA studies reflect reductions of 42% and 36% , recruited in the Respiratory Medicine Department of the Hospital Universitario Virgen de las Nieves in Granada (Spain) between April 2014 and April 2022. Of the 172 patients, 103 were candidates for mepolizumab and 69 for benralizumab . Of the The socio-demographic variables included age, sex, body mass index (BMI), smoking status, years with the disease, nasal polyps, previous respiratory disease, allergies, gastroesophageal reflux disease (GERD), sleep apnea-hypopnea syndrome (SAHS), chronic obstructive pulmonary disease (COPD), years with the treatment, treatment dose, and change to another monoclonal antibody therapy. Individuals were classified as non-smokers if they had never smoked or had smoked fewer than 100 cigarettes in their lives, as former smokers if they had smoked 100 or more cigarettes in their lives but did not currently smoke, and as current smokers. For BMI, following the WHO criteria, individuals were classified as underweight (BMI < 18.5), healthy weight (18.5 < BMI < 24.9), overweight (25 < BMI < 29.9), or obese (BMI > 30) .The clinical variables were collected according to the year before starting treatment with the biological therapy and after completing the first year of treatment. They included ICS maintenance doses expressed as fluticasone propionate µg equivalents, OCS bursts required in the follow-up period and maintenance OCS doses expressed as mg prednisone equivalents , blood eThe quantitative variables were expressed as mean (± standard deviation) for those that complied with normality and as median and percentiles (25 and 75) for those that did not follow a normal distribution. Normality was confirmed using the Kolmogorov-Smirnov test.t test for paired data and the Mann-Whitney U test (Wilcoxon rank sum test) for non-normal variables. The results were considered significant when the p value was less than 0.05.The clinical variables responsible for the response were compared before and after treatment using the McNemar test for qualitative variables. For quantitative variables that complied with normality, we used the t-test was applied to the variables that complied with normality. The Mann–Whitney U test was applied for non-normal variables. A multivariate (logistic regression) analysis was used to calculate the adjusted odds ratio (OR) and the 95% confidence interval (CI) for the possible prognostic factors of response to OCS bursts, maintenance OCS, lung function, and exacerbations. All the variables that were significant in the bivariate analysis were included in the model for the multivariate analysis. In the multivariate analysis, all variables that were not significant were eliminated, thus obtaining the final model for each type of response. All the tests were two-sided, with a probability of 0.05 or less considered statistically significant, and were performed with the R 4.2.0 free software.To evaluate the predictors of response at 12 months, the following were taken as response variables: reduction of bursts of OCS per year, considering a reduction of at least 50% in the bursts or absence of OCS bursts as a satisfactory response; reduction of maintenance OCS, considering a reduction of at least 50% in the maintenance OCS or absence as a satisfactory response; improvement of lung function, considering those that achieved an increase of at least 10% in FEV1 after 12 months’ treatment as responsive; and reduction of exacerbations per year requiring emergency department treatment and/or hospitalization, taking a reduction of at least 50% or absence of exacerbations as a satisfactory response. The bivariate analysis between the response and socio-demographic and clinical variables was performed using Pearson’s chi-squared test or applying Fisher’s exact test for the qualitative variables. For the quantitative variables, Student’s The efficacy and safety of biological therapies have been extensively studied and demonstrated in controlled clinical trials, but the results reported by this real-life study are very promising. We show how mepolizumab and benralizumab significantly improve lung function and reduce and/or prevent the presence of exacerbations and the use of oral corticosteroids in a large proportion of patients. Moreover, the search for predictive factors of response to biological therapies in real life may provide information for decisions on their clinical management. We can therefore conclude that the biological therapies studied have had a great impact on the quality of life of patients with severe uncontrolled asthma and the associated healthcare burden.