P < 0.001 for all). The relative risk of BPD was 1.42 (1.39–1.45) on total readmission and 6.53 (5.96–7.15) on intensive care unit readmission. Asthma prevalence was significantly higher in BPD group . In children with RDS, BPD could affect repetitive and worse LRI as an independent risk factor for respiratory morbidity during the first 2 years of life. BPD may also be a crucial risk factor for asthma in preschoolers.Bronchopulmonary dysplasia (BPD) can cause respiratory morbidity beyond the neonatal period. We aimed to analyze the association of BPD on childhood lower respiratory illness (LRI) and asthma among patients diagnosed with respiratory distress syndrome (RDS). This case–control study analyzed data between 2002 and 2015 from a nationwide database. We included 55,066 children with RDS. Two-year LRI and asthma at ages 3 and 5 were assessed. Readmission for LRIs within 2 years of birth occurred in 53.9% and 37.9% of the BPD (n = 9470) and non-BPD  cases, respectively. In the BPD group, the median number of hospitalizations, mechanical ventilation and oxygen use rates were significantly higher, while the hospitalization duration was significantly longer ( Following the introduction of pulmonary surfactant administration in the 1990s, very low birth weight (VLBW) and extremely low birth weight (ELBW) infant survival rates in Korea increased by 1.6 and 2.7 times, respectively, over 20 years3.Respiratory distress syndrome (RDS) requiring surfactant replacement occurs in approximately 1% of total live births globally. RDS has been steadily increasing in Korea and in western countries4. Despite advances in perinatal care, approximately 20–30% of VLBW infants develop BPD5. Children with BPD have higher rehospitalization rates in early childhood, mostly because of respiratory illness, longer hospital days, and higher wheezing or asthma rates than preterm or ELBW infants without BPD6. In Asia, few studies have investigated respiratory morbidity of BPD patients in preterms7. No study has evaluated the impact of BPD in children born with RDS worldwide. To our knowledge, this is the first large-scale nationwide study analyzing BPD as a risk factor for early respiratory morbidities and pediatric asthma and the first to investigate infants with RDS, not preterm or ELBW infants.The prevalence of bronchopulmonary dysplasia (BPD), a chronic lung disease caused by RDS, has increased because of improved preterm infant survival8. The NHIS provides access to the database for research, allowing nationwide large-scale and longitudinal analyses in Korea.The National Health Insurance Service (NHIS) provides health insurance to most Koreans (99.01%). The NHIS covers many medical services, including medical visits, admissions, intensive care unit (ICU) care, emergency care, and pharmaceutical services. At each doctor visit, institutions submit electronic health care utilization information to the NHIS for reimbursement, which is integrated into the NHIS databaseWe aimed to determine the influence of BPD on childhood lower respiratory illness (LRI) and asthma among a population who received pulmonary surfactant for neonatal RDS.All diagnosed diseases are recorded in the NHIS using codes based on the 10th Revision of the International Classification for Disease (ICD-10). From the NHIS database, we extracted data on children born between 2002 and 2015 who fulfilled either of the following criteria within 2 years of birth: diagnosed with RDS using ICD-10 code P22.0 or received exempted health insurance fees because of RDS with code V142. Patients were excluded from the study if death occurred during the initial neonatal ICU (NICU) hospitalization or if major congenital anomalies were present. Major congenital anomalies were defined as malformation or deformation of the nervous, circulatory, respiratory, digestive, or musculoskeletal systems; chromosomal abnormality; inborn errors of metabolism; or hydrops fetalis. Patients with external minor congenital anomalies, anomalies limited to the limbs, or isolated urogenital anomalies were included. ICD-10 codes used for the exclusion criteria are presented in Supplementary Table Demographic data, diagnosed illnesses, prescribed therapies, and admission history were collected. BPD was defined as a diagnosis with ICD-10 code P27.1 within 2 years of birth. VLBW infants born after 2011 could be identified using diagnosis codes that specify birth weight < 1500 g  or J46 (status asthmaticus), including all subsections, and prescribed with asthma medication at the same visitt test for continuous variables and Pearson’s Chi-square test with Yates’ continuity correction for categorical variables. The Mann–Whitney U test was used for non-normal distributions. P < 0.05 was considered statistically significant.Data were analyzed using R version 3.3 and SAS version 9.4 . Descriptive statistics were used to summarize the entire study population. Results are presented as frequencies or medians and interquartile ranges, as appropriate. Groups were compared using Welch’s two-sample This study protocol was reviewed and approved by the Institutional Review Board of Severance Hospital . As this was an observational study without intervention and the presentation of any identifying data, the requirement for informed consent was waived by the same IRB committee. All methods were carried out in accordance with Korean government’s guideline for health and medical data utilization.P < 0.001, Table P < 0.001, Table From 2002 to 2015, 69,245 patients  were diagnosed with RDS (P22.0). After applying the exclusion criteria, 55,066 patients (79.5%) were finally included in the analysis  vs. 1 (1–29), The relative risk (RR) of BPD on readmission because of LRI significantly and steadily increased from 2002 to 2015  died within 2 years. The mortality rate was significantly higher in the BPD group than the non-BPD group  were included in a subgroup analysis based on birth weight of < 1500 g or > 1500 g. BPD was diagnosed in 58.7% and 7.2% of the < 1500 g and > 1500 g groups, respectively. Compared with the non-BPD group, the BPD group had a significantly higher readmission frequency; more days in the hospital; and higher mechanical ventilator, non-invasive ventilator, and oxygen use on readmission within 2 years in both the < 1500 g and > 1500 g birth weight subgroups. The number of ICU admissions was not higher in patients with BPD in the > 1500 g group  and 5 . Total asthma prevalence decreased at age 5  and in the proportion of total births (3.8% vs 5.8%), although the total number of births decreased by 35%16. The proportion of BPD in the RDS population increased to 23.1% in 2007, compared with 17.0% in 200216. Two epidemics of mycoplasma pneumonia occurred, in 2006 and from 2010 to 201117, which might have affected BPD patients more severely. Rehospitalization rates in children with BPD during the first 2 years of life were similar to those reported in the United States19.The RR of BPD on readmission decreased from 2002 to 2005 but rapidly increased during 2005–2006, which was further emphasized when looking at ICU admission Fig. . This re9 showed that the average prevalence of asthma in all Korean children born between 2002 and 2015 peaked at 18.4% at age 3 and decreased to 14.7% at age 5. Therefore, we can infer that the prevalence of asthma is approximately 3 times higher in BPD patients than in the general population. Moreover, non-BPD patients with RDS were diagnosed with asthma 2.5 times more than the general population. Further investigation using a large-scale longitudinal cohort study containing detailed medical records is necessary to clarify the predominant risk factors for this high prevalence of asthma in the RDS population.A recent study by Sol et al.20 who suggested asthma diagnosis in children born before 28 weeks gestation is predominantly associated with post-NICU risk factors, especially low socioeconomic status, but not with neonatal complications, including BPD. Kim et al.21 reported that small for gestational age infants were associated with poor pulmonary function showing obstructive patterns within BPD patients within the first year of life. Therefore, the influence of BPD on asthma may be diminished when the population is limited to extremely preterm or VLBW infants because birth weight and prematurity are relatively predominant risk factors for asthma. Moreover, because asthma development is affected by multiple factors including genetic, prenatal, prematurity, birth weight, and postnatal environmental factors23, the impact of BPD on asthma may be less than that on LRIs. We found asthma-related hospitalization and the influence of BPD on asthma decreased at age 5 than at age 3, suggesting the influence of BPD decreases as children age. However, asthma development in BPD patients can result from LRI-related hospitalizations and their severity during the first 2 years of life. Previous studies have shown asthma is closely related to early life respiratory syncytial virus infection, and viral prophylaxis reduced childhood asthma prevalence25.Interestingly, the prevalence of asthma was not affected by BPD when we limited the population to only < 1500 g birth weight infants (data not shown); however, LRI-related readmission was influenced by BPD in the < 1500 g birth weight subgroup. This finding is partially consistent with the results of Jackson et al.27. Decreased lung function in childhood has also been suggested to be a risk factor for adult chronic obstructive pulmonary disorder30. BPD patients may persistently present with obstructive lung disease into adulthood32. However, long-term outcomes of survivors with BPD who were born before the current era of perinatal care may not be generalizable to more recent survivors. Long-term follow-up is necessary to investigate whether prematurity of BPD itself is a predominant risk factor for respiratory morbidities or if BPD is only a major synergistic factor.BPD diagnosis in early life can cause an early decline in adult lung function. Several longitudinal cohort studies revealed a decreased forced expiratory volume and decreased forced expiratory volume/forced vital capacity ratio at school age in preterm-born children9. However, as this is large-scale real-world data, the possibility of prescribing asthma medications for preventive purposes cannot be excluded in some BPD patients.Previous studies analyzed BPD as a risk factor for respiratory morbidity or asthma in VLBW or extremely preterm infants. Our study focused on a nationwide population with RDS requiring surfactant replacement. As the diagnostic code in claims data depends on input by each physician, the accuracy of diagnostic code input is critical. The diagnostic code for “RDS” must be accompanied by a pulmonary surfactant prescription and registered with the rare incurable disease code V142, which provides financial benefits for RDS patients from the national health insurance. Extraction of patient data using code V142 is more accurate and reliable than the diagnostic code related to ‘prematurity’ which has not been regulated by obligation for prescription or redemptions. We were able to compare the asthma prevalence in the RDS group with that in the general population using the same operational diagnosis34. Therefore, we suggest that the overlapping or misdiagnosis of TTN or pneumonia with RDS in our cohort has minimal effects on the conclusion we draw from the study.This study has some limitations, including those inherent in any retrospective study using claims data. Although a large number of participants in our study allowed us to investigate patients with RDS extensively, we could not obtain all perinatal and environmental variables because of insufficient detailed medical records. Therefore, we were unable to distinguish the extent of immaturity and BPD on respiratory morbidity. BPD diagnosis in our study population was based on the input of a diagnostic code by physicians and was presumed to be defined as “oxygen use for 28 days”. Subgroup analysis among VLBW infants was only possible in infants born after 2011 when the Korean Classification of Disease was updated. Infants with transient tachypnea of newborn (TTN) or pneumonia may have been incorrectly diagnosed as RDS and included in our study population. However, previous national multicenter studies reported that 93.5% and 87.9% of total RDS patients were < 37 weeks and < 2500 g respectively, whereas patients with TTN or pneumonia constituted only minimal portion in preterm or low birth weight infantsBy investigating the annual trends of decreased BPD mortality for over 10 years, we were able to explore the association between BPD and respiratory morbidity from a macroscopic viewpoint. In addition, we revealed the real burden on readmitted patients by focusing on the severity of the patients.Our study demonstrated that children with BPD required rehospitalization because of respiratory morbidities twice as frequently as children without BPD. The BPD population received approximately five times more intensive care, assessed by ventilator use and ICU admission rate than the non-BPD population. The prevalence of pediatric asthma at ages 3 and 5 were three times higher in BPD children than in the general population. Regular follow-up and care for patients with BPD are crucial, and a follow-up plan may be necessary to manage their long-term health.Supplementary Information.


Blood pressure (BP) and BP variability were determined using 24 h ambulatory monitoring. Vascular phenotyping included SphygmoCor® measurement of pulse wave velocity (PWV), pulse wave analysis-derived augmentation index (PWA-AIx), and central BP; EndoPAT™-2000® provided reactive hyperaemia index (LnRHI) and augmentation index adjusted to heart rate of 75bpm. Ultrasound was used to analyse flow mediated dilatation and carotid intima-media thickness (CIMT). In addition to standard statistical methods to compare normotensive and hypertensive groups, machine learning techniques including biclustering explored hypertensive phenotypic subgroups. We report that arterial stiffness  and central pressures were greater in incident hypertension than normotension. Endothelial function, percent nocturnal dip, and CIMT did not differ between groups. The vascular phenotype of white-coat hypertension imitated sustained hypertension with elevated arterial stiffness and central pressure; masked hypertension demonstrating values similar to normotension. Machine learning revealed three distinct hypertension clusters, representing ‘arterially stiffened’, ‘vaso-protected’, and ‘non-dipper’ patients. Key clustering features were nocturnal- and central-BP, percent dipping, and arterial stiffness measures. We conclude that untreated patients with primary hypertension demonstrate early arterial stiffening rather than endothelial dysfunction or CIMT alterations. Phenotypic heterogeneity in nocturnal and central BP, percent dipping, and arterial stiffness observed early in the course of disease may have implications for risk stratification.The study characterises vascular phenotypes of hypertensive patients utilising machine learning approaches. Newly diagnosed and treatment-naïve primary hypertensive patients without co-morbidities (aged 18–55,  The demographic and lifestyle risk factors for hypertension are well recognised. Less well defined is associated cardiovascular dysfunction at the onset of the disease process, and early heterogeneity of cardiovascular phenotypes within incident hypertension. Routine clinical phenotyping of hypertension based primarily on BP endures, despite the availability of recognised surrogate markers of cardiovascular dysfunction such as endothelial and microvascular impairment, large artery stiffening, and arteriosclerosis . StudiesDespite their importance in advanced disease, it remains unclear if vascular traits such as endothelial dysfunction, vascular stiffness or carotid remodelling can be identified early, in treatment-naïve, incident hypertensive patients free of major comorbidities. Accordingly, we aimed to characterise vascular phenotypes of young, untreated patients with incident hypertension in comparison to normotension; and utilising machine learning approaches, to identify if patient heterogeneity is already present at this early stage of hypertension. Defining such clinical and vascular phenotypes may facilitate risk stratification and permit future precision medicine approaches in hypertension management.Inflammatension project NCT04015635) was designed as a cross-sectional clinical and biomarker study of consenting patients from the West of Scotland aged 18 to 55 years with primary hypertension, and intention to match control participants on age, sex, and BMI. The study was approved by the West of Scotland Ethics committee. Sample size was based on a power calculation to detect differences in the immune system (NCT04015635), with consideration of published data detecting differences in vascular traits . Hyperte5635 was Office BP was measured in the sitting position after 5 min of rest, by a validated sphygmomanometer , with an appropriately sized cuff. Three measurements taken were summarised in data reporting as a mean value. ABPM performed for 24 h comprised twice-hourly BP measurements throughout the day in accordance with most recent European practice guidelines , and houMeasured using EndoPAT™-2000 . A 5-min baseline measurement was followed by 5-min proximal arterial occlusion through supra-systolic inflation of a blood pressure cuff. Occlusion was released and 5 min of post-ischaemic vascular responsiveness were recorded. The ratio of the signal pre- and post-occlusion generated a reactive hyperaemic index (RHI), automatically natural log transformed (LnRHI). Pulse waveforms obtained during baseline measurement provided mean heart rate and Augmentation Index corrected to a heart rate of 75 beats/min (AI@75). Contra-lateral arm was used as control.UNEX EF38G model  permitted ultrasound visualisation of the brachial artery and automated measurement of arterial diameter. The cuff was placed on the contra-lateral arm to PAT to prevent repeat-occlusion endothelial ‘priming’, with a 15-min time interval between techniques. Baseline arterial diameters were recorded; the cuff was then inflated to 50 mmHg above systolic pressure (max 250 mmHg) distal to the ultrasound for 5 min, and arterial diameter was reassessed following release of cuff. Arterial diameter variation across the cardiac cycle was corrected for using integrated heart rate recording. Integrated software analysis provided percent FMD, rest, baseline, and maximum arterial diameter measurements with wall-tracking capability.Performed supine after 10 min of rest with SphygmoCor XCEL . An appropriately sized cuff was placed on the upper arm, acquiring two brachial BP measurements with a 1-min interval. The cuff then partially inflated to capture the brachial artery waveform for 10 s, with automated analysis and integrated quality control. The report included central systolic, central diastolic, and Augmentation index (AIx). Two measurements were performed with a mean value used in data analysis.Determined using SphygmoCor XCEL. With the participant supine and rested, a BP cuff was applied to the femoral artery. The subtraction method was used to estimate the length of the aorta. Once the pressure probe detected the common carotid artery pulse-wave sufficiently, the leg cuff automatically inflated. Both pressure waves were captured simultaneously based on the systolic upstroke. Automated PWV calculation was reported in metres per second (m/s), with quality control analysis indicating pulse-to-pulse variability. If a repeat measure differed by >1 m/s, then a third measure was performed and the two with greatest concordance were recorded.B-mode ultrasonography of the right carotid artery performed with Acuson Sequoia c512 . Following published guidance, [Self-reported physical activity was assessed using the validated open-access ‘International Physical Activity Questionnaire ’ . The finThe InterHeart Risk Score Questionnaire is a self-reported scoring system to predict cardiovascular events and validated in diverse populations . The outBoth CIMT and FMD analysis were performed off-line in batches, by a single assessor, blinded to the participant groups.P < 0.05. Between-group comparisons employed 2-tailed T-test, Mann–Whitney or Moods’ test depending on distribution of the data. Analysis of continuous variables was based on correlation and multi-variable regression modelling . Statistical significance was assumed for 013. Statz-score). Distinct phenotypes were identified using Uniform Manifold Approximation and Projection (UMAP) as a dimensionality reduction technique, combined with Spectral Biclustering. Taking each in turn, UMAP learns the manifold structure of data by graphing neighbouring samples, where edge weights reflect similarities (or distances) between nodes according to a given metric . The embedded data is then projected to lower-dimensional space while preserving its topological structure. The optimal number of clusters to capture distinct groups was defined by Silhouette score. Shapley (SHAP) values were computed to better interpret discriminating features for each of the UMAP clusters.For machine learning approaches applied to the hypertensive group, variables that were highly correlated or with a substantial number of values missing were removed, giving 19 features in total. Missing data points were imputed from within-sex group median values, and data scaled to a columnar mean of 0 and standard deviation of 1 , Fig. r = 0.43, P < 0.001, Table Correlations were analysed within the whole study population Fig. , and sepr = 0.50, P < 0.001), PWV demonstrated weaker association with both . Though participants with ‘abnormal’ LnRHI results (<0.51) did demonstrate higher % FMD . Neither LnRHI nor % FMD correlated with measures of arterial stiffness or CIMT , and BMI was higher in the sustained HTN group, P = 0.004. Between group differences were apparent both for measures of arterial stiffness , and central pressures, all P ≤ 0.001. WCH subgroup demonstrated the greatest arterial stiffening, concordant across the different techniques; in contrast, MHN values were in the normotensive range, Table P < 0.001, Fig. Thirteen of 152 participants (9%) had elevated office BP but ABPM in the normal range, so called ‘white coat’ hypertension (WCH) . Table SWithin the hypertensive group, Spectral biclustering identified three distinct groups of patients (rows), characterised by eight groups of features (columns) Fig. . FMD, Lnn = 23) could be considered as ‘arterially stiffened’ hypertension. These patients trended toward being older (NS), 57% male, with a lower mean physical activity score , day and night mean values, office BP, and central BP . BP variation (SD) was lowest, % nocturnal dip was reduced (systolic dip 9.3 ± 4%), and a lower proportion of masked hypertension (MHN) patients were present . Arterial stiffening was apparent, with highest PWV  and AI@75 .Group 0 subjects n = 3 could bn = 33) with pronounced nocturnal dipping, so far ‘vaso-protected’ from major vascular impairment. These predominantly male (67%) patients appear fitter, with highest physical activity index, low resting HR, wider HR range, and SBP SD. BP values (Table P < 0.0001), day/night averages, office BP, and central BP; greatest nocturnal dip was also seen . MHN patients were over represented . This group showed lowest measures of arterial stiffness by PWV or AIx (Table Group 1 included subjects (es Table  were lown = 17), Table P < 0.0001), daytime BP, night-time BP, office BP, and central BP and had a low proportion of masked hypertension (MHN) patients . Mean nocturnal dip values were low . Regarding arterial stiffness, AIx derived from PWA was elevated, but resting HR was also higher and the HR-adjusted AI@75 as well as PWV were intermediate. Group 3 FMD values were highest but did not reach statistical significance. DBP SD was highest and SBP SD intermediate, despite reduced nocturnal dipping. Among all these between-group differences, nocturnal and central BP were the statistically strongest parameters  in clusters 0 and 2; PWV in cluster 1, and demographic features in cluster 2. Other features important for given clusters can be found in Figs. Characterising a unique cohort of newly diagnosed, untreated, hypertensive subjects without comorbidities or target organ damage; arterial stiffness appears to be the only vascular functional trait increased early in hypertension and clearly related to increased blood pressure. FMD-determined endothelial function was not altered, while EndoPAT™-2000® positively correlated to SBP, showing a possible compensatory response. Machine learning approaches identified a clear heterogeneity of newly diagnosed hypertensive subjects, with identification of three phenotypes based primarily on nocturnal- and central-BP, percent dipping, and arterial stiffness measures.Longitudinal studies of both healthy and co-morbid populations evidence arterial stiffening in newly diagnosed hypertension. Diverse measurement techniques studied include carotid-femoral and brachial-ankle PWV, augmentation index, and carotid elasticity, as determinants of longitudinal BP increase and as independent predictors of incident hypertension –20. The In contrast, measures of endothelial function were interesting in their absence of collinearity, or association with hypertension or arterial stiffness in whole-cohort analyses. FMD and EndoPAT™-2000® are not inter-changeable techniques , reflectunder-represented in the ‘non-dipper’ bicluster.Despite central BP correlating with brachial measures across the whole group Fig. , our subRobustness of the data is limited by the restricted sample size, and by the higher BMI in the hypertensive group, which is known to influence cardiovascular function, hence inclusion of BMI in adjusted analyses. Although researchers were blind to ABPM result and final grouping (ABPM being undertaken at the end of the study visit), bias may have arisen as the office BP was recorded during the visit. This was however unavoidable, as it forms an integral component of the vascular studies. Furthermore, it is challenging to ascertain if associations between arterial indices are true relationships, or rather demonstrate co-dependency on BP. Of note, earlier ABPM guidelines advised additional ABPM readings per hour compared to current accepted practice ; this coUMAP and bicluster machine-learning methodologies demonstrated concordant results regarding key features of central and nocturnal BP values, nocturnal dipping pattern, and measures of arterial stiffness; supporting the validity of the data. The detected biclusters were also broadly consistent with results observed in basic statistical analysis, and carry translational clinical implications as follows. Group 0 ‘arterially stiffened’ hypertension, were also sedentary, with greatest elevation in BP parameters, and both reduced nocturnal dip and BP variability. These features may suggest a longer duration of undiagnosed hypertension. A lower threshold commencing primary prevention  may benefit this group. Group 1, ‘vaso-protected’ hypertension, were fitter, with lowest BP measures, preserved nocturnal dip, least evidence of arterial stiffness. The group could represent hypertension earlier in its’ natural course, ABPM key for diagnosis with 39% having MHN. Higher SBP variability and daytime HR range may reflect more physical activity or alternatively a strong sympathetic drive, be it social stresses, or stimulants such as caffeine, which should be identified and targeted as part of management. Group 2, ‘non-dippers’, also demonstrated elevated BP variability despite loss of nocturnal dip, but MHN was rare. Genotypic differences may be present, as group 2 were female dominated in comparison to the other groups and ethnically more diverse. Non-dipping status has been linked to risk of CVD and arterial stiffness in studies of older participants , 46. As Hypertensive disease progression involves early arterial stiffness, already detectable in this newly diagnosed, young, primary hypertensive group in comparison to normotensive controls. Carotid atherosclerosis and impairment in endothelial function were not detected. WCH patients demonstrated arterial stiffening in excess of sustained hypertension; MHN vascular characteristics were akin to normotension. We further conclude that unsupervised machine learning is a valuable analysis tool, offering deeper clinical insights into nuances between hypertensive phenotypes, here driven by nocturnal and central BP, percent dipping, and arterial stiffness. Given the prognostic value of these parameters, such phenotypes may have important clinical implications for disease progression and individualised care.The clinical impacts of hypertension are varied between individuals, but vascular dysfunction is common in advanced hypertension.Widely accepted phenotypic patterns include white-coat, masked, and non-dipper hypertension.Arterial stiffening is already apparent in incident patients with primary hypertension.Nocturnal and central BP, and arterial stiffness are key parameters differentiating heterogeneity of hypertensive phenotypes.Machine learning techniques can maintain granularity of the data, offering deeper clinical insights.SUPPLEMENTARY MATERIAL CLEAN


Arterial blood pressure is one of the vital signs monitored mandatory in anaesthetised patients. Even short episodes of intraoperative hypotension are associated with increased risk for postoperative organ dysfunction such as acute kidney injury and myocardial injury. Since there is little evidence whether higher alarm thresholds in patient monitors can help prevent intraoperative hypotension, we analysed the blood pressure data before (group 1) and after (group 2) the implementation of altered hypotension alarm settings. The study was conducted as a retrospective observational cohort study in a large surgical centre with 32 operating theatres. Alarm thresholds for hypotension alarm for mean arterial pressure (MAP) were altered from 60 (before) to 65 mmHg for invasive measurement and 70 mmHg for noninvasive measurement. Blood pressure data from electronic anaesthesia records of 4222 patients  with 406,623 blood pressure values undergoing noncardiac surgery were included. We analysed (A) the proportion of blood pressure measurements below the threshold among all measurements by quasi-binomial regression and (B) whether at least one blood pressure measurement below the threshold occurred by logistic regression. Hypotension was defined as MAP < 65 mmHg. There was no significant difference in overall proportions of hypotensive episodes for mean arterial pressure before and after the adjustment of alarm settings . The risk of ever experiencing a hypotensive episode during anaesthesia was significantly lower in group 2 with an odds ratio of 0.84 (p = 0.029). In conclusion, higher alarm thresholds do not generally lead to less hypotensive episodes perioperatively. There was a slight but significant reduction of the occurrence of intraoperative hypotension in the presence of higher thresholds for blood pressure alarms. However, this reduction only seems to be present in patients with very few hypotensive episodes. During surgical procedures, monitoring and stabilising of vital signs is an essential part of an anaesthetist’s work. Embedded in the monitors software are thresholds which define the safe range of monitored signs. In case of a threshold violation, patient monitors give optical and visual signs, designed to catch the attention of the attending physician. These alarms result in significantly shorter response time of the attending physician: A study by Loeb and colleagues reported a mean response time to abnormal vital signs on the monitor display of 61 s . NowadayOne of the key vital signs monitored mandatory in anaesthetised patients is arterial blood pressure. Even short episodes of low intraoperative blood pressure (intraoperative hypotension) are associated with increased risk for postoperative organ dysfunction such as acute kidney injury and myocardial injury . TherefoOur hypothesis was that higher alarm thresholds for mean and systolic arterial pressure lead to less hypotensive events during anaesthesia.The aim of this retrospective observational cohort study was to investigate the impact of a higher threshold for hypotension alarm at the patient monitor in order to avoid hypotensive episodes during anaesthesia. The local ethics committee  approved the study under the protocol number 17-299 on 1st June 2017. The need for informed consent was waived due to the retrospective design.The study investigated blood pressure values of patients during anaesthesia in a large surgical centre at a German university hospital. The surgical centre contains 32 operating rooms (OR) and 22 induction areas with identical monitoring equipment . Embedded in the monitor software are predefined alarm settings. In July 2016, all patient monitor software was updated. With this update, alarm settings for low arterial pressure had been changed. Previously, the threshold for low mean arterial pressure alarm was set at 60 mmHg, for systolic arterial pressure at 90 mmHg . After the update, the monitor alarm went off at 65 mmHg for continuous invasive mean arterial pressure measurement and at 70 mmHg for intermittent oscillometric mean arterial pressure measurement via the upper arm cuff. The threshold for oscillometric systolic arterial pressure was set at 100 mmHg after the update, for continuous measurement it remained at 90 mmHg. Higher thresholds for oscillometric measurements were implemented because of increasing evidence of the method’s tendency to overestimate low blood pressure [The anaesthesiologists have not been notified about the change in alarm settings or its reason. We hypothesised that a higher hypotension alarm threshold draws the attention of the attending anaesthesiologist to a decrease in patient’s blood pressure earlier. This would cause earlier treatment and thus reduce the frequency of intraoperative hypotension. To verify this hypothesis we analysed two outcomes: ‘A’, the rate of hypotensive events per patient during anaesthesia before and after the higher hypotension alarm threshold and ‘B’, if the frequency of procedures with no single hypotensive event increased. Intraoperative hypotension is defined as mean arterial pressure below 65 mmHg and systolic arterial pressure below 90 mmHg .We included all patients who underwent procedures with an attending anaesthesiologist at the surgical centre in the 3 months before (group 1) and after (group 2) the implementation of altered alarm settings. The time interval was chosen in order to limit the effect of short-term events such as summer holidays. The patients had either general anaesthesia, regional anaesthesia, a combination of both, intravenous analgesia, or monitoring in standby by the anaesthetist. Excluded from the analysis were patients younger than 14 years, cardiac surgery and procedures with extracorporeal circulation or membrane oxygenation. If a patient underwent surgery more than once during the study period, we included only the first procedure.We extracted systolic and mean arterial blood pressure data from the electronic anaesthesia records  where all vital signs are stored at a sampling rate of 3 min. We screened for invalid measurements  and excluded these values. In addition, duration of anaesthesia, procedure, age, ASA physical status, blood loss and cumulative norepinephrine dose during anaesthesia were analysed based on the electronic anaesthesia record.One possible source of bias is that blood pressure during anaesthesia can easily be influenced by the attending anaesthetist who is aware of the study purpose. Since this analysis is a retrospective analysis and staff of the department has not been informed about the change in alarm settings or its purpose this effect does not exist for these data. Another possible source of bias is the summer holiday in the month just after the altered alarm settings. Therefore, we set the study period to 3 months before and after the change of hypotension alarm settings. A sample size calculation was not performed due to the retrospective study design.Excel  and R  were used for analysing the data.Continuous variables were checked visually for normal distribution, where some variables showed strong deviations from normality. Therefore, for all continuous variables the median and the interquartile range (IQR) are presented. Differences between the groups in the 3 months before and after the alteration of alarm settings were analysed using Wilcoxon’s test for quantitative variables and Fisher’s exact test for categorial variables.Intraoperative hypotension is defined as MAP below 65 mmHg and SAP below 90 mmHg . When inIn order to assess whether patients at risk for intraoperative hypotension have fewer hypotensive episodes with higher alarm thresholds, in addition to the main analysis that included all patients, we analysed patients with ASA status III or IV, patients older than 70 years and patients with general or combined general and regional anaesthesia separately. There were 8 subgroups: (A) patients with general anaesthesia, (B) patients with combined general and regional anaesthesia, (C) patients of ASA status 3 or 4, (D) patients older than 70 years, (E) patients older than 70 years and general anaesthesia, (F) patients older than 70 years and combined general and regional anaesthesia, (G) patients of ASA status 3 or 4 and general anaesthesia, (H) patients of ASA status 3 or 4 and combined general and regional anaesthesia. In each subgroup analysis we adjusted for number of measurements and age and the eight P values obtained for the different subgroup analyses were adjusted for multiple testing using the Bonferroni-Holm procedure .After screening for invalid pressure measurements and missing data, a total number 432,158 measurements for systolic arterial pressure and 432,147 for mean arterial pressure were available for analysis. In total there were 4222 patients treated in the observed time frame, where about 9% of these patients were treated several times. The statistical tests we used for testing differences between the two groups assume independency between the observations, which is why it was required that there is only one procedure per patient. Therefore, we excluded multiple procedures per patient by including only the first procedure in cases of patients with several procedures. This left 1982 patients and procedures in group 1 before the altered alarm settings and 2240 patients in group 2 after the altered alarm settings. Detailed data inclusion is presented in Fig. The number of measurements per procedure  was 81 (55–118) in group 1 and 71 (48–104) in group 2 and ranged from 2 to 590 measurements. The median and IQR of systolic, diastolic and mean arterial pressure per group are presented in Table Quasi-binominal regression analysis comparing the differences in proportions of hypotensive events below the threshold of 65 mmHg for mean arterial pressure and 90 mmHg for systolic arterial pressure showed no significant differences before and after the adjustment of alarm settings. The average of values below the threshold were 6.05% in group 1 and 5.99% in group 2 for mean arterial pressure (p = 0.881). Likewise, there was no relevant difference for systolic arterial pressure . This finding seems to be counter intuitive. One possible explanation is the theory of false alarms. In his essay, Breznitz explains the psychologic phenomenon of ignoring a warning when in the past no negative consequence followed the same alarm . It is pThe finding, that the proportion of hypotensive episodes was unchanged in the presence of higher alarm limits and even increased in some subgroups at risk for hypotension  is surprising at first sight. However, our findings are in concordance with the study by Kurz et al. who investigated the impact on triple low alerts . Triple The longer the procedures were in our study, the higher was the rate of threshold undershot. One reason for the higher rate of threshold undershot for longer procedures is certainly that the longer a procedure continues, the more opportunities for undershots arise. However, studies describing the characteristics of intraoperative hypotension by Saugel et al. found, that the lowest blood pressure values occurred typically after the induction before the start of surgery and not so much after hours of surgery , 19. TheA potential source of bias of our study was the time of altered hypotension alarm settings shortly before the summer holidays. The patients’ characteristics show that the patients included after changing alarm settings were healthier and had shorter procedures. This may also have contributed to the inability of detecting a reduction in hypotensive rates during surgery, because patients without chronic diseases are less prone to intraoperative hypotension . In addiOur study has limitations. First, it is a retrospective analysis of a single centre and may therefore not be generalisable to other settings. A prospective, multicentre study should be designed to confirm the findings. Second, it was not possible to analyse the number of hypotension alarms triggered or the manual change of setting by individual physicians.The strengths of the analysis are the large number of procedures included and that anaesthetists were not informed about the altered settings or its purpose. Therefore, we were able to study the impact of the alarm settings in absence of confounding new institutional protocols.In conclusion, higher alarm thresholds do not generally lead to less hypotensive episodes perioperatively. There was a slight but significant reduction of the occurrence of intraoperative hypotension in the presence of higher thresholds for blood pressure alarms. However, this reduction only seems to be present in patients with very few hypotensive episodes.


In order to solve some problems of subhealth and high chronic diseases, the diagnosis and treatment of value-added diabetic retinopathy are studied. In particular, diabetes, a high chronic disease, poses a great threat to people's health. With the continuous improvement of national health awareness, the medical field also begins to pay more attention to the diagnosis and treatment of value-added diabetic retinopathy. In order to improve the long-term treatment of value-added diabetic retinopathy through intelligent medical monitoring and systematic scientific efficacy analysis and evaluation, the purpose of this study is to explore how to effectively achieve the meta-analysis of long-term efficacy of proliferative diabetic retinopathy through intelligent medical treatment. Through the study of diabetic retinopathy, the system can help doctors to achieve unlimited further signs of parameter acquisition and transmission and build more mature after treatment of the results of the monitoring platform. At the same time, a conclusion based on vitrectomy was proposed to effectively improve the surgical efficacy of patients with proliferative diabetic retinopathy. Diabetes is a relatively common chronic disease in our daily life and also has the title of “chronic cancer”. Of course, the formation of diabetes is closely related to people's eating habits, genetic factors, drug stimulation, and other aspects. In addition, patients with severe diabetes may do harm to their kidneys, cardiovascular vessels, nerves, substance metabolism, and eyes to varying degrees . EspeciaIn recent years, reports at home and abroad agree that VEGF is the strongest known cytokine involved in the formation of PDR, plays a key role in the formation of PDR, and has the most important direct relationship with PDR. Foreign scholars from the cancer of guinea pig ascites found and proved that there is an active material to make vascular permeability increase, known as vascular permeability factor. Isolation and purification of bovine pituitary follicular stellate cells in vitro culture medium. VEGF can increase vascular permeability, especially the permeability of posterior capillary veins and venules. It is the strongest endothelial cell selective mitogenic factor and angiogenic factor known at present. It can specifically stimulate the proliferation of vascular endothelial cells and participate in a variety of physiological and pathological processes of neovascularization. VEGF is an autocrine and parsecretory growth factor, which plays a strong role in endothelial cell mitogen in vitro and can specifically act on endothelial cells, increasing vascular permeability and the formation of new vessels in vivo. Immunohistochemical methods confirmed the VEGF expression in retinal and optic nerve ganglion cells, retinal in diabetic patients without intraocular neovascularization . HypoxiaThe excellent system proposed and made with this research is mainly used for postoperative patients, patients in intensive care and patients with chronic diseases, and can realize the continuous measurement of vital signs heart rate, blood oxygen, body temperature, blood pressure, etc., for effective monitoring and additional treatment of patients . The whoPurchase and completion. Two pulse signals in multiple locations are collected by a corresponding photoelectric sensor, fitment, application, and led by AD through conditioning circuit, and then calculate the blood pressure of the substance measured by the blood pressure algorithm [ lgorithm .This metAbility to display real. OLED screens are used to display timely data to allow medical workers, patients, or patients' families to understand the actual data directly and indirectly, displaying the best words value of the measured object. Alarm alert. It is fluctuations in common event and affects the measurement result due to the change of the external environment and its own situation.   However, with the onset of offense, the notion of having a relationship in the first place zaps even when a strong partner is in a steady relationship. When the vibration is severe, it automatically warns and alerts overseas jump .Data communication. Data connection. In this project, Laura's communicate with that is used as a medium of transfer between this hard term the data frame format is formulated transmission of blood pressure data to the PC terminal of the nursing home after processing and calculation. The physical signal monitoring module combines the ability to monitor the heartbeat, blood oxygen, and body temperature in a timely manner. Currently, that all more monitor towards in hospitals are being performed a variety of physical sign monitors, and nurses should regularly visit departments to understand the this common with patients, so the changes of patients' physical sign parameters cannot be mastered in real time . The sysIn order to meet the portability, long distance, and low power consumption of the system, wireless communication is adopted in the physical sign monitoring and base station communication in this essay. At present, the mainstream wireless communication technologies include Bluetooth, WiFi, ZigBee, LoRa, etc. The technical parameters of wireless communication are shown in Simple networking and low power consumption. Since the monitoring system needs to be worn by patients for a long time, it needs to reduce power consumption as much as possible.Stable transmission and good performance. The acquisition end transmits data in real time, so the stability of data transmission has high requirements.Strong anti-interference, wide network coverage. In the hospital environment, buildings are dense, personnel are numerous and complex, and strong anti-interference ability is required [required .The application scenario of this system is in the hospital. Considering the complex environment, many obstacles, and long time to use, the Lora wireless communication mode is selected in this design based on the analysis of various factors . LoRa haLoRa improves the sensitivity of the receiver, resulting in a super link budget, which can greatly reduce transmission power. LoRa adopts a high spread factor to obtain a high signal gain . The SNRThe B/S network mode is the browser/server mode. The mode is on the client side and only requires the browser to interact with the server. The application layer is a web server, through which the interaction between the presentation layer and the data layer can be achieved, requests sent by the client are received, and business logic processing is carried out on the data layer according to the requested content . In B/S,MVC (Model View Controller) mode, its idea is to divide the system development into model, view, and controller three parts, each part undertakes corresponding tasks. Among them, the model part is responsible for managing all data, the view part is responsible for displaying all interface data, and the controller part is responsible for processing all business logic .In this system, we choose to use MySQL relational database management system. Based on database of the three major paradigm create forms to meet the needs of practical application, to create the steps, first, to create the database, and then in the database according to the needs of different departments and users to create forms, to determine the field name as far as possible use English to express, to determine the corresponding data field type and length and constraint conditions, and so on. Finally, in order to facilitate quick query, the primary foreign key association between tables. The design of this database mainly involves the storage, query, and modification of patient data information, medical staff information, patient physical sign parameter information, and patient history data .The auscultation method is called the Cauchy sound measurement. The device includes an inflatable cuff, a mercury manometer, and a stethoscope. Coriolis auscultation is regarded as the beginning of indirect measurement and has been widely used . CorleonI0 represents the incident light intensity, I represents the transmitted light intensity, ε represents the light absorption coefficient, which is determined by the nature of the substance and the incident light, and C represents the concentration of the substance and Irepresents the optical path.Pulse wave conduction time method, also known as photoelectric volume pulseography (PPG for short), is a noninvasive method to detect blood volume changes in arterial vessels by using photoelectric sensors . It makeFor human tissues, the absorption of light, muscle, skin, bone, fat, water, and venous blood does not change; however, due to the heart beating, the blood volume in arterial tubes will change, and the change of blood circulation regularly changes the absorption of light .E is elastic modulus, h is vessel wall thickness, ρ is fluid density, and D is the inner diameter of elastic tube under equilibrium state. The exponential relationship between elastic modulus and vascular transmural pressure was verified through experiments, and the following , p blood pressure.Pulse wave conduction time can be obtained indirectly by pulse wave propagation velocity, and formula  is as foollowing  was propK is called the Moens constant, K = 0.9 for the rubber tube and 0.8 for the human aorta.In 1878, Moens proposed the wave velocity formula  through The time at which a wave travels is the time a wave travels from one point to another during this process of pulse wave transmission in the arterial blood tube, which is commonly expressed as PTT or PWTT . When thT is the conduction time of pulse wave.In the abovementioned formula, S is the propagation distance of pulse wave and By substituting formula  and formAs this program, blood rushes into the arteries periodically, causing constant changes in blood pressure. In this process, the vascular wall will also be slightly deformed, and the changes in the inner diameter of arterial blood wall and thickness of arterial wall can be ignored. Therefore, the first term on the right of the abovementioned equation can be regarded as a constant, and the formula  can be oOr the following formula :(8)Δp=−2According to the social program, when simplified time is ignored, blood pressure has a linear relationship with pulse wave conduction time . OverseaWhere a and b have undefined coefficients and reflect individual arterial vascular characteristics, which will change with the change of vascular elasticity, but in the short term, individual A and B values are fixed.R wave, and the lowest point and peak of the pulse wave signal or the maximum point of first-order differential can be used to calculate the conduction time of pulse wave. Since the signal waveform is not fixed, the selection of characteristic points of pulse wave signal should be determined according to the time waveform. There are also some differences in the selection methods of feature points of signals collected in different ways.The specific steps are as follows: the characteristic points of the ECG signal are selected as the vertex of Here, the pulse wave peak point is an example to calculate the pulse wave conduction time. The principle of PTT measurement by the ECG signal and pulse signal is shown in In the two-channel pulse wave signal method, pulse wave signals need to be collected from two different parts of the aorta at the same time. The pulse wave conduction time can be obtained by defining the waveform conduction time by measuring the corresponding peak excellent important points of the two signals. In According to the theoretical deduction above, the following conclusions can be drawn: within a certain range, there is a linear relationship between pulse wave conduction time and arterial blood pressure. If the elasticity of vascular wall is not considered, the linear relationship  can be eOn this basis, the modification in this paper is based on the principle of static pressure difference of fluid. Raising the arm before and after measurement results in the change of blood vessel pressure in the arm of the tested individual, as well as the change of pulse wave conduction velocity and conduction time (PTT). Parameters A and B were determined by two sets of conduction time and blood pressure values obtained by two measurements taken when the arm was flat and when the arm was raised at a certain height. This method will not change the characteristics of blood vessels due to external influences, so the size of A and B will not be affected. Meanwhile, this method is a separate experiment corresponding to the tested individuals. According to the hydrostatics principle, the arm artery can be approximately regarded as a circular pipe. For the small volume element inside the fluid, its upper and lower area is set as dA and its height as dZ; then the force under the volume element can be expressed as P.dA, and the force formula  is as foFormula  can be oP at a certain point in blood vessel with the position change and the change in blood vessel height Δh is as follows , the relationship between the pressure Δ follows :(13)ΔP=−Then, the formula  for the In this process, the small volume element of vascular blood flow can be regarded as a static state. The relationship between pressure at a certain point in the vessel and height change can be expressed in formula  as folloTherefore, the change of the mean pressure of blood pressure in this segment of blood vessel can be denoted by equation (16):In this process, two sets of pulse wave conduction time  can be oFinally, formula  can be sThe method is simple and easy to implement to calibrate individual parameters by changing the height of the arm. For different individuals, parameters A and B can be calculated, which is of great practical significance in noninvasive continuous blood pressure measurement.All patients were operated by the same surgeon in the same surgical group in the two departments of fundus. 2 hours before surgery, the pupil was fully dilated with metol eye fluid. After conventional disinfection sterile tissue was laid, a mixture of 2% lidocaine 4 ml + 0.75% bupivacaine 4 ml was used for postbulbar, peribulbar, and subconjunctival anesthesia. A standard posterior vitrectomy with transplant ciliary tract was performed. If the opacity of the lens affects the surgical field of vision, posterior lens ultrasound comminution or anterior small incision cataract phacoemulsification should be performed simultaneously. Posterior lens ultrasonic comminution was performed for subluxation. If the posterior iris adhesion is complicated with old uveitis before surgery and the pupil cannot be dilated, a little sodium hyaluronate is injected into the anterior chamber during surgery to separate the posterior iris adhesion, and the iris hook is put into the anterior chamber to open the pupil. Intraoperatively, the vitreous body around the upper scleral puncture hole was cleaned to avoid the repeated access of the vitreous cutting head and optical fiber from the surrounding vitreous body pulling the retina to form serrated edge separation. Anterior vitreous, medial vitreous, posterior vitreous, and peripheral scleral top pressing were sequentially excised and basal vitreous were excised until all vitreous and vitreous fibrous proliferative membrane were removed. In the treatment of the preretinal proliferative membrane closely adhered to the optic disc and vascular arch, air scissors or omentum tweezers were used to lift the membrane from the surface of the optic disc and peel it off gradually. When the tight adhesion could not be removed, air scissors were used to cut it off from the base of the membrane, so that the large proliferative membrane could form multiple “islands” and then be removed with glass knife. For the subretinal proliferative membrane, according to the location and quantity of the proliferative membrane, the retinal was cut, removed, or dissociated after the retinal was cut by electrostaring retinal vessels. Intraoperative retinal hemorrhage can increase intraocular perfusion pressure to stop bleeding, and definite neovascularization bleeding can be stopped by intraocular electrocoagulation. Intraocular laser photocoagulation or scleral condensation of retinal hiatus was performed after the retina was flattened by gas-liquid exchange, internal drainage or injection of heavy water. Retinal laser photocoagulation was performed according to the condition of the retina. Patients with clear refractive interstitium underwent fundus fluorescein angiography and retinal laser therapy within 1 week after surgery. We fill the vitreous cavity with silicone oil or gas according to the position of retinal hiatus, eye volume, and intraocular pressure. The scleral puncture and bulbar conjunctiva incision were closed with 0/7 absorbable suture.In 61 eyes, 28 eyes were filled with silicone oil, accounting for 45.9%. Perfluoropropane (C3F8) filled 11 eyes, accounting for 18%; Intraocular fluid filling was found in 22 eyes (36.1%). Two eyes (3.3%) were ultrasonically pulverized. Phacoemulsification was not combined with intraocular lens implantation in 3 eyes (4.9%). Phacoemulsification combined with iOL implantation in 2 eyes (3.3%); Intraocular laser was used in 50 eyes (82%).U+ dexamethasone 1 mg was injected subconjunctival for 3–5 days. After the drug injection was stopped, Clonbitol and Beryl eye drops were placed on the conjunctiva of the eye, Telipital eye ointment was applied to the conjunctival sac, Beryl eye drops were stopped 1 week later, and the drug was stopped about 1 month after the operation.After 5–7 days of postoperative intravenous infusion of antibiotics, tobramycin 10,000 Postoperative visual acuity was the final corrected visual acuity during the follow-up period. According to literature reports, the standard of visual acuity improvement was: 0.1 before surgery, above 0.02 before operation, and above 0.05 after operation, 0.05 before operation, and 0.1 after operation; preoperative photosensitivity and postoperative recognition of fingers; preoperative manual postoperative index/1 m or more.The complications include neovascular glaucoma, retinal detachment, complicated cataract, vitreous hematosis, macular cystular edema, and secondary glaucoma.χ2 test of sample rate, p <0.05 was considered as excellent message.Patients were followed up for 6–12 months after surgery, and the data obtained during the follow-up were input into Excel software to calculate the mean value and standard deviation. SPSS13.0 software package was used for the As can be seen from χ2 test with multiple sample rates was used to compare the difference of postoperative visual acuity improvement rate among the three groups. The results were χ2 = 1.365, p  = 0.505 > 0.05, and there was no statistical difference in the postoperative visual acuity improvement rate among the three groups.As shown in χ2 test with multiple sample rates was used to compare the difference of postoperative visual acuity improvement rate among the three groups. The results were χ2 = 1.365, p  = 0.505 > 0.05, there is no statistical difference in this rate among the three groups.As shown in χ2 test with multiple sample rates was used to compare the differences in postoperative visual acuity improvement rates among the three groups. The results were χ2 = 6.746, p  = 0.034 < 0.05. The postoperative visual acuity improvement rates of the three groups were statistically different, and it could be seen from the table that the postoperative visual acuity improvement rates of PDR STAGE IV patients were significantly higher than those of PDR STAGE V and PDR Stage VI patients.As shown in The choice of vitreous filling varies with the severity of diabetic retinopathy. As shown in χ2 test of two independent sample rates was used to compare differences in postoperative vision improvement between the two groups. The result was χ2 = 0.721, p  = 0.396 > 0.05, indicating no statistical difference in this improvement rates between the two groups.Patients were divided into two groups according to whether total retinal photocoagulation was performed before surgery. As shown in Retinal detachment occurred in 2 eyes (3.3%), all at the PDRVI stage. One of the eyes had macular retinal detachment, which occurred 2 months after silicone oil extraction and underwent secondary vitrectomy and gas filling. Retinal detachment occurred in 1 eye with silicone oil filling 3 months after surgery, and silicone oil was removed. Intraoperative localized eminence of nasal retina was observed, and a new 1/5PD retinal hole and scleral condensation hole were found. Intraocular laser and gas filling were performed. At the last follow-up, the retina was completely reduced in both eyes.In this group, there were 59 eyes with lens before surgery, 5 eyes underwent phacoemulsification and 1 eye underwent fasciotomy due to intraoperative opacity of lens. One eye was treated with ultrasonic crystal comminution due to subluxation. After operation, 52 eyes were lens only, 3 eyes (5.8%) had cataract exacerbation, 2 eyes (3.8%) in PDRV stage, and 1 eye (1.9%) in the PDRVI stage. All eyes were filled with vitreous silicone oil, and 1 eye underwent phacoemulsification when silicone oil was removed. Cataract phacoemulsification combined with intraocular lens implantation was performed in 1 eye when silicone oil was removed, and cataract surgery was not performed in 1 eye due to poor fundus. One eye (1.9%) was filled with silicone oil in the vitreous cavity of PDRVI stage.Vitreous hemorrhage occurred in 2 eyes (3.3%). One eye of the PDRV stage (1.6%) was filled with vitreous infusion fluid. Vitreous hemorrhage occurred 1 day after surgery. After hemostatic symptomatic treatment, no absorption of blood accumulation was found, vitreous lavage was performed, and retinal neovascularization was performed with laser photocoagulation. One eye at the PDRVI stage (1.6%) was filled with vitreous silicone oil. Vitreous hemorrhage occurred 1 month after removal of silicone oil. Vitreous lavage was performed twice. Vitreous hematocele did not occur at the last follow-up.This paper designs and implements an intelligent medical monitoring system. Its main features are as follows: front monitoring module combined with Laura wireless provides timely monitoring of patients' blood pressure and heart rate, and the medical order displays and recognizes physical symptoms and controls in real time and stores affidavit information. It can be applied not only in hospital scenarios but also in community medical care, family medical care, or personal health monitoring. The system has realized the characteristics of miniaturization of monitoring equipment, high measurement accuracy, convenient operation, and wireless data transmission, providing more convenient and efficient conditions for medical staff. Proliferative diabetic retinopathy is a serious microvascular complication in diabetic patients and an important cause of vision loss in diabetic patients. Proliferative diabetic retinopathy results from extensive retinal ischemia resulting in a large number of neovascularization, resulting in repeated vascular hemorrhage, traction, or rheumatic retinal detachment, and concomitant neovascular glaucoma, resulting in severe visual impairment. Vitrectomy can remove vitreous hemorrhage, peel off the fibrous proliferative membrane in vitreous and on the retina surface and under the retina, remove the traction of the proliferative membrane on the retina, and make the retinal anatomical reset. Therefore, vitrectomy is an effective treatment for PDR. In recent years, vitrectomy has greatly reduced the blindness rate of PDR patients. It shows that the visual acuity improvement rate of 61 eyes of 50 PDR patients was 68.9% and 45.9%, respectively.


Extracorporeal shock wave lithotripsy (ESWL) is considered one of the best choices for the treatment of various kinds of urinary tract calculi, although it might cause acute kidney injury.To measure the urinary long non-coding RNA-messenger RNA (LncRNA-mRNA) panel before and after ESWL to evaluate post-ESWL renal injury in a reliable and non-invasive method.The study included 60 patients with renal stones treated with ESWL and 30 healthy volunteers. Voided urine samples were obtained before, 2 h, and 1 day after ESWL. We measured the urinary level of LncRNA  and mRNA  by real-time qPCR and compared the results with serum creatinine and eGFR.LncRNA  and mRNA  levels were higher in patients with renal stones when compared with healthy volunteers. They showed a statistically significant increase in the level of LncRNA-mRNA panel in baseline and after ESWL treatment.LncRNA  and mRNA  levels were significantly elevated following ESWL treatment, highlighting the usefulness of urinary biomarkers in identifying patients at higher risk of developing renal injury after ESWL treatment.The online version contains supplementary material available at 10.1007/s00345-022-03996-3. The prevalence of urinary stones is around 3–12% and its recurrence rates can reach up to 50% within 10 years  and mRNA [NLRP3 (NOD-like receptor and pyrin domain-containing 3) and GBP1 (guanylate-binding protein 1)] in the urine of renal stone patients treated with ESWL, then we compared with healthy volunteers to evaluate their usefulness as diagnostic biomarkers for post ESWL kidney injury.The study was carried out after approval from Ain Shams Faculty’s Medicine Ethical Committee from December 2020 to July 2021. The participants were 60 patients whose gender and ages matched with 30 healthy volunteers with no history of kidney or stone disease. All patients underwent ESWL; for the first time to treat radiopaque stone(s) of 2 cm in diameter or less, located in the kidney. They were recruited from the outpatient clinic of the Urology Department of Ain Shams University hospitals. Informed consent was provided by all participants. The level of kidney disease was staged according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative Classification . PatientThe procedure was done with 3500 shock waves and the frequency of shock waves was set at 60 shocks per minute.Each patient provided three urine samples in centrifugal tubes  and blood samples. Urine was then centrifuged at 4000 rpm for 10 min, and the urinary pellet was washed twice with phosphate-buffered saline. The resultant urine pellet was preserved at − 80 °C. Sera samples were collected and stored within 15 min at a temperature of − 80 °C.https://reactome.org/content/detail/R-HSA-844456).We have selected the NLRP3 mRNA gene, which is highly correlates with inflammation and is essential for proper inflammasome formation and processing. Firstly, we selected an inflammatory pathway closely linked to kidney injury using biosystems available at the NCBI gene database (available at ncbi.nim.nih.gov/gene) . Secondly, we selected the NLRP3 mRNA gene, which is closely linked to the inflammasome using the Reactome database  (available at https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=DetailsSearch&Term=114548) followed by validating its basal expression in the kidney using the Gene Cards database (available at https://www.genecards.org/cgi-bin/carddisp.pl?gene=NLRP3) . Thirdly, we selected SBF2-AS1 targeting NLRP3 mRNA using the “lncRNA2target” database (available at 123.59.132.21/lncrna2target/search.jsp) . The selection of lncRNA is based on how strongly it interacts with mRNA, the novelty in kidney disease, and their basal expression in the kidney (available at https://www.genecards.org/cgi-bin/carddisp.pl?gene=SBF2-AS1&keywords=SBF2%5C-AS1) .Then, the gene’s ontology was verified  (available at https://www.ncbi.nlm.nih.gov/gene/2633). We verified its expression in the Genecards database (available at genecards.org/cgi-bin/carddisp.pI?gene = GBP1&keywords = GBP1) . Finally, we used the “lncRNA2target” database to find a related lncRNA LincFOXF1 (lncRNA-FENDRR:19) (ENSG00000268388) which is supposed to control the expression of the GBP1 gene , followed by verifying its expression in the kidney (available at 123.59.132.21/lncrna2target/search.jsp) .Fourthly, we retrieved data on the GBP1 mRNA gene, which is involved in cytokine binding and inflammasome signaling, and was correlated with kidney injury   according to the manufacturer's protocol. Total RNA samples were dissolved in 30 µl of nuclease-free water. Quality and quantity were checked using NanoDrop spectrophotometer. cDNA libraries for mRNAs, LncRNAs and miRNAs were prepared using the miScript II RT Kit . 4ul of 5 × miScript HiFlex Buffer, 2ul of 10 × miScript Nucleics Mix, 1ul of miScript Reverse Transcriptase Mix and RNase free water were added to 2ug of RNA extract, then incubated at 37 °C for 60 min and at 95 °C for 5 min using the Rotor-Gene thermal cycler .2 SYBR Green ROX qPCR Master mix. Sequentially, specific primers of each gene were designed.RT2 LncRNA qPCR Assay for Human LncRNA  and mRNA  QuantiTect Primer Assay (NM_021202), RNase free water and 2ul template cDNA to a final volume of 20ul. Hs ACTB1SG QuantiTect Primer Assay (NM_001101) was used as a housekeeping gene in equalization of raw data like the invariant control for the samples and to compare with a reference sample. PCR programmed for relative LncRNA  quantification as follows: initial denaturation at 95 °C for 10 min; followed by 45 cycles at 95 °C for 15 s; then annealing at 55 °C for 30 s and extension at 70 °C for 30 s.LncRNA  and mRNA  expressions in urine samples of diseased groups and healthy control groups were quantified by qRT-PCR using QuantiTect SYBR-Green PCR Master Mix (Roche) and 10ul 2 × RTThe real-time cycler was programmed as follows: initial activation step at 95 °C for 15 min to activate HotStarTaq DNA Polymerase. 40 cycles of PCR were performed under the following conditions: at 94 °C for 15 s, 55 °C for 30 s and 72 °C for 30 s for extension, denaturation and annealing sequentially. Each reaction was carried out three times. Fold change and expression levels were calculated using the 2 − ΔΔCt method. The Rotor-Gene real-time PCR detection system  calculated the threshold cycle (Ct) value of each sample. The value was considered negative if higher than 36 Ct value. The amplification plot curve and melting curve were analyzed to confirm the specificities of the amplicons and Tm values.p value of 0.05 or less was supposed to be statistically significant.The data were statistically presented using SPSS 20. Independent t-test, chi-square test, and Mann Whitney test were used. The (ROC) curve was done to characterize the predictive value of the selected RNA-based biomarker panel for post ESWEL kidney injury. The Spearman correlation was carried out to detect the association between clinicopathological parameters and RNA panel expression. A two-tailed p > 0.05).In this study, there were no statistically significant differences between the two investigated groups regarding age, sex, body mass index, Serum Creatinine and eGFR and hypertension . We found that the four RNAs of all patients significantly increased in voided urinary specimens collected 2 and 24 h after ESWL compared with their pre-procedure baseline levels  and mRNA  significantly increased in 24 h post-ESWL. Baseline pre-ESWL voided urine samples collected from patients with renal stones revealed significantly higher positive rates in comparison with the healthy volunteers’ voided urine (p < 0.01). Baseline pre-ESWL voided urine samples collected from patients with renal stones revealed significantly higher RNAs levels when compared to healthy volunteers’ voided urine (p < 0.01) .Urinary markers continued to rise significantly 1 day after ESWL  values were used to estimate the discriminative power of our selected RNAs between patients with renal stone versus the control group .Comparing the diseased groups with healthy control groups shows that the best discriminating cutoff values of LncRNA  and mRNA  were 1.250, 1.250, 1.250 and 1.360, respectively. The sensitivities measured 91.7%, 76.7%, 78.3% and 78.3%, respectively. Accordingly, this result indicates that these thresholds could be used to differentiate/identify diseased patients from healthy subjects (Supplementary Table 2S).There was a highly significant correlation between all the investigated urine RNAs and serum creatinine. Also, there was a highly significant correlation between serum eGFR and FENDRR19, as well as a significant correlation between serum eGFR and SBF2-AS1.By studying the correlation between the studied RNA-based biomarkers, we found that there was a highly significant positive correlation between all of them [ and mRNA ] based on fold changes (R.Q.) among all the study groups. Results are shown in Supplementary Table 3S.p = 0.000,0.002, respectively).No baseline characteristic variables were found to have a significant association by the multilinear regression model. All the tested predictor variables are presented in Supplementary Table 4S. mRNA-NLRP3 and serum creatinine is the most significant predictor of kidney injury , and it is differentially expressed after overexpression of urine lncRNA SBF2-AS1. Previous reports on cell lines and tissue also indicated that interfering with the process of NLRP3 inflammasome activation can regulate kidney injury  based on fold changes (R.Q.s) among the human study groups.We have tried to identify baseline characteristic variables that could identify risky patients with significant renal injury after ESWL. We performed a univariate and multivariate analysis. Serum creatinine, Lnc-RNA-FENDRR-19 and NLRP3 mRNA were significant independent variables that significantly correlated with renal injury.Limitations of the study include its inclusion of a relatively small sample size. Moreover, in vitro and in vivo functional analyses are needed to clarify the biological mechanisms of RNA-RNA crosstalk in post ESWL renal injury by assessment of the selected RNAs in rat AKI animal model for further verification.Urine LncRNA  and mRNA  rise significantly post ESWL. Hence, they may be prospective clinical markers for assessing acute renal injury following ESWL.Supplementary file1 (DOCX 30 KB)Supplementary file2 (DOCX 1887 KB)Below is the link to the electronic supplementary material.


Asthma is a prevalent hyperactive airway disease with physical and emotional impact. Severe asthma is associated with considerable health-related quality of life (HRQoL). The aim of this study is to assess the quality of life through physical, emotional, social and occupational aspects and evaluate the factors affecting HRQoL in patients with asthma.This is a cross-sectional multicenter study conducted on adult asthmatic patients enrolled from community pharmacies across different Lebanese geographic areas.Having wheezing sometimes and most of the time (Beta = −0.144 and −0.552), experiencing anxiety sometimes and most of the time (Beta = −0.205 and −0.573), encountering sleep problems sometimes and most of the time (Beta = −0.270 and −0.553), having previous chest discomfort sometimes and most of the time (Beta = −0.421 and −0.713), and having depression most of the times (Beta = −0.415) were associated with higher lower quality of life scores. On the other side, holding a secondary level of education was associated with a higher quality of life score (Beta = 0.192).This study highlights that asthma affects adults' quality of life through social, emotional, physical, and occupational impacts. Improved follow-up and patient education may be essential in the future to stop disease progression and achieve ideal therapeutic outcomes. Asthma is a prevalent non-communicable disease identified by chronic airway inflammation affecting children and adults worldwide . DiffereEven though clinical and physiological variables are used to assess asthma, they may not be enough to assess the patient's interpretation of their state of health. Thus, quality of life (QoL) is a significant endpoint as it reflects the impact of the disease from the patient's perception. Improper asthma management can have a substantial effect on the QoL, including physical, emotional, occupational, and social impacts, where the symptoms differ from one patient to another , 5. QoL In asthma, QoL is assessed by using the Mini asthma quality of life questionnaire (Mini AQLQ) ; it is aIn Lebanon, asthma treatment in adults falls far short of the goals specified in the international asthma guidelines, similarly to many other countries around the world. This inadequate control of the illness is associated with disease progression and poor QoL . In LebaA cross-sectional multi-centered study was conducted between February and May 2019. Six Lebanese community pharmacies from all Lebanese districts gave consent to participate in the study from a total of 13 contacted pharmacies. An online software was used to randomly select different community pharmacies using the list of pharmacies provided by the Lebanese Order of Pharmacists (OPL).Patients enrolled in the study were between 18 and 65 years, diagnosed by a physician to have asthma according to GINA criteria , and takThe Institutional Review Board of the Psychiatric Hospital of the Cross approved the study and written informed consent was acquired from all participants before study enrolment. In addition, the study followed the oxford equator guidelines for cross-sectional multi-centered studies.via face-to-face interviews by trained researchers to ensure a higher quality of data collection. The first part of the questionnaire included patient demographics, such as gender, age, marital status, educational level  and socioeconomic status. The second part assessed the QoL of asthmatic patients using the Mini AQLQ, a validated tool with good reliability since it is discriminates patients with different levels of impairment and validity as it measures asthma-specific quality of life  to ensure a confidence level of 95%, based on a 66.7% expected frequency of anxiety in asthmatic adults and an odds ratio of 9 in the lack of similar studies in Lebanon. This study accounted for a possible non-response rate for this reason, oversampling is needed .t-test and ANOVA F tests were used for categorical variables with two or more levels, respectively. Multivariable linear regression using the Forward method was done for patient's QoL score assessment as the dependent variable, using variables that showed a p < 0.2 in the bivariate analysis. All reported p-values are two-sided, with alpha set at a significance level of 0.05.Using Statistical Package for Social Sciences version 21.0, statistical analysis was performed. Descriptive statistics were used for patients' characteristics, with frequencies and percentages for categorical variables and means ± standard deviations for continuous variables. Bivariate associations assessed through the Pearson correlation analysis for the continuous variables along with the HRQol score, and the Student Data was collected from 200 participants out of whom 172 were enrolled in the study as the others had mental disorders and thus were excluded. The mean (±SD) age was 31.79 ± 20.92 years, with the majority being females 96/172 (55.8%), single 117/172 (68.0%), and with secondary level of education 86/172 (50.0%). 69/172 (46.3%) of families had a medium monthly income.Patients reported frequently a discomfort affecting performance of difficult tasks (49.4%), discomfort due to coughing (48.3%) and the need to avoid going out due to weather changes (47.1%). Other asthma related symptoms reported less frequently are summarized in Based upon the Mini AQLQ, the majority of patients (90.1%) had poor QoL. The mean QoL scores (±standard deviation) for the four domains of the Mini AQLQ  were 3.5p = 0.020), non-married vs. married , high income vs. low income  and secondary and University vs. lower levels of education , and in those who had never have difficulty sleeping due to asthma  or never had depression  vs. most of the time. Similar results were found for feeling anxious, wheezing experience, discomfort due to coughing, discomfort related to difficult tasks and going out during weather changes. Bivariate analysis for factors associated with QoL score is summarized in n = 172, p < 0.001) which is not illustrated in the table.A meaningfully higher mean QoL score was found in males vs. females (4.88 vs. 4.50; The results of a first linear regression, taking the quality of life score as the dependent variable and several other factors as independent variables, showed that holding a secondary level of education was associated with higher QoL scores. However, participants who had wheezing, anxiety, sleeping problems, chest discomfort, and discomfort to avoid going out, discomfort due to coughing, and avoidance of tasks performance on a frequency of “sometimes” and “most of the times” compared to “never” had lower QoL scores shown in The study findings support the negative effect of asthma on quality of life and show the need for continuous patient monitoring and QoL evaluation during the course of the disease. Holding a secondary educational level was associated with higher QoL score, whereas aging, depression, wheezing, chest discomfort, anxiety, sleeping problems, and avoiding discomfort related to going out, discomfort due to coughing, and avoidance of tasks performance were significantly associated with lower QoL.Wheezing and chest discomfort are critical prognostic factors in asthma . Indeed,Our study findings demonstrate that insomnia is highly linked to poor QoL, consistent with the results of the study conducted by Luyster et al. . Sleep dOur results also support the previous findings in which greater depression and anxiety are associated with lower QoL among asthmatic patients , 36. MorOur findings show that older age was associated with low QoL scores, in line with previous literature , 39, 40.Quality of life is influenced by many factors, related to both the sociodemographic characteristics of the patients and comorbid disease conditions . This stThe majority of the individuals endorse a poor quality of life which can be explained by the fact that many participants had secondary level of education and were of the medium socioeconomic status. According to previous literature, patients of lower socioeconomic status often report poor health behaviors that may exacerbate asthma, including higher rates of current smoking, reduced consumption of fruits and vegetables, and obesity. Also, patients with lower educational level have lower socioeconomic status and may have higher exposures to indoor and outdoor allergens, and tend to be less complaint with medication, thus increasing risk for acute asthma exacerbations which impair the quality of life , 42.The study has some limitations. This is a cross-sectional study where the findings cannot establish a causal relationship. Moreover, this study might be also subject to selection bias as the study enrolled more females, young age participants, and single status which can influence the quality of life. The utilization of questionnaires in the general population, especially in elderly, may not always be precise and is limited by the difficulty in questions clear comprehension and influenced by recall bias which underestimates the association between different factors and quality of life. In this study, we accounted for several variables that could affect QoL; however, not all factors were accounted for as diseases, medications, and asthma severity. To remove the confounding effect of several variables, we performed a multivariate analysis; however, we could not ignore the possibility of residual confounding of the variables that we did not evaluate as cardiovascular disease, cancer, and hypertension. Accordingly, prospective studies, taking into account these limitations, are needed. The strengths of this study include the geographical distribution of participants recruited from different pharmacies across Lebanese and the use of the mini AQLQ questionnaire in the methodology, which is a validated tool utilized to assess the QoL.The study demonstrated that asthma affects patient's QoL that was assessed through physical, emotional, occupational and social negative impacts. Patient education is an important part of treatment however, to be successful, it should not only be limited to providing knowledge, but should impact behavior and lead to a consistent change in patient's behaviors. Pharmacists and patients need to cooperate together to improve an asthma care program that targets for optimizing asthma management for a symptom-free asthma disease. During counseling, pharmacists could provide patients with adequate information about the correct use of medications and associated risks of misuse, in addition to general awareness about avoiding asthma triggers to prevent exacerbations and thus improving the QoL. In conclusion, sustained efforts are needed to optimize patients' awareness on asthma disease and its management and to dispel their myths and misconception for an improved QoL.Health-care professionals can utilize the findings of this study to make suitable treatment strategies for asthma for the future and develop healthcare measures based on fundamental evidence. In addition to continuous medical therapy, asthmatic patients should be provided with healthcare education and psychological consultancy services. Therefore, training and psychological support should be provided to patients to ensure optimal therapeutic outcome and disease management. It is recommended that future studies assess other factors affecting QoL among asthmatic patients and methods for improving it.The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.The Institutional Review Board of the Psychiatric Hospital of the Cross approved the study and written informed consent was acquired from all participants before study enrolment. In addition, the study followed the oxford equator guidelines for cross-sectional multi-centered studies.DM, EF, and FE analyzed and interpreted the collected data from study participants. ZK, EF, DM, HS, PS, FJ, HA, and SH contributed in idea conceptualization and study design and interpretation of data. ZK, EF, DM, FE, HS, CA, SS, SH, PS, FJ, and HA were major contributors in writing the manuscript. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To evaluate changes in blood pressure (BP) values in patients with established coronary artery disease (CAD) over 20 years (1997–2017).  Consecutive patients aged <71 years and hospitalized for acute coronary syndrome or myocardial revascularization procedures were recruited and interviewed 6–18 months after their discharge from the hospital. BP was measured in 1997–1998, 1999–2000, 2006–2007, 2011–2013, and 2016–2017. The same five hospitals took part in the surveys at each time point. p < 0.001). Mean systolic and diastolic BP decreased significantly independent of age, sex, and education .  We examined 412 patients in 1997–1998, 427 in 1999–2000, 422 in 2006–2007, 462 in 2011–2013, and 272 in 2016–2017. The proportion of patients with BP at the recommended goal was 49.2% in 1997–98, 44.5% in 1999–2000, 44.7% in 2006–07, 51.1% in 2011–13, and 58.8% in 2016–17 ( The analysis of five multicenter surveys provides evidence of a decrease in BP in patients with established CAD over two decades. This trend is independent of age, sex, and the education level of the patients. Cardiovascular disease is the leading cause of death in developed countries . DespiteWe analyzed the data of the participants of the five surveys assessing cardiovascular prevention following hospitalization due to CAD that were conducted in 1997–1998 (survey I), 1999–2000 (survey II), 2006–2007 (survey III), 2011–2013 (survey IV), and 2016–2017 (survey V). The same five hospitals serving the city and surrounding districts (1.2 m inhabitants) participated in each survey. The methods used in these surveys had been published previously and were similar on each occasion , 14–17. 2.The patients were examined at 6–18 months after the index hospitalization. Data on patients' medical history and the medications used were obtained using a standard questionnaire. Education of the participants was assessed based on the number of years of schooling as well as a categorical variable (at least secondary education vs. lower than secondary education). Height and weight were measured in a standing position without shoes and heavy outerwear using standard scales with a vertical ruler. The scales were calibrated at the start of each survey. Body mass index was calculated according to the following formula: body mass index = weight (kg)/(height (m))Blood pressure was measured twice, on the right arm in a sitting position after at least five minutes of rest. The average of the two readings was used in the analysis. High blood pressure was defined using two approaches. First, we analyzed the proportions of patients achieving recommended BP (according to the European Society of Hypertension/European Society of Cardiology guidelines) at the time of each survey  in 1997–1998, 1999–2000, 2006–2007 and 2011–2013; <140/90 mmHg (<140/85 mmHg in diabetics) in 2016–2017) –21. The The survey protocols were approved by the institutional Bioethics Committee. Every patient signed an informed consent form.χ2 test was applied to all categorical variables. Normally distributed continuous variables were compared by the Student's t-test or analysis of variance. Variables without normal distributions were evaluated by the Mann–Whitney U test or the Kruskal–Wallis analysis of variance. Temporal trends were evaluated with linear regression for continuous variables and logistic regression for categorical variables with subsequent surveys coded as an independent variable. Multivariable logistic regression analysis was used to calculate the odds ratios of having BP at goal in surveys II, III, IV, and V compared to the first survey. As a sensitivity analysis, we used two definitions of high blood pressure (see above). In addition, we performed the analysis limited to patients with hypertension only. Generalized linear models as implemented in the Statistica 13 software  were used to provide the least square means after adjusting for the covariates including sex, age, education, and employment, index event, and body mass index. A two-tailed P value of less than 0.05 was regarded as indicating statistical significance.Categorical variables were reported as percentages and continuous variables as means with standard deviations (SD). The Pearson β-blockers were used by 59.0%, 63.9%, 87.4%, 80.7%, and 92.7% of the patients, angiotensin-converting enzyme inhibitors by 45.8%, 47.5%, 74.5%, 66.2%, and 74.8%, angiotensin receptor blockers by 0.0%, 0.0%, 5.3%, 12.5%, and 14.2%, calcium antagonists by 28.7%, 33.3%, 21.0%, 20.6%, and 27.7%, diuretics by 17.1%, 20.1%, 31.8%, 35.8%, and 41.2%, whereas other antihypertensive drugs by 0.5%, 2.1%, 2.4%, 6.8%, and 2.9% of the participants of the survey I, II, III, IV, and V, respectively.The following numbers of patients participated in the surveys: 415 in 1997–1998, 427 in 1999–2000, 421 in 2006–2007, 456 in 2011–2013, and 274 in 2016–2017. The characteristics of the studied groups are presented in p < 0.001) and diastolic BP (83.3 (11.7) mmHg in 1997–1998 vs. 84.7 (11.6) mmHg in 1999–2000 vs. 85.1 (11.5) mmHg in 2006–2007 vs. 80.9 (11.5) mmHg in 2011–2013 and 81.5 (11.9) mmHg in 2016–2017, p < 0.001). These trends were independent of age, sex, and education of the participants  and in patients with diabetes when systolic BP (p < 0.001), but not diastolic BP (p=0.35) was analyzed.icipants . The trep < 0.001). The multivariable adjustments did not change the results significantly. Proportion of hypertensive patients without diagnosis of hypertension during the index hospitalization was 13.5% in 1997–1998, 11.2% in 1999–2000, 6.5% in 2006–2007, 6.6% in 2011–2013, and 2.9% in 2016–2017 (p < 0.001). The multivariable adjustments did not change the results significantly.The criteria for hypertension were met by 67% of the patients in 1997–1998, 73.1% in 1999–2000, 87.5% in 2006–2007, 81.6% in 2011–2013, and 86.9% in patients studied in 2016–2017  and who had normal (<140/90 mm of Hg) BP during the control visit and who were not taking antihypertensive medication. Similarly, such patients were not considered hypertensive in other large epidemiological studies , 26, 27.In general, there are three reasons for poor BP control: the patient, the physician, and the healthcare system. The patient may not adhere to the medication regiment or may be resistant to it. As the mean number of antihypertensive drugs was lower in those achieving the BP goal (1.9 ± 1.0 vs. 2.1 ± 1.0), this may indicate lower compliance with medication in those not achieving the BP goal or that their hypertension was somewhat resistant to treatment. Low awareness of high BP as an important cardiovascular risk factor may also be one of the reasons. Low medication persistence is considered a major factor limiting the long-term effectiveness of antihypertensive treatment . A quiteNumerous studies have assessed the quality of medical care in connection with prevention and treatment of CAD, including the control of hypertension , 7, 31. Our analysis has some limitations. Firstly, we were unable to assess the influence of changes in BP on the risk of cardiovascular complications. Secondly, participants were limited to those who had experienced an acute CAD event or had undergone a revascularization procedure. Therefore, our results should not be directly applied to other CAD patients. Thirdly, the survey participants lived in a defined geographical area. Although the applicability of our results to other regions is uncertain, the trends described above reflect changes over time in the general population in Poland as well as in CAD patients from other European countries , 31. HowThe analysis of five multicenter surveys provides evidence of a decrease in BP in patients with established CAD over a period of two decades. The trend is independent of age, sex, and the education level of patients.