The association between the screening frequency of eGFR (yearly vs. non-yearly) and the substantial reduction in eGFR was studied with logistical models and adjusted with biochemical variables and preventive medications.Among the T2D patients with normal kidney function, non-yearly eGFR screening was significantly associated with substantial eGFR reduction in both unadjusted  and adjusted models  compared with yearly screening frequency. In the group of patients with impaired kidney function in the unadjusted model, non-yearly eGFR screening was significantly associated with substantial eGFR reduction , but became non-significant after adjustments .This study underscores the role of regular eGFR screening in the prevention of kidney function decline. Type 2 diabetes (T2D) is an alarming global pandemic that is affecting a steadily increasing number of people. In 2019, it was estimated that 463 million (9.3%) of the world’s adult population have diabetes, and the number is estimated to increase to 578 million (10.2%) by 2030 [It is well established that T2D is a major risk factor for a wide range of vascular diseases, including ischemic heart disease and stroke, as well as chronic kidney disease (CKD) . FurtherThe prevalence of CKD in patients with T2D is estimated to vary between 27.9 and 58.6% . TraditiIn patients with T2D, regular screening and monitoring of CKD are widely recommended , 14. HowThe effective prevention of complications, especially CKD, is highly important in patients with T2D . IntensiThe associations between cardiovascular risk factor control (glycosylated hemoglobin A1 (HbA1c), systolic blood pressure (sBP)) and prevention of renal function decline are well established , 14, 16.This study was a part of the Rovaniemi Primary Care T2D Study, which is a registry-based real-world study in a primary health care setting. Rovaniemi is a city and municipality located in northern Finland with a total population of 62,000 people living in both urban and rural areas. The study population consisted of 5104 patients who had received a T2D diagnosis between November 1, 2011 and February 19, 2019 at the Rovaniemi Health Center, Rovaniemi, Finland. The T2D diagnosis was based on the International Classification of Disease (ICD- [2). A substantial reduction in eGFR was defined as a reduction of ≥25% between the baseline and the follow-up in accordance with the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines in CKD evaluation and management [The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation formulation, which is based on age, sex, race, and serum creatinine level (μmol/l), was used to calculate the eGFR  vs. non-yearly (over 365 days), in line with the current national screening frequency recommendations , 19. TheWe assessed the sex, age, achievement of treatment goals of bioclinical variables , and prescription of antihyperglycemic and cardiovascular medications : statins (C10AA), any long-acting insulin , GLP-1 RAs (A10BJ), SGLT2i (A10BK), and angiotensin-converting enzyme inhibitors (ACEi) (C09A) or angiotensin II receptor blockers (ARB) (C09C) as potential covariates , 14, 16.Age was measured at the follow-up. Achievement of the treatment targets for HbA1c, LDL, and sBP was defined according to the national guidelines as follows: HbA1c < 53 mmol/mol, LDL < 2.5 mmol/l, and sBP < 135 mmHg . This waData on prescribed or renewed prescriptions of statins, any long-acting insulin, GLP-1 RAs, SGLT2i, and ACEi/ARB were collected from the national electronic prescription registry using ATC codes. Medication data  were further processed by calculating the midpoint of the study period for each patient. Baseline medication was defined as before whereas follow-up medication was defined as after the midpoint. If the prescription was valid at the midpoint, then it was assumed to be the same at the baseline and follow-up. Follow-up medication data were used in the logistic models.2) and considered a continuous variable. In addition to the previously mentioned bioclinical variables and medications, the following measurements were gathered from the patient records: hemoglobin , diastolic BP (mmHg), and medications (ATC codes), such as calcium blockers (C08CA), beta blockers (C07AB), diuretics (C03), metformin (A10BA02), gliptins (A10BH), glitazones (A10BG), sulphonylureas (A10BB), fibrates (C10AB), multiple daily insulin injections (A10AE or A10AC and A10AB), and ezetimibe (C10AX).Body mass index (BMI) was calculated by dividing the patient weight in kilograms by the square of their height in meters  and 95% confidence intervals (CIs) was performed to study the potential associations between substantial eGFR reduction and the screening frequency of eGFR. The logistic models were stratified by the baseline kidney function as normal (eGFR≥60 ml/min/1.73 m2) and impaired (eGFR< 60 ml/min/1.73 m2) kidney function, as the screening frequency recommendations differ between patients with and without impaired kidney function [p-value < 0.05 was considered statistically significant.Clinical outcome measures were presented as mean and standard deviation (SD) and categorical variables as proportions. Continuous variables were tested with the independent samples t-test, while the Pearson χp < 0.001) in the total population. A significant reduction in eGFR (≥25%) was observed in 12.6% (n = 582) of the population. The total number of prescribed antihyperglycemic and cardiovascular medications increased during the study period, as well as the usage of GLP-1 RAs and SGLT2i.The T2D study population consisted of 5104 patients with a mean age of 70.0 years (SD 12.7). The characteristics of the study population are presented in Table n = 4336) of the population had normal kidney function (Table p < 0.001 for both). A substantial reduction in eGFR was observed among 25.0% (n = 146) of the patients with impaired kidney function and 10.8% (n = 436) among those with normal kidney function (p < 0.001).At baseline, 87.4% , whereas the adjusted association did not reach statistical significance in the impaired kidney function group . Many of the other variables showed the same attenuating trend, with the achievement of the treatment targets for LDL and HbA1c, alongside SGLT2i and any long-acting insulin, being significantly associated in the unadjusted model but not in the adjusted model. Female sex and ACEi/ARB prescription were significantly associated in the adjusted model (OR 0.41 CI 0.20–0.84 and OR 5.16 CI 1.94–16.72).In this longitudinal study, we found that annual eGFR screening frequency was associated with significant renal function decline among 5104 primary care T2D patients with normal kidney function. This association was independent of the sex, age, bioclinical variables, and prescribed antihyperglycemic and cardiovascular medications. A similar trend in the association between annual eGFR screening and significant renal function decline was observed in the impaired kidney function group.To the best of our knowledge, earlier studies have not investigated the association of eGFR screening frequency with renal function decline among patients with T2D. Although international guidelines recommend the annual screening of CKD in patients with T2D and more frequent monitoring of kidney function if CKD is diagnosed, these guidelines are derived from expert opinion and indirectly from renoprotective medication research , 14. Thi2 are more likely to be monitored more closely and treated by a nephrologist than a primary care doctor [Yearly eGFR screening was associated with renal function decline in patients with normal kidney function. In the present study, we used a cut-off level of 25% as the substantial reduction in eGFR, in accordance with KDIGO guidelines . A simile doctor .. The changes in medication therapy on control visits, smoking status, physical activity, socio-economic status, and patient mortality were also not available for analysis, which can be considered a limitation of our study.The main strengths of our study are the real-life primary care setting that captures the majority of the T2D patients in the region, the large population size, and the longitudinal design. In Finnish health care, electronic patient registry data and electronic medicine prescriptions are extensively used as sources of comprehensive medical data. All of the patient samples were taken, processed, and analyzed by the same laboratory, avoiding possible discrepancies in the results. Concurrently, the study has several limitations that need to be considered while interpreting our results. Data on the patients treated and monitored by nephrologists  were not available. The majority of CKD patients with T2D are diagnosed and treated in primary care by general practitioners in European countries, with only patients with severely decreased eGFR and moderately to severely increased albuminuria requiring referral to a nephrologist. The findings of the current study are derived from a single center, and mainly of older patients and therefore should not be directly generalized to other patient groupsIn conclusion, the novel findings of the present study highlight the role of regular eGFR screening in the prevention of kidney function decline. This confirms the importance of regular eGFR screening in clinicians’ daily practice. Further studies are needed to determine the association of the screening frequency of albuminuria with renal function decline in the prevention of renal impairment in T2D patients, especially in primary health care settings.


It is known that Baba’s diabetic neuropathy classification (BDC) is useful in quantitative evaluation of Diabetic polyneuropathy (DPN). In this study, we aimed to investigate the possible association between BDC and various diabetic microvascular and macrovascular complications in patients whose neuropathy was evaluated with BDC. As the results, BDC was significantly correlated with the severity of diabetic retinopathy and nephropathy. BDC was also significantly correlated with history of myocardial infarction or cerebral infarction, carotid IMT, and ABI. These data suggest that BDC may be useful in predicting the presence of various diabetic microvascular and macrovascular complications. The data also support the idea that we should perform further investigation of other diabetes-related complications in patients with severe DPN. Diabetic polyneuropathy (DPN), a microvascular complication of diabetes, usually occurs in a relatively early stage of diabetes compared to other microvascular complications . DPN is We use this method when diabetic patients are admitted to our hospital to accurately assess neuropathy, and although it has been suggested that DPN is associated with pathological progression of atherosclerotic lesions, there are few reports on the association between BDC and microvascular and macrovascular complications of diabetes mellitus. In this study, we aimed to investigate the possible association between BDC and various diabetic microvascular and macrovascular complications in patients whose neuropathy was evaluated with BDC.This was a single-center, retrospective, cross-sectional study of patients with type 2 diabetes. A total of 357 patients eligible for the present study who were admitted to our hospital for treatment of type 2 diabetes at Kawasaki Medical School Hospital from April 1st, 2018, to March 31st, 2021. The Institutional Review Board of Kawasaki Medical School (No. 5594-00) approved the study protocol, including opt-out informed consent. This study was conducted by the principles of the Declaration of Helsinki. The flow of participants in this study is shown in Study participants’ age, duration of diabetes, history of smoking, history of alcohol consumption, and current medications were obtained at the time of admission. Cases who consumed more than 20 g/day of ethanol three or more times per week were excluded from the study. Smokers were divided into current smoker, past smoker, and never smoker. All patients were asked on admission by their physician whether they had an old cerebral infarction and an old myocardial infarction. Body weight, body mass index (BMI), abdominal circumference, grip strength, blood pressure, and pulse rate were measured upon admission. Blood glucose, HbA1c, lipids, and liver and kidney function data were assessed by fasting blood tests on the day following admission.2 and urinary albumin <30 mg/gCr; Stage 2 was defined as eGFR >30 mL/min/1.73 m2 and urinary albumin; Stage 3: eGFR ≥ 30 mL/min/1.73 m2 and urinary albumin ≥ 300 mg/gCr, and Stage 4: eGFR < 30 mL/min/1.73 m2. Referring to the Current Chronic Kidney Disease (CKD) Nomenclature Used by KDIGO, participants were categorized by eGFR as follows: G1 - >90mL/min/1.73m2; G2 - 60-89mL/min/1.73m2; G3a - 45-59 mL/min/1.73 m2; G3b - 30-44 mL/min/1.73 m2; G4 - 15-29 mL/min/1.73 m2. Participants were also categorized by creatinine-converted albuminuria as follows: A1 - <30 mg/gCr; A2 - 30-300 mg/gCr; A3 - >300 mg/gCr. Participants in this study did not include dialysis patients. CVR-R was evaluated using a twelve-lead electrocardiogram measuring device. CVR-R at rest was calculated by measuring the interval between the apexes of the R wave in 100 consecutive heartbeats in the resting supine position. CVR-R at deep breath was calculated from the interval variability of the R wave of 100 consecutive heartbeats during deep breathing. Three patients with atrial fibrillation were excluded when assessing CVR-R because it is impossible to assess CV-RR in these patients. For vibration sensation, a C128 tuning fork was applied to the endocondyle of the tibia, the vibration sensing time was measured on both sides, and the average value was calculated. Carotid IMT was assessed by an ultrasound technician with ultrasonographic equipment, Aplio series . The carotid IMT was evaluated in the common carotid artery wall 10 mm centrally from the carotid sinus. Two IMT points were measured within a 10 mm area, and the mean value was defined as mean IMT. The maximum diameter in the same measurement range was defined as max IMT. Ankle brachial index (ABI) was calculated by measuring blood pressure at the bilateral upper arm and ankle in the supine position and by the ratio of the blood pressure at the higher upper arm to the blood pressure at the respective ankles on the right and left sides. In this study, the lower values of the left and right ABIs were included in the analysis.The following is a brief description of the complications of diabetes mellitus and how to test them. NCS was performed by skilled technicians using MEB-2306 or MEB-2312 . NCS was performed in the upper and lower extremities on one side and, in the presence of DPN symptoms, on the more symptomatic side. The data obtained were analyzed by a neurologist. Modified Davis staging was used to evaluate diabetic retinopathy , and ophPost hoc testing was performed by the Tukey method. Mean IMT, max IMT, and ABI were evaluated by natural logarithm. JMP (16.0.1) was used for analysis and EXCEL for Mac (16.58) for table creation.The primary endpoint was the correlation between BDC and atherosclerotic lesions, and secondary endpoints were diabetes-related parameters on admission and factors that could correlate with BDC. Analysis between BDC groups was performed by chi-square test and ANOVA. ANOVA adjusted for age, gender, disease duration, smoking history, HbA1c, BMI, hypercholesterolemia medication, and hypertension medication was used to evaluate mean IMT, max IMT, and ABI among BDC groups. The clinical characteristics of the patients in this study are summarized in The correlation between BDC and diabetic retinopathy is shown in The correlation between BDC and carotid intima-media thickness (IMT) and ankle-brachial index (ABI), a measure of atherosclerotic lesions, was evaluated. Mean IMT was 0.84 ± 0.07 for BDC-0, 0.94 ± 0.03 for BDC-1, 0.89 ± 0.11 for BDC-2, and 1.13 ± 0.16 for BDC-3/4  . In thisPrevious studies on Baba classification showed an increased frequency of macrovascular complications such as myocardial infarction, stroke, and diabetic foot gangrene in patients with BDC 3-4, but there were concerns about bias due to other atherosclerotic factors . There hvia adipocytes and macrophages, and dyslipidemia is considered to be an influential factor in diabetic neuropathy . Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.YI designed the study. YI, SN, TI, EN, MO, TKu, HT, HI, JS, YF, YK, TKi, FT, MS, SN, TM, and HK treated patients and collected data. YI analyzed the data. YI, SH, TKi, FT, MS, SN, TM, and HK contributed to discussion. KK supervised the project. YI wrote the manuscript. HK reviewed and edited the manuscript. All authors contributed to the article and approved the submitted version.The abstract of this report was presented at the 60th General Meeting of the Chugoku-Shikoku Regional Meeting of the Japan Diabetes Society (Hiroshima).HK has received honoraria for lectures, received scholarship grants, and received research grant from Novo Nordisk Pharma, Sanofi, Eli Lilly, Boehringer Ingelheim, Taisho Pharma, Sumitomo Dainippon Pharma, Takeda Pharma, Ono Pharma, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Kissei Pharma, MSD, AstraZeneca, Astellas, Novartis, Kowa, Abbott. KK has been an advisor to, received honoraria for lectures from, and received scholarship grants from Novo Nordisk Pharma, Sanwa Kagaku, Takeda, Taisho Pharma, MSD, Kowa, Sumitomo Dainippon Pharma, Novartis, Mitsubishi Tanabe Pharma, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Sanofi.The remaining 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.


This study aims to explore the association between the frailty index and chronic heart failure (CHF).We collected data from the National Health and Nutrition Examination Survey (NHANES) (1998–2018) database to assess the association between CHF and frailty. Demographic, inquiry, laboratory examinations, and characteristics were gathered to compare CHF and non-CHF groups. Multiple logistic regression analysis was performed to explore the relationship between frailty and CHF. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence interval (CI) for mortality from all causes and cardiovascular disease (CVD).n = 1,125) and non-CHF  groups. In patients with CHF, the prevalence of frailty, pre-frailty, and non-frailty were 66.31, 30.93, and 2.75%, respectively. In multiple logistic regression, patients with CHF who were male , whose annual family income was over $20,000 , or with normal hemoglobin level  had a lower likelihood of frailty. CHF patients with hypertension , coronary heart disease , diabetes mellitus , and stroke  tended to be frail. Survival analysis suggested that pre-frailty and frailty were related to poor all-cause deaths  and CVD mortality . CHF patients with frailty were strongly connected with all-cause death .A total of 16,175 participants with cardiac and cerebrovascular disease were categorized into CHF (Frailty was positively associated with CHF. Patients with CHF who were male, whose annual family income was over $20,000, or with normal hemoglobin level were negatively correlated to frailty. For patients with cardiac and cerebrovascular disease as well as CHF, frailty was strongly connected with all-cause death. Chronic heart failure (CHF) is one of the leading causes of death globally. It is a complex clinical syndrome with symptoms and signs that result from any structural or functional impairment of ventricular filling or ejection of blood . The preIt was reported that the prevalence of patients with CHF was about 30–90% , 5. FraiTo the best of our knowledge, most studies focusing on CHF and frailty were prospective or retrospective studies, which had limited sample size and follow-up time. There are no articles on CHF and frailty in the online databases. The National Health and Nutrition Examination Surveys (NHANES) is a well-designed large-sample clinical registration database with a complete follow-up, which can well discuss the correlation between frailty index (FI) and CHF and the prognosis of CHF patients with frailty. Therefore, we used the NHANES database from 1998 to 2018 to study the relationship between frailty and CHF to supplement the clinical studies.http://www.cdc.gov/nhanes.Data were collected from the NHANES database, which is a cross-sectional survey among all non-institutionalized civilians in the United States. Trained interviewers and examinations collected data self-reported from participants using the Computer-Assisted Personal Interview system. NHANES data are published on a 2-year cycle. To obtain a large sample for analysis, a total of 10 cycles of data from 1999 to 2018 were included in this study. More details about NHANES are available at CHF, Coronary Heart Disease (CHD), angina, stroke, and heart attack were diagnosed based on the Monetary Choice Questionnaire (MCQ) by asking “Someone ever told you had congestive heart failure (or CHD/angina/stroke/heart attack)?”The diagnosis criteria for hypertension were as follows: (1) the answers to the MCQ questionnaire; (2) the patient's blood pressure; and (3) whether the patient is taking antihypertensive medicine; if the patient meets one of the above conditions, then the diagnosis of hypertension can be made.The diagnosis criteria for diabetes (DM) were as follows: (1) the answers to the MCQ questionnaire; (2) glycohemoglobin (%) > 6.5; (3) fasting glucose (mmol/l) ≥ 7.0; (4) random blood glucose (mmol/l) ≥ 11.1; (5) 2-h OGTT blood glucose (mmol) ≥ 11.1; and (6) use of diabetes medication or insulin. If the patient meets one of the above conditions, then the diagnosis of DM can be made.The diagnosis criteria of the prediabetic (preDM) phase were as follows: (1) patients who answered “yes” to the MCQ questionnaire; (2) glycohemoglobin (%): 5.7–6.5 mmol/L; (3) fasting glucose (mmol/l): 5.6–7.0; and (4) 2-h OGTT blood glucose (mmol): 7.8–11. If the patient meets one of the above conditions, then the diagnosis of prediabetic can be made.The details of the FI are listed in The detailed data extraction process from the NHANES is shown in t-tests. We used the Chi-square test to analyze categorical variables according to the number of cases and weighted prevalence [n (weighted %)]. The relationship between frailty and CHF was explored by the multiple logistic regression analysis. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence interval (CI) for mortality from all causes and cardiovascular disease (CVD).We used R (4.2.0) and R studio for data analysis. The weighting parameters were based on the weights provided internally by NHANES mainly. Weighting was performed using wtmec4yr when the data years were 1999–2000 and 2001–2002, and wtmec2yr when the data were for the remaining years. Continuous data were described by means and standard errors with categorical comparisons, using weighted 2, with a relatively balanced gender distribution; 15,050 were non-CHF participants while 1,125 were CHF participants. In terms of race, non-Hispanic white people accounted for 50.55% , followed by non-Hispanic black people , Mexican-Americans , other Hispanic races , and other races . The percentage of patients with frailty was 21.64% and pre-frailty was 48.04%. For patients with a CVD history, hypertension accounted for 78.55% , followed by preDM , DM , heart attack , CHD , stroke , and angina .Altogether 16,175 participants [mean age (±SE) 63.72 ± 0.21] were included in our analysis, which represented 85,222,240 adults in the United States. The mean BMI of participants was 30.00 ± 0.09 kg/mP < 0.001], with a higher BMI , a lower annual family income , and a lower percentage of education  than those without CHF. In terms of CVD history, patients with CHF had a higher ratio of hypertension, DM, angina, stroke, and CHD. It was an important phenomenon that patients with CHF presented a higher percentage of frailty than patients with non-CHF. In a routine blood test, patients with CHF had a combination of higher white blood count (WBC)  and neutrophilic granulocyte (Neu) , and lower hemoglobin (Hb)  and platelets . In blood pressure, patients with CHF had lower blood pressure than patients with non-CHF for systolic blood pressure  and diastolic blood pressure . There were non-significant differences in race, gender, and lymphocyte (Lym) percentage between patients with CHF and non-CHF. The data can be visualized in The basic information of CHF participants is shown in P < 0.01) and pre-frailty . Non-Hispanic white people had a lower percentage of frailty than pre-frailty and non-frailty while the rest of the races had the highest percentage of frailty in the research. Patients with frailty showed higher BMI compared to patients with pre-frailty and non-frailty  significantly. A greater proportion of patients with frailty were suffering from CVD and other chronic diseases, including CHF, hypertension , DM , angina , heart attack , stroke , and CHD , than patients with pre-frailty and non-frailty. There were more non-frailty patients with preDM than patients with frailty and pre-frailty . Patients with frailty were higher in WBC , Lym , and Neu  counts and lower in Hb  count. Regarding blood pressure, patients with frailty had lower SBP  and DBP . The data can be visualized in The co-linearity study was conducted to eliminate possible co-linear relationships between different factors. It indicates that there is significant covariance between the factors when the variance inflation factor (VIF) value is over 5. This situation is prone to logistic regression bias. Thus, some factors need to be excluded based on experience. It was suggested that there was covariance between FI and frailty , and WBC, Lym, and Neu  are the results of the covariance analysis of the factors associated with CHF. After removing FI, Lym, and Neu, the VIF values between the variables were < 5 and further regression analysis could be performed .n = 66.31%), pre-frailty (n = 30.93%), and non-frailty (n = 2.75%). There was no significant difference in age, race, education, prevalence of heart attack, and preDM, Plt, or SBP among the three groups of patients (P > 0.05). Female participants had a higher probability of frailty . However, male participants were more likely to have pre-frailty . Patients with CHF with annual family income < $20,000 were much easier to be frail instead of normal . While those patients with an annual family income of more than $20,000 tended to be normal instead of being frail . BMI was significantly higher in patients with frailty compared to patients with pre-frailty and non-frailty . A greater proportion of patients with frailty were suffering from cardiac and cerebrovascular disease and other chronic diseases, including hypertension , DM , angina , stroke , and CHD . In terms of a blood test, patients with frailty were lower in Hb  and higher in Plt  and DBP . The data can be visualized in P < 0.05).p < 0.001). The OR was 0.06 after the factors of age, sex, ethnicity, family income, education, BMI, diseases, and blood test were adjusted. There was a significant association between lower yearly family income and the higher prevalence of CHF with frailty . Besides, CHF patients with frailty tended to suffer from hypertension , stroke , DM , and CHD , respectively, than those without frailty. Except for hypertension , the rest variable of stroke was , DM was , and CHD was  after being adjusted. We also found that the Hb level improved by 1 g·dl, and the risk of CHF may decrease by 33% .It was found that female patients were more likely to acquire CHF with frailty than male patients . After adjusting factors of age, gender, ethnicity, family income, education, BMI, diseases, and blood test, the association was slightly weakened . A statistically significant distinction was found between increased OR CHF with frailty and lower yearly family income . Higher BMI , angina , heart attack , and stroke  were risk factors for CHF, and high school education or above was a protective factor for CHF  are all risk factors for CHF. After adjusting factors of age, gender, ethnicity, family income, education, BMI, diseases, and blood test, frailty was still strongly associated with CHF , advanced age , Non-Hispanic black , and co-morbidities  still exacerbated the likelihood of CHF after the correction for model , high BMI, and co-morbidities  were risk factors for CHF, while high income, high educational level, and elevated DBP were protective factors. Frailty . However, the increase in FI varies from different characteristics. Compared with female patients, male patients had a more significant increase in FI (P < 0.01 vs. P < 0.0001). Patients with CHF having less than high school education, with a BMI of 20–25, had a more significant increase in FI after CHD than the other patients.To further explore whether CHF comorbidities aggravate frailty, subgroup analyses were performed. As shown in P < 0.001). FI of male patients increased more significantly than that of female patients (P < 0.0001 vs. P < 0.01). The frailty of the BMI > 30 subgroup increased more significantly with DM . FI of Mexican American and Non-Hispanic white increased after the DM combination. Overall, it is suggested that FI increased in CHF patients with CHD and DM.As shown in In cardiovascular and cerebrovascular participants, altogether 4,912 deaths were documented including 1,376 CVD-related deaths. As shown in In 1,124 CHF patients with followed-up history, 593 deaths were recorded, including 230 CVD deaths. Compared with non-frailty CHF patients, the ratio of all-cause mortality in patients with frailty increased. The multivariate-adjusted HRs and 95% CIs for all-cause mortality from non-frailty to frailty are 1.00 (reference), 1.31 , and 2.14 , respectively. However, the ratio of CVD mortality increased without significance. The multivariate-adjusted HRs and 95% CIs for CVD mortality from non-frailty to frailty are 1.00 (reference), 1.40 , and 2.10 , respectively. This analysis suggested that CHF patients with frailty were associated with a poor all-cause survival rate and prognosis.To the best of our knowledge, our publication is the first NHANES-related study to assess the association between CHF and FI, taking into account both clinical and laboratory evaluations, which is significant for epidemiological research into CHF. Recently, the 2022 AHA/ACC/HFSA Guideline for the Management of Heart failure was published. Frailty was listed as a medical barrier to CHF self-care in stage C. Our study provides new evidence from the NHANES database that frailty is common in patients with CHF, and the FI can be used as a prognostic information both in patients with CHF and patients with cardiac and cerebrovascular disease. CHF patients with hypertension, DM, stroke, and CHD are positively connected with frailty while patients with CHF who are male, with annual family income over $20,000, and a higher Hb were protective factors to be frail. We also found that CHF patients with CHD or DM were frailer than patients without those two diseases. For patients with cardiovascular and cerebrovascular diseases and CHF, assessing frailty may be an effective way to predict the prognosis of patients.Multiple frailty measurements have been created to screen and assess frailty , 12. We Several studies have found a high frequency of frailty in people with CHF. Over 90% of patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study were frail (FI = 0.37 ± 0.11) . FrailtyFemale patients are frailer and have poorer health near the end of life, whereas male patients continue to outperform female patients on physical function tests, which is known as the sex paradox. In our study, female patients with CHF were more likely to be frail than male patients with CHF. Other studies indicated a greater heritability of several psychological and neurological features in female patients, such as depression , aches , fatigueThe results of a meta-analysis by Gordon et al.  includinRecent studies have evaluated targeted interventions such as supervised exercise training to reduce the frailty burden and improve heart failure patient-reported and clinical outcomes , 23. It According to a meta-analysis , more thA meta-analysis of 56 studies found that the prevalence of frailty among the elderly in high- and middle-income countries was 8.2 and 12.3%, respectively . We cameThese results suggested that in future, the healthcare system should provide universal awareness of the disease so that patients could be diagnosed and treated at an early stage. For low-income patients, the completion of the insurance system can guarantee effective and comprehensive medical care, which is another important prerequisite. Finally, more disease prediction models and detection tools will be invented with big data and new technologies. Early screening can be used to predict diseases and thus delay their onset. Disease education should be provided to poor patients so that they can be detected early and treated promptly, and reduce the cost of medical care.Several studies have been conducted on heart failure and frailty. A study conducted by Kitzman et al. found that 3-month physical rehabilitation improved cardiac function in patients with acute decompensated heart failure (ADHF) combined with frailty. At 6 months, the rates of rehospitalization for any cause in the intervention were also reduced. However, the death rate from any cause did not decrease . DapagliThe following are the limitations of this study. First, as a cross-sectional study, it was not possible to draw a cause-and-effect conclusion between frailty and CHF yet. Second, limited to the diagnosis of the NHANES database and the laboratory data, we cannot perform subgroup analysis of ischemic heart failure and sarcopenia. We also cannot analyze the association between Brain Natriuretic Peptide (BNP) and frailty as well as the cardiac ultrasound data. Third, because the participants reported the prevalent ailments themselves, there may be bias due to recollection. Finally, our study was restricted by database constraints to the US individuals only, so there could be geographical constraints, which meant our findings could not be generalized to all patients worldwide.The main implications of our research for future are as follows. First, the risk of frailty in patients with CHF is over three times higher than in patients with non-CHF according to our research. And a great proportion of cardiac and cerebrovascular disease and other chronic diseases were suffering from frailty, including hypertension, angina, coronary heart disease, stroke, and diabetes mellitus. Doctors need to focus on the management of frail patients with CHF in future studies. Additionally, gender-based studies of frailty in CHF could be undertaken. Third, it was found that family income played an important role in the risk of frailty. The awareness of frailty should be spread among patients with CHF, especially in remote and underdeveloped areas around the world. Finally, more programs could be explored according to different etiologies, Ejection fraction, and type B natriuretic peptide, to identify the risk factors of frailty over the world.In conclusion, our analysis revealed that frailty was strongly associated with CHF. Patients with CHF who were male, had annual family income over $20,000, or with normal Hb level were negatively correlated to frailty. For both patients with cardiac and cerebrovascular disease and patients with CHF, frailty was strongly connected with an increased hazard of all-cause death.The original contributions presented in the study are included in the article/Ethical review and approval were not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required for this study in accordance with national legislation and institutional requirements.XC, BL, CH, and XZ conceived the ideas and design of the study. XC and CH collected data from NHANES. YM, LY, JL, and XZ analyzed the data. MG, YL, and XC drafted the manuscript. DF and MW revised the final version of the manuscript and supervised the study. XC and CH contributed equally to this study and share the first authorship. All authors have read and approved the final version of the manuscript for publication.


Previous reports on the epidemiology, influencing factors, and the prognostic value of the components of PR interval in hospitalized heart failure patients were limited.This study retrospectively enrolled 1182 patients hospitalized with heart failure from 2014 to 2017. Multiple linear regression analysis was used to explore the association between the components of PR interval and the baseline parameters. The primary outcome was all-cause death or heart transplantation. Multivariable-adjusted Cox proportional hazard regression models were constructed to explore the predictive value of the components of PR interval for the primary outcome.In multiple linear regression analysis, higher height  as well as larger atrial and ventricular size were associated with larger P wave duration but not with PR segment. The primary outcome occurred in 310 patients after an average follow-up of 2.39 years. Cox regression analyses revealed that the increase in PR segment was an independent predictor of the primary outcome , whereas the P wave duration did not show significant correlation. When adding the PR segment to an initial prognostic prediction model, the likelihood ratio test and categorical net reclassification index (NRI) showed a significant improvement, but the increase in C-index was not significant. In subgroup analysis, increased PR segment was an independent predictor of the primary endpoint in patients taller than 170 cm  but not the shorter group (P for interaction = 0.006).In hospitalized patients with heart failure, longer PR segment was an independent predictor of the composite endpoint of all-cause death and heart transplantation, especially in the taller group, but it had limited significance in improving the prognostic risk stratification of this population.The online version contains supplementary material available at 10.1186/s12872-022-03028-3. The global burden of heart failure is still heavy and will increase in the foreseeable future . Heart fIt is generally believed that the PR interval on the electrocardiogram reflects the duration from the generation of the electrical activity in the sinus node and through its conduction in the internodal tract, the atrioventricular node, the His bundle, and the Purkinje fiber. The prognostic value of the PR interval was controversial in the community population –5, patieThe Copenhagen electrocardiogram (ECG) study  found thIn the presented retrospective cohort study, we consecutively enrolled hospitalized heart failure patients in a tertiary center for three years, with a median follow-up of 2.39 years, and aimed to explore the distribution characteristics, influencing factors and prognostic value of the P wave duration and PR segment.This study retrospectively enrolled hospitalized patients diagnosed with stage C heart failure from 2014 to 2017. Exclusion criteria: (1) under 18 years old; (2) did not meet the diagnostic criteria of heart failure; (3) absence of body surface 12-lead ECG data; (4) non-sinus rhythm , second or third-degree atrioventricular block, or pre-excitation syndrome; patients diagnosed with paroxysmal atrial fibrillation but baseline ECG suggesting sinus rhythm were not excluded; (5) after implantation of a pacemaker, cardiac resynchronization pacemaker, or implantable cardioverter defibrillator; (6) died during the hospitalization.Patient demographic data, New York Heart Association (NYHA) functional class, physical examination at admission, comorbidities, drug use, and laboratory results were collected by qualified cardiologists by reviewing previous medical records. The estimated glomerular filtration rate was calculated according to the modified MDRD formula . The diaInformation Technologies, the United States). The participant was required to rest quietly for 5 min in a supine position. Then a standard 12-lead ECG was collected for 10 s at a paper speed of 25 mm/s and a voltage of 1 mV for every 10 mm amplitude. Among the ECG parameters, heart rate, PR interval, P wave duration, QRS complex duration, QT interval, and corrected QT interval were automatically measured by the electrocardiographs. For those who did not report the above data due to the acquisition mode, we used the distance tool of Foxit PDF Reader software to manually measure the required data on lead II in the pdf format of the ECG image.The standard body surface 12-lead electrocardiogram of the selected patients was collected at admission. Three models of twelve-lead electrocardiograph were used for ECG acquisition: Fukuda FX7402, Fukuda FX8322 , and GE MAC1200ST  who were blinded to the patients' clinical status and prognosis. If the interpretation result was uncertain, it would be decided after a discussion with senior cardiologists. The manually measured QT interval was corrected by heart rate according to the Bazett’s formula . InterobAmong the research variables, the PR interval was defined as the duration from the time the P wave leaves the baseline to the time the next QRS complex leaves the baseline. The duration of the P wave was defined as the time from the start to the end of the P wave. The PR segment was defined as the time from the end of the P wave to the time the first QRS complex leaves the baseline, which can be calculated from the time difference between the PR interval and the P wave duration.The primary endpoint of this study was defined as the composite of all-cause death or heart transplantation, whichever occurred earlier was recognized as the outcome event. Regular telephone or outpatient follow-ups were conducted to find out the outcome status. Outcome determination was implemented by qualified cardiologists who had undergone standard training.The research protocol strictly complied with the Declaration of Helsinki and has been approved by the Ethics Committee of Fuwai Hospital affiliated to Peking Union Medical College. All participants have signed written informed consent.The normal distributed continuous variables were represented by the mean (standard deviation). The non-normal distributed continuous variables were represented by the median, the 25th percentile, and the 75th percentile. The categorical variables were represented by the frequency (percentage). For the baseline data grouped by binary categorical variables, the normally distributed continuous variables, non-normally distributed continuous variables, and categorical variables were compared using the two independent sample t-test, Mann–Whitney U test, chi-square test or Fisher's exact test, respectively.In the univariable correlation analysis between baseline variables and the research variables, Pearson correlation analysis was used for binormal continuous variables, point-biserial correlation analysis was used for binary variables and continuous variables, and Spearman rank correlation was used for other cases. For the baseline variables that are significantly correlated with the research variables in the single-factor correlation analysis, the stepwise regression method was used to construct a multiple linear regression model to explore the possible influencing factors of the research variables. The multiple imputation method was used to deal with the missing values in the original data.In this study, the Kaplan–Meier method was used to draw the unadjusted survival curves, and the log-rank test was used for comparison between groups. Unadjusted, age and gender-adjusted, and multivariable-adjusted Cox proportional hazard regression models were constructed in the original cohort to explore the predictive value of the research variables for the primary outcome. The combinations of covariates in the multivariable-adjusted Cox model were determined based on the significant variables in the univariable Cox regression combined with clinical experience. The multivariable-adjusted Cox regression model 1 was adjusted for age, sex, body mass index, systolic blood pressure, natural log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, estimated glomerular filtration rate, heart rate, QRS complex duration, and the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs). The multivariable-adjusted Cox regression model 2 was adjusted for age, sex, NYHA class, natural log-transformed NT-proBNP level, platelet count, serum chloride, serum creatinine, and serum uric acid levels. The multivariable Cox regression model 3 was adjusted for age, sex, NYHA class, natural log-transformed NT-proBNP level, the use of digoxin, ACEI/ARBs, aldosterone receptor antagonists, and the use of diuretics.As the sensitivity analysis, we constructed a propensity score-matched cohort and performed multivariable-adjusted Cox proportional hazard regression analysis in this population. The propensity score was calculated by multivariable logistic regression analysis. The matching variables of the propensity score-matched cohort included age, sex, systolic blood pressure, history of hypertension, use of ACEI/ARBs, hemoglobin level, serum albumin level, serum potassium level, estimated glomerular filtration rate, heart rate, and QRS complex duration. The multivariable Cox regression model in the propensity score-matched cohort was adjusted for covariates the same as model 1 in the original cohort. The propensity score-matched cohort was matched at a ratio of 1:1 by the nearest neighbor matching method without replacement, and the balance diagnosis was evaluated by calculating the standardized mean differences of the baseline variables after matching.We used the likelihood ratio test, categorical and continuous net reclassification index  (NRI), tIn addition, the interaction between research variables and covariates was explored in the multivariable Cox proportional hazard regression model, and subgroup analysis was performed accordingly.A two-sided P < 0.05 was defined as statistically significant. All statistical analysis was performed using R software version 3.6.2 .A total of 1182 hospitalized heart failure patients were finally included, of which 894 (75.6%) were male. The average age and standard deviation were 54.35 ± 16.08 years old. The median (25th–75th percentiles) was 114.00 ms (104.00–126.00 ms) for P wave duration, and 57.97 ms (42.00–75.36 ms) for PR segment, respectively.Table P > 0.05) (Table The PR segment was longer in the event group than in the non-event group (62.00 ms compared to 56.00 ms), but the difference in the P wave duration was not significant . However, the PR segment was scarcely correlated with the sizes of the atria and ventricles . As for the PR segment, in the univariable model, the age and sex-adjusted Cox regression model, as well as the multiple Cox regression models adjusted for multiple factors in the original and the propensity score-matched population, the increase of the PR segment was an independent predictor of the primary endpoint Table . The basThe evaluation of the incremental contribution of the PR segment to the three-year primary outcome risk was shown in Table In the interaction test of the Cox proportional hazard regression analysis in the total population, it was found that sex and height had significant interactions with the prognostic predictive value of the PR segment . The subgroup analysis was performed accordingly . In the female population, the above analysis showed no significant difference . When classified by height, the PR segment was significantly associated with the primary outcome in the subgroup taller than the median of the total population (i.e. 170 cm) but not in shorter patients , and the intraclass correlation coefficient for intraobserver agreement was 0.993 (95%CI: 0.988 to 0.996).The main findings of this study were as follows: (1) Longer P-wave duration but not PR segment was associated with higher height and larger atrioventricular diameters reported by echocardiography. (2) Longer PR segment was an independent predictor of the primary outcome, while the P wave duration did not show a significant correlation with the primary outcome; whereas adding the PR segment to the existing prognostic prediction model for patients with heart failure improved the predictive accuracy significantly but weakly. (3) Larger PR segment was an independent predictor of an increased risk of the primary outcome in patients taller than 170 cm but not in shorter patients.The median PR interval in our population was similar to that in the heart failure population reported by Nikolaidou et al. . CompareWe found in this study that the P wave duration but not the PR segment was significantly correlated with height as well as the sizes of atria and ventricles measured by transthoracic echocardiography, which was consistent with previous studies –28. BesiSeveral studies had reported little prognostic value of the P wave duration in patients with stage C chronic heart failure. Escobar-Robledo et al.  reportedTo our knowledge, this study is the first to report the prognostic value of the PR segment for hospitalized patients with chronic heart failure. Previous reports in the community population suggested that the PR segment was not an independent predictor of all-cause death  or new-oAdding the PR segment to the existing prognostic prediction model for patients with heart failure improved the predictive accuracy significantly but weakly. Patients with heart failure usually have heterogeneous underlying diseases, multiple complications, and complex prognostic factors. A single indicator requires a strong prognostic value to significantly improve the existing prognosis prediction models. In previous heart failure prognosis prediction models such as the Seattle heart failure model , GISSI-HIn the big data era, the value of ECG is being further unlocked with the methods of artificial intelligence (AI), especially deep learning. The advantages of ECG such as convenience, inexpensiveness, easy to store and transfer into digital format, and containing huge objective information made it a highly appropriate material for the application of novel data mining tools. For deep learning, the feature extraction process was automated, thus avoiding possible bias during the pattern recognition process by human. The ECG already showed promising ability in the prediction of left ventricular systolic dysfunction , atrial The modifying effect of height on the prognostic value of the PR segment has not been reported in the same population or outcome as ours. Height, as a seemingly harmless physical examination index, was found to be related to the risk of new-onset atrial fibrillation in the community populations and patients with left ventricular dysfunction in a series of studies –42, and The strength of this study relies on the rigorous statistical analysis and multi-layer authentication of the results. In the survival analysis, multivariate Cox proportional hazard regression models were constructed combining clinical experience rather than only based on the univariate Cox regression results to determine possible confounding factors that need to be adjusted, including strong prognosis predictive factors such as NT-proBNP. The three multivariate Cox models were adjusted respectively for other ECG indicators, laboratory results, and medications in addition to the demographic data. Furthermore, the multivariate Cox model after propensity score matching was used as a sensitivity analysis to minimize the selection bias and to confirm the reliability of the prognostic analysis results.Its limitation firstly derives from the nature of single-center retrospective cohort study. The confounding factors cannot be adjusted completely, and we could only report the correlation but not causality. The study enrolled only Chinese patients and lacked ethnic variation. Secondly, the external validity of the results also remains to be verified. Thirdly, the cause of death was available for not all the deceased subjects in the current study. Moreover, due to the good compliance with the optimized drug treatment in our cohort, the use of drugs affecting the atrioventricular node electricity conduction such as β-blockers was quite common (91.5%), so the subgroup analysis of the population of patients not using antiarrhythmic drugs was not carried out. Finally, the study adopted a single standard 12-lead electrocardiogram at admission, whereas the ECG of patients with heart failure may change significantly at different stages of the disease course. Therefore, future studies are needed to determine the change of the research variables at admission and discharge or before and after a fixed follow-up period on the prognosis of patients with heart failure.In hospitalized patients with heart failure, increased PR segment was an independent predictor of the composite endpoint of all-cause death and heart transplantation, but the incremental prognostic risk stratification value was limited. In the interaction and subgroup analysis, increased PR segment was an independent predictor of enhanced risk for the primary outcome in patients taller than 170 cm but not in shorter individuals.Additional file 1. Fig. S1: Univariable correlation analysis of the P wave duration, the PR segment and other ECG and transthoracic echocardiographic parameters.Additional file 2. Fig. S2: The distribution of the standardized mean differences before and after propensity score matching. A. P wave duration; B. PR segment.Additional file 3. Table S1: Baseline characteristics of the propensity score-matched cohort grouped by the medians of the P wave duration and the PR segment.


Background: It is sometimes difficult to distinguish between asthma and bronchiectasis as their symptoms overlap, and these two diseases are associated with pulmonary tuberculosis (PTB) or pneumonia.Objective: The purpose of this study is to determine the effects of bronchodilator drugs, steroids, antidepressants drugs, and antianxiety drugs on the risks of PTB or pneumonia in patients with bronchiectasis–asthma combination or bronchiectasis–asthma–chronic obstructive pulmonary disease combination—BCAS cohort.Methods: After propensity score matching, we retrospectively studied patients with BCAS (N = 620) and without BCAS  through an analysis. The cumulative incidence of PTB or pneumonia was analyzed through Cox proportional regression. After adjustment for sex, age, comorbidities, and medications , we calculated the adjusted hazard ratios (aHR) and their 95% confidence intervals (95% CI) for these risks. Similar to OSs, ICSs are associated with an increased risk of PTB or pneumonia, lumping these two as steroids (ICSs/OSs).Results: For the aHR (95% CI), with non-LABAs/non-OSs as the reference 1, the use of LABAs [0.70 (0.52–0.94)]/OSs [0.35 (0.29–0.44)] was associated with a lower risk of PTB or pneumonia. However, the current use of LABAs [2.39 (1.31–4.34)]/SABAs [1.61 (1.31–1.96)], steroids [ICSs 3.23 (1.96–5.29)]/OSs 1.76 (1.45–2.14)], and BZDs [alprazolam 1.73 (1.08–2.75)/fludiazepam 7.48 (1.93–28.9)] was associated with these risks. The current use of LAMAs [0.52 (0.14–1.84)]/SAMAs [1.45 (0.99–2.11)] was not associated with these risks.Conclusion: The current use of LAMAs/SAMAs is relatively safe with respect to PTB or pneumonia risks, but LABAs/SABAs, steroids, and BZDs could be used after evaluation of the benefit for the BCAS cohort. However, we must take the possible protopathic bias into account. Asthma is an inflammatory and immune-related disease. Bronchiectasis is a chronic, progressive, infective, immune-related, and inflammatory obstructive airway disease . MeanwhiBCAS is associated with frequent hospitalizations, concomitant gastroesophageal reflux disease, hypersensitivity to non-steroidal anti-inflammatory drugs, and high blood eosinophil counts and represents an additional phenotypic feature of severe eosinophilic asthma . In precOne study indicated that previous pneumonia, pulmonary tuberculosis (PTB), and non-tuberculous mycobacterium (NTM) increased the risk of bronchiectasis . SimilarData for this retrospective, population-based cohort study were obtained from the National Health Insurance Research Database (NHIRD), which was launched in 1995 and covers almost 99% of the 23 million people in Taiwan. We used the Longitudinal Health Insurance Database 2000, which maintains the registration data of everyone who was a beneficiary of the National Health Insurance program during the period of 1996–2000. Data on the medical services provided by programmers are collected by the National Health Insurance Administration and entered into the NHIRD. This longitudinal database contains population-level demographic and administrative information, including sex, birth year, region of residence, dates of admission and discharge, prescription drugs, surgical procedures, and diagnostic codes. The International Classification of Diseases Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes are also listed, with a maximum of five codes. In the NHIRD, the ICD-9-CM and procedure coding system are used to define the diagnostic and procedure codes, respectively. In accordance with the Personal Information Protection Act, individual identifiers are encrypted before release for research. The NHIRD has been used for various studies and provides high-quality information on diagnoses, hospitalizations, and prescriptions.The NHIRD encrypts personal information to protect patients’ privacy. It provides researchers with anonymous identification numbers associated with relevant claims information, including sex, date of birth, medical services received, and prescriptions. Therefore, patient consent is not required to access the NHIRD. The study protocol was approved by the Institutional Review Board of China Medical University (CMUH104-REC2-115-AR4), which also specifically waived the informed consent requirement.To evaluate the risk of PTB or pneumonia in patients within the BCAS cohort, we selected a cohort of patients who had two outpatient visits or an inpatient visit for the BCAS cohort and a comparable non-BCAS cohort .N = 664) and the newly diagnosed non-BCAS cohort  between 1 January 2000 and 31 December 2012.The BCAS cohort includes six bronchiectasis + asthma (pure BCAS) and seven bronchiectasis + asthma + COPD (BCAOS). The non-BCAS cohort (without bronchiectasis–asthma combination or without bronchiectasis–asthma–COPD combination) includes 1 pure bronchiectasis =  − 4 BCOS − 6 BCAS − 7 BCAOS; 2 pure COPD =  − 4 BCOS − 5 ACOS − 7 BCAOS; 3 pure asthma =  − 5 ACOS − 6 BCAS − 7, BCAOS; 4 bronchiectasis + COPD (BCOS); 5 COPD + asthma (ACOS); and 8 others—such as patients with steroids use. The exclusion criteria include 1) diagnoses of PTB (ICD-9-CM codes 010–012) and pneumonia (codes 480–486) before entry into the study, wash out period 1996–1999; 2) age <18 years; and 3) incomplete demographic information  Shantak. We idenN = 620) and the non-BCAS cohort  were found (These patients in the BCAS cohort were matched to patients in the non-BCAS cohort by age (5-year range), gender, comorbidities, smoking status, medications, and year of index date according to incidence density sampling. After 1:4 matching, the BCAS cohort . Both cohorts were observed from the index date to the date of diagnosis of (PTB or pneumonia), withdrawal from the National Health Insurance program, or to the end of 2013, depending on whichever occurred first. Patients were followed up until death or the end of the study period (31 December 2013).The incidence of PTB or pneumonia was defined as a new diagnosis and at least one visit with inpatient claims data or two visits with outpatient claims data after the index date. The ICD-9 CM, Anatomical Therapeutic Chemical (ATC), and full names list are presented in t test and the chi-square test to compare differences in baseline characteristics and comorbidities between the BCAS cohort and non-BCAS cohort. The incidence density rate  was analyzed to estimate the incidence of PTB or pneumonia among the cohorts stratified by gender, age, comorbidities, and medications. The annual incidence density rate was calculated by dividing the number of new diagnoses of PTB or pneumonia by the number of person-years for patients at risk for PTB or pneumonia for each year between 2000 and 2013. The risks of PTB or pneumonia between these two cohorts were compared through Cox proportional hazard regression models. The analysis was adjusted for gender, age, comorbidities, and medications for the BCAS cohort. We set our significance threshold at α = 0.05 for a priori hypotheses. Significance in subsequent explanatory analyses was defined as p < 0.01. Statistical analysis was performed using SAS .Propensity score matching was used to balance the groups with respect to the known variables and to increase their comparability. Although some unmeasurable confounders may exist disproportionally between the study groups, propensity score matching can optimally balance the distributions of measured covariates as much as a randomized trial does. We estimated the patients’ propensity scores through a non-parsimonious multivariable logistic regression, with receipt of patients with or without BCAS as the independent variable. We incorporated clinically relevant covariates  into our analysis—the primary analysis. PTB or pneumonia was the dependent variable . We usedt test: p < 0.001). The majority of patients were more than 35 years old. Several significant differences in gender, age, grouped comorbidities, and grouped medications were observed between the BCAS and non-BCAS cohorts; the use of LABAs, ICSs, OSs, leukotriene receptor antagonist, and montelukast was more frequent in the BCAS cohort than in the non-BCAS cohort.No significant difference in the distribution of age groups was observed between the two cohorts because of the success of the incidence density sampling . The meaThe incidence density rate of PTB or pneumonia was higher in the BCAS cohort than in the non-BCAS cohort  . These rp = 0.008)  . The are= 0.008) .Before the experiment of propensity score matching, we performed a logistic regression to calculate the propensity score. Then, we estimated the probability of the BCAS cohort on the basis of the baseline variables, namely, index year, sex, age, history of comorbidities, and medicine. Finally, we performed multivariable Cox proportional hazards model stratification on the non-BCAS cohort to estimate the risks of PTB or pneumonia in the two cohorts.Users of drugs were defined as those who received at least one prescription for drugs  between the BCAS cohort diagnosis date and index date. The date of prescription and number of days supplied were identified. The use of drugs was approved in Taiwan in January 2000 and was placed on the listing of NHI drugs for reimbursement in February 2001. The drug users were defined as patients who received prescription for >28 days and after index date, and those who did not receive drug prescription were classified as non-users of drugs. The immortal time bias is eliminated. Any drugs prescribed after index date and before the endpoints for the subjects were considered as exposure.https://www.nhi.gov.tw/Content-). The initial visit for new patients and first prescription could help us to confirm if the patients are alive or not. These strict policies help us to eliminate the immortal time bias in this study (The Taiwan government launched the pay-for-performance of asthma (asthma P4P program) in 2001 to encourage clinics and hospitals to provide patient-centered care and focus on disease management. This program includes initial visit for new patients, outpatient care, hospitalization, first prescription, emergency visits, and drug refill prescription , and biochemistry and pulmonary function tests . In TaiwIn this study, asthma was defined with ICD-9 CM code 493, combined with at least two prescriptions of anti-asthmatic drugs. Anti-asthmatic drugs include LABAs/LAMAs/SABAs/SAMAs/leukotriene receptor antagonist/montelukast/ICSs/OSs . BronchiIn the non-BCAS cohort (1 + 2 + 3 + 4 + 5 + 8), only 3 and 5 have the asthma component. The BCAS cohort (6 + 7), including 6 and 7, all have the asthma component; thus, the frequency of asthma therapies  in the BCAS cohort was higher than the non-BCAS cohort .During 1996–1999, tuberculosis and pneumonia were excluded before entry study, and only incident PTB or pneumonia were entered into the study . The latency of the reactivation of the latent TB infection (LTBI) is about 2–5 years . Thus, tCurrent methods for the diagnosis of LTBI are tuberculin skin test (TST) and interferon-gamma release assay (IGRA). The use of interferon for detecting LTBI was initiated from 2009 in Taiwan based on a published report . Also, lpost-hoc, looking back. Owing to the data of CXR, TST, and IGRA, smear or culture for bacteria and TB was unavailable in the NHIRD. As mentioned before, we excluded PTB or pneumonia before the entry study. However, post-PTB or post-pneumonia was a predisposing factor of airway disease  the risks of PTB or pneumonia were higher in the BCAS cohort than in the non-BCAS cohort; 2) compared to the non-BCAS cohort, in the BCAS cohort, bronchodilator (LABAs/SABAs) and steroid use was associated with risks of PTB or pneumonia, but BZDs and LAMAs/SAMAs were not; 3) current LABA/SABA and steroids use and BZDs use were associated with risks of PTB or pneumonia, but current LAMA/SAMA use was not associated with risks of PTB or pneumonia; and 4) the use of non-LABAs, non-OSs, and non-BZDs as reference 1 revealed that LABA, OS, and BZD use was associated with low risks of PTB or pneumonia.The elevated neutrophil levels in sputum were associated with more exacerbations, low lung function, and greater duration and severity of bronchiectasis. Similarly, neutrophil elastase, derived from neutrophils, was found to be associated with an increased severity of bronchiectasis . The subA) receptors. The macrophage GABAA receptor expression was regulated by bacterial Toll-like receptor agonists and cytokines, indicating an endogenous role in the immune response  the primary effect of the BCAS cohort such as triplet  was a critical factor of the PTB or pneumonia; 2) the BCAS cohort such as pure BCAS (6) with comorbidities such as diabetes, stroke, and heart disease might be the relevant factor in subsequent PTB or pneumonia; and 3) perhaps steroids and BZDs have synergistic effects on these factors, leading to PTB or pneumonia.As such, protopathic bias is a systematic error that occurs when measured exposure status medications may be affected by the latent onset of the target outcome—PTB or pneumonia. The lag-time approach consists in excluding from exposure assessment (PTB or pneumonia) the period immediately preceding the outcome detection date (≤30 days) . In thisIn summary, because of the risks of PTB or pneumonia, LABAs/SABAs, steroids, and BZDs may be used in the BCAS cohort after benefit evaluation. However, LAMAs/SAMAs are safe options for the management of the BCAS cohort. Notably, we must take possible protopathic bias into account when we explain these findings.The accuracy of medical records in the NHIRD is high, making it a valid resource for population-based research on PTB or pneumonia. Bronchodilator and steroid use in Taiwan follows international guidelines . PatientPossible limitations of this study are bias and confounding variables, such as confounding by indication, protopathic bias, and surveillance bias. We used several strategies to control for bias and confounding variables, such as the new user design (entry after cohort) and the propensity matching method. With this framework, the results are not as accurate as those of randomized control trials. Data on lifestyle changes (exercise and diet) in low-adherence and high-adherence patients are unavailable in the NHIRD. Interferon use was associated with PTB infection. Owning to the higher frequency use of steroids than the interferon use in BCAS cohort and non-BCAS cohort, we replace the immunosuppressant (including the interferon) with steroids for analysis. However, this is another limitation. Finally, not all patients received HRCT in this study but at least two CXR for comparison of the irreversible change of bronchial tree  in outpatient visit or hospitalization. These confounding factors may have led to some bias in this study.The LAMAs/SAMAs are relatively safe with respect to PTB or pneumonia risks, but LABAs/SABAs, steroids, and BZDs could be used after evaluation of the benefit for BCAS cohort. However, we must take the possible protopathic bias into account.For pulmonary tuberculosis or pneumonia in predominant bronchiectasis–asthma, the long-acting/short-acting beta2 agonist, steroids, and benzodiazepines are to be used with caution; long-acting/short-acting muscarinic antagonists were relatively safe.


P<0.05 for all). In contrast, during unattended BP measurement, systolic BP, diastolic BP, heart rate, and skin sympathetic nerve traffic were modestly, albeit in most instances significantly, reduced, whereas muscle sympathetic nerve traffic remained almost unchanged. During unattended BP measurement, peak systolic BP was 14.1 mm Hg lower, peak heart rate was 10.6 bpm lower, and peak skin sympathetic nerve traffic was 8.5 bursts/min lower than the peak values detected during attended BP measurement. Thus the cardiovascular and neural sympathetic responses to the alerting reaction elicited by BP measurement in the presence of a doctor are almost absent during unattended BP measurement, during which, if anything, a modest cardiovascular sympathoinhibition occurs. This has important implications for comparison of studies using these different BP measurement approaches as well as for decision concerning threshold and target BP values for treatment.Whether blood pressure (BP) values differ when BP is measured with or without the presence of a doctor (attended and unattended BP measurements) is controversial, and no information exists on whether and to what extent neurogenic mechanisms participate at the possible BP differences between these measurements. In this study, we assessed continuous beat-to-beat finger systolic BP and diastolic BP, heart rate, muscle, and skin sympathetic nerve traffic (microneurography) before and during BP measurement by an automatic device in the presence or absence of a doctor. This was done in 18 untreated mild-to-moderate essential hypertensive patients . During attended BP measurement, there was an increase in systolic BP, diastolic BP, heart rate, and skin sympathetic nerve traffic and a muscle sympathetic nerve traffic decrease, the peak changes being +5.3%,+8.4%,+9.4%,+30.9%, and −15.2%, respectively ( A controversial aspect is whether this type of BP measurement provides values that are lower than those associated with traditional measurements, that is, those obtained in the presence of medical personnel. Although denied by the SPRINT investigators,2 this is supported by the results of studies which have shown (1) attended BP measurement to be associated with an increase in BP,6 which, in contrast, does not appear to change if BP is measured automatically or semiautomatically when the patient is alone in the room6 and (2) unattended BP measurement to be lower than traditionally measured office BP, although variably modestly to markedly different values have been reported in different studies.10 This is related to the clinical problem of which BP may provide a better insight on patients’ usual BP values,10 leading to a better diagnosis of hypertension and a more accurate prediction of the risk of future cardiovascular events at the individual patient level, two issues on which evidence is limited.9Following its use in the SPRINT ,1134–1137See Editorial, pp 11 to obtain information also on the neural involvement of the observed hemodynamic changes. Data were compared with those obtained in the same patients during the attended BP measurement procedure, which has been previously shown to be characterized by a BP rise, a tachycardia, and a sympathetic overdrive.12No study has ever assessed beat-to-beat BP and heart rate (HR) during unattended BP measurement, thereby providing direct evidence on whether and to what extent this procedure is associated with BP and HR changes. This has been the goal of the present study in which unattended BP measurement was used in hypertensive patients under continuous beat-to-beat BP and HR recording. Continuous beat-to-beat recording was extended to efferent postganglionic sympathetic nerve traffic to skin and skeletal muscle districts via the microneurographic techniqueThe data that support the findings of this study are available from the corresponding author on reasonable request.13 All patients were pharmacologically untreated and their evaluation was carried out on an outpatient basis. The study protocol was approved by the Ethics Committees of the Institutions involved. All patients gave written consent to the study after being informed of its nature and purpose.The study population consisted of 28 patients with a newly diagnosed mild-to-moderate high BP state recruited for this specific study between 2018 and 2020. However, due to loss or instability of sympathetic nerve traffic recordings (see below), the study was successfully completed in 18 patients  with an uncomplicated essential hypertension of mild-to-moderate degree. Patients were not considered for the present study if they exhibited (1) BP values outside the range defining a moderate hypertensive state; (2) clinical, laboratory, or instrumental evidence of secondary causes of the BP elevation; (3) signs, symptoms, or history of heart failure, coronary, or cerebrovascular events; (4) alterations in echocardiographically determined left ventricular diameters, left ventricular ejection fraction or left ventricular mass; (5) atrial fibrillation or other major cardiac arrhythmias; (6) clinical or instrumental evidence of valvular heart disease; (7) history of excessive alcohol consumption (>60 g/d in men and >40 g/d in women), or use of antidepressant drugs; (8) major concomitant diseases, such as renal insufficiency, diabetes, obesity, severe sleep apnea, and other conditions known to affect the neuroadrenergic function.14 which was programmed to automatically perform BP measurements. It was also measured continuously by a finger photoplethysmographic device  capable of proving accurate and reproducible beta-to-beat systolic BP (SBP) and diastolic BP (DBP) values.12 HR was monitored continuously by the R wave of an electrocardiographic lead. Respiration rate was monitored by a strain gauge pneumograph positioned at the midchest level. Multiunit recordings of efferent postganglionic sympathetic nerve activity to the skeletal muscle (muscle sympathetic nerve traffic [MSNA]) or the skin (skin sympathetic nerve traffic [SSNA]) district were obtained through a tungsten microelectrode inserted into the right or left peroneal nerve posterior to the fibular head, as previously described.13 Simultaneous MSNA or SSNA, beat-to-beat BP, and beat-to-beat HR recordings were digitized with a sampling frequency of 1000 Hz . The muscle or skin nature of the neurograms was assessed by the criteria outlined in previous studies.13 Neurograms were accepted only if they did not show simultaneous skin and muscle sympathetic nerve traffic and if the signal-to-noise ratio was >3.13 MSNA and SSNA were quantified over each minute as number of bursts. This quantification provides values that have been shown to be highly reproducible on a short-term basis when assessed twice in the same session by a single investigator.15BP was measured by a validated automated oscillometric device ,t test for paired observations was used to locate the statistical significance of the difference, after the Bonferroni correction. The Pearson correlation coefficient was used to determine the relationships between MSNA, SSNA, HR, SBP, or DBP. All analyses were performed with SAS software version 9.3 . The symbol ± refers to the SEM. A P<0.05 was taken as the level of statistical significance.All 18 patients were evaluated 1 to 2 weeks after a third medical visit when the mild-to-moderate essential hypertensive state had been conclusively established. As shown in Figure In the whole group of patients, the average office SBP/DBP values obtained during the visits preceding the study were 153.2±3.4/101.7±2.7 mm Hg. As illustrated in Figure The relationships between the peak changes of the different variables during attended or unattended BP measurements are shown in Table 12 in our patients, automatic assessment of BP values in presence of a doctor (referred to as attended BP measurement) was associated with an increase in SBP and DBP, a tachycardia, a marked increase in sympathetic nerve traffic to the skin vascular district and a reduction in sympathetic nerve traffic to the skeletal muscle circulation. The novel finding of our study, however, is that this cardiovascular and neural response pattern was strikingly different from the one seen when BP was measured in absence of a doctor , which was accompanied by a modest but significant SBP reduction, a decrease in SSNA, and a nonsignificant decrease or no change in HR and MSNA, respectively. Thus, the attended and unattended BP measurement procedures are by no means superimposable for their effect on the cardiovascular system and postganglionic sympathetic nerve activity. That is, attended BP measurement triggers excitatory cardiovascular responses and changes in sympathetic activity that are similar to those that characterize in animals the fight or flight reaction, originally described by Cannon16 and confirmed later by other investigators,18 and in humans the involvement in emotional tasks.20 This is entirely absent during unattended BP measurement which in contrast appears to be associated with inhibitory effects on both the cardiovascular and the sympathetic nervous system, albeit of less magnitude or consistency than the excitatory effects associated with attended BP measurement. Of interest is the observation that the above-mentioned beat-to beat BP changes appear to be more related in their temporal occurrence to the start of the automated BP measurement rather than to the presence/absence of the doctor.In line with previous studies,12 This may be explained by the fact that, at variance from previous studies, in the present study (1) the doctor was not actively involved in the BP measurements, which were obtained by an automatic device and (2) the attended BP measurement session included a relatively long baseline period. This may have attenuated the emotional impact of the doctor’s presence and favored more modest excitatory cardiovascular responses. However, these attenuated excitatory effects did not make the difference with the effects of the unattended BP measurement procedure negligible because during unattended BP measurement peak SBP was 14.1 mm Hg lower, peak HR 10.6 bpm lower, and peak SSNA 8.5 bursts/min lower than the peak values seen during attended BP measurement. As further discussed below, these considerable differences have important implications for the decision of which should be the threshold and target BP values for the treatment of hypertensive patients, the adoption of values derived from the unattended BP measurement procedure favoring lower values.In our patients, the SBP, DBP, HR, and sympathetic responses to attended BP measurement were less pronounced than those described in previous studies in which these variables were continuously recorded before and during BP measurement by a doctor.22 its quantitative correlation with the BP and HR increases indicating its change as part of an integrated response pattern to an emotional stimulus. In this setting, however, the concomitant reduction in MSNA may appear more difficult to be explained because of the widely held opinion that the sympathetic activation that accompanies emotional behaviors is generalized to the entire sympathetic nervous system. We can speculate the MSNA reduction that accompanies attended BP measurement has a baroreflex origin, that is, it reflects an inhibition of sympathetic control of skeletal muscle circulation by the white coat-dependent BP rise and the consequent baroreceptor stimulation.13 This implies that the baroreflex exerts a skeletal muscle circulation control which can override an opposing central command. Another more likely possibility, however, is that the MSNA reduction is part of the integrated response of the central nervous system to the emotional stimulus because in both the defense reaction of experimental animals and the emotional states of man, sympathetically mediated cardiac excitation and vasoconstriction are accompanied by skeletal muscle vasodilatation.20 It should be emphasized that both possibilities imply a heterogeneity of sympathetic control of the cardiovascular system, a concept supported by the evidence by Grassi et al,13 Esler et al,23 and Esler24 in contrast with the older notion affirming that sympathetic activation is always generalized.The increase in SBP, DBP, and HR that occurred during attended BP measurement leaves no doubt about its origin from an alerting response of the patient, justifying the popular definition of this phenomenon as white coat effect. In the present study, this is further supported by the concomitant increase in SSNA, because sympathetic nerve traffic to the skin vascular district has been shown to respond to emotional stimuli,25 Third, in our patients, we found a significant correlation between the peak HR and the peak MSNA or SSNA changes observed during attended or unattended BP measurement. This would suggest that HR in this context may represent a reliable adrenergic marker, capable to mirror the sympathetic changes observed during automated BP measurement. It should be mentioned, however, that a significant correlation, like the one we detected in the present study in a small number of patients, can hardly modify the conclusion of our previous studies showing the limited value of HR as adrenergic marker.27 Finally, both during attended and unattended BP measurements, the neural and cardiovascular changes occurred during the period in which BP was repeatedly measured by the automatic device. This observation suggests that the reported changes were triggered not just by the presence or absence of the doctor per se but by the different psychological effects of BP measurements. Further data, however, are needed to clarify this point.Several other results of our study deserve to be mentioned. First, in our patients, unattended BP measurement led to a modest but significant SBP and SSNA reductions, which correlated with each other and with a reduction in HR. This suggests that this BP measurement procedure is not devoid of effects on neural cardiovascular control but that it may somewhat paradoxically have a small relaxing effect on the patient. Second, the results of the present study draw attention to the fact that attended and unattended BP measurements not only lead to different BP but also to different HR values. This has a practical implication because, in recent guidelines, HR is indicated as an important cardiovascular risk factor , and HR measurement is recommended at any visit in which BP is measured.28 no data are available on the reproducibility of the cardiovascular responses to attended BP measurement or of the sympathetic nerve traffic responses to either measurement procedure. Finally, in our attended BP measurement session, the doctor was not actively involved in the BP measurements which were obtained, as in the unattended BP measurement session, via an automatic device. In other words, there was no active participation of the doctor at the BP measurement at variance with what may happen in clinical practice. However, doctors make use of automatic BP measurement devices rather than the traditional sphygmomanometer more and more frequently.Our results have some limitations. One limitation is that the complexity of the experimental procedure restricted the number of patients included in the study. A second limitation is that our findings refer to mild-to-moderate hypertensive patients and thus any extrapolation to patients with more severe high BP states should be made with caution. A third limitation is that, although in a previous study we have shown that over the short-term the pressor and tachycardic responses to attended BP measurement are reproducible,29 will interfere with the neurogenic and hemodynamic responses to unattended and attended BP measurement and modify the differences described in the present study. Even for central agents, the answer to this question is not obvious, given the evidence that rilmenidine may leave unaffected the BP and sympathetic response to mental stress.30In conclusion, by providing direct evidence that during unattended BP measurement patients’ BP, HR, and skin sympathetic activity exhibits a fall rather than the clearcut rise that accompanies the alerting response elicited by attended BP measurement, our study strongly supports the conclusion that the BP values provided by the two measurement procedures differ and that the difference is far from being quantitatively marginal. This will translate into nonmarginal differences in the medical decision about the threshold and target BP values to consider for antihypertensive treatment that may be only generated by use of different BP measuring procedures rather than by the effects of treatment on cardiovascular events. In this context, however, it should also be mentioned that our observations were collected in untreated hypertensive patients. It would thus be important to investigate whether and to what extent use of antihypertensive drugs directly or indirectly acting on the sympathetic nervous system ,None.None.


Studies based on kidney biopsies are important for the epidemiological understanding of nephropathies.To describe the main nephropathies diagnosed through renal biopsies, and compare them with regards to gender, time, healthcare insurance and age.A population-based retrospective study that reviewed all kidney disease diagnoses obtained by biopsy of a native kidney from pathology services between 2008 and 2019 in Joinville, Brazil.Of 778 biopsies performed, 44.5% were primary nephropathies and 28.5% were secondary. The highest prevalence was focal segmental glomerulosclerosis (FSGS) [18.1%], followed by tubulointerstitial nephropathy (TIN) [15.9%] and IgA nephropathy (IgAN) [9.1%]. There was a growing increase in the prevalence of TIN among elderly and uninsured patients over the period. In the multivariate analysis, among the primary glomerulopathies, males had a higher risk for the occurrence of IgAN , as well as being a protective factor for the occurrence of lupus glomerulonephritis (LGN) . Advancing age and dependence on a public healthcare decreased the likelihood of having a diagnosis of LGN . Patients without private healthcare insurance were more likely to have TIN .Sex, age and type of medical healthcare insurance may be related to the occurrence of some nephropathies. The increased risk of TIN in individuals without a private healthcare plan may be an indication of inequalities in health care. Joinville is the third largest city in southern Brazil , with an estimated population of approximately 515 thousand inhabitants, according to the Brazilian Institute of Geography and Statistics (IBGE)The variables considered were based on the data informed when the renal biopsy sample was sent to the pathology laboratory. Data on sex, age, date of biopsy, presence of private health insurance, clinical information on suspected etiology of kidney disease (primary or secondary causes) were obtained from the medical records of each laboratory.The diagnosis of kidney disease was considered based on histopathological findings of optical microscopy and immunofluorescence. In addition to the histological type, nephropathies were considered primary or secondary based on the information reported by the biopsy requester regarding the presence or absence of associated systemic diseases that could be related to the kidney disease. Thus, based on histological findings and presence or absence of systemic diseases, nephropathies were divided into 4 main categories: primary glomerulopathy (PGP), secondary glomerulopathy (SGN), tubulointerstitial nephropathies (TIN) and other diagnoses (OD). PGP was defined as: IgA nephropathy (IgAN), membranous glomerulonephritis (MGN), focal segmental glomerulosclerosis (FSGS), crescentic glomerulonephritis (CrescGN), minimal lesion disease (MLD), membranoproliferative GN (MPGN), mesangioproliferative nephropathy (non-IMP MsPGN). SGP were further subdivided into lupus glomerulonephritis (LGN), dense deposit disease (amyloidosis or myeloma) and diabetic nephropathy (DN), hypertensive nephrosclerosis (AHNS) and vascular nephropathy (VascN), the latter encompassing thrombotic microangiopathy, hemolytic uremic syndrome, interstitial tubular nephritis - whether acute or chronic; and acute tubular necrosis have been encompassed as tubulointerstitial nephropathies (TIN). Other diagnoses (OD) also included all those findings not categorized in the previous descriptions.Categorical variables are presented by the frequency of their absolute number and percentage. Numerical variables are presented as mean and standard deviation. The chi-square test was used to compare the distributions of the main nephropathies. The distribution of the main primary and secondary glomerulopathies and tubulointerstitial nephropathies were also evaluated by age , sex, type of medical care (private vs. public) and by period , using the chi-square test. Univariate and multivariate analyses were performed using logistic regression to assess the association of sex, age group, type of medical care and period with the occurrence of the most prevalent histological types  within each specific group (PGP or SGP). Similarly, we evaluated the association of these variables concerning the occurrence of TIN in relation to all other diagnoses. The analyses were performed using the STATA version 15 software.Of the total sample (n = 877), 27 tumor biopsies and 72 samples with no renal material available were excluded. The final sample was 778. When analyzing the distribution of the main etiologies and nephropathies , there wRegarding the main diagnoses of PGP , there wRegarding the distribution of the main causes of SGP , there wIn the multivariate analysis, considering sex, age, type of medical care and the period analyzed , there wIn the present study, based on a large population sample, FSGS was the most prevalent histological type among primary glomerulopathies, and, among secondary nephropathies, LNG was the most present. A significant increase in TIN cases was found in the analyzed periods, especially in older patients without healthcare insurance and in the last four years studied. Male gender was associated with a higher occurrence of IgAN, while advancing age, male gender and the absence of a private healthcare plan decreased the chance of occurrence of LNG. On the other hand, patients without healthcare insurance had a greater chance of having TIN, with this risk being greater in the last four years analyzed.,The São Paulo registry of renal biopsies was one of the first attempts to cover a larger sample of nephropathies diagnosed through renal biopsies from 11 pathology centers in São PauloRegarding the type of medical care, it is known that less than 30% of the Brazilian population has a private healthcare planRegarding the most common histological types, in the present study, FSGS, IgAN and MGN were respectively the most prevalent among the primary causes, while LGN and ASHN were, respectively, among the secondary causes. In the São Paulo registry of renal biopsies, FSGS (29.7%), MGN (20.7%) and IgAN (17.8%) were the most prevalent forms of diagnosed primary glomerulopathies,,When the variables studied in the present study were evaluated  for the occurrence of the main diagnosed nephropathies, men had approximately twice the risk for the occurrence of IgAN compared to women. It is known that IgAN is more prevalent among men than women (2:1 ratio) among North American and European individuals,The present study has important limitations that need to be considered when generalizing its findings. First, this is a retrospective-based study with possible limitations in the clinical information available upon referral to the pathology laboratory. The criteria as to the primary and secondary etiology were based exclusively on the clinical impression of the requesting physician at the time of the biopsy. Thus, it is not possible to rule out an information bias with misclassification as to the primary or secondary etiology. However, this criterion has been adopted in other studies involving retrospective databases, despite its limitationsIn conclusion, the present study corroborates findings already reported in other studies on trends in histopathological diagnoses of renal biopsy carried out in Brazil. Concurrently, we raise questions about the lack of access to histopathological diagnosis of kidney diseases in the public healthcare system, and possible causes of kidney disease that may be associated with this inequality of access to health care.