Impaired kidney function and albuminuria are associated with increased risk of heart failure (HF) in patients with type 2 diabetes (T2D). We investigated whether rapid kidney function decline over time is an additional determinant of increased HF risk in patients with T2D, independent of baseline kidney function, albuminuria, and other HF predictors.2/year) and odds of HF hospitalization or HF death during the first 4 years of follow-up was estimated by logistic regression. The improvement in risk discrimination provided by adding rapid kidney function decline to other HF risk factors was evaluated as the increment in the area under the Receiving Operating Characteristics curve (ROC AUC) and integrated discrimination improvement (IDI).Included in the study were 7,539 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with baseline urinary albumin-to-creatinine ratio (UACR) data, who had completed 4 years of follow-up and had ≥ 3 eGFR measurements during that period . The association between rapid kidney function decline  experienced rapid kidney function decline and 255 (3.4%) experienced a HF event. Rapid kidney function decline was associated with a ~ 3.2-fold increase in HF odds , independent of baseline CVD history. This estimate was not attenuated by adjustment for potential confounders, including eGFR and UACR at baseline as well as at censoring . Adding rapid kidney function decline during follow-up to other clinical predictors  improved HF risk classification .In patients with T2D, rapid kidney function decline is associated with a marked increase in HF risk, independent of starting kidney function and/or albuminuria. These findings highlight the importance of serial eGFR measurements over time to improve HF risk estimation in T2D.The online version contains supplementary material available at 10.1186/s12933-023-01869-6. Heart failure (HF) is a frequent complication of type 2 diabetes (T2D), contributing to the excess morbidity and mortality characteristic of this disease –5. Up toA major risk factor for HF among patients with T2D is the presence of diabetic kidney disease (DKD). Large epidemiological studies have shown that both clinical alterations characteristic of DKD – impaired glomerular filtration rate (GFR) and increased urinary albumin excretion – are associated with an increased risk of HF independently from each other –12. A feIn this study, we analyzed longitudinal data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial to investigate the association of rapid kidney function decline over time with risk of HF in patients with T2D, and to assess whether this was independent from kidney function and albuminuria at baseline. We also assessed whether accounting for changes in eGFR over time improved prediction of the risk of HF events as compared to standard clinical predictors.The aim of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial (NCT00000620) was to investigate whether cardiovascular event rates could be reduced by intensively targeting hyperglycemia to HbA1c < 6.0%, compared to a standard target of HbA1c between 7-7.9% , 18. For2 per year). eGFR was estimated in ACCORD at baseline and at regular intervals during follow-up from serum creatinine, measured by the Roche Creatinine Plus enzymatic method , using the 2021 CKD-EPI Serum Creatinine equation [2 per year. Urine creatinine was determined enzymatically on a Roche Double Modular P Analytics automated analyzer. Urine albumin was determined by immunonephelometry on a Siemens BN II nephelometer. Albuminuria was defined as UACR ≥ 30 mg/g, with microalbuminuria defined as UACR between 30 and 299 mg/g and overt proteinuria as UACR above 300 mg/g.Exposures of interest were the eGFR and UACR at baseline and at the last visit before the HF event or 4 year censoring and the rate of eGFR change during follow-up . All baseline laboratory values were obtained centrally at the University of Washington Northwest Lipid Metabolism and Diabetes Research Laboratory. The WATCH-DM HF risk score was calculated from age, BMI, systolic and diastolic blood pressure (SBP and DBP), fasting plasma glucose, serum creatinine, HDL cholesterol, QRS duration on EKG, prior myocardial infarction, and prior coronary artery bypass graft classes and used to subdivide participants in 5 HF risk classes as described by Segar et al .Analyses were run in SAS v9.4 . Normally distributed continuous variables were presented as mean  and analyzed by independent t-test for difference in means between groups. Non-normally distributed continuous variables were presented as median (inter-quartile range) values and analyzed by t-test after log transformation. Categorical variables were presented as counts (percentages) and analyzed by chi-square tests to examine differences among groups.In order to examine the association of rapid kidney function decline with the risk of HF events, unadjusted (Model 1) and adjusted (Models 2–5) odds ratios and their 95% confidence intervals were estimated by multivariable logistic regression models. Analyses were adjusted for ACCORD clinical centers and treatment assignments (Model 2) and for potential confounders that were selected based on their association with HF and/or rapid kidney function decline in ACCORD, including age, sex, diabetes duration, BMI, waist circumference, HbA1c, SBP, DBP, HDL cholesterol, triglycerides, smoking history, CVD history, diuretic therapy, beta-blocker therapy, and renin-angiotensin blocker therapy at baseline and mean Hba1c during follow-up (Model 3).2 and normoalbuminuria (UACR < 30 mg/g), (2) eGFR ≥ 90 mL/min/1.73 m2 and albuminuria (UACR ≥ 30 mg/g), (3) eGFR 60–89 mL/min/1.73 m2 and normoalbuminuria, (4) eGFR 60–89 mL/min/1.73 m2 and albuminuria, (5) eGFR < 60 mL/min/1.73 m2 and normoalbuminuria, and (6) eGFR < 60 mL/min/1.73 m2 and albuminuria. To account for the potential influence of kidney function at the end of the follow-up on our results, we additionally adjusted our analyses for the last eGFR and UACR measures before the HF event or censoring (Model 5).To account for the potential influence of kidney parameters at baseline: (i) we additionally adjusted the analyses for eGFR and UACR levels (continuous variables) at baseline (Model 4); and (ii) we performed subgroup analyses across strata based on eGFR and UACR levels at baseline: (1) eGFR ≥ 90 mL/min/1.73 mThe following sensitivity analyses were also carried out: (1) To account for the potential influence of CVD history, we performed stratified analyses by prevalent CVD at baseline (no vs. yes). (2) To account for the potential influence that the period over which eGFR slope was calculated could have on our results, we re-did the analysis excluding individuals whose eGFR slope spanned < 2 years, in line with previous literature ; (3) To The improvement in risk discrimination provided by rapid kidney function decline during follow up before the HF event, when added to baseline and follow-up WATCH-DM HF risk score, eGFR, and UACR, was evaluated as the area under the Receiving Operating Characteristics (ROC) curve (AUC)  and inte2/year and were defined as having “rapid kidney function decline”. The median rate of eGFR loss in these subjects was − 7.5  as compared to -0.8  ml/min/1.73 m2/year in the rest of participants . As shown in Table Included in the study were 7,539 ACCORD participants, who competed 4 years of follow-up and/or had a HF event over this time period, had available UACR data at baseline, and for whom at least three eGFR values were available in the time span between four months after randomization and the HF event or the 4-year censoring . A median of 6 eGFR values were available for each participant IQR 5, 11) over a median of 3.3 years , corresponding to a median of 1.9 eGFR per year (IQR 1.7–3.2) . Based on eGFR slope estimates during follow-up, 1,573 participants (20.9%) had a rate of eGFR loss ≥ 5 ml/min/1.73m1 over a 2/year), p = 0.0002), resulting in a higher prevalence of rapid kidney function decline during follow-up   experienced a HF episode in the first 4 years of follow-up. As compared to other participants who did not experience HF over 4 years follow-up , these individuals were more frequently male and were characterized by older age, longer duration of diabetes, higher baseline BMI, waist circumference, HbA1c, triglycerides, and UACR, lower baseline diastolic blood pressure, total cholesterol, HDL cholesterol, and eGFR, a more frequent history of CVD, HF, and smoking, and more frequent treatment with diuretics and beta-blockers (Table .4% experAssociation of rapid kidney function decline with HF risk in relation to kidney parameters at baseline.2) and albuminuria . The odds of HF were the lowest for participants with eGFR ≥ 90 or 60–89 and normoalbuminuria, highest for those with eGFR < 60 and albuminuria, and intermediate for the remaining groups (Supplementary Table 4). As shown in Fig. 2, increased baseline UACR, and rapid kidney function decline during follow-up had a 15-fold increase in the odds of a HF event as compared to those with none of these risk factors . Greater than 7-fold increases in the odds of HF were also observed among participants who had experienced a rapid GFR decline and had albuminuria or an eGFR < 60.Further adjustment for eGFR and UACR at baseline, considered as continuous variables (Model 4), did not substantially change the association between rapid kidney function decline during follow-up and odds of HF   and base2 per year) was associated with a 3.2-fold increase in the risk of HF as compared to no or slow kidney function decline, irrespective of cardiovascular risk factors, glycemic control, and history of CVD. The association of rapid kidney function decline with HF risk was also independent of kidney function and albuminuria at baseline. When an indicator of rapid kidney function decline during follow-up was added to these baseline characteristics and the other HF predictors captured by the WATCH-DM score, it significantly improved HF risk discrimination.In patients with T2D followed for 4 years, rapid kidney function decline  was associated with a 1.4-fold increase in the risk of HF [A limited number of studies have investigated the association between rate of eGFR changes and HF risk in the general population, without focusing on patients with diabetes , 16. Thesk of HF , 16 our 2). This suggests that the increased risk of HF was related to the rapid rate of kidney function decline rather than the lower kidney function per se. In other words, among patients with the same degree of impairment of kidney function during follow-up, those who experienced such decline over a shorter period of time were more likely to have HF as compared to those in whom kidney function declined more slowly. Thus, evaluating kidney function and albuminuria at any given point in time may not be sufficient for patients with T2D since additional crucial information may be provided by monitoring the eGFR trajectory over time.One notable feature of our findings is that the association of rapid kidney function decline with HF risk was independent of eGFR levels and albuminuria at baseline. Interestingly, it was also independent of the last eGFR measured before HF or the end of follow-up, which, as expected, was much lower in patients with rapid kidney function decline than in all other participants . Therefore, the generalizability of our findings needs to be confirmed in patients with diabetes who are at lower cardiovascular risk and/or are treated with newly developed glucose lowering drugs such as GLP-1 receptor agonists and SGLT2 inhibitors. Furthermore, data were not available on the different clinical presentations of HF (preserved vs. reduced ejection fraction), which may have different etiologies and predictors. Lastly, as in any observational study, the possibility of residual confounding cannot be entirely ruled out.2 per year, even in the presence of eGFR over 60 ml/min/1.73 m2 and normoalbuminuria, may be a cost-effective strategy to both halt further decline in renal function and prevent the development of HF.In summary, in this analysis of data from the ACCORD clinical trial, we found that rapid kidney function decline over time was independently associated with the risk of subsequent HF in patients with T2D. These results strongly suggest that close monitoring of the eGFR trajectory over time may improve prediction and, therefore, prevention of HF in patients with diabetes, beyond what can be provided by considering individual eGFR measurements. Using rapid kidney function decline may help the early identification patients who could especially benefit from preventing treatment such as SGLT2 inhibitors – a class of drugs that has recently been found to have remarkable kidney and cardiovascular protective properties  MonitoriBelow is the link to the electronic supplementary material.Supplementary Material 1


There is an increased prevalence of psychological distress in adults with asthma. Psychological distress describes unpleasant feelings or emotions that impact the level of functioning. It is a significant exacerbating factor in asthma control. Addressing factors that contribute to psychological distress in those asthma patients improves asthma outcomes. So, this study aimed to assess the prevalence of psychological distress and associated factors among asthmatic patients at Hawassa public hospitals, Ethiopia, 2021.Institution-based cross-sectional study design was used to select 394 asthma patients. Proportional allocation and systematic sampling techniques were used to select study participants. A logistic regression model was used to assess the predictors and psychological distress of the asthmatic patient. The association was interpreted using the odds ratio and 95% confidence interval.A total of 394 asthma patients participated in the study, giving a response rate of 93.4%. The prevalence of psychological distress among asthmatic patients was 51% [95%CI: 46%-56%]. Participants who had comorbid medical illness , experienced stigma , chewed khat , had poor social support and had uncontrolled asthma were significantly associated with psychological distress in asthmatic patients.This study demonstrated that the prevalence of psychological distress was found to be high among asthmatic patients. Social support, stigma, chewing khat, comorbid medical illness, and poor asthmatic control had significantly associated with psychological distress in asthmatic patients. Asthma is a lifelong respiratory disease characterized by airway obstruction, airway inflammation, and bronchial hyperresponsiveness that produce recurrent episodes of wheezing, coughing, and dyspnea . PatientPsychological distress (PD) had both emotional and physiological manifestations that interfere with activities of daily living. It is characterized by symptoms of depression, anxiety, and somatic symptoms , 4. EvidGlobally, WHO estimates that 300 million people were suffering from asthma, with approximately 250,000 deaths annually . The GloPsychological factors seem to have a major role in asthma; thus, including psychological assessment in patients’ treatment is quite reasonable . PsycholIn Canada, the ratio of psychological distress among people with asthma as compared to healthy individuals ranged from 1.1 to 2.7 . AnotherThe body of evidence shows that psychological distress has an impact on asthma patients daily lives, subjective interpretation of symptoms, and adherence to treatment ; MoreoveThe presence of psychological morbidity is, however, frequently unrecognized or not assessed by the usual clinicians treating asthma patients. So far, there is no data on the prevalence of physiological distress among asthmatic patients and its associated factors in Ethiopia. Hence, this study aimed to assess the prevalence of psychological distress and associated factors among asthma patients attending public hospitals located in Hawassa, Ethiopia. Identifying and controlling factors like psychological distress aids or improves patients’ control of their asthma over and above pharmacotherapy and helps to reduce the burden of asthma.A cross-sectional study was conducted from March 20 to April 20/2021 at Hawassa University Comprehensive Specialized Hospital and Adere General Hospital, Hawassa, SNNPR Ethiopia. Hawassa is the regional city of SNNPR located 273 km from the capital city of Ethiopia, Addis Ababa. The two public hospitals, namely HUCSH and HAGH provide both outpatient and inpatient health care services to about 15 million and 350,000 people respectively since their opening in 2004.All asthma patients on follow-up at Hawassa University comprehensive specialized hospital and Adare general hospital were the source population.All adult asthmatic patients whose ages were ≥ 18 years and who had a follow-up in HCSH and Adare Hospital were included. Patients in respiratory distress who were not able to respond due to severe illness were excluded.The sample size was determined by using a single population proportion formula by considering the following assumptions: prevalence of PD among asthma = 50% (0.5) because there is no previous study done on this topic in Ethiopia, the value of Zα/2 = 1.96 which is Z score of 95% confidence interval, and margin of error = 5% (0.05).This yields an initial sample size of 384. By considering adjustment for the expected non-response rate (10%), the final calculated sample size was 422.The two public hospitals had asthmatic chronic follow-up units that were conveniently selected. During the data collection period at each chronic follow-up outpatient department (OPD), 600 and 285 patients were attended at HUCSH and Adare hospital respectively. The samples were proportionally allocated to each hospital. A Systematic sampling techniques was used to select study participants. After the first respondent drown by lottery method then every two intervals was interviewed till the sample size was reached.Psychological distress of the asthmatic patient was a dependent variable.Socio-demographic characteristics ; clinical factors ; behavioral factors  were independent variables.Based on the Global Initiative for Asthma (GINA) guidelines, as follows: symptoms within 4 weeks, none of the symptoms were considered controlled, 1–2 symptoms were considered partly controlled, and 3–4 symptoms were considered uncontrolled. This tool uses frequency of symptoms, night waking due to asthma, limitation of activity, and frequency of reliever medication use . This toIs the support gained from family and non-family members. The score ranges from 3 to 14, with high values representing strong levels of social support and low values representing poor levels of social support. The Oslo social support scale (OSSS)-3 score can be operationalized into three broad categories of social support. 3–8 poor social support, 9–11 moderate social support, and 12–14 strong social support .The item score sum ranges from 10 to 50, which indicates an increasing degree of psychological distress. The score ranges from 10–19 likely to be well, 20–24 likely to have a mild disorder, 25- 29 likely to have a moderate disorder, and 30- 50 likely to have a severe disorder. Respondents had psychological distress when their score on the scale were 22 or above  more likely to develop PD than those who didn’t had co-morbid medical diseases. Respondents who had controlled their symptoms were 77% less likely to develop PD than those who had uncontrolled asthma . Those who experienced stigma were 3.6 times more likely to develop PD than those who were not stigmatized . Those respondents who had strong social support were 89%  to develop PD than those who didn’t chew khat  , and in This study revealed that the level of asthma symptom control was significantly associated with PD. Respondents who had controlled their symptoms were 77% less likely to develop PD than those who had uncontrolled asthma [AOR: 0.229, 95%CI (0.066–0.797). This finding is supported by studies done in Egypt  and CanaRespondents who had comorbid medical diseases were 6 times more likely to develop PD than those who didn’t have any comorbid medical diseases; this is in line with another study done in US National Health Interview Survey . This coIn this study, respondents who had strong social support were 88%less likely to develop PD than those who had poor social support; this idea is supported by a study done in Jordan . This miIn the current study, those participants who chewed khat were significantly associated with PD, which is supported by the US National Health Interview Survey report . Khat usThe present study showed that stigma 146(37.1%) of asthmatic patients were a significant associated with developing PD. This is supported by the descriptive study in Jordan 72.8% of participants feel sometimes stress due to people's influence and misunderstanding of the disease and about 68% of them believed that people sometimes can do nothing for them .Due to the cross-sectional design of this study, it is not possible to draw any conclusions regarding causality. The interviewer assessed the patient's substance use, and as result, the patient may be afraid to answer the truth.Generally, in this study, more than half of the participants had psychological distress. This study also identified that factors like social support, stigma, chewing khat, comorbid medical illnesses, and asthma symptom control level were significantly associated with PD in asthmatic patients.Attention should be given to factors that cause psychological distress in asthmatic patients by giving clear and honest information on the triggering factors of their disease and medication adherence. There should be designed programs to give training to healthcare personnel to increase their clinical acumen at recognizing PD. It is better for future researchers to undergo longitudinal research on risk factors for PD and to study other additional variables that may cause PD.


BackgroundThe global burden of chronic kidney disease (CKD) has been on an alarming increase in the last two decades. The morbidity and mortality associated with CKD are even worse in Nigeria, like other developing countries, due to multiple socioeconomic and demographic factors in the country. CKD contributes to the increasing need for hospital admission. Hypertension and chronic glomerulonephritis have been the leading causes of CKD in Nigeria. However, diabetic nephropathy has recently gained more significance as a cause of CKD in developing countries.Aim and methodsThis study aimed to describe the current trend in the burden and population characteristics of CKD in Southern Nigeria. This is a cross-sectional, hospital-based study. The study recruited adult patients with prehemodialysis CKD seen in renal clinics over a two-year period (November 2014 to October 2016). Data were obtained using a questionnaire and from the clinic register. All participants were clinically assessed, including history, anthropometric measurements, and urinary albumin-creatinine ratio.ResultsA total of 1,549 patients were seen at the Medical Outpatient Clinic over the study period. CKD accounted for 9.7% of medical outpatient clinic attendance. The mean age of participants was 49±13 years. The leading causes of CKD were diabetes mellitus (32%), chronic glomerulonephritis (30%), and hypertension (22%). Among the participants, CKD stages 3, 4, and 5 were prevalent in 26.7%, 43.3%, and 14.7%, respectively.Conclusion and recommendationCKD is very prevalent among medical clinic patients. Diabetic nephropathy seems to be a more significant cause of CKD than was previously reported. Late presentation of patients to nephrologists remains an obstacle to improving CKD outcome in Nigeria. There is need for more intensive preventive measures and early intervention. The global burden of chronic kidney disease (CKD) has been on an alarming increase in the last two decades . The morA South-South Nigerian community study among rural adults reported a prevalence of CKD of 27.2% . Thus, CConsequently, the economic burden of the disease is worse in SSA due to a higher indirect cost in the form of man hour loss at workplace. Several studies have reported a male predominance in the CKD population in Nigeria ,17. HoweThe cost of renal replacement therapy in Nigeria is highly prohibitive, leading to a more than 70% drop-out rate within one month of hemodialysis . The catThe study was conducted at the renal unit of the Department of Medicine, Delta State University Teaching Hospital (DELSUTH), Oghara, South-South Nigeria, from November 2014 to October 2016 (spanning a period of two years). DELSUTH is a state-owned teaching hospital established by the Delta State Government in 2010. The health facility has 230 beds and it serves as the major tertiary health institution in the state and also a referral center for a large catchment area in the Southern part of Nigeria, including Edo, Bayelsa, Ondo, and Anambra states.This is a hospital-based descriptive cross-sectional study. Ethical clearance was obtained from the Ethics Committee of DELSUTH. Consenting CKD patients attending the two renal clinics were recruited consecutively. However, patients in KDIGO  CKD stage 1, those with acute-on-chronic kidney disease, and those already on dialysis were excluded to avoid classification bias. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease (MDRD) equation. A structured interviewer-administered questionnaire (close-ended) was used to obtain information on demographic data and the health status of participants. All participants were subjected to a thorough clinical assessment with emphasis on past medical history, social history, drug history, anthropometric measurements, blood pressure measurement, fundoscopy, urinalysis, fasting blood glucose, serum creatinine, urinary albumin-creatinine ratio (UACR), hepatitis B virus, hepatitis C virus, HIV screening, and renal ultrasonography.2 [CKD was defined and classified according to the 2012 KDIGO guidelines . Diabeti2 .Statistical analysisThe Statistical Package for Social Sciences (SPSS) computing program version 22 was used for data management and analysis. Frequency of parameters is presented in tables, graphs, and pie charts. All continuous variables are presented as mean± SD, whereas categorical variables are presented as percentages and proportions. Mean of continuous variables was compared using Student's t-test, whereas categorical variables were compared using the chi-square test.Prevalence of CKD in the medical outpatient clinicDuring the study period, 1,549 patients attended the Medical Outpatient Clinic. Predialysis CKD patients constituted 9.7% of the total number of medical outpatient clinic patients. This is represented in Table Sociodemographic characteristics and health status of participantsThe mean age of participants was 49±13 years. The mean age of males was 47±12 years, which was significantly lower than that of females . Of the patients, 89% were less than 65 years of age, and 46.7% were in the age group of 45-64 years. There were 92 males and 58 females, making a male-to-female ratio of 3:2. Of the participants, 45%, 12%, 20%, and 23% were traders, farmers, civil servants, and others , respectively. Majority (60%) of respondents earned between 10,000 and 100,000 nairas (US$28- US$280) per month. Only 25 (16.7%) earned more than 100,000 nairas (US$280) per month, and 32 (23.3%) were either unemployed or earned less than 10,000 nairas (US$28) per month. This is shown in Table CKD risk factors among participants2  and 46 30.7%) had a history of hypertension and diabetes, respectively. Based on urinary albumin excretion (UAE) rates, only 20 (13.3%) were normoalbuminuric, whereas 41.3% and 45.3% of participants had microalbuminuria and overt albuminuria, respectively. Of the study group, 107 (71%) had no history of smoking, 31 (21%) had a previous history of smoking, and 12 (8%) had a current history of smoking. Also, 32 (21.3%) had a significant history of nephrotoxic agent use, 12 (8%) had a family history of kidney disease, and 28.7% had BMI equal to or greater than 30 kg/m0.7% had Etiology and stages of CKD among participantsDiabetic nephropathy, chronic glomerulonephritis, and hypertensive nephrosclerosis were the leading causes of CKD in this population, accounting for 32%, 30%, and 22.6%, respectively. A total of 13 (8.6%) cases could not be attributed to a particular etiology, and 87 (58%) of the participants presented in either CKD stage 4 or 5. Only 23 (15.3%) cases presented in stage 2, as shown in Table This study showed that CKD accounts for a high proportion of clinic patients seen in our medical outpatient clinic. The 9.7% prevalence of CKD among medical outpatient clinic patients is comparable with an earlier South-West Nigerian study, which reported CKD to account for 8-10% of medical admission . The preThe observation of the mean age of male CKD patients being lower than that of their female counterparts is similar to an earlier report by Ulasi and Ijoma in a South-East Nigerian study . The reaThe predominant occupation of participants was trading. While this could be a coincidence, the sedentary lifestyle associated with trading may contribute to CKD risk factors such as hypertension, diabetes mellitus, and obesity. Most participants in this study earned between 10,000 and 100,000 nairas ($28 and $280) per month. The catastrophic health spending in the developing countries wherein individuals mostly pay for Medicare out of pocket will undoubtedly further impoverish this CKD population with incomes already below the poverty line . It is tThe prevalence of hypertension in this study of 42.7% falls within the overall prevalence in Nigeria of 8.0% to 46.4% . The disThe leading causes of CKD in this study were diabetes nephropathy, chronic glomerulonephritis, and hypertensive nephrosclerosis, accounting for 32%, 30%, and 22.6%, respectively. Of those with diabetic nephropathy, 11% had no prior history of diabetes before presentation. This observation is both surprising and concerning as most earlier reports in Nigeria have observed much less significance of diabetes as an etiology of CKD ,12. HoweThis study, despite its strength of using the highly sensitive UACR in detecting UAE, had limitations, which included a one-time UACR, which did not differentiate between reversible and persistent proteinuria as well as being a single-center study, which will not allow generalization of findings. However, the findings in this study will stimulate future prospective studies on the subject.CKD is a major cause of medical outpatient consultation. Diabetic nephropathy seems a more significant etiology of CKD than was previously reported. Late presentation of CKD patients to nephrologists continues to be a norm in the developing countries. This calls for a concerted effort to raise awareness and implement programs for early screening and diagnosis of diabetes and CKD, especially in the high-risk populations.


Using general anesthesia on animals causes significant changes to the heart and blood vessels that disrupt normal cardiovascular performance. Blood pressure (BP) is used for closely monitoring hemodynamics in anesthetized animals. However, BP is affected by various factors and may not always accurately correlate with the total body blood flow. Pulmonary artery thermodilution (PATD) is the gold standard for cardiac output (CO) measurements, but, due to the high risks associated with its invasiveness, it is not performed in clinical settings. This study evaluates noninvasive electrical cardiometry’s (EC) performance in measuring CO and other hemodynamic variables in healthy anesthetized dogs during acute blood volume manipulation. The EC measurements consistently underpredict the CO values as compared with PATD, but have a better performance when acute blood loss occurs. Even though the EC readings have a slightly higher error than the accepted error, this method is very good at showing trends in the CO measured using PATD. Other EC-derived variables are able to closely track the changes in the CO measured using PATD. In clinics, noninvasive EC may benefit the patient care quality for anesthetized dogs by monitoring the trends in hemodynamics and guiding anesthetists to diagnose and treat cardiovascular complications.p < 0.05 are considered significant. The EC measurements consistently underpredict the CO values as compared with PATD, and the LCC is 0.65. The EC’s performance is better during hemorrhage, thus indicating its capability in detecting absolute hypovolemia in clinical settings. Even though the percentage error exhibited by EC is 49.4%, which is higher than the standard (<30%), EC displays a good trending ability. Additionally, the EC-derived variables display a significant correlation with the CO measured using PATD. Noninvasive EC may have a potential in monitoring trends in hemodynamics in clinical settings.In animals, invasive pulmonary artery thermodilution (PATD) is a gold standard for cardiac output (CO) monitoring, but it is impractical in clinical settings. This study evaluates the agreement between PATD and noninvasive electrical cardiometry (EC) for measuring CO and analyzes the other EC-derived hemodynamic variables in six healthy anesthetized dogs subjected to four different hemodynamic events in a sequential order: (1) euvolemia (baseline); (2) hemorrhage (33% blood volume loss); (3) autologous blood transfusion; and (4) 20 mL/kg colloid bolus. The CO measurements obtained using PATD and EC are compared using Bland–Altman analysis, Lin’s concordance correlation (LCC), and polar plot analysis. Values of  General anesthesia is routinely required to perform a variety of surgical, medical, and diagnostic procedures in veterinary medicine. Anesthetic drugs can contribute to significant intraoperative hemodynamic alterations that can lead to further disturbances in cardiac performance ,2. In anRight heart catheterization is an invasive technique for evaluating the CO via pulmonary artery thermodilution (PATD), and has been considered the ‘gold standard’ since the 1970s ,9. This TM’ algorithm, which assesses the cyclic variations in the thoracic electrical impedance during a cardiac cycle. The acceptable performance and accuracy of EC for conducting advanced hemodynamic monitoring has been reported in critically ill adult human patients [EC), stroke volume (SVEC), thoracic fluid content (TFC), corrected flow time (FTC), stroke volume variation (SVV), contractility index (ICON™), variation in contractility (VIC™), systolic time ratio (STR), pre-ejection period (PEP), and left ventricular ejection time (LVET) during the induction and treatment of hypovolemia in isoflurane-anesthetized dogs. Our hypotheses are that: (1) the EC will display an acceptable agreement with PATD in this experimental scenario; and (2) the EC-derived variables will correlate with the variations in CO as measured using PATD in this canine hemorrhagic shock model.Electrical cardiometry (EC) is one of the newer noninvasive technologies for continuously measuring the CO and other EC-derived variables. With four skin electrodes, EC estimates the CO using the ‘electrical velocimetrypatients , women rpatients , childrepatients , and cripatients ,17,18. Epatients , transpupatients , and PATpatients , it has patients ,23. Therpatients ,25,26,27patients . StudiesThis prospective, crossover, non-randomized experimental study utilized six adult purpose-bred, male, healthy Beagles  that were owned by the Virginia-Maryland College of Veterinary Medicine. The dogs were certified as ‘healthy’ by performing a thorough physical exam, complete blood count, and serum chemistry panel. They had free access to water, food, and enrichment toys, and were housed in a temperature- and light-cycle-controlled facility. The study design and procedures were approved by the Virginia Tech University-Institutional Animal Care and Use Committee (protocol number 20-235). Three weeks after the end of the study, all the dogs were successfully adopted into single family homes.TM Cuffed Basic; Medtronic Animal Health, Minneapolis, MN, USA) was secured using a tie and connected to a ventilator-integrated anesthesia workstation  via a rebreathing system. Isoflurane  in oxygen (1–2 L/min) was used for anesthetic maintenance with a targeted end-tidal concentration of isoflurane (ETISO) of 1.6–1.8%. An infrared gas analyzer linked to a multiparameter monitor  was in place to continuously measure the ETISO. The lead II electrocardiogram (ECG), heart rate (HR), esophageal temperature, partial pressure of end-tidal carbon dioxide (PETCO2), and peripheral oxygen saturation were also recorded using the same monitor. The body temperature was maintained between 36.7 and 38.1 °C throughout the experiment using a forced-air warming device  and a circulating water blanket . During the entire study period, no fluids were administered to eliminate the possibility of the fluid volume affecting the blood volume and skewing the hemodynamic data.The dogs were allowed 2 weeks to acclimatize to the laboratory environment. About 12 h prior to the experiment, food was withheld, but ad libitum access to the water was provided. On the day of the experiment, a 20-gauge, 2.95 cm catheter  was aseptically inserted in the right cephalic vein, and preoxygenation was performed for 5 min using a fitted facemask with 4 L/min oxygen flow. Intravenous (IV) propofol  was titrated to effect until endotracheal intubation was achieved. The endotracheal tube  was used for catheterizing the dorsal pedal artery with the purpose of measuring the systolic, diastolic, and mean arterial blood pressures. The catheter was connected to a disposable pressure transducer  via a saline-filled noncompliant short tubing and a 3-way luer lock stopcock, and the entire system was flushed with heparinized saline (3 units/mL). Prior to anesthetizing each dog, the transducer and the multiparametric monitor were calibrated using a digital pressure manometer. To assess the accuracy and linearity, the transducer was verified against the mercury manometer by use of a 2-point calibration technique (0 and 150 mmHg). The calibration was deemed acceptable when the difference between pressure exerted by the manometer and the displayed pressure on the multiparametric monitor was <2 mmHg. The transducer was situated at a height that approximately corresponded to the right atrium and zeroed to atmospheric pressure. Rocuronium  was administered as an IV bolus 0.4 mg/kg followed by a constant rate infusion of 0.4 mg/kg/h to cause and maintain neuromuscular paralysis. The train-of-four supramaximal stimulation  of the common peroneal nerve tested the blockade’s effectiveness. The dogs were mechanically ventilated using a volume-controlled ventilation mode with the tidal volume fixed at 12 mL/kg and the respiratory rate at 10–20 breaths/min to maintain PETCOEC, SVEC, and HREC); (2) fluid status variables ; and (3) contractility variables . The area on the left aspect of the neck alongside the common carotid artery and the left lower aspect of the thorax were clipped and thoroughly cleaned to remove any dirt and skin debris. After ensuring the areas were dry, 4 Cardiotronic  electrocardiographic electrodes attached to adhesive patches were placed on the prepped skin areas, with 2 electrodes on the left aspect of the neck (at the level of common carotid artery) and 2 electrodes on the left thoracic area (at the level of the T8-T13 vertebrae corresponding to the location of the descending thoracic aorta) [Electrical cardiometry using the ICON monitor  provides continuous recordings of: (1) blood flow variables  . The eleEC using the following equation:EPT (mL) is the volume of electrically participating tissue calculated from the body mass and height indicating a patient constant, VFT (s−1) is the ohmic equivalent of the mean aortic blood velocity during left ventricular ejection derived from the peak aortic blood flow acceleration, and LVET (s) is the left ventricular ejection time [Electrical Velocimetry™  is the physiological modeling and equation present in the ICON monitor that assesses the changes in the thoracic electrical bioimpedance during the cardiac systole and subsequent volumetric changes in the aorta that occur ,29,30. Aion time ,29,30.EC (L/min) is then calculated as the product of SVEC and HR recorded using EC (HREC). The physiologic model in the ICON monitor then correlates the measured changes in thoracic electrical bioimpedance to derive other hemodynamic variables such as TFC, FTC, ICON™, VIC™, STR, PEP, and LVET. The COEC, SVEC, and HREC are averaged over a 1 min interval as set on the internal database. To ensure the EC data’s reliability, the HREC values are verified against the pulse rate from the pulse–oximetry and arterial pressure waveforms as well as the HR from the ECG before every recording of the COEC, SVEC, HREC, and other EC-derived hemodynamic variables. Moreover, to maintain the data accuracy, the EC-derived values are only recorded when the signal quality index displayed on the ICON monitor is 100. The SVV calculation is automatically performed using the ICON internal software with the following formula and is simultaneously noted at each datapoint as an average during 1 min:max and SVmin are the maximum and minimum stroke volume (mL), respectively, over one respiratory cycle.The COmax and PEPmin are maximum and minimum pre-ejection periods (ms), respectively, over one respiratory cycle.The PEP (ΔPEP) variation is manually calculated by noting the maximal and minimal PEP values during inspiration and expiration, respectively, during one respiratory cycle. These measurements are repeated over three different respiratory cycles  and are each averaged. The formula used for the ΔPEP calculation is as follows ,32:ΔPEP PATD determination. The catheter’s proximal and distal ports were connected to another set of disposable pressure transducers , and these were calibrated and positioned in a similar manner to the arterial pressure transducer. The appropriate computation constant was selected on the monitor screen based on the catheter model, volume, and injectate’s temperature as recommended by the manufacturers [The dogs were then transitioned to dorsal recumbency for PATD instrumentation and remained in this position for the entire study period. Due to this change in the body position, the arterial pressure transducer was re-zeroed to atmospheric pressure. Using the modified Seldinger technique, a 5 Fr 13 cm double lumen central venous catheter  was aseptically placed in the left jugular vein. This catheter’s function was to draw a fixed blood volume to induce acute hemorrhagic shock, and to transfuse blood and Hydroxyethyl Starch during hemorrhage treatment. The same technique was used to place a 6 Fr 8.5 cm hemostasis introducer  in the right jugular vein, through which a 5 Fr 75 cm PA thermodilution Swan Ganz catheter  was advanced by pressure–waveform guidance until its distal tip was located in the PA. The accurate positioning of the distal and proximal ports was confirmed by observing the characteristic pressure waveforms and pressure values of the main pulmonary artery and right atrium, respectively, upon connection with the CO monitor . The proximal injectate port was used for injecting the cold saline bolus during the COacturers .PATD reading was timed at the end of the expiration, and a 3 mL bolus of chilled (from 2 °C to 5 °C) 0.9% sodium chloride solution was injected over <3 s into the proximal port of the Swan Ganz catheter. At each data timepoint, a CO reading corresponded to the mean of 3 consecutive measurements within 10% variation. The injections were always manually administered by the same person and spaced at least 90 s apart. Three researchers  were assigned to collect the specific data and were blinded to the readings obtained by the others.Each COUpon completing instrumentation, each dog was subjected to a sequential non-randomized experimental design to induce acute changes in the blood volume . Ten minWhen the final data were acquired, the rocuronium infusion was discontinued. The jugular and arterial catheters were removed, and recovery was initiated by turning off the isoflurane vaporizer. Upon extubation, 0.3 mg/kg IV methadone was administered to all dogs and they were transferred to individual cages; their cardiopulmonary parameters and catheter sites were monitored hourly for the first 4 h, every 3 h for the next 8 h, and every 8 h for a total of 96 h. The pain scores were assessed using the Glasgow composite pain scale short form  and evalhttp://estatistica.bauru.usp.br/calculoamostral/ accessed on 1 September 2021).Using a literature search of veterinary studies comparing CO measurement techniques with the gold standard PATD ,36,37, aThe Shapiro–Wilk and D’Agostino–Pearson tests were used to assess the physiological variables at each time point and the hemodynamic event. The data for all normally distributed variables were reported as mean ± standard deviation (SD). To compare the differences across the variables during the hemodynamic event occurrences, a one-way analysis of variance for repeated measures was performed.t test (parametric data) or Wilcoxon Signed Rank test (non-parametric data) to compare the differences among the paired samples. The correlation between COPATD and several variables  was assessed using the least squares regression analysis. The statistical analysis was carried out using SAS Version 9.4  and p < 0.05 values were considered statistically significant.A Tukey’s Honest Significant Difference (post hoc test) was applied to the paired comparisons and, if there was a lack of sphericity, Greenhouse and Geisser corrections were performed. This was followed by a pairwise PATD−COEC difference was used. Since the CO measurements being evaluated were distributed over a wide physiologic range and there was a lack of normality exhibited by some variables, the bias was calculated. The bias was expressed as a percentage of the average CO values, as previously reported [For calculating the bias for each observation, the COreported ; the forEC was overpredicted compared to the COPATD. The limits of agreement (LOA) were calculated as RB ± 1.96 × SD to include a 95% confidence interval (CI). As per the previously published standard for comparing the CO methods, the overall RB was required to be <30% for an acceptable performance using the test method (EC) when compared to the gold standard method (PATD). Additionally, the absolute value of RB for each observation was compared with the 30% value to establish an estimate for the overall performance.Here, a positive RB (%) value suggests that the CO value was underpredicted by the EC when compared with the PATD, and a negative RB (%) indicates that the COPATD and COEC, and the Lin’s concordance correlationPATD and COEC values [EC and COPATD was influenced by the original measurement’s magnitude (proportioning effect), the BA analysis for non-uniform differences was performed. For such instances, the bias was linearly regressed against the average bias [EC‘s trending ability along with investigating the agreement between the COPATD and COEC [A linear regression analysis was conducted to evaluate the correlation in the measurements between the COcibility . Bland–AC values . When thage bias . A polarand COEC ,43. The p = 0.88), time spent in hemorrhagic shock (p = 0.39), and time spent during blood transfusion (p = 0.22) and colloid administration (p = 0.26) between all the dogs.The anesthetic induction and maintenance were uneventful in all dogs and there was a smooth emergence from the general anesthesia during recovery. In each dog, successful placement of the Swan Ganz thermodilution catheter was performed without any complications. No missing data for the PATD and EC were reported, and all dogs successfully completed the experiment. The dogs were normothermic throughout the experiment (37.6 ± 0.9 °C) as well as during the recovery period. After completion of the study, the jugular and arterial catheter sites did not show any evidence of substantial hematoma or subcutaneous bruising. Two out of the six dogs required an additional dose of 0.3 mg/kg IV methadone because of the pain scores at the 10 h timepoint post-extubation. The cardiorespiratory parameters, appetite, demeanor, and excretory functions were within the normal limits throughout the 96 h post extubation period. There were no differences in the total anesthesia time , but they significantly improved after the autologous blood transfusion (p = 0.041). After a colloid infusion, both methods detect a significant rise in the CO values (p = 0.032).For each dog, a pair of CO measurements was obtained using the PATD and EC techniques for each of the five timepoints during baseline, hemorrhage, autologous blood transfusion, and colloid administration. Twenty pairs of CO measurements were collected for each dog and, overall, 120 pairs of measurements were obtained from all six dogs. The mean PATD − COEC) is 0.55 ± 0.38 L/min. The mean ± SD of the relative bias (%) between the two methods is 27.7 ± 16.8% (LOA: from −5.1% to 60.5%). Approximately fifty percent (50%) of the 120 observations have an absolute value of relative bias >30%. The percentage error expressed as (1.96 × SD of the bias/mean CO) × 100 is calculated as 49.4%, which is not within the acceptable range as proposed in the literature [The mean ± SD of the bias between the two methods (COterature . To compEC = 0.72 × COPATD (r2 = 0.94). A positive mean relative bias (27.7%) and slope (<1) about Y = X indicates the EC underpredicts the CO when compared with the PATD. The Lin concordance correlation coefficient between the COPATD and COEC is ρc = 0.65 (p < 0.001).The regression in line Y = X  yields tPATD − COEC) is normally distributed as reported by the Shapiro–Wilk test and the D’Agostino–Pearson test. Considering there is a large variation in the mean relative bias across different hemodynamic events, a BA analysis for non-uniform differences was conducted. This analysis shows a positive trend  between the bias and the average CO data , SVV (p = 0.015), and ΔPEP (p = 0.024), with a simultaneous decrease in SVEC (p = 0.021), TFC (p = 0.019) and FTC (p = 0.014). Following the administration of blood, as the COPATD stabilized, the HREC, SVV, and ΔPEP significantly reduced (p < 0.001) and SVEC, TFC, and FTC were significantly higher compared to the values during hemorrhage. After the colloid infusion, as there was a further increment in the COPATD values, the HREC, SVEC, TFC, and FTC show significant changes in the same direction as the COPATD (p < 0.001). In contrast, the SVV and ΔPEP values decline significantly (p < 0.001). The changes in the COPATD are significantly (p < 0.001) correlated with SVEC (r2 = 0.91), TFC (r2 = 0.83), FTC (r2 = 0.89), SVV , VICTM (p = 0.029), and LVET (p = 0.010), while the STR (p = 0.015), and PEP (p = 0.018) are significantly higher. Once the dogs were administered the blood transfusion and the colloid infusion, ICONTM, VICTM, and LVET significantly increased, and the STR and PEP were significantly reduced as compared with the values during hemorrhage (p < 0.001). The changes in the COPATD are significantly (p < 0.001) correlated with ICONTM (r2 = 0.82), VICTM (r2 = 0.78), STR (r2 = 0.81), PEP (r2 = 0.84), and LVET (r2 = 0.87).The mean PATD and COEC. The overall 49.4% error is not within the acceptable range (<30%) published as a standard [Even though PATD is considered the de facto ‘gold standard’ in human and veterinary medicine ,33,36,37standard . InteresPATD values and demonstrates a lower concordance with PATD and a higher percentage error, it shows a very good trending ability throughout the wide range of CO values studied during the hemodynamic events. Moreover, it performs better when the dogs suffer from acute absolute hypovolemia. In clinical scenarios, clinicians may accept a CO method that may not provide highly accurate absolute measurements but is still able to reliably detect trends whenever CO values change [While performing a method comparison study on CO monitoring, using the right tools to fairly assess the technology is important. Some recommended steps ,45,46 ars change ,23. Theys change . AccountPATD − COEC) is 0.55 ± 0.38 L/min. The mean ± SD of the relative bias (%) between the two methods is 27.7 ± 16.8% (LOA: from −5.1% to 60.5%). When comparing EC’s performance across the different hemodynamic events, the mean ± SD (LOA) of the relative bias is reported as 33.6 ± 4.4% (from 24.9% to 42.4%) for the baseline, 4.9 ± 12% (from −18.8 to 28.7%) for the hemorrhage, 35.6 ± 7.3% (from 21.1 to 49.9%) for the blood transfusion, and 36.7 ± 14.5% (from 8.1 to 65.2%) for the colloid infusion. Although the EC consistently underpredicts the PATD measurements, its performance is significantly better during the acute hemorrhagic shock. We speculate that the significant increase in CO observed after blood transfusion and colloid infusion may have resulted in higher velocity of blood flow in vessels. This combined with low blood viscosity during the hyperdynamic state may have disrupted the laminar flow and converted it to turbulent flow by increasing the critical Reynolds number. This chaotic blood flow could have impacted the orientation of the erythrocytes and changes in bioimpedance, thus contributing to inaccuracies when higher CO values were measured. When the COEC values are compared with the CO values measured using transpulmonary thermodilution (COTPTD) in anesthetized piglets under normal conditions, volume resuscitation, inotrope infusion, and severe hemorrhage [TPTD greater than 15% lead to a change in the COEC in the same direction 93% of the time. The BA analysis shows a mean difference between the two techniques of −0.63 L/min with a SD of 0.64 L/min. The lower and upper LOA are −1.88 and 0.62 L/min with a percentage error of ±82.8%. The COEC measurements underestimate the high and overestimate the low COTPTD measurements. The large area of fat and muscle deposition around the cervical area of the piglets is presumed to have interfered with the EC’s functioning [EC versus CIPATD is −0.22 ± 0.52 L/min/m2 with LOA of from −1.25 to 0.81 L/min/m2. The difference between the methods is most pronounced for the low CI measurements compared with from normal to high CIs. The trend analysis for the CIEC compared with the CIPATD revealed a concordance of 88% with a significant correlation. The percentage error during the wide range of the CIPATD recordings is from 19.4% to 41.2%, thus exceeding the acceptable value (<30%) [EC in piglets and dogs is attributed to the species differences in the aortic arch’s location in the thorax, the skin resistance, and the thoracic cavity’s width [EPT) by using anthropometric measures such as the body mass and height to estimate the thorax’s electrically participating volume. Predominantly determined by the patient weight, the mass-based volumetric equivalent of the thoracic blood volume is determined using human subjects in stable normal states and unstable cardiopulmonary disease states [Our study shows the mean ± SD of the bias between the two techniques  is an easy noninvasive method for continuously measuring the CO. It delivers a low-amplitude, high-frequency electrical current across the thorax and the voltage is obtained by the electrodes applied to the skin of neck and thoracic wall. Assessing the CO is performed by detecting variations in the electrical resistance of the thorax during volumetric changes in the aorta over a cardiac cycle ,9. Severleration ,30. The leration ,30. The leration ,9. PerfoC values ,9. In vePATD such that they decrease with hemorrhage and normalize to baseline values after autologous blood transfusion. In a hypervolemic state, after administration of a colloid bolus, the highest TFC values are reported. These findings are in accordance with the results from human subjects undergoing autologous blood harvest [PATD, indicating that this variable can correspond to acute changes in the hemodynamics. Mechanical ventilation induces cardiopulmonary interactions that can be beneficial for assessing the relationship between SV and the dynamic variables such as SVV and ΔPEP. During positive pressure ventilation, the greatest variations in SV happen in the face of hypovolemia. The EC-derived SVV can successfully guide fluid therapy in anesthetized dogs ventilated with different ventilation modes [PATD in our study dogs and accurately tracks the hemodynamics. However, because the physiology behind the SVV and ΔPEP is analogous with the other dynamic variables, they may be unreliable during spontaneous ventilation, positive end-expiratory pressure, tidal volume <8 mL/kg, low respiratory system compliance, open-chest conditions, cardiac rhythm irregularities, right-sided heart failure, altered vascular tone, and intra-abdominal hypertension.Monitoring the fluid balance is a crucial concept in anesthesia and critical care units. In the past two decades, extensive work has been performed in the area of ‘fluid responsiveness’ to prevent fluid overload in patients. This can be favorable for decreasing morbidity and mortality, improving patient outcomes, and shortening hospitalization days. The EC-derived hemodynamic variables provide vital information regarding the fluid status and myocardial contractility. Thoracic intravascular and extravascular fluid content affect TFC values that are calculated from the thoracic electrical bioimpedance. Variations in TFC are known to reflect the total fluid changes ,50. In o harvest . Both th harvest . Similaron modes  as well on modes . We see on modes ,32, justTM and VIC values are significantly decreased during hypovolemia in the anesthetized dogs as expected due to the diminished ventricular preload. It is also possible that the systolic function may also have been disrupted due to the ongoing negative effects on the left ventricular–arterial coupling and mechanical efficiency as previously reported in anesthetized dogs [The PEP is the time interval from the onset of electrical stimulation of the ventricles  to the aortic valve opening. The LVET interval is the time from the aortic valve opening to closing , denoting the aortic flow’s duration. Both these parameters represent a fine balance between the intrinsic contractile function, left ventricular preload, and afterload, but the PEP is also influenced by electrical activation ,52,53. Tzed dogs ,2. When zed dogs ,52,53. Tzed dogs .EPT derived from the human population to other species also needs further exploration. The sequence of subjecting the dogs to drastic variations in the blood volume was not randomized because this specific order was crucial to identify whether the EC can reflect the hemodynamic picture in these dogs. This was also essential to avoid the crossover effect of hypervolemia if induced prior to hypovolemia. The order of the PATD and EC was also not randomized during the data collection. Since the PATD measurements involved multiple 0.9% saline injections, we wanted to rule out any impact of the administered volume on the EC. Therefore, the EC recordings always preceded the PATD data acquisition.This study has the following limitations. The sample size was small, which causes the receiver operating characteristic curves to not generate. Hence, the predictive values, cut-offs, sensitivity, and specificity for the EC-derived variables are not reported. Considering this study primarily focuses on hemodynamics, we attempted to control factors such as the body temperature, use of drugs with cardiovascular effects, sympathetic stimulation, and anesthetic depth to isolate the impact of blood volume changes on the hemodynamic variables. Moreover, this work is an experimental study in healthy Beagle dogs. We realize this does not align with clinical scenarios and, hence, evaluating the EC in routinely anesthetized canine patients with systemic diseases is warranted. A larger study population and data set are required to confirm our study’s observations. The conveyance of the patient constant VEC is consistently good throughout the experiment as compared to the COPATD. The TFC, FTC, SVV, and ΔPEP can assess the volume status and act as surrogates to COPATD, and this may have a clinical benefit in canine patients for monitoring fluid therapy. The ICONTM, VIC, PEP, and STR also provide critical hemodynamic information regarding the impact of acute hemorrhage on the contractile function. Electrical cardiometry is a pivotal noninvasive technique that derives hemodynamic variables that can guide anesthetists to anticipate, diagnose, and treat cardiovascular complications perioperatively, and may help improve the quality of patient monitoring and management in anesthetized dogs. Future studies demonstrating EC’s utility for canine patients undergoing cardiothoracic surgeries, sepsis, pulmonary edema, cardiogenic shock, cardiothoracic trauma, cardiopulmonary resuscitation, volume resuscitation, and receiving inotropic and vasopressor therapy will be fundamental in determining the clinical benefit of this noninvasive CO method in small animal medicine.This study is one of the first exploratory studies to report the assessment of EC-monitor-derived CO  and other hemodynamic variables during the induction and treatment of acute hemorrhagic shock in isoflurane-anesthetized dogs. A positive mean relative bias (27.7%) and slope (<1) about Y = X indicate that the EC underpredicts the CO when compared to the PATD. The agreement between the two methods significantly improves during acute hemorrhage, thus indicating that EC may be able to identify sudden variations in the hemodynamics during absolute hypovolemia in canine patients undergoing general anesthesia. Even though the concordance between the two methods is 0.65 and the percentage error observed during comparisons of the absolute measurements between PATD and EC is 49.4%, the trending ability of the CO


P < 0.0001). Patients undergoing vitreoretinal surgery with gas insertion had statistically significant intraocular pressure rise even with 8-floor ascent in the immediate post-operative period. Further studies are needed to evaluate the change in intraocular pressure with a larger range of altitudes and different gases.To evaluate the impact of elevator travel on intraocular pressure after vitreoretinal surgery with gas tamponade. Patients undergoing pars plana vitreoretinal surgery with and without gas insertion were recruited on post-operative day 1. All intraocular pressures were measured three times by Tono-Pen AVIA  on the fourth floor and, after rapid ascent in an elevator, on the 12th floor of the hospital. All patients were observed and asked for any symptoms of pain or nausea for at least 15 min. In this study, 54 patients were recruited. Twenty-seven patients underwent vitreoretinal procedures with gas insertion, while 27 patients without gas insertion acted as controls. The mean age of patients was 60.9 years. The mean changes in intraocular pressure of the patients with gas insertion (+ 1.39 mmHg) were greater than those without gas insertion (− 0.43 mmHg) and statistically significantly different (95% CI 1.17–2.48,  The number of tall buildings in modern cities will inevitably increase given the global population rise and increased urbanisation.Hong Kong ranks first in the world in terms of the number of skyscrapers, with at least 78 completed skyscrapers over the height of 200 m (656 ft), 517 skyscrapers over 150 m (492 ft), as well as more than 9000 high-rise buildings over 23 m (75 ft)3. There is well-established evidence against air travel in post-vitrectomised patients with gas insertion. However, evidence on the effect of acute ascent in elevators in tall buildings on intraocular pressures in post-vitrectomised eyes with gas tamponade is still lacking.Injection of intraocular gas is an integral part of many vitreoretinal surgeries. Patients are advised to avoid air travel as the low cabin pressures at high altitudes can cause expansion of the intraocular gas and induce dangerous elevations in intraocular pressureThe aim of this study was to evaluate whether travelling in elevators has any significant effect on intraocular pressure, and hence whether travelling in modern elevators in high-rise buildings should be avoided in the immediate postoperative period for patients with intraocular gas in-situ.This prospective case–control study was conducted according to the tenets of the Declaration of Helsinki and the study protocol was approved by the Joint Chinese University of Hong Kong—New Territories East Cluster Institutional Review Board (IRB). Written informed consent was obtained from all participants.The inclusion criteria were patients undergoing pars plana vitreoretinal surgery with insertion of gas (Group A) and without gas insertion (Group B). Exclusion criteria were eyes with glaucoma, optic nerve atrophy, anti-glaucomatous medications. Pregnant or lactating women, children under 13 years old, patients unable to sit up independently or inability to give consent were also excluded.Post-vitrectomy patients were recruited on post-operative day 1 at the Department of Ophthalmology and Visual Sciences at the Prince of Wales Hospital (PWH), Hong Kong between January 2016 and December 2021. Dilated fundal examination was done for each patient by vitreoretinal specialists who used standard clinical assessment techniques to determine the percentage of gas fill. All patients’ intraocular pressures were measured at the fourth floor and the 12th floor in the hospital 3 times by Tono-Pen AVIA . The mean value of the three measurements were recorded. The patients would be observed and asked for any pain and nausea after travelling to the 12th floor for 15 min.P-value of less than 0.05 was considered statistically significant.Statistical analysis was performed using the SPSS program . Independent sample T-test was used to determine any significant difference between the two groups. A Fifty-four patients were recruited in our study. The mean age of all participants was 60.9 years. The number of male and female participants was 29 and 25 respectively. The gas used in 92% of patients with Group A was 12% C3F8. The demographic data and clinical features of the two groups of patients are summarized in Table P < 0.0001). One patient with gas insertion felt nauseated after going up in the elevator. (Table The mean change of intraocular pressure of patients in Group A (with gas insertion) was + 1.39 mmHg SD = 1.42) while that of Group B (without gas insertion) was − 0.43 mmHg (SD = 0.92). The range of mean intraocular pressure change of Group A and Group B were − 1–4.333 mmHg and − 2.333–1.333 mmHg respectively. The mean change in intraocular pressure of the patients with gas insertion was statistically significantly greater than those without gas insertion 10. In a study by Osman et al., the margin of intraocular pressure measurement in the normal patient group was reported to be ± 3.8 mmHg by the Tono-Pen XL and ± 2.7 mmHg by the Goldmann applanation tonometer11. We aimed to investigate the difference in intraocular pressure before and after elevator travel of the same eye of the same patient, using the same operator, thus minimizing the effect of measurement error. It should be noted that the Tono-Pen may underestimate intraocular pressure by 4.5 mmHg at an actual intraocular pressure of 15 mmHg in an air-filled eye, and by even more at higher intraocular pressures12. Therefore, it is plausible to speculate that the actual difference in intraocular pressure observed in our study could be even more significant12.In this study, we utilized the Tono-Pen AVIA  to measure intraocular pressure due to its portability, independence from gravity, and minimal influence from corneal thicknessThis study was limited by the number of floors in our hospital, and it is not possible to extrapolate our result to higher floors since atmospheric pressure decreases exponentially with altitude. Despite this limitation, a statistically significant change in intraocular pressure was found between the two study groups. In Hong Kong, most residential buildings are at least 30 stories and can reach 60–70 floors. The intraocular pressure changes on those patients living on upper floors is likely to be clinically significant. The study was also not standardized as there were different surgeons, port sizes, percentages of gas fill and suturing of sclerotomy wounds. Despite these limitations, the patients in both groups had good wound sealing without any leakage on post-operative day 1. Further standardized studies are needed to test a larger range of ascents to higher altitudes to establish guidelines on how high and how fast patients can ascend in elevators after vitreoretinal surgery. Future work could explore the use of mathematical modeling to simulate intraocular pressure changes at different altitudes (Supplementary Table In conclusion, the findings of this study indicate a statistically significant elevation in intraocular pressure among post-vitrectomy patients with gas insertion during elevator travel, even when traveling between a modest number of floors. As urbanization and population growth continue, this pilot study provides valuable insights and highlights the need for further investigation into the potential safety implications of elevated intraocular pressure in individuals residing in cities with abundant tall buildings and skyscrapers.Supplementary Table S1.


The aim of the present study was to evaluate whether arterial stiffness is affected in the patients with hypoparathyroidism through pulse wave analysis (PWA). Sixty-three patients diagnosed with hypoparathyroidism and sixty volunteers were evaluated for the study. When 21 patients were excluded in the hypoparathyroidism group due to exclusion criteria, the research continued with 42 patients and 60 volunteers who are similar to the patients in terms of age, gender and body mass index (BMI). Fasting plasma glucose after 10 hours of fasting, creatinine, thyroid stimulating hormone (TSH), free thyroxine (fT4), albumin, calcium, phosphorus, magnesium, 25-OH vitamin D, parathormone (PTH) and urine calcium results in 24-hour urine for the patients in the hypoparathyroidism group were recorded. Evaluation of arterial stiffness was performed by Mobil-O-Graph 24h PWA device. Systolic blood pressure (SBP) (p = 0.01), diastolic blood pressure (DBP) (p = 0.005), mean blood pressure (p = 0.009), central SBP (p = 0.004), central DBP (p = 0.01) and pulse wave velocity (PWV) (p = 0.02) were found higher in the hypoparathyroidism group. A positive correlation was detected between phosphorus level and SBP [(p = 0.03. r = 0.327)], central SBP  and PWV . We detected that age and serum phosphorus levels were independent predictor variables for PWV . We detected that hypoparathyroidism causes an increase in blood pressure and arterial stiffness. The most significant determinant factors were detected as advanced age and hyperphosphatemia. The patients diagnosed with hypoparathyroidism should be closely monitored and treatment planning should include to prevent the patients from hyperphosphatemia. Hypoparathyroidism is an endocrine disorder characterized with lower levels or dysfunction of parathormone (PTH). Lower PTH levels within normal limits accompanied by hypocalcemia are classical for hypoparathyroidism. In addition, phosphorus levels may be higher. Hypoparathyroidism occurs due to insufficient hormone synthesis or accidental damage to or removal of the parathyroid glands during surgery or PTH receptor resistance very rarely. The most common cause of hypoparathyroidism in adults is surgical procedures on the neck and other causes include autoimmune diseases, genetic, infiltration, radiation and HIV infection .Significant effects of the changes in PTH, calcium and phosphorus levels on cardiovascular system are well known. PTH receptors were shown in endothelial and myocardial cells and direct hypertrophic effects of PTH on myocardial cells were reported . HypocalThere are several invasive and non-invasive methods as well as scoring systems used to predict the increase in cardiovascular mortality and morbidity. Arterial stiffness is accepted as an independent risk indicator for cardiovascular diseases ,11. ArteThere is limited number of studies focusing on effect of hypoparathyroidism on arterial stiffness parameters and conflicting results were obtained in such studies.The aim of the present study was to evaluate whether arterial stiffness which is an independent parameter for cardiovascular diseases is affected in hypoparathyroidism through pulse wave analysis (PWA).The present study enrolled the patients diagnosed with non-surgical or permanent surgical hypoparathyroidism (≥ 6 months) and healthy volunteers without any parathyroid gland disease or systemic disease referring to endocrinology and metabolism and internal medicine polyclinics of our hospital between January 2018 and December 2018.Inclusion criteria were being adult (≥ 18 years), existence of non-surgical or permanent surgical hypoparathyroidism (≥ 6 months) diagnosis, having normal thyroid functions, corrected serum calcium level ≥ 7 mg/dL and asymptomatic presentation. Control group included healthy volunteers with normal levels of serum calcium, magnesium, phosphorus, parathormone levels and similar characteristics in terms of age, gender and body mass index (BMI).The exclusion criteria for both groups included the following; participants whose ages under 18, presence of any chronic disease , hypothyroidism or hyperthyroidism, smoking, pregnancy and lactation. In this context, 63 patients with hypoparathyroidism referring to our hospital were examined and 42 patients who accepted to participate into the study and 60 healthy volunteers were included into our study .2).After history taking of 42 patients with hypoparathyroidism and 60 healthy volunteers, routine physical examinations were performed and findings were recorded. BMI was calculated through the formula weight (kg) / height , serum creatinine (0.57-1.11 mg/dL), thyroid stimulating hormone (TSH) (0.55-4 mIU/mL), free thyroxine (fT4) (0.78-1.48 ng/mL), albumin (3.5-5.2 g/dL), calcium (8.4-10.2 mg/dL), phosphorus (2.5-4.5 mg/dL), magnesium (1.8-2.4 mg/dL), 25-OH vitamin D (25-80 ng/mL), parathormone (15-65 pg/mL) and calcium in 24-hour urine. Corrected calcium was calculated in all participants [Corrected calcium = total calcium + 0.8 x ]. Corrected calcium value was multiplied with phosphorus and calcium-phosphate (CaXP) product levels were calculated.Approval of the ethical committee was obtained for the research (2012-KAEK-15/1577). Verbal and written informed consent was obtained from all participants of the present study.Arterial stiffness was detected through a Mobil-O-Graph PWA/ABPM device  which performs cuff-based oscillometric method of measurement from brachial artery. Mobil-O-Graph PWA device was approved by blood pressure measurement BHS (British Hypertension Society) and ESH (European Society of Hypertension); and device reliability was demonstrated in comparison through invasive and non-invasive methods for PWA ,15. The Statistical analysis of the data was performed through SPSS 22.0 package program. Statistically significance level was accepted as p < 0.05. Descriptive statistical analyses of the patient and control groups were performed. Categorical data were reported as number and percentage. Kolmogorov-Smirnov test and histogram graphs were utilized to detect whether the data were compliant to normal distribution. Normally distributed data were expressed as mean and standard deviation. Non-normally distributed data were expressed in median and minimum-maximum. Student T test was used to evaluate normally distributed countable data whereas Mann-Whitney U test was used to evaluate non-normally distributed countable data. Chi-square test was implemented to compare categorical data. Correlation analyses were performed through Spearman’s and Pearson’s correlation tests. A multivariate regression analysis was done to detect independent variables predicting PWV. Since PWV data are not normally distributed, logarithmic transformation was performed.In the hypoparathyroidism group, 33 (78.6%) patients were followed due to surgical permanent hypoparathyroidism, 1 (2.4%) patient was followed because of autoimmune polyglandular syndrome, and 8 (19%) patients were followed because of primary idiopathic hypoparathyroidism.There was not any statistically significant difference between two groups in terms of gender, age and BMI. Furthermore, we did not detect any statistically significant difference between the groups in terms of plasma glucose, serum creatinine, TSH, fT4, albumin, magnesium, 25-OH vitamin D levels . Serum PCorrelation of arterial stiffness data with demographic data as well as biochemical parameters were reviewed in all participants. A positive significant correlation was detected between PWV and age , BMI  and FPG . There is not any significant correlation between two groups in terms of creatinine, TSH and fT4.A significantly negative correlation was detected between serum calcium level and SBP, DBP, MAP, cSBP, cDBP, cPP and PWV. A significantly positive correlation was detected between serum phosphorus level and SBP, DBP, MAP, cSBP, cDBP, cPP and PWV. A significantly negative correlation was detected between serum parathormone level and SBP, DBP, MAP, cSBP, cDBP, cPP and PWV .A positive correlation was detected between phosphorus level and SBP, cSBP and PWV . A significantly negative correlation was detected between PTH and AP, cSBP and cAP . The only parameter which has correlation with CaXP product was PWV . There was not any significant correlation detected between arterial stiffness parameters and serum calcium level as well as 24-hour urine calcium excretion.We performed a linear regression analysis to detect independent variables to predict PWV. Since PWV does not distribute normally, we performed a logarithmic transformation for linear regression analysis. According to the univariate analysis result, we included age, BMI, serum low density lipoprotein cholesterol (LDL-C) and serum phosphorus levels to investigate whether such parameters are independent variables to predict PWV. We detected according to the multivariate linear regression analysis that age and serum phosphorus levels were independent predictor variables for PWV  .We detected that PWV which indicates arterial stiffness as well as central and peripheral blood pressures were significantly higher in the patients with hypoparathyroidism. Furthermore, we also detected a positive correlation between PWV and serum phosphorus level, CaXP product; and age and serum phosphorus levels were the only independent variables which predict PWV.Hypoparathyroidism presents with hypocalcemia and hyperphosphatemia similar to chronic kidney disease of which secondary hyperparathyroidism is detected ,5. HyperThere are very limited number of studies focusing on hypocalcemia-hyperphosphatemia associated with hypoparathyroidism on cardiovascular system. Meena and cols. compared intima-media thicknesses of carotid artery, aorta and renal artery of 30 patients who were between 20 and 40 years of age and diagnosed with sporadic idiopathic hypoparathyroidism with healthy controls. Intima-media thicknesses of all three arteries were significantly higher in the hypoparathyroidism group when compared with the control group. However, there was not any correlation between intima-media thicknesses of the carotid artery, aorta and renal artery and calcium, phosphorus, CaXP product, vitamin D or PTH values. The most important limitations of their study were limited number of the cases and constricted age range of the patients . AgarwalLiterature screening revealed that there is not any study which compared PWV and blood pressure of the patients with surgical or non-surgical hypoparathyroidism with healthy population. The only study on arterial stiffness in the patients with hypoparathyroidism that we detected in the literature was conducted by Underbjerg and cols. who compared 56 patients diagnosed with non-surgical hypoparathyroidism and 30 patients diagnosed with pseudohypoparathyroidism in terms of BP and PWV. Calcium and PTH level were found higher in the pseudohypoparathyroidism group whereas there was not any difference between two groups in terms of CaXP product and phosphorus level. Although PWV was detected higher in the non-surgical hypoparathyroidism group, there was not any correlation between PWV and CaXP product, Ca and P levels. No difference of systolic, diastolic and mean AP was detected between two groups. Blood pressures were not correlated with CaXP product, PTH, Ca and P levels in the non-surgical hypoparathyroidism; however, a negative correlation was found between PTH level and diastolic blood pressure as well as mean arterial pressure in the pseudohypoparathyroidism group . There aSince calcium levels usually decrease when phosphorus levels increase, we detected that blood pressures and PWV which is negatively correlated with calcium level are positively correlated with phosphorus level. Positive correlation of phosphorus level with SBP, cSBP and PWV in the hypoparathyroidism is completely in line with systolic blood pressure and arterial stiffness increase which are typical hemodynamical outcomes of vascular calcification developed because of hyperphosphatemia. Furthermore, such results obtained in the present study prove togetherness of BP increase and arterial stiffness increase as demonstrated in many studies -29.The findings obtained in the present study indicate that hypoparathyroidism which is not identified as classical cardiovascular risk factor may be accepted as a cardiovascular risk factor when our findings are supported with further studies. Moreover, the positive correlation between PWV and phosphorus level and presence of hyperphosphatemia as an independent predictor for PWV reveal the necessity of protection of the patients with hypoparathyroidism from hyperphosphatemia as much as possible.One of the major studies searching the effect of hypoparathyroidism on risk of cardiovascular disease and mortality was conducted by Underbjerg and cols. in 2018. The aforementioned study conducted in Denmark screened long term health records of 431 patients including 380 (88%) patients diagnosed with surgical hypoparathyroidism and 51 (12%) patients diagnosed with non-surgical hypoparathyroidism to investigate the association between risk of cardiovascular disease and mortality. A significantly positive association was found between mortality and higher phosphorus level and CaXP product whereas there was not any significant association found between hyperphosphatemia and risk of cardiovascular disease. It was shown that there is an association between increase of cardiovascular disease and deep hypocalcemia and frequency of hypercalcemia episodes . InclusiVadiveloo and cols. compared 116 patients with surgical hypoparathyroidism and 106 patients with non-surgical hypoparathyroidism followed for 9 years with the control group in terms of cardiovascular disease risk and mortality. An increase was detected in cardiovascular disease risk and mortality in all hypoparathyroidism groups when compared with the control group. However, it was specified that such risk increase is caused by non-surgical hypoparathyroidism group and there was not any difference between surgical hypoparathyroidism group and the control group in terms of cardiovascular disease risk and mortality . It may Almost a consensus exists on the hypothesis that cardiovascular disease risk and mortality increases in the patients diagnosed with non-surgical hypoparathyroidism. However, the articles in the literature report different results in the patients with surgical hypoparathyroidism in terms of cardiovascular disease risk and mortality. Our study included history of surgery in hypoparathyroidism group by 78.6%; and SBP, DBP, MAP, cSBP, cDBP and PWV were detected higher in the hypoparathyroidism group when compared with the control group. Results of the present study seems to support arterial stiffness and cardiovascular risk increase in the surgical hypoparathyroidism group. The positive correlation that we detected between phosphorus level and PWV may be considered that arterial stiffness increase may be caused by the increase in vascular calcification.We preferred arterial stiffness measurement to detect cardiovascular risk in the patients with hypoparathyroidism. Since validity and reliability of this method was shown in many studies, we also used it to detect cardiovascular risk in some endocrinological diseases in our previous studies -35. IncrOur study has some limitations. Cross-sectional design is one of the limiting factors. Furthermore, we continued with the cases who had high blood pressure during arterial stiffness measurement even those patients were not diagnosed before, considering that possible etiology may be secondary hypertension due to hypoparathyroidism and cardiovascular effects. If such cases were the patients with primary hypertension who were not diagnosed before, they might have increased blood pressure and PWV average of the hypoparathyroidism group. Another limitation is lack of subgroup analysis due to limited number of the patients with non-surgical hypoparathyroidism. The strongest part of the present study was the finding that there was not any difference between two groups in terms of traditional cardiovascular risk factors such as age, gender, BMI, FPG, LDL-C and thyroid function tests.Consequently, we detected an increase of arterial stiffness which is a reliable indicator for cardiovascular disease risk in hypoparathyroidism. We detected a positive correlation between hyperphosphatemia and PWV in the patients with hypoparathyroidism. Furthermore, we also detected that the independent predictor for PWV was phosphorus level. Therefore, the patients with hypoparathyroidism should be closely monitored for phosphorus-calcium balance and development of cardiovascular disease. We believe that our study would guide further comprehensive studies.