Methods: Adult outpatients with mild-to-moderate or severe asthma had accelerometer assessment of DPA. Severe asthma patients who were commenced on mepolizumab had their DPA reassessed after 12 months. Results: For the total cohort (n = 36), daily step count, time in moderate-to-vigorous physical activity (MVPA), MVPA volume and Movement Intensity (MI) were 7806 ± 3823 steps, 123  min, 657 ± 255 MET·min and 1.96 (0.45) m/s2, respectively. All patients met at least one recommendation for DPA but less than half met recommendations for vigorous DPA. Patients on mepolizumab therapy increased daily step count , time in MVPA , MVPA volume  and MI  for the same amount of moving time; lung function, asthma control and health-related quality of life also improved. Conclusions: Analysis of the first national data on DPA in asthma and novel comparison against current applicable guidelines and identified beneficial thresholds showed borderline levels of DPA with room for improvement especially for severe asthma patients. In a non-sedentary cohort of severe asthma patients, mepolizumab conferred significant and meaningful improvements in DPA.For the various asthma-specific beneficial effects of physical activity, daily physical activity (DPA) and the potential of asthma therapies on DPA require better characterization. Hence, we aimed to determine (a) the DPA of asthma patients, and (b) the effect of add-on mepolizumab on the DPA of severe asthma patients.  Asthma is a heterogeneous chronic inflammatory disease of the airways that is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory limitation . With a Following the modern paradigm of other chronic conditions, there is increasing focus on physical activity in asthma. Increasing insights into the nature of asthma and effective therapies have allowed for a paradigm shift towards active lifestyle. Enhancing and achieving normal levels of daily physical activity (DPA) is increasingly considered an important element for successful management and outcomes in asthma. Beyond benefiting all-cause mortality, risk of cancer and chronic disease, health-related quality of life (HRQoL) and other important aspects of general health, physical activity exerts asthma-specific effects. Consistent evidence links higher levels of physical activity with favorable pathophysiological and clinical effects in asthma including improved airway inflammation and hyperresponsiveness, lung function, asthma control, exacerbation rate, and healthcare use . HoweverBiologic therapies are rapidly transforming the management and outcomes of patients with severe asthma. Although severe asthma has a low estimated prevalence of 3–10% in the total asthma population, it represents the most challenging and significant type of asthma by disproportionally affecting high on morbidity and mortality and accounting for a major share of healthcare utilization and cost as well as socioeconomic cost in asthma . In the Therefore, this study aims to determine both (a) the levels of DPA in patients with mild-to-moderate and severe asthma and cross-reference them with current guideline recommendations, and (b) whether mepolizumab add-on therapy improves DPA in patients with severe eosinophilic asthma.The study was conducted in a prospective, observational design. It consisted of two arms of parallel design: (1) the physical activity arm, and (2) the mepolizumab arm. For the physical activity arm, consecutive adult patients with adequately established and documented asthma of any severity who attended the Asthma Outpatient Clinic, “Sotiria” Chest Diseases Hospital were eligible. Eligible patients for the mepolizumab arm were those who additionally met the definition of severe asthma  and pred1), forced vital capacity (FVC) and eosinophil blood count were retrieved from the medical record. All subjects completed the Asthma Control Test (ACT) and the “past 4 weeks” version of St. George’s Respiratory Questionnaire (SGRQ). Patients on the mepolizumab arm also completed the Global Rating of Activity Limitation questionnaire (GRALQ) before and after therapy, and the Global Impression of Change in Activity Limitation questionnaire (GICALQ) after therapy.At the study entry point, the most recent values of forced expiratory volume in 1 s . The MoveMonitor device has a sample frequency of 100 samples/s and a range of −6 g to +6 g and has been extensively validated and used for activity detection and energy expenditure estimation in younger as well as older healthy populations and in chronic obstructive pulmonary disease (COPD), in both ordinary and sedentary conditions ,16,17,182; 9.81 m/s2 = 1 unit of gravitational acceleration g) and daily moving time (min), as provided by the algorithm for all whole-body moving activities . We calculated the daily time spent in MVPA by summing the time in moderate physical activity (3–5.9 METs) and the time in vigorous physical activity (≥6 METs). In order to compare against guidelines for physical activity [DPA was assessed through measurement of daily step count, daily time spent in moderate-to-vigorous physical activity  (min), daily MVPA volume (METs.min), daily Movement Intensity  advise that adults should engage in at least 150–300 min of moderate-intensity  aerobic physical activity throughout the week or do at least 75–150 min of vigorous-intensity (≥6 METs) aerobic physical activity throughout the week or an equivalent combination of moderate-and vigorous-intensity activity , preferably spread evenly over four to five days a week, or every day . When co1, ACT score and SGRQ score as well as associations between all of the DPA parameters were examined using Pearson’s or Spearman’s correlation coefficient, depending on the distribution of the data. Paired samples t-tests or Wilcoxon signed rank tests were used to examine for changes with therapy in DPA parameters, FEV1, ACT score, SGRQ score and eosinophil count. The level of significance was set at p < 0.05.Data were analyzed using the SPSS statistical package v28.0. Normal distribution of the data was checked using the Shapiro-Wilk test. Data are expressed as mean ± standard deviation or median (interquartile range) for continuous outcomes, and as counts and percentages for categorical variables. Independent samples t-tests or Mann–Whitney U-tests were used for comparisons of differences in clinical characteristics and DPA parameters  between patients with mild-to-moderate asthma and patients with severe asthma. Chi-square tests were used for detection of between-group differences in compliance with guideline recommendations. Associations of DPA parameters with FEVA total of 38 patients were enrolled between January 2018 and March 2020. The study was prematurely concluded due to the advent and persistence of the coronavirus disease 2019 (COVID-19) pandemic in Greece. The decision was made for health and safety reasons but also due to the prolonged public mobility restrictions and lockdowns imposed at a national and global level, which could introduce systematic error (bias). Two patients (6%) with mild-to-moderate asthma were excluded due to poor wearing compliance. Thirty-six patients were therefore considered in the analysis for the physical activity arm of the study, of whom 15 had mild-to-moderate asthma and 21 had severe asthma. Sixteen of the patients with severe asthma had eosinophilic asthma and commenced on mepolizumab therapy. Twelve patients successfully completed 12-month therapy and were included in the analysis for the mepolizumab study arm; two patients dropped out due to the worsening of asthma symptoms, and 2 patients were excluded for not following the instructed medication . Of note1 (p = 0.001), ACT score (p < 0.001) and SGRQ score (p < 0.001). All of the patients were on regular therapy with at least a combination of inhaled corticosteroids and long-acting beta agonists.The complete patient characteristics are shown in 2 and moving time 94 ± 43 min. As shown in For the whole patient cohort, the daily step count was 7806 ± 3823 steps; time in MVPA 123  min, MVPA volume 657 ± 255 MET·min, MI 1.96 (0.45) m/s1 . Daily MI (but not any of the other DPA parameters) associated with ACT score . There were no associations between any DPA parameter and SGRQ score . There were strong associations between daily step count, time in MVPA, MVPA volume and MI and moving time .For the whole patient cohort, there were significant associations between DPA and FEVThe percentage of all patients who met current recommendations for moderate, vigorous or combined moderate and vigorous daily physical activity was 100%, 42% and 100%, respectively, without between-group differences .2, FEV1% pred. 68.6 ± 26.5; ACT score 15 (5); SGRQ score 58.8 (34.5) on the mepolizumab arm showed significant increase in daily step count , daily time in MVPA (from 97(70) to 117(64) min, p = 0.003), daily MVPA volume  and daily MI (from 1.72 (0.50) to 1.83 (0.48) m/s2, p = 0.003) (p = 0.906).After 12-month therapy, the 12 patients  . There w1 , ACT score  [p = 0.004) [p < 0.001), but not eliminated.Patients also exhibited meaningful improvement in FEV= 0.003)  and SGRQ= 0.004) . There w2 (6%). This accelerometer-derived improvement matched self-reported improvement in DPA. Clinically significant improvements also occurred for lung function, asthma control and HRQoL.In this study of patients with moderate-to-severe and severe asthma, the levels of DPA are deemed borderline satisfactory. All the patients met at least one recommendation for DPA but less than half met recommendations for vigorous DPA and there was space for improvement in all the aspects of DPA, especially for patients with severe asthma. Importantly, in a non-sedentary cohort of older patients with severe asthma, mepolizumab increased meaningfully daily step count by 646 steps (9%), time in MVPA by 20 min (20%), MVPA volume by 87 MET·min (17%) and MI by 0.11 m/sIndividually, all patients met at least one of the recommended thresholds for moderate activity, vigorous activity or an equivalent combination of MVPA . HoweverIn terms of the weekly MVPA volume, the performance of our patients (3828 ± 2651 MET·min/week for severe asthmatics and 4323 ± 1707 MET·min/week for mild-to-moderate asthmatics) may seem in excess in relation to the recommended range of 600 to 1200 MET·min/week . HoweverThe daily step count was 7806 ± 3823 steps for the total cohort, 8209 ± 3815 steps for patients with mild-to-moderate asthma, and 7518 ± 3896 steps for patients with severe asthma. There are still no evidence-based public health guidelines recommending a range for steps per day for health benefits to cross-reference our data against. However, the patients with severe asthma only reached the threshold of the “somewhat active” category (7500–9999 steps per day) in a widely endorsed step-defined ladder of physical activity ,32. CrucThe observed increase in DPA with mepolizumab therapy is meaningful as it translates directly to clinical benefits and helps the patients to achieve beneficial goals for physical activity. Strong evidence shows that increments in daily step count as well as duration or frequency of MVPA are associated with a progressively lower risk of all-cause mortality ,34,35,36To our knowledge, the present is the second study to investigate the effect of any asthma therapy on DPA. Carpagnano et al.  found si2 for the total cohort. The MI in m/s2 represents a direct measure of the absolute power of movement. It has been extensively investigated in COPD, where it was shown to be an important aspect of DPA, ranging 1.5 to 1.9 m/s2 depending on the disease severity and study population [2, our patients with severe asthma showed similar performance to generally older patients with at least moderate COPD. Finally, we observed modest associations of DPA with FEV1. This is in line with the finding by Hennegrave et al. [1 associated modestly with daily step count in asthmatic patients. van’t Hul et al. [Herein, we provide the first data on MI in asthma expressed in acceleration units, being 1.96 0.45) m/spulation ,41,42 anpulation . With a e et al.  that FEV m/spulatl et al.  found nol et al. .A review of previous available studies on DPA in severe asthma patients is provided in The main limitation of this study is the small sample size, which reduces the generalizability of results. As suggested by the large mean differences, significant between-group differences in DPA as well as significant associations of DPA may have been overlooked due to the inadequate statistical power. Another limitation is the absence of a control group for the mepolizumab arm to strengthen the results of the study. Our data is from a single center, but our patients are considered representative of a public referral center for asthma and severe asthma in Greece. Finally, the authors would like to acknowledge the negative impact of the COVID-19 pandemic, leading to the premature termination of the study as the public physical activity remains limited compared to the pre-pandemic era. Ongoing recommendations for physical distancing, quarantine measures for people with COVID-19, individual precautionary behaviors and fear of disease are leading to the adaptation of new habits that continue to bear a strong negative impact on day-to-day life physical activity and sedentary behavior worldwide ,50. ThisBy showing meaningful improvements in several parameters of the DPA of patients with severe asthma with mepolizumab therapy, this study adds to the limited available evidence on the effect of biologic therapy on physical activity in asthma. Larger multicenter studies are needed to validate our preliminary results, but the potential of a single, add-on intervention on improving such an important patient-centered and challenging outcome is appealing. For the multiple significant general health- and asthma specific- benefits of physical activity, DPA reflects long-established behavioral patterns that are often difficult to amend even when the disease severity and control improve. Longer-lasting interdisciplinary approaches targeting beyond asthma-specific endpoints may therefore be required to help patients meet recommendations and achieve their maximum potential in DPA and lifestyle pursuits. This is an important consideration not only for patients with severe asthma who plausibly draw the major share of interest, but for all the patients with asthma, who often present suboptimal levels of DPA.


The primary outcome was the neurological status, according to the Cerebral Performance Categories (CPC) scale, upon discharge. Of 119 (48.6%) survivors, 95 (38.8%) had favorable neurologic outcomes (CPC 1 or 2). There was a U-shaped relationship between mean arterial blood gas tensions and poor neurological outcomes. The risk of poor neurological outcome was lowest in patients with the second tertile of mean PaCO2 (30–42 mm Hg) and PaO2 (120–160 mm Hg). In a multivariable analysis, third tertile of mean PaCO2, third tertile of mean PaO2, age, shockable rhythm, out of hospital cardiac arrest, duration of cardiopulmonary resuscitation, and ECPR at cardiac catheterization lab were found to be significantly associated with poor neurologic outcomes. Additionally, hypercapnia and extreme hyperoxia were found to be significantly associated with poor neurological outcomes after ECPR. Therefore, maintaining adequate arterial levels of oxygen and carbon dioxide may be important for favorable neurological prognoses in survivors after ECPR.Our aim is to assess the optimal levels of oxygen and carbon dioxide for the prognosis of favorable neurologic outcomes in survivors after extracorporeal cardiopulmonary resuscitation (ECPR). We obtained the mean levels of PaCO Neurological prognoses in survivors after successful cardiopulmonary resuscitation (CPR) from cardiac arrest are of the utmost importance . To imprAberrant oxygen levels may be associated with poor prognosis after cardiac arrest ,7. HyperIt remains unknown whether the optimal target of arterial blood gas tension after extracorporeal cardiopulmonary resuscitation (ECPR) is similar to that of conventional CPR. In survivors after ECPR, brain recovery may be related to CBF autoregulation, native circulatory restoration, and amount of extracorporeal membrane oxygenation (ECMO) support ,11. HoweThe present research comprised a retrospective, single-center, and observational study. In this study, ECPR was defined as successful implantation of veno-arterial ECMO and pump-on with cardiac compression during index procedure in patients with cardiac arrest ,11. ECPRPatients were 18 years or older and underwent ECPR during hospitalization between January 2010 and December 2018 in Samsung Medical Center. All consecutive patients who underwent ECPR during the study period were included in the study. Of these patients, those aged below 18 years, those with Glasgow Coma Scale (GCS) > 12 on admission to the intensive care unit, those with an inappropriate indication for ECPR, those who had pre-existing severe neurologic disease or damage before arrest including traumatic brain injury, major stroke, malignant brain tumor or severe dementia, and those with insufficient medical records were excluded from the study . This st2) and partial pressure of oxygen (PaO2) in arterial blood gas samples 72 h after ECPR. The sampling interval was determined by the treating physician. The mean PaCO2 and PaO2 were calculated using entire blood gas measurements 72 h after ECPR. The primary outcome was neurological status upon discharge, as assessed by the Glasgow-Pittsburgh Cerebral Performance Categories (CPC) scale (range: 1 to 5) [An expert nurse in the ECMO team was responsible for data collection and all data for all patients receiving ECPR were systematically recorded. We obtained the levels of partial pressure of carbon dioxide  assessed the CPC score by thoroughly reviewing the patient’s medical records. If the investigated scales did not match with each other, the intensivists discussed and corrected the scale.t-test for continuous variables, whereas the Chi-square test was used for categorical variables. We classified the subjects into three groups based on the distribution of the concentration of oxygen and carbon dioxide, using cut-off values between the groups. All possible ranges of oxygen and carbon dioxide were grid-searched to find the cutoffs of both variables. However, since the number of subjects with a low level of carbon dioxide was not sufficient, the cutoff value was fixed at 30 mm Hg, i.e., the generally accepted level [p values of less than 0.05 were considered statistically significant. Statistical analyses were performed with R Statistical Software .Continuous variables are presented as means ± standard deviations, and categorical variables are represented as numbers with subsequent percentages. Data comparisons were carried out using Student’s ed level ,15,16,17In this study, 245 patients were analyzed . The meaAmong 245 patients, 119 (48.6%) survived until discharge from the hospital. Of these, 95 (CPC 1 or 2) had favorable neurologic outcomes while 24 (CPC 3 or 4) had poor neurologic outcomes. The entire distribution of CPC scales is shown in 2 and PaO2, the second tertile groups had the highest number of patients with favorable outcomes , third tertile of mean PaO2 , age , shockable rhythm , out of hospital cardiac arrest , CPR duration , and ECPR at cardiac catheterization lab  were found to be significantly associated with poor neurologic outcomes  and prolonged CPR duration >30 min) were related to poor neurologic outcomes after ECPR . There w min wereThis study has several limitations. First, it was conducted over a long period. In the meantime, post-cardiac arrest management may have evolved, which may have affected the clinical outcomes during the study period. Second, the effects of continuous ECMO flow on cerebral autoregulation were unclear in this study. Lastly, it is hypothesized that extreme hyperoxia may be obtained in ECPR patients with a markedly impaired heart. Extremely high oxygen levels in the right radial artery may mainly be caused by the flow of ECMO. It is unclear whether the poor clinical outcomes were related to hyperoxia itself or impaired heart function. Although the present study provides valuable insights, prospective large-scale studies are needed to evaluate the optimal levels of oxygen and carbon dioxide for favorable neurologic outcomes after ECPR.In this study, we observed a U-shaped relationship between poor neurological outcomes and mean arterial blood gas tensions in the first 72 h after ECPR. However, hypocapnia, normocapnia, hypoxia, and normoxia demonstrated no relationship with poor neurological outcomes, whereas hypercapnia and extreme hyperoxia were found to be significantly associated with poor neurological outcomes. Therefore, it is proposed that maintaining adequate arterial levels of oxygen and carbon dioxide may be important for favorable prognoses of neurological outcomes in survivors who underwent ECPR.


Yet, there are no screening algorithms for this condition. We developed a risk prediction model to guide targeted screening for patients with AS. (2) Methods: We performed a cross-sectional analysis of all echocardiographic studies performed between 2013 and 2018 at a tertiary academic care center. We included reports of unique patients aged from 40 to 95 years. A logistic regression model was fitted for the risk of moderate and severe AS, with readily available demographics and comorbidity variables. Model performance was assessed by the C-index, and its calibration was judged by a calibration plot. (3) Results: Among the 38,788 reports yielded by inclusion criteria, there were 4200 (10.8%) patients with ≥moderate AS. The multivariable model demonstrated multiple variables to be associated with AS, including age, male gender, Caucasian race, Body Mass Index ≥ 30, and cardiovascular comorbidities and medications. C-statistics of the model was 0.77 and was well calibrated according to the calibration plot. An integer point system was developed to calculate the predicted risk of ≥moderate AS, which ranged from 0.0002 to 0.7711. The lower 20% of risk was approximately 0.15 (corresponds to a score of 252), while the upper 20% of risk was about 0.60 (corresponds to a score of 332 points). (4) Conclusions: We developed a risk prediction model to predict patients’ risk of having ≥moderate AS based on demographic and clinical variables from a large population cohort. This tool may guide targeted screening for patients with advanced AS in the general population.  Calcific aortic stenosis (AS) is the most common valvular heart disease in Western countries  and the AS can be readily diagnosed using Doppler echocardiography with accuracy, reasonable cost, and at no risk to the patient. Once reliably diagnosed, it can be treated effectively with interventions that improve survival and quality of life ,7. In thPrevious efforts have not been sufficient to reliably characterize AS risk factors and successfully use them to generate a risk score for general screening recommendations to identify patients with moderate or severe AS. In particular, this was due to the small size of the available cohorts and/or the lack of control groups. Towards this end, we leveraged a large echocardiography database to develop a prediction model to identify patients with AS based on readily available demographic and comorbidity information. This cross-sectional study was conducted at Yale-New Haven Hospital, a tertiary care center in the United States, serving the community of the greater New Haven area and a large fraction of the population of the state of Connecticut . Echocardiography data and electronic health records (EHR) were queried for all patients ≥ 18 years old who had at least one study during the calendar years 2013–2018. These criteria yielded 146,876 studies obtained on 48,524 unique patients. The Institutional Review Board at Yale University approved this study, and individual consent was waived.A series of exclusions led to the final analytic cohort of 38,788 patients, as shown in Patients with ≥ moderate AS were identified using the Doppler echocardiography parameters clinically used to define AS. The most severe value of the following parameters was considered : 2 and or dimensionless valve index (DVI) ≤ 0.5 and or maximum flow velocity (V-max) ≥ 3 m/s, and or mean pressure gradient (PG-mean) ≥ 20 mmHg.Aortic valve area (AVA) ≤ 1.5 cmCandidate variables included demographics , clinical characteristics , medications , and previous interventions including coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), defibrillator and/or pacemaker implantation. Demographics, BMI, history of smoking, and medications were directly abstracted from the EHR. Comorbidities and interventions were queried in the form of ICD-10 codes .Distribution of patient demographics, comorbidity, and medications between patients with ≥moderate AS and those with no AS were compared by Student’s t-test for continuous variables and by chi-squared test for categorical variables, respectively. Association between the risk of moderate/severe AS and patient demographics, comorbidity, and medications were evaluated using the multivariable logistic regression. The variables included in the regression model were chosen based on stepwise variable selection, optimizing the Akaike Information Criterion (AIC) value.We evaluated the model discrimination ability using the area under the receiver-operator characteristics curve (AUROC), which characterizes model discrimination and ranges between 0 and 1, with a higher value corresponding to better discrimination. AUROC is the proportion of the times patients with an event were accurately classified to have a higher probability of event within all possible pairs of patients with and without an event. Calibration was characterized using continuous calibration plot.p < 0.05 was considered statistically significant. All analyses were carried out using SAS 9.4 .To enhance clinical implementation of the models in assessing patients’ risk of having the disease and, accordingly, the need for echocardiographic testing, we further developed a simple integer scoring system based on the β coefficients for each predictor variable in the logistic regression models. A two-tailed p < 0.0001), more likely to be males, Caucasian race, with higher prevalence of hypertension, dyslipidemia, coronary artery disease (CAD), pulmonary hypertension, heart block (HB), atrial fibrillation (AF), cerebral infarction, peripheral vascular disease (PVD), chronic kidney disease (CKD), diabetes mellitus (DM), dementia, inability to walk, heart failure (HF), dilated cardiomyopathy, pacemaker, defibrillator, PCI, and CABG and were more likely to be on beta-blockers, CCBs, ACEIs, and diuretics , use of aspirin , use of CCBs , use of diuretics , CABG , CAD , dyslipidemia , pulmonary hypertension , cardiomyopathy , HB , AF , CVD , PVD , CKD , DM , chronic liver disease , history of obesity , pacemaker , and heart failure . The risk of having moderate or severe AS decreased with African American race (AA) , races other than Caucasian and AA  and history of dementia  .The models achieved good predictive discrimination with an AUC of 0.77  and wereThe current lack of clinical tools to facilitate targeted screening of the population for patients with increased risk of ≥moderate AS is concerning given the increasing burden of the disease and its association with poor outcomes when diagnosed late or left untreated. Furthermore, timely intervention in this subpopulation can lead to significantly improved quality of life and survival, and therefore, a reliable screening program for AS would have an impact on patient outcomes. This contrasts with other conditions such as abdominal aortic aneurysm and lung cancer, for which successful implementation of nationwide screening programs led to the mitigation of their consequences ,13,14. GMany of the risk factors that showed the importance in the model are shared by other atherosclerotic diseases such as CAD and PAD. According to the model, the risk of advanced AS incrementally increased after age 40, although fast progression and earlier disease onset have been shown in certain groups, including patients with bicuspid aortic valve and patients with chronic kidney disease ,16. AdvaThe model has the potential to be a valuable tool in clinical practice, given its simplification to an integer (points) system and reliance on variables that are readily available in most EHR systems. Yet, implementation of the model in a clinical setting should start with caution as the model has not been validated in prospective studies. The results of the model do not show a certain threshold at which screening should be recommended. A score of 207–235 (predicted risk of 5–10%) can be used as a threshold in the beginning, and further validating studies can help fine-tune it. Starting with a low threshold is reasonable considering the high prevalence of AS and the safety profile of echocardiography without contrast exposure. Additionally, echocardiography as a screening test for AS can be valuable as a screening test for other diseases that are prevalent in this population, such as thoracic aortic aneurysms, by providing information on aortic size. This study has some limitations. It is a single-center study, which might limit the generalizability of the results, even though the cohort is very large and included patients from nearly all backgrounds. However, the model has not been externally validated, and its implication in clinical settings requires caution until its validity is proven by other studies. The study included all comers with ≥moderate AS and the history of previously diagnosed versus incidental finding of AS is unknown, and the effect of such information on the analysis is uncertain. Finally, the study relied on claims data (ICD-10 codes) to assess the presence or absence of comorbidities, and such data are reported to be subject to over- or under-reporting.We developed a risk model to identify patients aged between 40 and 95 years who are at increased risk of having ≥moderate AS based on demographic and clinical characteristics. Discrimination and calibration of the model were good. This prediction rule may guide the targeted screening of patients at increased risk of having advanced AS.


To evaluate the impact of home-delivered, medically tailored meals and medical nutrition therapy among food-insecure patients following hospitalization for congestive heart failure by comparing clinical outcomes to a retrospectively matched cohort.Patients at high risk for readmission and food insecurity received up to three months of medically tailored meals and medical nutrition therapy after discharge. Pre-intervention and post-intervention weight, body mass index, blood pressure, and dietary intake were assessed. A combination of difference-in-difference and logistic regression models were used to compare changes between cohorts and evaluate impact attributable to the program.Thirty-nine program participants were compared to a matched cohort of 117 unexposed patients. Participants experienced a marginal reduction in body mass index and an increase in systolic and diastolic blood pressure; however, these results were not statistically significant. To determine relevance to clinical cut-offs, logistic regressions were used, demonstrating that exposure to the intervention resulted in higher odds of a categorical reduction in blood pressure (OR: 1.85), though this did not reach statistical significance (95% CI: 0.67–5.32). Pre vs. post trends indicated that more-healthful foods and drinks increased numerically or remained similar to baseline, while less-healthful foods decreased numerically or remained similar to baseline.These findings highlight the need for more longitudinal research on medically tailored meals and medical nutrition therapy interventions using clinical outcomes while setting realistic suggestions for program implementation. This study additionally illustrates the promise of integrating electronic medical record data and matched cohorts into medical nutrition program evaluation within the health sector.The online version contains supplementary material available at 10.1186/s40795-022-00602-y. As the United States population ages, the prevalence of congestive heart failure (CHF) continues to rise . AccordiThe rising prevalence of CHF has been matched by increasing rates of hospitalization. Nearly 25% of patients hospitalized with CHF are readmitted within one month of discharge, , 5, withImportantly, dietary behaviors have been identified as preventable causes of rehospitalizations among patients with CHF . Sodium The Dietary Approaches to Stop Hypertension (DASH) diet, which is high in fruits and vegetables, whole grains, fish and poultry, and low in saturated fats and sodium, has long been implemented in the management CHF , 14, andA further barrier to consumption of heart healthy diets linked to socioeconomic status and malnourishment is food insecurity. Severity of food insecurity ranges across a spectrum of limited access, to insufficient quantity and/or quality of food, to anxiety about having enough food to eat . Food inAn innovative and upcoming strategy to address both food insecurity and barriers to a balanced diet among those with diet-related chronic disease is the provision of medically tailored meals (MTM). MTM delivery consists of home-delivered meals crafted by Registered Dietitian Nutritionists (RDN) that align with the nutritional needs of one’s medical condition . ParticiTo our knowledge, no interventions to date have addressed whether home-delivered meals following discharge may improve nutritional status and clinical outcomes among food-insecure patients with CHF. Hummel and colleagues conducted the first and only known pilot study (GOURMET-HF) evaluating the efficacy of 4 weeks of home-delivered, sodium-restricted meals among patients discharged from a CHF hospitalization . Their iTo address this gap, our safety-net hospital partnered with a community-based organization to provide three months of home-delivered MTM and adjunctive Medical Nutrition Therapy (MNT) to recently hospitalized, food-insecure patients with CHF who were at high risk for readmission. The primary purpose of this quality improvement initiative was to enhance clinical care by helping patients conform to evidence-based dietary recommendations for CHF. As the first pilot study of its kind, we secondarily sought to evaluate the feasibility, safety, and degree of patient engagement in this novel approach to care for CHF. We hypothesized that among those receiving MTM and MNT, intake of foods high in saturated fat and sodium would decrease, fruit and vegetable consumption would increase, and readmission rates would be improved relative to national average Medicare CHF readmission rates. Additionally, we hypothesized that receipt of MTM and MNT and associated dietary improvements would promote physical health outcomes, leading to reductions in weight, BMI, and blood pressure among program participants compared to a matched cohort.Grady Memorial Hospital partnered with Open Hand Atlanta, a social service organization that offers prepared meal delivery and nutrition education programs to citizens of Atlanta with diet-related disease. From May 2019 to July 2020, Open Hand prepared, packaged, and home delivered MTM, defined as meals designed by a RDN that reflect evidence-based dietary guidelines for the management of CHF . In addiThose who completed the intervention in full received 3 home-delivered MTM per day for a total of 3 months. Fresh meals were delivered once per week, or patients could request fresh-frozen options for convenience or storage purposes. MTM consisted primarily of whole grains, fresh fruits and vegetables, fish and poultry, with limited sodium and saturated-fat containing foods. Sodium content was restricted to less than 660 mg per meal and 2,000 mg per day in accordance with American Heart Association (AHA) guidelines . Daily iPatients also received MNT, consisting of three individual sessions with a RDN at baseline and following 6 and 12 weeks of their participation. During these sessions, RDNs educated patients on heart healthy eating behaviors, assessed nutritional status and body weight, and promoted patients’ adherence to evidence-based dietary guidelines for CHF.Patients were recruited from Grady Memorial Hospital, Atlanta’s largest safety-net healthcare system that provides care to low-income and uninsured populations who experience food insecurity at higher rates than those in the greater metro-area . Patientn = 39) and matched patients (n = 117). This study was deemed exempt from review by the Institutional Review Board at Emory University as part of a quality improvement initiative and form of program evaluation. All participants consented for participation in the intervention verbally, as this research involved no more than minimal risk.To provide a more robust analytical sample and a comparison group, this study used an intervention-recipient matched cohort design in which individuals who received MTM and MNT were matched with patients with CHF who were identified through EMR data and did not receive the intervention. Matched patients were retrospectively identified based on biologic sex, age (± 3 years), Community Needs Index (CNI) score , and number of all-cause inpatient admissions (± 2 admissions) in the previous year. For each patient exposed to the intervention, three patients that matched these criteria were identified. To preserve patient privacy, a de-identified analytic data set was created. Therefore, the final analytic sample included all individuals exposed to the intervention for any amount of time  data were used to provide biometric and relevant demographic information recorded as part of a clinic or hospital visit during the intervention period for all intervention participants and matched controls. In addition to the demographic criteria outlined in the matching schema, race and ethnicity were included as covariates in the analyses to account for potential impacts of structural racism and discrimination on health outcomes , 39. BodTo assess daily intake frequencies of foods and beverages, patients who participated in the intervention were asked to complete the FRESH Foods Survey , a validDescriptive statistics, including means, frequencies, and cross-tabulations, were used to assess all individuals’ demographic and biometric characteristics at both pre- and post-timepoints. Difference-in-difference models were used to analyze the effect attributable to intervention exposure by comparing the difference in differences with change in biometrics modeled continuously. The difference in difference approach is commonly used in natural experiments and intervention settings as a means of estimating a causal effect of interest  . In thesAs aforementioned, all biometrics were measured and collected by clinicians and modeled continuously for the difference-in-difference analyses. The difference-in-difference for body mass index is defined as follows:i in hospital j in cohort c (where cohorts represent exposure to the intervention):For individual i refers to participant covariates outlined above. INTERVENTIONj represents intervention exposure, while POSTc indicates the time-point at which the measure was taken (pre-or post-intervention). The interaction term (INTERVENTIONj * POSTc) captures the causal effect of interest .Defined as such, Yijc refers to the biometric outcome of interest. XAdditionally, logistic regressions were used to assess changes in individuals’ BMI and blood pressure categories before and after the intervention. This approach was chosen given that categorization of health outcomes may provide a more clinically relevant or meaningful representation of change. More specifically, logistic regressions modeled odds of categorical improvement in blood pressure such that any reduction from hypertensive or elevated levels pre-intervention to a lower category post-intervention was counted as an improvement. All models were adjusted for age, sex, inpatient admissions, and CNI scores to account for residual imbalance after matching and missingness of data. Our analyses followed the intention-to-treat principle whereby individuals who enrolled in the intervention were analyzed as part of the intervention even if participation ended before completion of the full three months of MTM and MNT. Model estimates are presented with 95% confidence intervals (CI). Statistical analyses were performed using R software . Power estimates suggest that our sample size is sufficiently powered to detect a medium effect (Cohen’s d of 0.5).n = 11), there were few changes statistically significant at the 0.05 alpha level. Changes that were less than an alpha level of 0.10 and |> 0.500| effect size were therefore deemed meaningful changes. All data analysis was completed with SAS software . With a sample size of 11, the probability that the Wilcoxon tests would detect an effect at an alpha level of 0.10 is lower than the conventional 0.8 threshold, suggesting our tests are underpowered.Pre-post changes in dietary variables were assessed using the Wilcoxon signed rank test and by calculating Cohen’s d effect sizes. As expected for an exploratory analysis of a small sample   Table . The dif2 9. kg/m2 vsCompared to matched controls, individuals exposed to the intervention had lower systolic and diastolic blood pressures, on average, at both timepoints Table  and 4. In = 11) showed a statistically significant increase in fruit and milk consumption of 0.71  and 0.66  times per day, respectively  , participants who completed the standardized food questionnaire pre and post intervention  of those enrolled participated in at least all three months of MTM. Our initiative builds upon this prior research by demonstrating the potential positive effects of a longer duration of nutritional support paired with formal nutrition education following discharge for food insecure patients with CHF.The results of this pilot study shed light on the potential impacts of a novel dietary intervention among this particularly vulnerable and under-supported patient population. Our analyses of this MTM and MNT pilot program did not find statistically significant change in weight, BMI, or blood pressure compared to a matched cohort. However, the improvements in our patients’ dietary intake, along with a 90-day readmission rate less than the national average, suggests that MTM and MNT may be beneficial for clinical status and readmission rates among patients at our local hospital who have been recently hospitalized with CHF. To our knowledge, only one other study has assessed the impact of MTM among patients with CHF. The results of this pilot study reinforce those of the GOURMET-HF trial, illuminating that home delivery of MTM is feasible and low risk for patients with CHF, as 82% .While MTM delivery attempts to address food insecurity, unmeasured compounding issues such as poverty, lack of transportation, and lack of adequate housing may persist among many recipients . TherefoThese limitations are balanced by several strengths. These include the enrollment of a predominantly minority and socioeconomically vulnerable sample of individuals frequently left out of research on nutrition interventions for chronic disease. Overall, this study population was representative of the safety-net hospital population from which it was drawn. This study is also one of few to assess healthcare utilization, dietary quality, and biometric and anthropometric outcomes in conjunction. Finally, the retrospective cohort design of the study provided additional control for unmeasured, confounding factors.Future research is needed among a larger cohort of patients to determine the true significance of the clinical and/or dietary changes observed, as well as the long-term impact of this intervention. Food insecurity, perceived quality of life, physical activity, and metabolic markers should also be assessed throughout the intervention and during follow up to elucidate its effects more clearly.In conclusion, the results of the study have implications for the employment of MTM and MNT for food-insecure patients with CHF at Grady Hospital, and possibly beyond. This intervention may help address the significant barriers to heart-healthy diets encountered by this patient population, such as cost, access, and knowledge of appropriate foods, and help promote dietary compliance. While previous research on MTMs has documented lower health-care costs and utilization among recipients , 31, addAdditional file 1:SupplementalTable 1. Demographics for individuals with pre- and post- weight and BMI data.Additional file 2:SupplementalTable 2. Demographics for individuals with pre- and post- blood pressure data.Additional file 3:Supplemental Table 3. Pre-Post Changes in DietaryIntake of Food Groups, Measured inTimes Per Day (n=11).


Objective: To investigate the incidence and characteristics of deep vein thrombosis (DVT) in kidney transplantation recipients and analyze whether the anatomical side of DVT was associated with the side of the transplanted organ.Methods: A single-center retrospective medical record review of patients who received a kidney transplant between January 2004 and July 2019 and who subsequently developed DVT. Only patients who received unilateral kidney transplants were included in the study. Patients who underwent concomitant pancreatic transplants, bilateral kidney transplants, or repeat procedures were excluded.P < 0.05). Patients with ultrasound-confirmed DVT had higher mean Caprini scores than patients with negative duplex ultrasounds (P < 0.5). Approximately 53% of transplant patients with ultrasound-confirmed DVT had a 1:1 correlation of transplant side to the side of DVT. Cohen kappa statistic 0.03 indicated no correlation between the side of DVT and the side of transplant.Results: Of the 2449 kidney transplants performed during the study period, 1482 were included in the analysis . Of 606 duplex ultrasound tests, 115 results confirmed the presence of DVT. The incidence of symptomatic DVT was 4.7%. The most common time of DVT diagnosis was within four weeks after transplantation. Type 2 diabetes, heart failure, acute myocardial infarction, sepsis, chronic obstructive pulmonary disease/abnormal pulmonary function, and being confined to bed were associated with DVT after kidney transplant (all Conclusions: The incidence of DVT after kidney transplant was lower than the incidence reported in the literature. Being confined to a bed may be a risk factor for DVT after transplant surgery. Kidney transplant recipients who had a positive duplex ultrasound had higher Caprini risk assessment scores than transplant recipients who had negative duplex ultrasounds. There was no correlation between the side of the DVT and the side of the transplant. Deep vein thrombosis (DVT) is a well-recognized complication that occurs in patients as an interplay between vascular endothelial injury, stasis of blood flow, and hypercoagulability . DVT remThis work has been previously presented at the following meeting: American Venous Forum Annual Meeting, Amelia Island, Florida, March 3-6, 2020.This single-institution retrospective record review study was approved by the Henry Ford Health System Institutional Review Board - Edsel Board (No. 11971) before its initiation, and the need for informed consent was waived.Patient sample and variablesWe retrospectively queried the transplant database at our quaternary care center for all patients who underwent kidney transplants between July 2004 and September 2019. This list was cross-referenced with the vascular surgery database for patients who had duplex ultrasound for DVT during the same time period. Only patients who received unilateral kidney transplants, which was defined as a unilateral abdominal incision made during the operative course, were included in the study. Patients who underwent concomitant pancreatic transplants, bilateral kidney transplants, or repeat procedures were excluded. Patient demographics , comorbidities , periprocedural details , and postoperative outcomes (positive duplex ultrasound) were collected from the electronic medical record.DVT identificationDuplex ultrasonography is considered the gold standard for confirmation of DVT. All DVT imaging was done according to a protocol set by our institution. All symptomatic patients  underwent bilateral lower extremity duplex ultrasound. If a common femoral vein (FV) thrombus was visualized or if continuous flow was present, the examination would include the iliac veins. Compression with and without transverse transducer compression in dual screen was done for the lower extremity veins, including the common FV at the level of the junction, proximal FV, profunda femoris vein, mid-FV, distal-FV, mid great sephanous vein, popliteal vein, gastrocnemius vein, posterior tibial vein, and peroneal vein. Spectral waveform demonstrating respiratory variation was done for the common FV, sephanofemoral junction, profunda femoris vein, mid-FV, and popliteal vein. A color Doppler image in the sagittal plane was done if the posterior tibial vein or the peroneal vein were not compressible with transducer compression. Additional images to document areas of suspected thrombus, including the small saphenous vein, soleal veins, and superficial veins, were done when clinically relevant. Upper extremity and central duplex ultrasound results were excluded from the study. Data from the same day of surgery through five years after kidney transplantation were collected from medical records. The time difference between a positive duplex ultrasound to the day of the kidney transplant surgery was used to define the incidence of DVT. The anatomical sides of DVT compared to the side of kidney transplants were used to define laterality. An adaptation of the Caprini risk assessment model was used to define and identify risk factors for DVT development in our patients .Venous thromboembolism prophylaxisAll adult surgical patients received pharmacological prophylaxis for venous thromboembolism (VTE) according to our institutional protocol unless they had a low risk for VTE development or if pharmacological prophylaxis was deemed clinically inappropriate by the provider. It was under the physician’s discretion whether to prescribe VTE prophylaxis . Our protocol uses unfractionated heparin in all kidney transplant patients. Intermittent pneumatic compression devices or graduated compression stockings are ordered at the physician’s discretion.Statistical analysis for DVT lateralityAll analyses were performed using SAS 9.4 . All continuous variables were reported as mean ± standard deviation, while categorical variables were reported as frequency and column percentages. The main question addressed in this study was whether the lower extremity ipsilateral to the transplanted kidney was at higher risk of developing DVT after transplant surgery. Cohen’s kappa statistic was used to test the level of agreement between the kidney transplant incision and DVT laterality variable and to test our hypothesis that the kidney transplant and DVT sides tended to be the same . Statistical significance was set at P < 0.05.Statistical analysis for DVT risk factorsEach risk factor in the Caprini risk assessment model was defined as a categorical variable. Risk factors were compared in both kidney transplant recipients with either positive or negative duplex ultrasounds. Responses for each risk factor were defined as a continuous variable. For responses in each category, univariate two-group comparisons were performed using independent 2-sample t tests if the variables were normally distributed and Wilcoxon signed-rank tests if the variable was non-normally distributed. For each risk factor, univariate two-group comparisons were performed using chi-square tests when expected cell counts were > 5 and Fisher exact tests when expected cell counts were < 5. Statistical significance was set at P < 0.05.Patient characteristicsDuring the study period, 2449 kidney transplants were performed at our quaternary care center. After exclusion of 967 patients who received either concomitant pancreatic, bilateral, or repeat transplants, 1482 patients met the inclusion criteria  had a 1:1 correlation of the transplant side to the side of DVT Table . HoweverFactors associated with risk of DVTThe Caprini risk score was used to assess differences between symptomatic kidney transplant recipients who had positive duplex ultrasound results and patients who were symptomatic but had negative ultrasound results. Type 2 diabetes, heart failure, acute myocardial infarction, sepsis, chronic obstructive pulmonary disease/abnormal pulmonary function, and being confined to bed were significantly associated with having a positive duplex ultrasound test result for DVT .In this study, we showed that the side of kidney transplantation was not associated with the side of DVT development in patients who developed post-transplant DVT. Despite the extensive literature that has addressed the vascular complications associated with kidney transplantation, there is limited information on the laterality of DVT after kidney transplantation, and our study may present a step to fill this knowledge gap. In 1987 a single-center, retrospective study by Allen et al. , the autVery few studies have documented the laterality of DVT development relative to a medical procedure. Motohashi et al.  documentOther studies also observed that patient age and prolonged bed rest were likely significant risk factors for post-transplant DVT ,6. Our sLimitationsThis article is based on a single-center retrospective study, and conclusions drawn from this study are subject to the limitation of retrospective studies. Causal relationships cannot be determined. Prior studies before 1995 looking at the development of DVT utilized different modalities of a gold standard, including venography, compared to detection in our cohort. However, early mobilization in the surgical intensive care unit may also influence a lower incidence of DVT compared to the literature. Finally, this study was performed at a quaternary care center. Many patients were referred to our center for the sole purpose of undergoing kidney transplantation and did not receive further follow-up.The incidence of DVT after kidney transplants in our study was lower than the incidence reported in the literature. Being confined to bed may be a risk factor for DVT after transplant surgery. Kidney transplant recipients who had a positive duplex ultrasound had higher Caprini risk assessment scores than transplant recipients who had negative duplex ultrasounds. Development of DVT was most common in the first month after kidney transplant. The incidence of DVT was not higher on the side of transplantation.


We compared prevalence of kidney disease determined by proteinuria of ≥  + 1 and or kidney disease improving global outcomes (KDIGO) eGFR criteria of < 60 ml/minute/1.73m2. Estimated glomerular filtration rate was calculated using three creatinine-based equations: a) Full Age Spectrum equation (FAS), b) chronic kidney disease-Epidemiology collaboration (CKD-EPI) 2021 equation, c) CKD EPI 2009 (without and with race factor) equation. CKD was determined after followed up at 90 days post enrollment to determine the chronicity of proteinuria of ≥  + 1 and or KDIGO eGFR criteria of < 60mls /minute/1.73m2. We also compared prevalence of CKD determined by KDIGO eGFR criteria of < 60mls /minute/1.73m2 vs age adapted eGFR threshold criteria for defining CKD.This was a prospective study conducted among adult patients admitted on medical wards between September 2020 to March 2021. Spot urine samples were collected to assess for proteinuria and blood samples were collected to assess serum creatinine levels. Kidney disease was defined as proteinuria of ≥ 1 + on spot urine dipstick and or KDIGO eGFR criteria of < 60 ml/minute/1.73mAmong the 357 patients enrolled in the study, KDIGO eGFR criteria of < 60mls / minute determined using FAS and CKD-EPI 2009 without race factor equations and or proteinuria of ≥  + 1 showed the highest overall prevalence of kidney disease at 27.2%.Prevalence of confirmed CKD at 90 days was highest with proteinuria ≥  + 1 and or KDIGO eGFR criteria of < 60mls/min determined using CKD EPI 2009 without race factor Equation (15.1%).2 using FAS and CKD-EPI 2009 without race equations identifies the largest number of patients with CKD. Health care systems in sub-Saharan Africa should calculate eGFR using FAS equations or CKD-EPI 2009 without race equations during basic screening and management protocols.Use of KDIGO eGFR criteria of < 60mls / minute /1.73mThe online version contains supplementary material available at 10.1186/s12882-022-02865-w. TherIn Africa there are no studies comparing of CKD prevalence with the various estimated glomerular filtration rate (eGFR) equations. However in Uganda, a few studies evaluating kidney function have used different eGFR equations in different settings including use of Cockcroft Gault formula and Modification of Diet in Renal Disease (MDRD) in outpatient clinic setting , use of 2 determined using three eGFR equations among patients admitted on medical wards of Masaka Regional Referral Hospital (RRH).These studies have shown a generally high burden of kidney disease in these settings. However, no studies have compared the estimated magnitude of kidney disease by comparison prevalence with different equations in any Ugandan health care facility. Appreciating which equation identifies the largest number of patients with kidney disease or CKD at regional referral hospitals is important as these facilities are first point and sometimes the only point of care for most patients in the country. This study compared the prevalence of kidney disease by proteinuria ≥  + 1 and or KDIGO eGFR criteria of < 60mls/minute/1.73mThis was a prospective study conducted among adult patients admitted on the medical wards of Masaka RRH. This is the largest government hospital in Masaka district, which is located in south central Uganda. The hospital provides both preventive and curative services to over two million people. This hospital has 330 bed capacity with the medical wards using up over 21% of the hospital beds. Medical wards admit patients with various medical conditions including but not limited to anemia, liver cirrhosis, heart failure, malaria, diabetes mellitus and hypertensive disorders. The hospital has no specialized nephrology clinic. However, it runs a daily general medical outpatient clinic, hypertension and diabetes mellitus clinics at least once a week.All adult patients admitted to the medical wards of Masaka RRH between September 2020 and November 2020 were consecutively screened for eligibility to join the study. Patients were enrolled if: 1) were aged 18 years and above; 2) were admitted on medical wards for at least 24 h; 3) provided written informed consent. Patients were excluded if they had no phone contacts to allow follow-up. Details are shown by study patient flow chart in Fig. A detailed questionnaire was administered to all enrolled patients by study personnel. The questionnaire captured information on demographics and risk factors for kidney disease. A venous blood sample and a midstream spot urine sample were collected from all patients using aseptic techniques. Approximately 4mls of venous blood was drawn from each patient into a syringe then placed into a red top vacutainer to assess for serum creatinine. The eGFR were calculated using the chronic kidney disease-Epidemiology collaboration (CKD-EPI) 2021 equation which was used for identifying the patients with kidney disease in the field for sub-sequent follow-up. Given that CKD-EPI 2021 equation has not been validated in Africa, at analysis, eGFR has also been estimated using two additional creatinine-based equations: a) Full Age Spectrum (FAS) equation with specific Q values for African people and b) CKD EPI 2009 (without and with race factor) equation –12, howe2 [Follow up phone call was conducted for all patients meeting the definition of kidney disease, 90-days following the baseline assessment. During the phone call, we established if patient was either still alive or had deceased but without establishing cause of death. Kidney disease was defined as proteinuria of ≥ 1 + and or kidney disease improving global outcome (KDIGO) eGFR criteria of < 60 mls/minute/1.73m2 and or proteinuria of ≥  + 1. Interval censoring strategy was used to determine the study outcomes.Outcome of interest as patients returned for clinic visit after 90 days was either CKD or no confirmed CKD. Clinical end point of the study was: 1) no confirmed CKD, 2) developed CKD. Lost to follow up (LTFU) was defined as going 2 months without attending a scheduled study visit. Chronic kidney disease was defined as ≥ 90 days of KDIGO eGFR criteria of < 60mls /min /1.73m2 and with the age-adapted eGFR threshold definitions for CKD [Prevalence of CKD was also compared between the KDIGO eGFR criteria of < 60 ml/min/1.73m for CKD .The venous blood collected was centrifuged within one hour of collection to obtain serum. Sample analysis for serum creatinine was conducted at Masaka RRH laboratory using Jaffe method traceable to an isotope dilution mass spectrometry . SCr wasP value for the respective relationships. P-value of ≤ 0.05 was considered statistically significant.All data was entered into Microsoft office excel database, then exported to STATA version 13 software package for analysis. Continuous and discrete variables were summarized into medians with interquartile ranges (IQR). Categorical variables were summarized into frequencies and percentages. Proportions and bivariate analysis were used to identify risk factors associated with kidney disease by deriving percentages, odds ratios (OR), confidence intervals (CI) and 2 as calculated by each eGFR equation divided by the total number of patients enrolled. Proportion of patients who developed chronic kidney disease was calculated as number of patients with ≥ 90 days of decreased eGFR of < 60mls/min/1.73m2 as calculated by each equation and or proteinuria divided by total number of patients with kidney disease at baseline.The prevalence of kidney disease was calculated as total number of patients with proteinuria of ≥ 1 + and or decreased eGFR of < 60mls/min/1.73mPrevalence of kidney disease at baseline determined by age adapted eGFR threshold definition was calculated as number of patients having age adapted eGFR definition of CKD divided by total number of patients enrolled.Proportion of patients who developed CKD was calculated as number of patients with age-adapted eGFR threshold definitions of CKD at ≥ 90 days divided by number of patients followed up having kidney disease by age-adapted eGFR threshold definition of CKD at baseline screening.Between September and November 2020, a total of 717 patients were screened for eligibility to join the study, of which 357 (49.8%) were enrolled. Reason for exclusion of the 360 potential patients included lack of a phone contact to allow follow-up 327/360 (90.8%), age < 18 years 32 (8.9%), and 01 (0.3%) refused to consent to participate in the study. The median age of the 357 patients enrolled was 47 (IQR 32–63) years, males constituted 52.9%, and majority of had no or only primary education (75.9%). Details of baseline characteristic are presented in Table 2 calculated by various eGFR creatinine-based equations as shown in details by Fig. 2 vs age-adapted eGFR thresholds for CKD as shown in Fig. Out of 357 patients enrolled, the overall prevalence of kidney disease was compared using proteinuria ≥  + 1 and or KDIGO eGFR criteria of < 60 ml/min/1.73mP = 0.056, previous history of diarrhea or vomiting in past 3 months with OR 2.15 CI 1.33–3.47 P = 0.002 and heart failure with OR 3.52 CI 1.05–11.81 P =  < 0.042. Details are shown in Table 2 in Table Median age of 94 patients with kidney disease was 51 (IQR 35–67) years. Risk factors found to be associated with kidney disease were: age ≥ 60 years with OR 1.8 CI 0.98–3.31 2 determined by CKD EPI 2009 without race factor equation, 11 patients were lost to follow-up, 61 died and confirmed CKD was highest at 13/86 (15.1%) in comparison with other eGFR equations. Details are shown in Fig. Out of 97 patients found to have kidney disease using proteinuria of ≥  + 1 and/or KDIGO eGFR criteria of < 60 ml/min/1.73m2, details are shown in Fig. Overall prevalence of confirmed CKD at 90 days by age-adapted eGFR threshold definition was compared with overall prevalence of confirmed CKD at 90 days by KDIGO eGFR criteria of < 60 ml/minute/1.73m2 using three creatinine-based equations among patients admitted on medical wards in Masaka RRH between September and November 2020. We found that at least two in every 10 patients had kidney disease with KDIGO eGFR criteria of < 60mls / minute /1.73m2 using full age spectrum and CKD-EPI 2009 without race factor equations and or proteinuria of ≥  + 1 showing the highest overall prevalence of kidney disease at 27.2%. These findings in our study are similar to those in a cross sectional study conducted in sub-Saharan African population which also found that adjustment for race did not improve the performance of GFR estimating equations and showed that creatinine-based FAS and CKD-EPI equations performed reasonably well [2 for CKD identifies 0.3–3% slightly more patients with kidney disease than age adapted eGFR thresholds for CKD definition while using all eGFR serum creatinine-based equations. This is similar to findings of a nationwide study which was conducted in Iceland which revealed that using age-adapted eGFR thresholds resulted in a lower CKD prevalence [As the overall burden of kidney disease increases, there is a need for increased screening, early identification and management of cases to prevent adverse outcomes from the disease processes. In this study, we compared prevalence of kidney disease determined by proteinuria of ≥  + 1 and or KDIGO eGFR criteria of < 60 ml/minute/1.73mbly well . Secondlevalence .Traditional risk factors found to be associated with kidney disease included: advanced age ≥ 60 years, hypertension, diabetes mellitus, heart failure, previous use of NSIADS and previous episodes of vomiting in past 3 months. The observed a high prevalence of kidney disease in this study could be due to multiple etiologies since patients were admitted on the medical wards due to various disease conditions. Many of the patients with kidney disease had known risk factors for kidney disease including advanced age ≥ 60 years, diabetes mellitus, previous episodes of vomiting in past 3 months, hypertension and heart failure –17.Irrespective of the original cause of kidney disease, its high prevalence is of concern as this can easily progress to CKD, kidney failure and death in this population. Indeed, the observed prevalence is higher than what has been described previously in Uganda. A study by Nyende et al. in 2020 estimated the prevalence of kidney disease at 2.5% among HIV patients attending an out-patient clinic  and also2 determined by CKD EPI 2009 without race factor performing best with CKD incidence at 15.1% while CKD EPI 2009 with race factor performing worst with incidence of 12.8%. CKD was confirmed basing on evidence of ≥ 90 days of patients having KDIGO eGFR criteria of < 60 mls/minute/1.73m2 and or proteinuria of ≥ 1 + . This agrees with findings of a cross sectional study in sub-Saharan which found that the ethnic factor for CKD-EPI equations was not accurate in African population as it overestimates GFR. The lack of precision due to ethnic factor for the CKD EPI equations was probably because the factors were developed in African American people with different anthropometrical characteristics [The incidence of CKD among patients with kidney disease was also high with one in every ten patients having CKD after 90-days of follow-up with CKD confirmed by proteinuria ≥  + 1 and/or KDIGO eGFR criteria of < 60 ml/min/1.73meristics .The study is not without limitations. Due to cost implications of diagnostic tests in our setting, we studied a relatively small number of patients and study patients were screened once  at the baseline screening of patients. However, screening patients twice would have provided more precise results. Secondly our study was conducted among admitted patients without comparison to healthy community populations.2 using FAS and CKD-EPI 2009 without race equations identified more patients with CKD in comparison with other eGFR equations including the most recently introduced CKD EPI 2021. To promptly identity more patients with CKD, health care systems in sub-Saharan African countries should consider calculating eGFR using FAS or CKD-EPI 2009 without race factor equations during basic screening and management protocols.Prevalence of kidney disease was high. Use of KDIGO eGFR criteria of < 60mls / minute /1.73mAdditional file 1. Prevalence of abnormal kidney function and 90-days outcomes among patients admitted on medical wards of Masaka Regional Referral Hospital in Uganda.Additional file 2. Supplementary Table 1. eGFR determined using different eGFR calculators and definitions of kidney disease. Supplementary Table 2. Shows prevalence of kidney disease at baseline and confirmed CKD at ≥ 90 days using age adapted eGFR threshold definitions by various eGFR calculators.


A Wilcoxon test was used to assess the ordinal data . Results: Nine individuals  aged 57 ± 15.4 years were enrolled. All participants completed the intervention without adverse events. All participants reported positive scores from 4 (very satisfying) to 5 (extremely satisfying) in the safety and feasibility questionnaire. No significant differences were observed in blood pressure and oxygen saturation during the intervention sessions. However, significant increases were observed in heart rate from 82.6 ± 9.1 beats/min (pre-session) to 88.1 ± 6.8 beats/min (post-session) (p = 0.027). Conclusions: LBPP is a safe and feasible rehabilitation tool to use with individuals with chronic stroke.Background: Lower body positive pressure (LBPP) may provide a novel intervention for gait training in neurological conditions. Nonetheless, studies investigating the safety and feasibility of LBPP in patients with stroke are insufficient. Objectives: The purpose of this study was to evaluate the safety and feasibility of LBPP as a rehabilitation intervention for individuals with chronic stroke. Methods: Individuals with chronic stroke were recruited from the community to participate in LBPP gait training three times a week for six weeks. The LBPP’s safety and feasibility were documented throughout the study and at the end of six weeks. Safety and feasibility referred to the incidence of adverse events, complications, the participant and therapist satisfaction questionnaire, and the device limitation including but not limited to technical issues and physical constraints. In addition, blood pressure, pulse rate, and oxygen saturation were taken pre- and post-session. Dependent  Stroke is a neurological disease characterized by chronic major disability worldwide , which cBody-weight supported treadmill training (BWSTT) is recommended for gait training in contemporary rehabilitation practice  and has The physiological response of healthy individuals to LBPP has been extensively evaluated ,15,16,17Nevertheless, studies on the safety and feasibility of LBPP in patients with stroke are lacking. Few studies have assessed the effectiveness of LBPP in individuals with chronic stroke ,22,23,24This was a an exploratory study with a single group receiving the same intervention and measures. The study protocol was approved by the Institutional Review Board at Qassim University (reference number 20-05-04) and registered at ClinicalTrials.gov with ID number NCT04767334.A convenience sample of individuals aged between 18 and 70 years with chronic stroke was recruited through local advertising and word-of-mouth by co-investigators in the Qassim region. All participants signed an informed consent form before testing or data collection. The principal investigator (PI) explained the research project and its risks and benefits to participants upon enrollment. Next, a medical history and demographic questionnaire were completed. Participants were screened by an experienced physical therapist for eligibility to participate in this study. Inclusion criteria were: (1) hemiparesis caused by brain stroke; (2) a minimum of 6 months since the stroke; (3) able to walk a minimum of 10 m with or without assistive device; (4), have no other neurological or orthopedic issues that affect ambulation; (5) functional ambulation ≥3 in the functional ambulation category ; (6) no Demographic and clinical variables: Participant characteristics, self-reported comorbidities such as diabetes and hypertension, self-reported medications, and self-reported history of falls in the previous 12 months, were obtained at the baseline.Safety and feasibility: The safety and feasibility of the LBPP were evaluated by reporting adverse events such as falls or fainting, complications, attrition rate, the participants’ and therapists’ satisfaction questionnaire, and the device limitation. The participants and therapist satisfaction questionnaire items  were assessed using a numerical rating scale rating from 0 (extremely dissatisfied) to 5 (extremely satisfied)  Appendi.In addition, we assessed and reported vital signs including heart rate, blood pressure, and oxygen saturation at the beginning of LBPP gait training and at the end of each session. Heart rate, blood pressure, and oxygen saturation were measured utilizing the Welch Allyn Connex Spot Monitor (CSM)  with a manual cuff applied to the left arm. The participants and therapists were asked to rate their level of satisfaction for each satisfaction questionnaire item at the end of the intervention protocol. The time and number of sessions were documented for each participant.Functional Ambulation Category (FAC): This is a clinical gait assessment that categorizes walking ability into six levels based on the amount of physical support required, regardless of assistive device use. It ranges from 0 to 5, where 0 indicates that the patient cannot walk  and 5 indicates that the patient can walk without physical support on any surface (independent ambulation) . The FACAfter providing informed consent, participants completed a demographic, medical history, and surgical history form. Additionally, they were evaluated for eligibility.Each participant started by warming up on a standard cycle ergometer for 5–10 min, followed by manual therapy, therapeutic exercises, and LBPP gait training. Manual and therapeutic exercise consisted of passive and active ROM, joint mobilization, passive and active stretching, manual resistance exercise, postural control and balance, and upper extremity control. To use the LBPP, participants wore neoprene shorts with a kayak-type skirt attached at the level of the waist . Then, tFor gait training, all participants walked in LBPP one session a day (for up to approximately 40 min), three times a week, for a total of six weeks. During the gait training, the camera provided video feedback of each foot strike. For each session, before and after the LBPP gait training, vital signs including heart rate, blood pressure, and oxygen saturation were taken. In session one, the LBPP chamber was set to unload 50% of the participant’s body weight. The percentage of the unload decreased gradually by approximately 2% per session in the following sessions. Based on the participant’s capacity, the physical therapist’s support and treadmill speed were evaluated and adjusted accordingly. During the gait training, the participant could stop whenever they needed to.t-test to determine whether there were any significant differences between the two time intervals. Ordinary data such as FAC were assessed using the Wilcoxon test. Differences were considered statistically significant when p < 0.05.The SPSS (Version 28.0) software program was used for all statistical analyses. Descriptive statistics including the means (with standard deviations) and median (with interquartile range (IQR)) were calculated for the demographic variables and main outcome measures. The safety and feasibility of the LBPP gait training were assessed by the reporting of adverse events, complications, attrition rate, participant and therapist satisfaction questionnaires, and the device limitations. In addition, we reported vital signs such as heart rate, blood pressure, and oxygen saturation before and after each LBPP gait training session. Comparisons between the pre- and post-sessions for vital signs were conducted using a dependent n = 1) completed 16 sessions before withdrawing due to cold weather and transportation issues; another participant (n = 1) completed six sessions before withdrawing due to family circumstances; and two other participants (n = 2) completed 12 sessions before withdrawing due to orthopedic problems . The fall and knee pain were not related to the study intervention. Therefore, nine participants completed the 18 sessions and were included in the analysis  aged 57 ± 15.4 year with chronic stroke for 4.8 ± 3.9 years. The height of the participants was 175 ± 16.4 cm, and their weight was 80 ± 11.6 kg. The demographic characteristics of the participants are listed in All participants completed the rehabilitation protocol without adverse events. The participants and therapists reported positive satisfaction scores ranging from 4 (very satisfying) to 5 (extremely satisfying) in the therapist and participant satisfaction questionnaire. Two participants reported that the camera feedback was helpful for gait and posture correction; one participant complained of a noisy sound from the air compressor and the device. The LBPP treadmill’s speed ranged from 0.2 to 2.5 km/h, with an average of 0.83 km/h. The single session during gait training in LBPP lasted an average of 37.95 min. The body weight loading increased by approximately 34% over the treatment period, from 50% to 84% of the body weight.p = 0.034). Furthermore, the blood pressure, pulse rate, and oxygen saturation were documented pre- and post-session. Statistical analysis showed no significant differences in blood pressure or oxygen saturation (p < 0.05). The average blood pressure-systolic remained unchanged from the pre-session with a value of 143 ± 23 mmHg to post-session 141 ± 26 mmHg (p = 0.46). Similarly, the average blood pressure-diastolic remained unchanged from the pre-session with a value of 79 ± 2.9 mmHg to the post-session 78 ± 4.3 mmHg (p = 0.43). The average oxygen saturation pre-session value was 96% ± 1 compared to the post-session value of 95.2 ± 1 (p = 0.065). However, there was a significant increase in the pulse rate from 82.6 ± 9.1 beats/min (pre-session) to 88.1 ± 6.8 beats/min (post-session) (p = 0.027). There was a statistically significant difference in FAC before  and after  intervention . However, in the literature, attrition rates of 30–70% are often reported, especially when the study design is a longitudinal study over a period of time [This study monitored the cardiovascular responses pre and post each session. Heart rate and blood pressure are common cardiovascular response measures used to assess safe exercise intensity . In thisThe drawback of LBPP technology is that the therapist cannot provide manual cues to the patient’s lower extremity during gait training. Additionally, LBPP is not provided with a harness to support patients who have weaker lower extremity muscles and cannot stand in the device. Moreover, the transfer getting in and out of the device usually requires two therapists to assure the safety of patients with hemiparesis. This current study confirmed that stroke survivors can be trained on LBPP. This is, to the best of our knowledge, the first study that formally investigated the safety and feasibility of LBPP in chronic stroke. LBPP provides the patient with intense, repetitive gait training over an extended period that leads to task-specific rehabilitation. This study suggests that using LBPP might be a good decision in rehabilitation practice. It can provide the patient with higher doses of training with minimal assistance from a single therapist, which is usually sufficient. However, further studies with a larger sample size in the stroke population are needed to confirm our findings.There were a few limitations to the current study including the relatively small sample size, which would have made it difficult to generalize the findings. Additionally, our small group was not homogeneous in disease duration or severity, which likely influenced our findings. Moreover, because our participants were, on average, community ambulators, our sample was probably not representative of all stroke patients. The LBPP requires individuals to be ambulatory; therefore, only individuals with stroke who are able to stand and walk can be trained. Further explorations of the effects of LBPP on mobility and balance function are warranted. Moreover, all participants were in a chronic stage of stroke, so further research should examine the cardiovascular and metabolic response in individuals with subacute stroke.In summary, the current study showed that LBPP is safe and feasible to use with individuals with chronic stroke. Cardiovascular responses were stable and within the normal limit during pre- and post-walking exercise on the LBPP. Further investigation of the LBPP should be evaluated in a variety of neurological conditions such as spinal cord injury and multiple sclerosis.


Of these, an identified locus with lead single nucleotide variant (SNV) rs140804918  on chromosome 7 was most promising due to its close proximity to HGF, a gene known to be involved in kidney development. Based on their known molecular functions, both KCTD20 and STK38 could explain the suggestive significant association with lead SNV rs148413365 on chromosome 6. Our findings need replication in an independent cohort of CSFK patients before they can be established definitively. However, our analysis suggests that common variants play a role in CSFK aetiology. Future research could enhance our understanding of the molecular mechanisms involved.Congenital solitary functioning kidney (CSFK) is a birth defect that occurs in 1:1500 children and predisposes them to kidney injury. Its aetiology is likely multifactorial. In addition to known monogenic causes and environmental risk factors, common genetic variation may contribute to susceptibility to CSFK. We performed a genome-wide association study among 452 patients with CSFK and two control groups of 669 healthy children and 5363 unaffected adults. Variants in two loci reached the genome-wide significance threshold of 5 × 10 Living with a solitary functioning kidney from childhood predisposes to kidney injury later in life, with up to 80% of children with a solitary functioning kidney showing signs of kidney injury at 18 years of age . Even inA congenital solitary functioning kidney (CSFK) is most often the result of developmental kidney anomalies, such as unilateral kidney agenesis (UKA), multicystic kidney dysplasia (MCDK), or kidney hypo/dysplasia (KHD). These anomalies fall within a spectrum of anomalies referred to as congenital anomalies of the kidney and urinary tract (CAKUT), which are thought to partly have a shared aetiology . SeveralTBX5 and a rare variant with a MAF of 0.05 and OR of 7.2 near PTK7 [Environmental risk factors, such as maternal diabetes, overweight, and the use of artificial reproductive technologies, have been shown to play a role in CAKUT aetiology ,7,8. Forear PTK7 . Up to nPatients with CSFK were derived from the AGORA  data- and biobank . This daTwo healthy control populations were used. In 2011, 39 Dutch municipalities selected random samples of 150 or 300 inhabitants born between 1990–2010 for the AGORA data- and biobank. These children and their parents were invited to participate in AGORA via regular mail. Over 2000 families filled out a questionnaire, while mothers and children from a subsample of 748 families also donated a saliva sample for DNA isolation. Due to this relatively small control population available in the AGORA data- and biobank, we included a second control population of 6468 participants who donated blood samples for the Nijmegen Biomedical Study (NBS) . NBS is Genotyping of all patients’ DNA samples was performed by deCODE genetics  using Infinium Global Screening Array deCodeGenetics_V3 , which contains variants present on the Infinium Global Screening Array (GSA) v3.0 BeadChip as well as 50,000 high-quality markers from the OmniExpress bead chips in order to make data derived from these two chips more compatible. The AGORA controls were genotyped using Infinium Global Screening Arrays, while the NBS controls were genotyped using OmniExpress bead chips .https://www.cog-genomics.org/plink/2.0/ accessed on 30 July 2021) [p-value < 1 × 10−10 (for patients) or <1 × 10−6 (for controls), or a MAF < 0.01. Samples were removed if the call rate was <98%. We used the Kinship-based INference for Gwas (KING) toolset to check family relationships within the cohort and to remove individuals related up to the 3rd degree [Quality control (QC) was performed separately for all three cohorts using the PLINK toolset (ly 2021) . First, d degree . Before imputation, the datasets containing patients and controls were merged. We decided to use a two-stage approach for the analyses. Since the patients and AGORA controls were genotyped using similar chips, we started our analyses with the patients and AGORA controls. Due to a limited number of controls, however, the power to detect an association in this dataset was limited. We had 80% power to detect variants with an allelic OR of 3.2 for a MAF of 0.05, an OR of 2.5 for a MAF of 0.10, and an OR of 2.1 for a MAF of 0.25 with genome-wide significance. In contrast, the NBS cohort had more power given the higher sample size , but could be more prone to array-specific batch effects.n = 524,412 in the AGORA cohort and n = 207,692 in the NBS cohort). Genotypes of the samples were phased using Eagle (v. 2.4.1) and imputed using Minimac (v. 4) with 1000 Genomes Project Phase 3 data as a reference panel [To enable this approach, we created two datasets: the patients were merged with the controls from the AGORA data- and biobank to form the AGORA dataset, and the patients were merged with the controls from the NBS to form the NBS dataset. Imputation was based on the overlap in variants genotyped in patients and controls  was used to infer independent genomic risk loci, and we selected loci with at least 5 SNVs showing suggestive significance [https://genetics.opentargets.org/ accessed on 19 August 2022) to estimate relatedness with nearby genes. Furthermore, we obtained information on topologically associated domains from TADKB (http://dna.cs.miami.edu/TADKB/ accessed on 12 September 2022) [https://regulomedb.org/ accessed on 12 September 2022) [https://apps.kaessmannlab.org/evodevoapp/ accessed on 12 September 2022) [Using PLINK, ORs were calculated for each SNV using logistic regression models. Analyses were limited to variants with a Minimac imputation quality score (r2) of 0.6 and a minor allele count of 20 (for patients and controls combined). The first four principal components and sex were included as confounders. Inflation was visually inspected using quantile-quantile (QQ) plots, and results were depicted in Manhattan plots, which were created in Rstudio using the ‘qqman’ package. Variants with a ificance . To furtificance  or, if Gificance . We restificance , checkeder 2022) , while ter 2022)  was useder 2022) .The AGORA data- and biobank contained DNA from 184 prospectively collected patients with a solitary functioning kidney and saliva samples from 660 patients collected for the SOFIA study . For 10 p-value below 1 × 10−5, and 11 genomic risk loci were identified. After restricting to loci with at least five SNVs, six were visualized using LocusZoom and listed in After quality control see  and impup-value below 1 × 10−5. Twenty-four of these loci contained at least five SNVs and were further investigated  and QQplot . Sixteenstigated .p-values  gene  gene A. Moreovvariants . The SNVnception , which anception .p-value of 1.2 × 10−10 in the NBS dataset. The MAF in cases was 0.017, but only 0.002 in the NBS controls and the GoNL database and 0.003 in the AGORA controls, which increases the likelihood of a false positive association. This variant is located in an intergenic region, approximately 500 kbp from the SMIM21 gene, and has a RegulomeDB score of 0.07 , these SNVs had low RegulomeDB scores   C. Theref1)  is generally applied, and replication in an independent cohort is required before an association is established. In our study, two variants reached the genome-wide significance threshold. Unfortunately, we were unable to find an independent cohort with a large enough number of CSFK patients to replicate our findings, which is an important limitation of our study. Although replication in other populations remains needed, the fact that the MAFs of the identified SNVs were consistent across different control populations reduces the chance of type one errors. An important feature of a GWAS is the unbiased testing of many common variants across the genome. This approach has the advantage that it enables the identification of genes or pathways not previously linked to a certain trait. However, it has the inherent risk of false positive results as well. To reduce this risk, a strict threshold for genome-wide significance , but this would have led to insufficient power to identify relevant associations. Although patients with known disease-causing mutations or syndromes were excluded, we were unable to investigate the presence of monogenic causes or pathogenic CNVs in most patients (~75%), which would have increased our ability to identify SNVs involved in CSFK aetiology. A strength of our study was the large and homogeneous study population, including only patients with CSFK due to UKA, MCDK or KHD, which are phenotypes likely sharing a common aetiology. Furthermore, we restricted our analyses to participants with the two most common ancestral backgrounds and were able to use two large geographically matched control populations.Ideally, our analyses would have been further stratified based on subtypes  and the intended foundation of a European Health Data Space will hopefully facilitate such initiatives. −8. Of these, the identified locus with lead SNV rs140804918 on chromosome 7 was most promising due to its close proximity to HGF, a gene of which the role in kidney development could be larger than expected so far. In addition, variants in 30 loci reached the suggestive significance threshold of 1 × 10−5. Of these, SNV rs148413365 on chromosome 6 was most promising as both KCTD20 and STK38 could explain the suggestive significant association based on their molecular functions. Due to the lack of an independent replication cohort, these findings need replication before they can be established, and future research is warranted to enhance our understanding of the molecular mechanisms involved in the origin of CSFK.In conclusion, we identified several variants that reached or approached genome-wide significance in our GWAS of CSFK. Variants in two loci reached the genome-wide significance threshold of 5 × 10