In chronic hemodialysis (HD) patients, intradialytic hypotension (IDH) is a complication that increases mortality risk. We run a pilot study to analyzing possible relationships between optical coherence tomography angiography (OCT-A) metrics and IDH with the aim of evaluating if OCT-A could represent a useful tool to stratify the hypotensive risk in dialysis patients. A total of 35 eyes (35 patients) were analyzed. OCT-A was performed before and after a single dialysis session. We performed OCT-A 3 × 3 mm and 6 × 6 mm scanning area focused on the fovea centralis. Patients were then followed up to 30 days (10 HD sessions) and a total of 73 IDHs were recorded, with 12 patients (60%) experiencing at least one IDH. Different OCT-A parameters were reduced after dialysis: central choroid thickness (CCT), 6 × 6 mm foveal whole vessel density (VD) of superficial capillary plexus (SPC) and 6 × 6 mm foveal VD of deep capillary plexus (DCP). At logistic regression analysis, IDH was positively associated with baseline foveal VD of SCP and DCP, while an inverse association was found with the choroid. In Kaplan–Meier analyses of patients categorized according to the ROC-derived optimal thresholds, CCT, the 3 × 3 foveal VD of SCP, the 3 × 3 mm and 6 × 6 mm foveal VD of DCP and the 6 × 6 mm foveal VD of SCP were strongly associated with a higher risk of IDH over the 30-days follow-up. In HD patients, a single OCT-A measurement may represent a non-invasive, rapid tool to evaluate the compliance of vascular bed to HD stress and to stratify the risk of IDH in the short term. The pathogenesis of this condition remains partly unexplained although dysfunctions of the nervous autonomous system8 and various factors related to the hemodialytic procedure like rapid or excessive ultrafiltration9, excessive reduction in osmolality10 and reaction to the dialyzer membrane or machine tubing, seem to play a key role. Normal response to hypotension implicates various auto-regulatory mechanisms including the stimulation of sympathetic nervous system aiming at preserving blood flow in vital organs. In other districts, protection mechanisms intervene to maintain adequate blood flow to the metabolic demand of the tissues. This phenomenon can be observed, for instance, in renal arterioles, in coronary circulation or in retinal microcirculation13. The observation of ocular microcirculation gives us an exceptional chance to directly evaluate in vivo the reactions of human circulation to stress stimuli. Indeed, the ocular microcirculation is involved in systemic disease and early changes in vascular structures may predict the development of systemic vascular disorders16. Although the study of fundus oculi is mostly employed to assess hypertensive organ damage17, there is now evidence that also systemic hypotension may trigger important vascular changes and even retinal damage as the consequence of local hypoperfusion19. The effects of hemodialysis on choroid and retinal thickness have already been investigated by structural optical coherence tomography (OCT)20 and with the optical coherence tomography angiography (OCT-A)22, a new method for visualizing the retinal vasculature and choroidal vascular network that permits a tridimensional evaluation of vascular features such as vessels density. However, to date, no study focused on the possible clinical impact of frequent hypotensive episodes, as those occurring during hemodialysis, on the retinal structures.Intradialytic hypotension (IDH) is a frequent complication of hemodialysis (HD). It’s associated to a high hospitalization rate and to end-organ damage, which is likely mediated through organ ischemia, and consequently to an increased mortality risk. IDH was estimated to affect one third of patients with a higher incidence in subjects with older age, diabetes and cardiovascular comorbidities, longer dialysis vintage, worst nutritional status or higher body mass indexIn this pilot prospective study, we thus aimed at analyzing possible relationships between various OCT-A metrics and intradialytic hypotension and to evaluate whether OCT-A could represent a useful tool to stratify the hypotensive risk in dialysis patients.22. Blood pressure (BP) was monitored using an automated sphygmomanometer integrated in the dialysis machine, every 20 min during and immediately following the dialysis session. Pre-dialysis blood pressure was measured in the non-access arm at the beginning of HD after 10-min rest with the patient seated in the dialysis chair before placement of a dialysis needle. Post-dialysis blood pressure was measured at the end of the session, 10-min after disconnecting the patient from the dialysis circuit. HD modalities were kept constant during the whole study period23. All the sessions consisted of standard HD using standard dialysis solutions, with bicarbonate buffer. The dialyzer used was a Flexya dialysis monitor . Adequacy of dialysis was assessed using KT/V, calculated as the natural logarithm of the ratio between initial and final urea concentration. Dialysate sodium concentration was the same for all the patients at 140 meq/L and dialysate temperature maintained at 36.5 °C. Mean UF rate for hour never exceeded 0.6 mL/Kg/hour with the clinical endpoint to reach an adequate dry weight.Chronic hemodialysis patients from the Dialysis Unit of the University Magna Graecia of Catanzaro, Italy were screened for eligibility to participate into the study. The study was conducted in agreement with the Declaration of Helsinki for research involving human subjects and was approved by the local institutional review board . A fully informed consent was obtained from all participants. All subjects were on regular renal replacement treatment with a rhythm of 4-h sessions/three times a week, had a stable dry-weight for at least 3 months before entering the study and had achieved a normotensive edema-free state. Exclusion criteria were dialysis vintage < 6 months, recent history of hospitalization for cardiovascular diseases, symptomatic pre-dialysis hypotension and severe cognitive or physical impairmentMeasurement of OCT-A metrics was performed immediately before and after the first hemodialysis session of the week (Monday or Tuesday) at the Medical Retina & Imaging Unit of the Department of Ophthalmology, University Magna Graecia of Catanzaro. All measurements were performed by qualified ophthalmologists (A.C. and V.G) experts in retinal imaging, next to the dialysis unit.Each patient underwent dilated fundus ophthalmoscopy, structural OCT and OCT-A. Ocular exclusion criteria included any other retinal diseases , ocular media opacity, any previous eye surgical intervention or laser photocoagulation in the study eye, poor quality images with significant artefact, inaccurate or incorrect segmentation at the level of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), or subject’s inability to abstain from blinking or movement during image acquisition.24. Decorrelation is a mathematical function that quantifies this variation. SSADA splits the OCT signal into different spectral bands, thus increasing the number of usable image frames, in which each undergoes a decorrelation analysis24. Blood flowing through vessels causes a change in reflectance over time and results in localized areas of flow decorrelation between frames.OCT-A was performed using XR Avanti AngioVue OCTA . This system uses a split-spectrum amplitude decorrelation angiography (SSADA) algorithm and operates at 70,000 A-scans per second using a light source of 840 nm. SSADA detects variations in reflected OCT signal amplitudes between two consecutive scansEn face images were acquired focusing the fovea centralis Fig. .Figure 124. We performed OCT-A 3 × 3 mm and 6 × 6 mm scanning area focused on the fovea centralis. The instrument software automatically segmented OCT-A scans into four en-face slabs: the SCP, the DCP, the outer retinal plexus and the choriocapillaris plexus. In this study we focus on SCP, DCP plexuses. The software detected the perfused vessel structures within an inner offset at − 3 to − 15 μm from the inner limiting membrane (ILM) for the evaluation of SCP and within an inner offset at − 15 to − 70 μm from the ILM for the DCP. The instrument software calculated automatically vessel density (VD) of SCP and DCP in the whole image, foveal and parafoveal zone and it also calculated automatically the foveal avascular zone (FAZ) area expressed in mm2 in the Retina plexus. VD was defined as the percentage of blood flow signal within a defined area. Foveal zone VD was defined as the area with a diameter of 1 mm; parafoveal zone VD was defined as the area with a diameter of 3 mm. For each patient were collected the following parameters: SCP VD and DCP VD of whole image, foveal and parafoveal zone and FAZ for both OCT-A 3 × 3 mm and 6 × 6 mm scans. Structural OCT was performed using RTVue OCT , a high-speed and high-resolution spectral domain OCT device with central wavelength of 840 nm, scan rate of 26,000 A-scans/s, and axial resolution of 5 μm. In this study we were used horinzontal B-scan images centered on the fovea to manually measure central choroidal thickness (CCT) at the fovea: the vertical distance between the hyperscattering retinal pigment epithelium layer and the chorioscleral interface was measured manually using a software caliper built into the custom-made OCT image viewer. The three-dimensional macular scan protocol set to 7 × 7 mm containing 101 horizontal line scans each consisting of 513 A scans were used to calculated automatically central retinal thickness (CRT). All measurements were replicated in both eyes of the same patient and, if successful, a weighted mean of the two values was computed for each parameter and used for analysis.Each scan consisted of 304 × 304 A-scans with two consecutive B-scans at each fixed position. To reduce motion artifacts, each scan consisted of one orthogonal horizontal and vertical scan25.After the baseline assessment, patients were prospectively followed up to 30 days and any hypotensive episode occurred during the correspondent ten dialysis sessions was recorded. Intradialytic hypotension episodes were defined as systolic blood pressure drop during dialysis greater than 20 mmHg or a decrease in mean arterial pressure of 10 mm Hg during dialysis with symptoms such as dizziness, headache, confusion, nausea, sweating requiring nurse intervention considering always a nadir systolic pressure < 90 mmHgThe analyses were performed using the SPSS package , the MedCalc Statistical Software (version 14.8.1) and the GraphPad prism software .Data were presented as mean ± SD for normally distributed values (at Kolmogorov–Smirnov test), median [IQ range] for variables with skewed distribution or frequency percentage. Differences between groups were determined by the unpaired T-test for normally distributed values, the Mann–Whitney U test for non-parametric values and the chi-square followed by a Fisher’s exact test for frequency distributions. Pre-post dialysis variations of retinal parameters were analyzed by a paired-T-test or by a Wilcoxon signed-rank test for non-parametric values.26. In addition, the Pearson (R) correlation was used to test correlations between such parameters and the absolute number of intradialytic hypotension episodes in each patient. A Receiver Operating Characteristics (ROC) analysis was employed to calculate the area under the curve (AUC) for every retinal parameter significantly associated with the outcome at bivariate logistic regression. AUCs were compared by a non-parametric approach. The best cut-off values were computed by the Youden index. Kaplan–Meier curves considering the time to the first intradialytic episode were generated for patients with retinal parameters above or below the optimal, ROC-derived threshold and compared by a Log-Rank test28. All results were considered significant if the p value was ≤ 0.05.Bivariate logistic regression analyses were performed to establish significant predictors of intradialytic hypotension among retinal parametersThe source population consisted of 35 chronic haemodialysis patients. After the initial screening, 15 patients were excluded because refused to participate or due to the presence of significant retinal or ocular alterations hampering the reliability of measurements in both eyes. The final study cohort included 20 prevalent patients with a total of 35 eyes being correctly analyzed. The overall intra-patient concordance of measurements between the two eyes was very high for all parameters (R ranging from 0.899 to 0.995). Mean age of patients was 63.7 ± 11.4 years and the majority of them were male (69.2%). The median dialysis vintage was 25 months (IQR 12–41). Only 20% of patients were diabetics and the prevalence of cardiovascular comorbidities was relatively low (4.6–33%). Conversely, almost all patients (89.7%) were on anti-hypertensive treatment. Table All OCT-A metrics were measured before and after a single hemodialysis session. Overall, the majority of parameters remained unchanged at dialysis end, a significant reduction being noticed only for central choroid thickness , 6 × 6 whole VD of SCP  and 6 × 6 foveal VD of DCP   were registered. All hypotension events were resolved with appropriate therapeutic management and no clinical sequelae. Twelve patients (60%) experienced at least one hypotensive episode (mean 6.08 ± 2.89). At baseline, these individuals were older and had significantly lower systolic and diastolic blood pressure and LDL cholesterol but higher serum ferritin levels as compared with individuals without hypotensive episodes. With respect to retinal parameters, they displayed a statistically thinner choroid (p = 0.04) and a reduced 6 × 6 FAZ (p = 0.03) but a larger 3 × 3 and 6 × 6 foveal VD of SCP , as well as a larger 3 × 3 and 6 × 6 foveal VD of DCP . No statistical differences were noticed with respect to other parameters. Table Pre-dialysis OCT-A metrics were tested separately into a bivariate logistic regression analysis to find possible associations with the occurrence of intradialytic hypotension. As summarized in Table The diagnostic capacity to identify patients with intradialytic hypotension episodes was tested by ROC analyses for each parameter significantly associated with the outcome at logistic regression. The AUC for 3 × 3 foveal VD of SCP was statistically not significant. Conversely, the AUCs of CCT, 3 × 3 foveal VD of DCP and 6 × 6 foveal VD of SCP and DCP were all significant , although not different from each other  bioavailability and inducing systemic inflammation39. In IDH patients, the response to hypotension in single vascular districts aims at re-establishing a stable blood volume after fluid excess removal but these mechanisms are often inadequate. Interestingly, pre-dialysis choroid thickness showed an impressive ability to predict the occurrence of IDH, as showed by both diagnostic and survival analyses. Dysregulation of ocular blood flow was deeply studied and observed in diabetic retinopathy with significant neuronal and glial changes leading to a reduction in the functional hyperemia response and in basal blood flow40. Our findings could therefore be interpreted as a typical morphological adaptation of vascular bed in certain patients, suggesting that OCT-A could represent a surrogate, non-invasive way to evaluate autonomic vasomotor function in dialysis patients.Currently, OCT-A and analytic softwares have facilitated automated and manual processing of macular perfusion dataIn our analysis, also VD of DCP and SCP plexuses in foveal shots predicted the occurrence of hypotensive episodes.37, also predicting cardiovascular mortality42. Differences in retinal vessels density in the IDH group could also reflect endothelial dysfunction. In normal subjects the reduction of systemic blood pressure results in the constriction of pericytes and reduction in blood flow to choroidal and retinal capillaries mediated by oxidization and nitration stimuli46. Reduction in ocular blood pressure causes the release of vasodilator factors such as adenosine47 and N-methyl-D aspartic acid48.Differently from choroid, retinal circulation is similar to brain circulation but lacks of autonomic innervation. The capillary unit consists of a continuous endothelium and intramural pericytes. Structural retinal changes are known as early indicators of the presence and severity of coronary artery disease49 recently showed that a drop of ocular perfusion pressure under 80 mmHg, consequent to systemic hypotension, activates vasodilatory mechanisms able to maintain retinal blood flow. Feedback autoregulation was blunted by the administration of L-NAME (N omega-nitro-l-arginine methyl ester) a well-known inhibitor of nitric oxide synthase (NOS) used to show endothelium-dependent relaxations of arteries50. Maintenance of blood flow patency is age-related51. In this context, uremia was often considered a model of accelerated aging52 and serious vascular dysfunction. Exposure to the uremic toxic milieu and repetitive episodes of hypotension as observed in some HD patients could also lead to loss of this regulation system53.In a healthy animal model, Tami et al.Our study has some strengths and limits that deserve mentioning. The main strength was the homogeneity of cohort, the sequential pre-post dialysis evaluation of retinal parameters and a prospective phase that was long enough to capture a sufficient number of IDH episodes according to validated criteria. The main limit is probably represented by the small, single-centre evaluation and the lack of information on markers able to demonstrate dysregulation of autonomic nervous system. However, despite the limited number of cases analyzed, we reported a significant number of patients experiencing IDHs and a quite high absolute number of episodes over the follow-up period, which allowed to uncover significant associations between retinal parameters and hypotensive episodes at both logistic and survival analyses and to define a strong diagnostic capacity at ROC analyses for some of these parameters. In conclusion, in this pilot study, we found OCT-A as a potential tool to screen and measure the compliance of vascular bed to hemodialytic stress. Larger investigations are needed to confirm whether this approach may represent also an alternative way to stratify patients according to the risk of developing dangerous hypotensive complications in the short-mid-term.


Accurate prediction of the rise of blood pressure is essential for the hypertensive intracerebral hemorrhage. This study uses the hybrid feature convolution neural network to establish the blood pressure model instead of the traditional method of pulse waves.  The pulse waves of 100 patients were collected, and the pulse wave was decomposed into three bell wave compound forms to obtain the accurate pulse wave propagation time. Then, the mixed feature convolution neural network model ABP-net was proposed, which combined the pulse wave propagation time characteristics with the pulse wave waveform characteristics automatically extracted by one-dimensional convolution to predict the arterial blood pressure. Finally, according to the prediction results, 20 patients were treated before the high blood pressure appeared (model group), and another 20 patients with a daily fixed treatment scheme were selected as the control group. P = 0.035). After treatment, the scores of self-care ability of daily life and limb motor function in the model group were higher than those in the control group (P < 0.05). There were 8 cases (13.6%) in the model group and 17 cases (28.3%) in the control group due to the recurrence of cerebrovascular accident (P = 0.043).  In 80 training sets, compared with linear regression and the random forest method, the hybrid feature convolution neural network has higher accuracy in predicting blood pressure. In 20 test sets, the blood pressure error was eliminated within 5 mmHg. The total effective rate in the model group and the control group was 95.0% and 85.0%, respectively ( Drug treatment guided by a blood pressure model based on a hybrid feature convolution neural network for patients with hypertensive cerebral hemorrhage can significantly and smoothly reduce blood pressure, promote the health recovery, and reduce the occurrence of cerebrovascular accidents. Hypertensive intracerebral hemorrhage is a typical cerebrovascular emergency and critical disease in neurosurgery . It is oHowever, multiple causes may induce readmission in the postoperative recovery period. The disability and mortality rates are significantly higher than those of the first bleeding, and the prognosis is lacking . RebleedIn recent years, medical research has shown that cerebrovascular events' timing is closely related to the circadian rhythm of human blood pressure . With thMachine learning has made great progress in the establishment of various prediction models , 14. To A total of 120 patients with hypertensive intracerebral hemorrhage who were hospitalized in our hospital were selected. There were 74 males and 46 females, aged 56 ± 14 years old. The selection criteria were as follows: (1) patients had hypertensive cerebral hemorrhage diagnosed by computed tomography (CT) after admission and confirmed by operation; (2) patients were admitted to the hospital within 3 h after the onset of the disease, craniocerebral surgery was performed within 24 h after the onset of the disease, and the postoperative blood pressure of the patients was above 165/95 mmHg; (3) mental retardation was excluded; and (4) other chronic diseases were excluded.The vital sign signals collected from the medical information system in 80 patients were used as the training sets. The remaining 40 patients were used as the testing sets and were randomly divided into two groups. The established model is verified in 20 patients, and they were treated before the high blood pressure appeared (model group), and another 20 patients with a daily fixed treatment scheme were selected as the control group. There was no significant difference in gender, education level, and course of disease between the two groups.The algorithm flowchart of this study is shown in Remove baseline drift: wavelet decomposition is used to remove the low frequency ECG and PPG parts to achieve the purpose of removing the baselineDivision of cardiac cycle: firstly, the R wave peak of the ECG is chosen as the starting point of the cardiac cycle; secondly, the cardiac cycle of PPG and ABP was divided. According to the time relationship, the first cardiac cycle of PPG and ABP was found from each R wave peak, and the ECG starting point and PPG and ABP segments belonging to the same cardiac cycle were combined; finally, the true systolic blood pressure (SBP) and diastolic blood pressure (DBP) were determined according to the ABP fragmentNoise sample removal: rules are used to remove the cardiac cycle with obvious abnormal waveform shape, such as the long cardiac cycle caused by the wrong division of the starting point in PPG and ABP and the distortion of signal shape caused by equipment acquisitionThe signals used in this study include the electrocardiogram (ECG), photoplethysmograph (PPG), and arterial blood pressure (ABP). PPG is the finger volume pulse wave. The pretreatment includes the following stages:The pulse wave contains rich physiological information. The main characteristic points are pulse wave starting point A, main wave peak B, tide wave starting point C, tide wave ending point D, descending gorge E, and repetition wave peak F .The main wave peak B is caused by ventricular contraction, blood from left ventricular to aorta, reflecting the ability of ventricular ejection and compliance of blood vessels, etc. The peak F of the heavy pulse wave is caused by the diastolic period of the heart; the closure of the aortic valve prevents blood from returning to the ventricle, reflecting the elasticity of the artery and the closing function of the active pulse valve. B and F are the two most important characteristic points in a cardiac cycle. Therefore, B and F are selected as the termination points to calculate PTT and are recorded as PTT-p and PTT-d, respectively, as shown in B is obtained by calculating the maximum position of PPG in a cardiac cycle, and F is obtained by continuous wavelet decomposition of PPG with gaus1 wavelet basis. The first zero crossing point after B is E, and the second zero crossing point is F.This study proposes a new blood pressure prediction model ABP-net, which uses 1D-CNN to automatically extract the waveform features of PPG and predict blood pressure, and solves the problem of feature points being difficult to extract, as shown in ABP-net is a convolutional neural network with mixed features, and the grey identification part is a model constructed with PTT features. In this study, PPG segments of the same cardiac cycle are also added to the network as input. One-dimensional convolution is used to extract the waveform features of the pulse wave, and the full connection layer is used to synthesize and select the extracted waveform features, and then, PTT features are used for blood pressure prediction. The model input contains two types of features: PTT is the traditional numerical feature and PPG is the formal feature . ABP-net effectively integrates numerical features and formal features, which provides a new idea for using different types of features to model together, and improves the effectiveness and accuracy of the model by using the association between the two types of features and the output. ABP-net contains a variety of processing modules, and the dotted part is the residual structure.μi(x) be the x-th node of the i-th feature map at input and N the number of input feature maps, vj(x)  the x-th node of the j-th feature map at output and M the number of output feature maps, then Conv-1D is operated as follows:ki,j is the convolution kernel, connecting the two feature maps ui and vj, the length of the convolution kernel is K, S is the sliding step of the convolution kernel, and bj is the bias.The input-output feature maps in Conv-1D are all 1-dimensional; for a single sample, let B = {x1, x2, ⋯, xn}  and the algorithm be as follows:μB is the expectation of sample set B, σB2 is the variance, yi is the result normalized to batches of xi, and γ  and β  are parameters to be learned, determined by training. When used in the 1-dimensional convolution section, set B is the set of values over all positions of that feature map for all samples of that match on the same feature map.BN solves the problem that the distribution of inputs at a certain layer in a deep network changes due to previous changes in network parameters. Let a batch be The activation function enables the model to obtain nonlinear modeling capability, and the ReLU functiondoes not cause a gradient disappearance problem and is computationally simple, making the model forward computing faster.Pooling can reduce feature dimensionality while acquiring the main information in a feature map and is divided into two types, maximum pooling and average pooling.Pooling of maxima:Pooling of means:pi is the result after pooling of eigenvectors ui, K is the pooling window size, and S is the window sliding step.The other modules are the traditional neural network modules, FC is the fully connected layer, and AVG is the input format that is needed to convert the output of the convolutional layer into a fully connected layer with the method of averaging.y =  be the real output of blood pressure and n is the size of a batch. In this study, batch gradient descent method is used to train the model and optimize the MSE.Model training is to update the network parameters iteratively to make the loss function converge to the global minimum in the training set. ABP-net is a regression model with blood pressure as the output. The loss function is defined as the mean square error (MSE). Let Patients in the control group received the routine blood pressure control measures: antihypertensive drugs three times a day and the rehabilitation did not control the time. The observation group used the model-predicted blood pressure increase pad to give targeted treatment. This seems to be a routine treatment after this.Medication control: the patients adopted the best medication time according to the physiological rhythm: three times per day at 6:00, 15:00, and 22:00; two times per day at 6:00 and 22:00; and one time per day at 6:00Early limb function training: the training time of patients was based on the diurnal variation of blood pressure and avoided the peak time of blood pressure. Generally, they were selected from 6:00 to 7:00, 14:00 to 16:00, and 19:00 to 21:00. The blood pressure peak period was reduced, the activity was moderate, and the rest was increased to prevent the recurrence of cerebrovascular accident due to the further increase of blood pressure after the activity. The limb function training included passive limb movement exercise, active body movement, and daily life self-care activity trainingFollow-up: strengthen follow-up supervision after discharge. Taking the family as the center, the patients can understand the harmfulness of hypertensive cerebral hemorrhage and the importance of continuous medication and limb function training, improve the medication compliance of patients, teach the sense and family members to measure blood pressure, and enhance the self-care ability of patientsAccording to the circadian rhythm fluctuation of blood pressure in patients with hypertensive intracerebral hemorrhage, the model group was given nursing intervention measures such as adjusting medication time and guiding patients' early limb function training according to the circadian rhythm fluctuation of blood pressure. The detailed biological clock control methods were as follows:Via follow-up monitoring for 1 year, the antihypertensive effect and recurrence of the cerebrovascular accident in the two groups were monitored and compared. The Barthel score was used to evaluate the ability of daily living. The Fugl-Meyer score was used to evaluate limb motor function.markedly effective: the systolic and diastolic blood pressure decreased to the normal level or the diastolic blood pressure decreased by 10 mmHg and fell to the normal range; (2) effective: the effective blood pressure decreased significantly, but did not fall to the normal range, or the diastolic blood pressure decreased less than 10 mmHg but returned to normal or the diastolic blood pressure decreased by 10-19 mmHg or the systolic blood pressure decreased more than 40 mmHg; and (3) invalid: the blood pressure drop did not reach the effective index.The blood pressure changes at 6:00, 4:00, 18:00, and 22:00 every day were compared to determine the measurement position, time, and sphygmomanometer, and the therapeutic effect was determined by a specially assigned person as follows: (1) t test; the gender, education level, treatment effectiveness, and readmission rate of the two groups were compared by chi square test.The age, Barthel score, and Fugl-Meyer score of the two groups were compared by For each model, the prediction accuracy of DBP is higher, which indicates that DBP has higher correlation with PTT and PPG. For the traditional regression model, the model constructed by PPG is better than the model constructed by PTT, but the accuracy is lower than that of the ABP-net model, which shows that the ABP-net model is effective for the integration of PTT features and PPG features and has greater advantages than other models .χ2 = 4.444, P = 0.035).The antihypertensive effect of the two groups is shown in P < 0.05). The details are shown in Compared with the data before treatment, the daily life self-care ability and limb motor function after treatment in all the two groups were improved. After treatment, the score of the model group was higher than that of the control group .Eight (13.3%) patients in the model group and 17 (28.3%) patients in the control group were readmitted to the hospital because of recurrence of cerebrovascular accident. The recurrent rate between the two groups was statistically significant (5, and the mortality rate of cerebral hemorrhage patients is 38%~43% [Hypertensive intracerebral hemorrhage is a common primary intracerebral hemorrhage, which is caused by the rupture of blood vessels when blood pressure rises abruptly on the basis of cerebral artery disease caused by hypertension. In recent years, the incidence rate has increased year by year, about 81/10 38%~43% . For pat 38%~43% . In the With the exploration of the physiological and pathological rhythm of hypertensive cerebral hemorrhage and the time rhythm of drug action, it has been recognized that the drug treatment effect of hypertensive cerebral hemorrhage is related not only to the pharmacological effect of antihypertensive drugs but also to the blood pressure fluctuation time rule, the medication time rule of patients itself . With thThe circadian rhythm curve of blood pressure in patients with hypertensive intracerebral hemorrhage is similar to that in normal people, but the overall blood pressure level is higher and the fluctuation range is larger. Even if the blood pressure has decreased after treatment, the rhythm can still exist. At 2:00-3:00 in the morning, it was at the lowest point and then showed an upward trend. After getting up in the morning, it rose rapidly, reaching the first peak at about 8:00-9:00 am and slightly higher at 5:00-6:00 p.m., which was the second peak, and then began to decline slowly. Therefore, the 24 h ambulatory blood pressure monitoring curve showed a double peak and a valley. In the traditional method of administration, the drug was administered by the method of average distribution, three time per day . As the In this study, we applied time nursing, according to the time law of circadian blood pressure changes; the patients with hypertensive intracerebral hemorrhage were given medicine three times per day at 6:00, 15:00, and 22:00; two times per day at 6:00 and 22:00; and one time per day at 6:00. The blood pressure of hypertensive cerebral hemorrhage patients increased at 6:00, and the concentration of drugs in the blood was very low after overnight metabolism. At 6:00, the effective pharmacological actions in the body can be supplemented as soon as possible, so that the peak effect of antihypertensive drugs corresponds to the morning blood pressure peak, which is conducive to the control of morning peak blood pressure. At 15:00, the antihypertensive drug is given before the second peak of the blood pressure fluctuation, which can reduce blood pressure in time and reduce the damage to target organs after the blood pressure rises. The effective blood concentration can be maintained at night by administration at 22:00 and can reduce the incidence of complications.And then, the drug treatment under the guidance of the hybrid feature convolution neural network was used, and the blood pressure prediction model of patients with hypertensive cerebral hemorrhage was established. Using the model to predict the blood pressure increase point of patients, targeted treatment for patients can significantly and smoothly reduce blood pressure, promote health recovery, and reduce the occurrence of cerebrovascular accidents.Early limb function training can promote the reorganization of the central nervous function, significantly improve the body motor function, reduce the degree of damage and disability, promote the recovery of nerve function, improve the quality of life, and reduce the burden of society . AccordiIn summary, mastering the drug treatment under the guidance of a hybrid feature convolution neural network and establishing the blood pressure prediction model of patients with hypertensive intracerebral hemorrhage can reduce the blood pressure of patients with hypertensive intracerebral hemorrhage, promote health recovery, and reduce the occurrence of cerebrovascular accidents. It has very important practical significance to improve the survival quality of patients with hypertensive intracerebral hemorrhage, which is worthy of further clinical investigation.


Uncontrolled hypertension can result in severe clinical conditions such as stroke, chronic kidney disease and congestive heart failure, especially in African American populations. To the knowledge of the authors, the effect of time sequence on blood pressure (BP) using an Automated Office Blood Pressure (AOBP) device has not been documented in an African American cohort. The objective of this study was to investigate the possible influence of time sequence of measurement (pre- and post-physician visit) on BP readings in an African American cohort, in the presence or absence of a Medical Assistant (MA) via AOBP monitoring.A two-phase, single-blinded, non-randomized trial was conducted at MI-based Ascension Providence Hospital with a convenience sample of hypertensive patients. BP readings were taken using both an Omron 907  and a Welch Allyn (WA) Connex Spot Monitor  AOBP devices. Descriptive statistics were generated, and T-tests were performed.In Phase 1, (N = 148), the mean systolic/diastolic readings for the pre-physician visits (141/82 mmHg) were statistically significantly higher than the post-visit readings (134/80 mmHg) (p ≤ 0.02). Post-visit physician readings from either AOBP device did not differ statistically (p = 0.72). In Phase 2 (n = 50), the presence of an MA resulted in significantly higher readings than when an MA was absent, however, the results of Phase 2 also supported the trends for lower BP post-physician visit found in Phase 1.Based on the consistency of these results, a post-physician visit AOBP reading, in the presence or absence of an MA, may provide a more accurate BP measurement to determine whether or not to treat hypertension in African American patients. Hypertension is defined as a systolic blood pressure (BP) greater than 130 mmHg or diastolic BP greater than 80 mmHg or taking medicine for hypertension. It is one of the most frequently encountered conditions in adult primary care, with a higher prevalence and greater disease burden in African American populations.Automated Office Blood Pressure (AOBP) monitoring is a method of obtaining blood pressure with a single or multiple reading automated system allowing patients to rest comfortably prior to measurements being obtained.BP is traditionally measured at the beginning of an office visit, prior to seeing a physician. African American individuals have been historically underrepresented in clinical trials assessing blood pressure diagnosis/treatment, despite shouldering a greater proportion of the overall disease burden.Complicating BP measurement is the fact that the presence of clinic staff while measurement is taken may itself increase BP. Sometimes referred to as “Whitecoat Hypertension,” this can be a common phenomenon associated with overestimation of a patient’s true average BP, leading to difficulties in appropriately diagnosing and treating patient hypertension.The purpose of this study was to determine the effect of time sequence in the measurement (pre- and post-physician visit) of blood pressure in an African American cohort in the presence or absence of a MA. More specifically, the objectives of this study were twofold: 1) to determine the concordance of single vs multiple reading automated BP devices pre- and post-physician visit without a clinic staff  present; and 2. to determine whether the presence of a MA altered the concordance of the AOBP measurements pre- and post-physician visit.Prior to data collection, the study was approved by Ascension Providence IRB. From April 2017 to December 2018 a two-phase, prospective, single-blinded and non-randomized trial was conducted at the Ascension Providence Hospital Academic Internal Medicine clinic.A convenience sample of male and female African American patients who were 18 years and older with a previous diagnosis of hypertension who were attending clinic for a routine visit were recruited and consented. Exclusion criteria included history of end-stage renal disease with an arterio-venous fistula , arm circumference >20 cm or < 7 cm, history of breast cancer with previous mastectomy or upper extremity lymphedema, as the presence of any of these factors could have skewed sample BP readings. All eligible patients coming for their scheduled visits were screened by an MA and asked if they wanted to participate in the study. Once a potential participant was identified, the MA provided a study information sheet. If the patient agreed to participate, a written consent was obtained in the exam room.During the Phase 1 pre-physician visit period (intake), patients were placed in an exam room, feet on the floor, and an initial single measurement BP (“Pre Omron single)” was taken by an MA using an Omron 907  AOBP device. Immediately following their physician visit, two measures were done. First, a series of three unobserved measurements were obtained within a five-minute pre-programmed interval using a Welch Allyn (WA) Connex Spot Monitor  device while the patient was alone in the room. The three readings were averaged (Post WA multiple). Second, this was followed by a final single measurement BP (“Post Omron single”) by the MA. The two post readings were used to determine concurrence between the two devices.All BP measurements during Phase 2 were conducted in the same manner as Phase 1, but on two groups of patients. To determine the possibility of Whitecoat effect, one group had an MA in the room  during the WA device measurements. The second group had the “MA out of the room ” during the automated WA BP measurements. Patients in the MA out group were under the care of one physician and patients in the MA in group were under the care of another physician.In addition to the blood pressure readings, demographic & medical history were abstracted from patients’ charts. This included: age, gender, height, weight, BMI, major comorbidities , cardiovascular disease, smoking, obstructive sleep apnea, and whether or not the patient was receiving prescribed blood pressure medications.SPSS Version 23 . Statistical significance was set at p < 0.05. During Phase 1 and Phase 2, a two-tailed paired Student’s t-test was performed to compare differences in sample patients’ blood pressure readings within a subgroup. During Phase 2, an independent Student’s t test was performed to compare differences between patient subgroups.Descriptive statistics were generated, and inferential statistical analyses were conducted by the second author (NJ) using A total of N = 148 African American patients with a mean age of 59.5 (SD = 13.2 years) were included, 88 (59.5%) of which were female. Patients’ average BMI was 33.4 (SD = 13.5). The sample has documented diabetes as the most common comorbidity, with 47 (32%) patients having this condition. A total of 33 (22%) of patients were smokers, while 10 (7%) had obstructive sleep apnea. As expected, most patients ) were on at least one prescribed BP medication, while 76 (51%) were on calcium channel blocker (CCB) and 69 (47%) were on diuretics as additional medications .The same trends were observed with sample diastolic readings, where the Pre Omron single was higher by at least 1.67 points compared to the Post WA multiple (p = 0.02) and Post Omron single (p = 0.02). The Post WA multiple (80.22 mmHg) and Post Omron single (80.02 mmHg) diastolic readings were not statistically significantly different (p = 0.73).When the two groups  were compared, there was no statistically significant difference by gender (p = 0.25), BMI (p = 0.16), or by comorbidities of diabetes mellitus, coronary artery disease, smoking or hypertension . In addiWhen comparing the two subgroups, a significant difference in all BP readings were noted . For allIn the MA out group, Pre Omron single vs Post WA multiple resulted in a statistically significant difference in systolic (p < 0.01) but not in diastolic (p = 0.21) BP readings. The Pre vs Post Omron single readings yielded a statistically significant difference in systolic (p < 0.01) but not in diastolic (p = 0.25) BP reading. The differences in Post Omron single vs Post WA multiple were not statistically significant for systolic (p = 0.32) but were statistically significant for diastolic (p < 0.01) BP readings.In summary, Phase 1 demonstrated a significant difference between pre- and post- physician visit BP readings, indicating that the sequence of BP measurement could be an important factor. Phase 2, confirmed Phase 1 in that all post - physician measures were lower compared to pre-physician visit BP measures. During Phase 2, patients in both groups exhibited significantly lower post-physician systolic BP readings compared to their pre-physician visit. The diastolic, although trending towards lower post BP readings, did not reach statistical significance. We have concluded that this may be due at least in part to our smaller sample size.In addition, our initial findings indicated that the multiple readings with Post WA multiple were not statistically different when compared to the Post Omron single reading. This may be important since AOBP with multiple reading devices has been correlated with ABPM.ABPM was superior for predicting clinical outcomes.In terms of Whitecoat effect, we found some evidence for this in Phase 2 results in this population of patients. The Whitecoat effect is consistent with what is found in the literature.This information can be potentially beneficial to our clinic and others since most BP measurements are taken at the beginning of the visit. These study findings may help improve accuracy and prevent over or under treatment of hypertension. For example, post-physician AOBP monitoring without an MA present may be useful in African American predominant areas and lead to greater blood pressure measurement accuracy, diagnosis, and improved hypertension treatment.This study has several limitations. We did not randomize the sequence of Omron single and WA multiple device readings during post- physician visit measurements. In addition, although we saw a similar trend between Phase 1 and 2 results, the small number of patients in Phase 2 yielded statistically inconclusive results. Also, age differences between the MA in and MA out subgroups  may have skewed our results.Future studies could include a trial which measures a Pre and a Post Omron single reading coupled with Pre and a Post WA reading. This would be to exclude the possibility that the phenomenon we are observing is related to multiple readings. It is also important to confirm the correlation between the Post WA multiple and Post Omron single readings at the end of the visit. A subsequent RCT to compare end of office visit readings to either home blood pressure readings or 24-hour ambulatory monitoring is also recommended.Based on these study results, measuring a patients’ blood pressure a second time at the end of their office visits may provide more accurate representations of their typical out of office blood pressures. Post-physician AOBP monitoring without an MA present may be particularly useful for African American patients and lead to greater blood pressure measurement accuracy, diagnosis, and improved hypertension treatment.The authors declare no conflicts of interest.


On average, all groups experienced reductions in blood pressure and/or blood glucose of approximately 10% and 20%, respectively. The proportions of patients with their condition controlled also increased. As NCDs remain underfunded and under-prioritized in low-income countries, the integrated program in Kono demonstrates the possibility of improving outpatient NCD care in Sierra Leone and similar settings.This study is an evaluation of the first cohort of patients enrolled in an outpatient non-communicable disease clinic in Kono, Sierra Leone. In the first year, the clinic enrolled 916 patients. Eight months after the enrollment of the last patient, 53% were still active in care, 43% had been lost to follow-up (LTFU) and 4% had defaulted. Of the LTFU patients, 47% only came for the initial enrollment visit and never returned. Treatment outcomes of three patient groups [HTN only ( Health systems in the global south, primarily structured to address acute health problems, are underprepared to address the growing epidemic of non-communicable diseases.We demonstrate an example of an outpatient clinic and improvement in the outcomes of patients with hypertension and diabetes in the first year of its operation.We further recommend that NCDs are prioritized for funding and further integrated with existing longitudinal health services such as HIV.Sierra Leone is a West African country with a population of 7.5 million . It is aAccording to recent estimates, NCDs account for approximately 33% of deaths in Sierra Leone, 14% attributed to cardiovascular diseases, 3% to cancers, 2% to chronic respiratory diseases, 2% to diabetes, and 12% to other conditions [In recognition of the growing NCD epidemic, the Government of Sierra Leone through the Ministry of Health and Sanitation (MoHS) developed its first National NCD Policy and Strategic Plan in 2013 . HoweverAs in many low- and middle-income settings, primary and secondary health care services in Sierra Leone are structured to support patients presenting primarily with acute conditions. The provision of high quality NCD services, on the other hand, requires a comprehensive and continuous care delivery model to allow for patient registration, assessment, treatment, counselling and longitudinal follow-up , 10—a moAffordability presents another challenge for NCD care provision. In Sierra Leone, the MoHS waives user fees under the Free Healthcare Initiative for select populations, such as pregnant and lactating women, children under the age of 5 years, and other vulnerable groups including EVD survivors . NCD patIn light of the NCD epidemic in Sierra Leone, Partners In Health (PIH), an international non-governmental organization, in collaboration with the MoHS, established one of the first integrated NCD clinics at Koidu Government Hospital (KGH) in Kono district in 2018. Kono is located in the eastern part of the country, bordering Guinea, with a population of approximately 506,000, 75% of which live in rural areas .KGH is a public district hospital jointly operated by the MoHS and PIH. It is the only referral hospital in Kono, serving over 90 primary health care facilities distributed throughout the district. The ~ 200-bed facility provides inpatient services such as surgery, deliveries, and adult and pediatric admissions. Outpatient services include HIV and TB diagnosis and treatment, antenatal care, vaccinations, mental health clinic and a general outpatient department. In addition to the patient groups supported by the Free Healthcare Initiative, KGH provides free services to patients with physical disabilities, mental health disorders and other socially or economically disadvantaged persons through the partnership with PIH. Patients enrolled in the new outpatient integrated NCD clinic also received health services free of charge.This study is an evaluation of the initial cohort of hypertensive and diabetic patients enrolled during the first year of the clinic’s operation, conducted through a retrospective chart review. The objectives of the study were to assess patient enrollment and outcomes after 8 to 20 months of follow-up and describe the challenges and lessons learned throughout the implementation process. Despite the increasing recognition of NCD mortality and morbidity in Sierra Leone, there is no published literature on the implementation, management and outcomes of integrated NCD programs. This study aims to inform future implementations of longitudinal NCD care in Sierra Leone and in similar resource-limited settings.The KGH NCD clinic was established in February of 2018 and initially focused on patients with hypertension (HTN) and diabetes mellitus (DM). The clinic was operated primarily by community health officers (CHO) and state enrolled community health nurses (SECHN) under the mentorship of medical doctors (MD) and organized under the task-shifting model. SECHNs registered patients, took and recorded demographic information and basic clinical measurements in patient charts, and conducted lifestyle counseling. Initially, MDs conducted clinical consultations, which included medical history, physical examination, ordering laboratory tests (if needed), and prescribing medications. Overtime, stable patients were handed over to the CHOs, while MDs focused on more clinically complex cases. The clinic was staffed by a combination of MoHS and PIH health workers, but overseen and continuously mentored by PIH doctors. Laboratory tests and dispensing of medications were integrated into the normal lab and pharmacy systems, but financed by PIH. The PIH monitoring and evaluation team provided clerical and data systems support. A limited logic model for the integrated outpatient NCD program is shown in Fig. Patients were enrolled in care if they had been previously diagnosed (in another location) and already on treatment, previously admitted to KGH due to complications from one of these conditions, or after initial screening conducted on specific clinic days. New HTN patients based on the initial screening were enrolled in care if they had two blood pressure measurements ≥ 140/90 mmHg taken at least two minutes apart. New DM patients were enrolled if they had a random blood glucose level ≥ 11.1 mmol/L and diabetes symptoms  or a fasting blood glucose level ≥ 7 mmol/L.During registration, patients received unique identifiers linked with clinical charts, which were maintained and updated throughout their care. During the first visit, CHOs and SECHNs took and recorded demographics and basic clinical measurements, including age, sex, height, weight, blood pressure, and blood glucose level. A clinical consultation followed. Follow-up appointments were scheduled based on the individual patients’ condition. During follow-up appointments, patients’ clinical charts were updated with new basic measurements, clinical notes and laboratory test results, and their prescriptions were refilled free of charge. CHOs and SECHNs also conducted lifestyle modifications counselling via individual and group health talks, focused on dietary advice  and regular exercise.In 2019, the MoHS was in the process of developing NCD treatment guidelines and job aids for use in the government health facilities. We adapted the treatment guidelines from the draft MoHS documents, supplemented by the HEARTS technical package [N = 982) who enrolled in care within the first year of the clinic’s operation . However, 66 patients were considered as ‘discharged’ and excluded in the analysis stage because they had only come to the clinic once (self-referred), had normal blood pressure and blood glucose levels, never received a diagnosis or medications and did not return. The total resulting cohort of 916 patients was analyzed.We initially included all patients  and a maximum of 20 months . Baseline and follow-up data were abstracted from the clinical charts to describe enrollment characteristics and evaluate retention in care and blood pressure and blood glucose control of HTN and DM patients, respectively. Baseline and follow-up measurements refer to measurements recorded at the first and last visit within the study period, respectively. The primary outcomes in the analysis were retention in care and good control of the condition. Other analysis variables included routine metrics recorded in the clinical charts  between baseline and follow-up using a paired sample t-test, with statistical significance determined by a p-value < 0.05. The effects of demographic and clinical measurements on the binary primary outcomes (LTFU and blood pressure or blood glucose control status) were assessed using logistic regression. Data analysis was conducted using R software (version 3.6.1).We tested five available variables as predictors of blood pressure and blood glucose control: sex, age category, BMI category at baseline, controlled blood pressure or blood glucose at baseline, and treatment duration. The same variables, plus controlled blood pressure or blood glucose at follow-up, minus treatment duration were tested as predictors of LTFU in the full cohort Table .The Sierra Leone’s Office of Ethics and Scientific Review Committee approved this study. Informed consent was waived because all data were collected through routine clinical care and de-identified before being retrospectively analyzed.In the first year of operation, the clinic enrolled a total of 916 clients Fig. . InitialThe majority of the overall cohort were female (65%), older than 45 years of age (80%), and overweight or obese (56%) at enrollment. Because the majority of the cohort was composed of HTN patients, the characteristics of HTN and HTN/DM patient subgroups were similar to the overall cohort Fig. , Table 2At the end of the observation period, approximately half of the first year cohort 53%) were still active in care, 43% had been LTFU, and 4% had defaulted . According to a paired sample t-test conducted on the smaller subgroup of patients who had blood pressure measurements at baseline and follow-up (n = 541), on average SBP and DBP decreased by 23.4 mmHg (p < 0.001) and 9.5 mmHg (p < 0.001), respectively. Additionally, the BMI of the HTN patients decreased slightly between baseline and follow-up visits by 1.1 units (p < 0.001).A total of 720 patients in the cohort had HTN diagnosis only. The average systolic blood pressure (SBP) and diastolic blood pressure (DBP) at baseline for these patients were approximately 171 (± 29) and 99 (± 17) mmHg, respectively. At follow-up, both values decreased to 149 (± 27) and 90 (± 15) mmHg, respectively , on average, blood glucose level decreased by approximately 3 mmol/L (p < 0.05). No change in the BMI of the DM patients was observed between baseline and follow-up.A total of 51 patients in the cohort had DM diagnosis only. The average random blood glucose level at baseline for these patients was approximately 16.5 (± 6.6) mmol/L and decreased to 12.4 (± 5.5) mmol/L at follow-up . According to a paired sample t-test on patients who had blood pressure measurements at baseline and follow-up (n = 78), on average SBP and DBP decreased by 19.6 mmHg (p < 0.001) and 5.0 mmHg (p < 0.05), respectively.A total of 96 patients in the cohort had HTN and DM comorbidities. The average SBP and DBP at baseline for these patients were lower than for HTN patients only at approximately 163 ± 28) and 96 (± 15) mmHg, respectively. At follow-up, both values decreased to 146 (± 25) and 91 (± 14) mmHg, respectively . According to a paired sample t-test conducted on a smaller subgroup of patients who had blood glucose measurements at baseline and follow-up (n = 71), on average, blood glucose level decreased by approximately 3 mmol/L (p < 0.01). No change in the BMI of HTN/DM patients in this sub-group was observed between baseline and follow-up.The average random blood glucose level at baseline for these patients was lower than of patients who had DM diagnosis only, at approximately 13.8 (± 5.9) mmol/L, which decreased to 10.8 (± 5.5) mmol/L at follow-up Fig. , Table 2Only controlled blood pressure at baseline was a significant predictor of controlled blood pressure at follow-up in a univariable model , and only for the HTN but not for the HTN/DM patients. None of the tested variables were significantly associated with blood glucose control in any of the patient subgroups. HTN patients who had controlled blood pressure at baseline were also less likely to be LTFU at the end of the observation period as compared to those who enrolled in care with their blood pressure uncontrolled . This association was only observed in the HTN patient population but not in the other subgroups.In the first year of its operation, the NCD clinic grew very rapidly, enrolling over 900 patients. The cohort was comprised of predominantly patients with HTN, women, individuals over 45 years of age, and those classified as overweight or obese according to their BMI. Furthermore, most patients (> 90%) were enrolled in care with their condition uncontrolled. These observations support the underlying assumption that in the early stages of service provision, the target population is that with severe symptoms, prominent risk factors, and better health seeking behaviors. From the limited location data recorded in the patient files, it is also true that in the first year, the clinic was reaching largely the urban and peri-urban population of Koidu town, with fewer patients coming from the district’s interior.According to the most recent census, 506,000 people reside in Kono district, 230,000 adults aged 18 + , there aA recent nationally representative population-based study in Kenya showed that only 15% of individuals with HTN were aware of their elevated blood pressure and only 27% of those who were aware were on treatment . At the In terms of treatment effects, the program demonstrated success among all patient subgroups. Percentage of patients with controlled blood glucose increased from approximately 8% to 22% over an average treatment duration of 36 weeks, considering DM and HTN/DM patients. Other studies conducted in specialized diabetic clinics showed higher rates of glycemic control of approximately 40%; however, these were often patients who had been on treatment for five years or more . The 22–The relatively high LTFU rate (around 40%) in our study was similar to those reported in other early NCD program implementations , 28. ImpOver the first year of the clinic’s operation, many challenges were identified. For example, the rapid increase in patient numbers meant shortages of space, staff, and medications. The small consultation room and few clinicians allotted to the clinic for one day per week meant that patients waited in long queues, were seen in crowded spaces with limited privacy, and had shorter and less frequent appointments than desired. Over time, the clinic was moved to a larger space, increased its staffing, and began operating with increased frequency (two days per week) in order to meet the demand.Another significant challenge is the lack of home-based follow-up to address high LTFU rates. This can be addressed by integrating with the existing community health worker (CHW) program that currently assists HIV and TB patients with medication adherence and accompaniment to the health facility for medication refills, laboratory tests, and clinical assessments. More generally, NCDs could be similarly embedded into the HIV care provision platform as part of an integrated chronic care model. This model has been successfully implemented in several instances, including by PIH in Neno district in Malawi  and as pAn additional area of improvement and integration is the patient record. The existing unstructured paper-based data system consisting primarily of unstructured clinical notes resulted in limited data that could be manually abstracted and analyzed in this study. The use of a single follow-up measurement, resulting in different treatment durations for each patient in the study was a limitation in the analysis. Although we confirmed that treatment duration did not significantly affect any of the variables we analyzed, at minimum, a structured patient card that systematizes the data collected at each visit for a specific condition would allow for more interesting and robust analyses, including multiple observations per patient. In fact, shortly after this analysis, a combined HTN/DM patient card modeled from those used by PIH in Malawi and Liberia, was introduced.Beyond the patient card, an electronic medical record (EMR) is the ultimate goal for any such longitudinal care program. In many countries like Sierra Leone, in the context of vertically-funded programs, patients can be seen in different physical spaces, by different health care providers, and on different clinic days for multiple conditions. An EMR can link the records together and enable holistic treatment of the patient with his/her health information available to all health care providers. Data systems, although rarely seen as such, can underpin the integration of multiple health services for a patient-centered approach.Despite some progress in recent years, NCDs remain underfunded and under-prioritized by health systems of low-income countries that remain focused on episodic care and relief of acute symptoms with weak links up the referral pathway to specialized care and down to communities . ChronicWe showed in this manuscript that an integrated NCD model can work in rural Sierra Leone as part of an NGO-supported program. The PIH model, built on the premise of high-quality free health care, overcomes several barriers, namely lack of financial means to seek care, non-functioning equipment, and an unstable supply of quality drugs . The nex


The cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ΔCBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow.n = 15), patients with asymptomatic severe internal carotid artery stenosis , and patients with acute ischemic stroke  were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol . In a sub-group , mean arterial pressure (MAP) was measured dynamically during the protocol.Transcranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (p = 0.890) but not in patients with AIS  or ICA stenosis ). MAP in AIS patients did not return to baseline values , but in ICA stenosis patients and controls did. Instead ipsilesional but not contralesional CBF was correlated with MAP .After elevated positioning, DCS CBF returned to baseline supine values in controls (The observed associations between ipsilateral CBF and MAP suggest that short HOB position changes may elicit deficits in cerebral autoregulation in cerebrovascular disorders. Additional research is required to further characterize this phenomenon.The online version contains supplementary material available at 10.1186/s12883-021-02179-8. Static cerebral autoregulation (CAR) maintains cerebral blood flow (CBF) during variations of the cerebral perfusion pressure , 2 by moIn the past, CBF responses to the manipulation of HOB position have been employed to monitor a surrogate of static CAR impairment in patients with cerebrovascular disease –20. The The mechanisms underlying these responses are complex, reflecting a combination of factors including static CAR, venous blood return to the heart due to posture change, changes in intracranial pressure and blood volume, mean arterial pressure (MAP), and other neuroreflex mechanisms , 21–23. °) to 30° and from 30° to supine (0°) were not associated with neurologic deterioration, although paradoxical responses, i.e., CBF increase after HOB elevation, were identified in approximately 20% of patients with brain-injury, and obstructive sleep apnea (OSA) syndrome   and did not recover back to its baseline values (p < 0.001) as shown in Fig. n = 15), ΔrCBF was 0.3% , and it recovered back to baseline values (p = 0.890). We have compared the two groups using the data derived from the same protocol (BCN15–17 and the controls of the BCN-study) since the other protocols on ischemic stroke did not have controls. The ΔrCBF was different between the AIS (n = 38) and control (n = 15) groups (p = 0.038).In AIS patients , ΔrCBF was 8.6%  and it did not recover back to its baseline values (p = 0.003) as shown in Fig. n = 15) (BCN-study protocol) and no difference was found (p = 0.082).In ICA stenosis patients  or unilateral ICA stenosis (p = 0.936). Only subjects with optical data available from both hemispheres were included in this sub-analysis (n = 62).The observed ΔrCBF responses did not differ between hemispheres, for example due to the presence of either acute stroke , and a non-significant change of 1.4 mmHg  was observed in ICA stenosis patients , and also in controls, − 1.9 mmHg  , Fig. A significant MAP increase of 2.6 mmHg 0.5, 4.7] was observed in AIS patients  in the early hours (≤ 48 h) from the stroke onset, Fig. p = 0.600) between ΔrCBF and ΔMAP parameters. However, there were no detectable differences in the MAP/CBF association between the two hemispheres of the same patients  possibly due to the high variability in the measurement and limited sample size.In patients with AIS, ΔrCBF measured in the ipsilesional hemisphere was positively associated with ΔMAP as 6.0%/mmHg  . Again, the contralesional hemisphere did not exhibit a similar association being 8.6%/mmHg   between both parameters. This did not imply that there were intra-subject differences (p = 0.682). Similarly, there was no association between CBF and MAP in control subjects (p = 0.605).In patients with ICA stenosis, the CBF changes that were observed on the ipsilesional hemisphere were associated with ΔMAP as 11.0%/mmHg   but not in controls (p = 0.890). This finding is similar to prior observations in patients with moderate and severe obstructive sleep apnea (OSA) [We have identified a significant increase in CBF from the first supine position to the second supine position in AIS and ICA stenosis patient groups (ea (OSA) . This isea (OSA)  has showp = 0.018) which was not observed in the ICA patients nor in the control group (p > 0.05). This raises the question of whether there is a significant impairment of the cerebral autoregulation which may imply a risk situation for the patient. We note that it is also known that AIS itself affects the resting arterial blood pressure if the compensatory mechanisms are damaged [A significant increase of ΔMAP was observed in AIS patients from the first supine position to the second supine position , as well as with the group of subjects with ICA stenosis (p < 0.001). Notably, this association was not detected in the contralesional hemisphere of the AIS or ICA stenosis patients , nor was there an association between CBF and MAP in control subjects (p = 0.605). The question that arises is whether this implies that impaired static CAR is hemispheric. Since the association between CBF and MAP are often considered to be an indication of impaired CAR [We have observed that the CBF changes in the ipsilesional hemisphere were associated with MAP changes in subjects with AIS studied within 48 h after stroke onset  from an on-going study (currently at n = 72 subjects) on a similar population of acute ischemic stroke patients have confirmed that this is true for the patient population too. The minimal changes observed in some individuals are not expected to correlate with MAP. Moreover, the use of different protocols, from different centers, separated over time has increased the variability between studies. For example, the MAP assessment was continuous in a small subset but intermittent in all the others and different instruments were used. One study (PENN05–07) had a further limitation in utility due to lack of blood pressure measurements. We include this study as it provides critical data for the first result in our present analysis: the effect of return-to-supine on CBF. Furthermore, the studies cover a time period of 12 years with different protocols. The clinical care and management has evolved during this period including changes in patient demographics. Furthermore, technology has developed and our methods have also changed in this 12 year period. Despite these differences, importantly, similar results were found across studies which strengthens the results reported in this work. Therefore, our results are encouraging to suggest future multi-center studies with common protocols and similar clinical management at the point-of-care.Our study has several other limitations. Unfortunately, data of ASPECT and TOAST classification is missing in one of the three cohorts. Final infarct volumes were calculated utilizing different imaging techniques and at different time points, which precludes a comparison among patients and cohorts. Even though EtCOhallenge . Our unpThe ΔrCBF increase found in the contralesional hemisphere in our hypothesis generating study needs further exploration. One of the reasons of this result could be caused by small number of subjects compared to the amount of heterogeneity in the results. It is important to note that the result is hemispheric which rules out that the optical data is dominated by systemic changes due to partial volume effects. Future studies could address these findings by relying on the utilizing more recent advances in technology, by combination of DCS with near-infrared spectroscopy and by the so called fast measurements evaluating beat-to-beat hemodynamic changes , 47, 48 Currently, a routine evaluation of static CAR is not utilized in clinical practice for several reasons. Among these are the lack of a gold-standard methodology and the requirement to induce hemodynamic changes. The stimuli utilized by many methods  have issues with safety and patient compliance. HOB manipulations are simpler and safer compared to these methods, even in patients with acute brain injury. In this contribution, we have shown that the increase in correlation between DCS-measured CBF and MAP during serial HOB position changes is a promising protocol to assess static CAR performance in patients with both acute and chronic cerebrovascular disease. Further studies are needed to ascertain whether this information can be used to individualize management of patients with cardiovascular disease.A brief and mild HOB challenge elicits evidence of cerebrovascular autoregulatory deficits. DCS can be used to monitor these changes at the bed-side, and after further validation, may ultimately help to individualize clinical management in AIS.Additional file 1.


Background: Electronic devices for measuring blood pressure (BP) need to go through independent clinical validation as recommended by different authorities, both in general and specific populations. The aim of this study was to assess the validity of the Omron RS6 (HEM-6221-E) wrist oscillometric devices in obese Sudanese patients.Methods: Of 90 obese individuals invited for recruitment, 33 were included in the study, and had their BP at the level of the wrist measured using Omron RS6 and standard mercury sphygmomanometer. Two observations were made and the mean was taken. BP differences between the two methods for the 33 participants were classified into three categories , according to the European Society of Hypertension-International Protocol revision 2010 (ESH-IP2) criteria. This was then used to assess the validity of the tested Omron RS6 device.Results: Participants had a mean age of 56.97 years (standard deviation (SD), 8.75; range, 36-79). Average systolic blood pressure (SBP) was 146.21 mmHg , and average diastolic blood pressure (DBP) was 93.82 mmHg . There was a good agreement between the two observations using the OMRON RS6 and the standard sphygmomanometer: −4 to + 3 mmHg for SBP and −4 to +4 mmHg for DBP, with the mean difference of 1.73±1.11 mmHg for SBP and 1.49±1.02 mmHg for DBP.Conclusion: Thus, the Omron RS6 (HEM-6221-E) is a valid and suitable measure of BP according to ESH-IP2. It is a global public health issue, and is recognized to be the major factor contributing to the burden of heart disease, stroke, kidney failure and premature mortality and disability all over the world. In spite of this burden, a simple preventive and non-invasive measure such as checking and monitoring blood pressure (BP) is expected to decrease the associated cardiovascular mortality with hypertension dramatically. Hypertension is mostly symptomless particularly in the early stages unless there are complications or other reasons to reveal it, which is why many people go undiagnosed. Moreover, those who are diagnosed may not have access to treatment and may not be able to successfully control their hypertension long term. In order to ensure that the disease is well-controlled, BP should be monitored regularly.Hypertension is defined as systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg. Therefore, these electronic devices must be of certain accuracy. As a result, many BP measuring devices have been validated to meet international standards for the use by the general population. However, few studies for the validation of electronic devices in specific groups, such as the elderly, infants and obese individuals, have been done.Accurate BP readings via a reliable device is equally important, since this will influence diagnosis and treatment. Generally, there are electronic, mercury and aneroid devices that are used to measure BP. The World Health Organization recommends the use of affordable and reliable electronic devices that have the option to select manual readings, because mercury is toxic and aneroid devices need calibrations and trained personnel for use. Secondly, obesity affects individuals in very different ways, and many obese people have an significantly increased arm circumference. Hence, if BP is not measured with an appropriately sized cuff it will lead to false high readings, which may conduce unnecessary treatment. In order to solve the problem of adiposity, some studies use the forearm instead of the arm to measure BP in obese individuals, which results in overestimated BP by approximately 7-15 mmHg – this has to be corrected with equations. Recently, a study targeting obese individuals compared the BP readings using two devices, one at the level of the arm  and the other at the wrist level  to a standard method. These authors found that the electronic device's readings varied significantly from the readings obtained by the standard sphygmomanometer and did not meet the required criteria for obese adults. In this study, we aimed to evaluate BP measurements among obese hypertensive Sudanese patients using the radial artery (wrist level) compared to the standard brachial measured using a mercury sphygmomanometer and non-electronic stethoscope to attain more valuable information about the validity of using such a method.For overweight and obese individuals, BP measurement is more challenging. First, obesity itself plays a major role in elevating BP through increasing insulin resistance and creating a cycle that eventually ends to metabolic syndromeOmron RS6 (HEM-6221-E) is a fully automated device for self/home BP measurement at the wrist level using the oscillometric method. Inﬂation is by automated fuzzy logic–controlled electric pump and deﬂation is by automatic pressure release valve. It measures 87 mm × 64 mm × 14 mm (width × height × depth). It has a single wrist cuff, which can be used for wrist size between 13.5–21.5 cm. The device demonstrates the pulse and BP (SBP and DBP) in a digital liquid crystal screen. The device can detect a BP range from 0 to 299 mmHg and pulse rate from 40 to 180 beats/min. Additionally, it can save the last 90 BP readings and it has a position sensor for the wrist and the ability to detect irregular pulse and body motion.2), adult (age ≥25 years), male and female hypertensive patients, able to give informed consent. BMI was computed from measured weight and height using standard methods. Individuals with abnormal rhythm or uncertainly DBP were excluded.A cross-sectional study was conducted at Gadarif Hospital outpatient clinic in eastern Sudan. Patients who fulfilled the following inclusion criteria were enrolled in the present study: obese (body mass index (BMI) ≥30 kg/mThis study was conducted among the obese Sudanese population. A total of 90 participants volunteered to take part in the study and met the inclusion criteria, with at least 30 men and 30 women. Participants were invited to take part in the study during their regular doctor’s appointment.Participants were recruited to ensure a uniform distribution of test pressures across the BP range: 90–180 mmHg for SBP and 40–130 mmHg for DBP. The participants were divided into three groups as per their SBP and DBP readings: SBP – low (90–129), medium (130–160), and high (161–180); for DBP – low (40–79), medium (80–100) and high (101–130). Readings outside these ranges were included and were either categorized as low or high. In each of the three SBP and DBP ranges, a minimum of 10 to 12 patient was included according to the European Society of Hypertension-International Protocol revision 2010 (ESH-IP2) guidelines with at least 10 men and 10 women in the sample size . Procedure. In the outpatient clinic, BP measurements were taken in a room with a comfortable temperature, and ambient noise kept to minimum to avoid disruption during auscultation. Patients who fulfilled the inclusion criteria were allowed to rest for 10 minutes sitting on a chair in upright position with their legs uncrossed and back supported, with complete exposure of the left arm and forearm (at the time of BP checking) so there were no intervening clothes between the cuff and the arm, which might reduce the blood flow. Participants were encouraged to avoid talking or using mobile phones. The arm circumference was checked, and the suitable cuff applied. All the measurements were obtained from the left arm at the heart level.BP measurements were obtained first by the standard mercury sphygmomanometer then alternating with the test device, so that we obtained nine consecutive BP measurements from each participant: five measurements from the standard mercury sphygmomanometer and four measurements from the tested device.Blood pressure measurements. The manufacturer of the Omron RS6 (HEM-6221-E) was asked to provide a standard model, and the automated device was used after familiarization sessions in the outpatient clinic for one week, during which time the team performed 12 test measurements and accustomed themselves to the device and the study. No problems in this familiarization period were encountered. For the standard test, two stethoscopes and two mercury sphygmomanometers with different cuff sizes were carefully checked prior to the study.The working team composed of three personnel, two observers and a supervisor, well trained in BP measurement using standard mercury sphygmomanometer and stethoscope with well-fitting earpieces. They were of good health, hearing, and sight and able to follow the menisci at eye level from 40 mmHg to 180 mmHg. The two observers measured BP using two mercury sphygmomanometer and these readings were used as a reference. Observers were blinded from each other’s readings and from the device readings. They took BP measurement simultaneously and record them to the nearest 2 mmHg. The supervisor checked the agreement of BP values between the two observers so that any readings that varied by 4 mmHg or more were repeated. The supervisor measured the BP using the test wrist device. Two observations were made.Before measuring BP, the observer measured the arm circumference in order to use the appropriate size cuff for the standard mercury sphygmomanometer: small cuff for an arm circumference 17–21.9 cm, a regular cuff for an arm circumference of 22–31.9 cm, a large cuff for an arm circumference of 32–42 cm and for patients with arm circumference more than 42 cm an extra-large cuff is used. was used as a guide for data analysis. Accordingly, data was analyzed, presented and expressed to assess the ability of the device to pass or fail to pass the validation protocol requirements. SPSS (version 22) and Microsoft Excel software were used to perform all data analysis. Measurements obtained by the two observers for the standard device were compared and their average was taken, which was later compared with the test device SBP and DBP. The numbers of differences for the tested device and the observer using mercury sphygmomanometer within 5, 10, and 15mmHg, were calculated for both SBP and DBP then the average differences of the values with the standard deviation between the SBP and DBP of the mercury and the tested device were obtained. Finally, Bland–Altman plots were performed for both SBP and DBP to show the differences of device-observer versus average device and observer values for all the 99 pairs of comparisons.The ESH-IP2Ethical approval was received from the Ethics Committee at the Faculty of Medicine, Gadarif University, Sudan (reference number: 2017/09). Written informed consent to participate was collected from each participant before taking part in the research.In total, 90 obese participants were screened for inclusion into this study, 57 were excluded . Therefore, data related to 33 participants (12 men and 21 women) who fulfilled the requirements and the criteria of the ESH-IP protocol were analyzed.Mean (±standard deviation) age of participants was 56.97±8.75 years ; mean wrist circumference was 22.58±3.25 ; mean height was 163.52±13.54 cm ; and mean BMI of 38.74±8.26 . The mean BP values for SBP was 146.21±23.07 mmHg  and for DBP was 93.82±16.06 mmHg . Respondents' characteristics and BP measurements are summarized inThere was adequate agreement between the tested wrist BP measuring device (Omron RS6 (HEM-6221-E)) and the mercury sphygmomanometer . All theIn this study, the Bland-Altman plot showing the observers differences in SBP and SBP reveal that there is adequate agreement between the tested wrist BP measuring device (Omron RS6 (HEM-6221-E)) and the mercury sphygmomanometer . The SBP also showed that the OMRON RS7 device fulfils the validation criteria of ESH-IP validation protocol in two independent study centres among subjects, showing inter-centre reproducibility.A very recent study, however another study reported that the device failed to fulfil the ESH-IP revision 2010 requirements among obese subjects. Deutschet al. used the Omron RS6 position sensor with PSON or PSOFF, which showed that the position sensor is important for the function of the device at the wrist level and it improves the accuracy of the measurements by decreasing variations in wrist height.In our study, the screening process to include and exclude participants was time consuming. In addition, there was a difficulty in recruiting participants with high blood pressure. According to the validation protocol of ESH-IP, three studies have already been carried out to confirm the validity of the Omron RS6 (HEM-6221-E) device. Validation among the general population confirmed the general validity of the deviceThis study included only participants meaning that extrapolation of the results should be done with caution to individual who are not obese. Moreover, device accuracy needs to be adjusted to wrist circumference and position during measurement.The tested device, Omron RS6 (HEM-6221-E), achieved all the required standards for self/home measurement of blood pressure at the wrist level set by the ESH-IP, and accordingly would safely be recommended for personal use at home among obese patients provided that the manufacturer’s instructions are followed.https://doi.org/10.17605/OSF.IO/7S5D3 (registered on 18th October 2020: osf.io/w7dtn).Open Science Framework: Validation of the wrist blood pressure measuring device Omron RS6 (HEM-6221-E) among obese Sudanese patients compared with a standard mercury sphygmomanometer: a cross-sectional study according to the European Society of Hypertension International Protocol Revision 2010,Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).Data are available under the terms of the This study investigated the validity of the Omron RS6 (HEM-6221-E) wrist oscillometric devices in the blood pressure monitoring for 33 Obese Sudanese patients. This manuscript is well written and obtained results confirming their hypothesis. However, there are several studies that blood pressure levels were different between the level of the arm and that of the wrist. It should be noted that, based on much evidence, blood pressure is recommended to be measured in the upper arms, using an appropriate cuff size for the arm circumference. In the case of home blood pressure monitoring for obese patients, blood pressure should be measured at the level of the arm  using a larger cuff.Is the work clearly and accurately presented and does it cite the current literature?YesIf applicable, is the statistical analysis and its interpretation appropriate?YesAre all the source data underlying the results available to ensure full reproducibility?YesIs the study design appropriate and is the work technically sound?YesAre the conclusions drawn adequately supported by the results?YesAre sufficient details of methods and analysis provided to allow replication by others?YesReviewer Expertise:NAI confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. The article presents a successful validation of a blood pressure monitor in an obese population. It satisfies the methodological requirements for a validation study and is written clearly and succinctly. It is to be noted (as the authors do) that a validation study of the same monitor in an equivalent population has been previously conducted and found the monitor failed validation. This is perfectly reasonable in itself, but perhaps raises the question of why the authors felt another validation study was warranted, and if they have any insights into the reason for the difference in results. Arguably related to this, some of the discussion of previous studies  should be in the background.Is the work clearly and accurately presented and does it cite the current literature?YesIf applicable, is the statistical analysis and its interpretation appropriate?YesAre all the source data underlying the results available to ensure full reproducibility?YesIs the study design appropriate and is the work technically sound?YesAre the conclusions drawn adequately supported by the results?YesAre sufficient details of methods and analysis provided to allow replication by others?YesReviewer Expertise:Blood pressure monitoringI confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.


Background and Objectives: There is evidence for ketamine efficacy in treatment-resistant depression (TRD). Several safety and tolerability concerns arise that some psychotropic agents may provide blood pressure or/and heart rate alterations. The aim of this study is to review blood pressure measurements in course of the treatment with ketamine on treatment refractory inpatients with somatic comorbidities in the course of MDD and BP. Materials and Methods: The study population of 49 patients comprised MDD and BP subjects treated with ketamine registered in the naturalistic observational protocol of treatment-resistant mood disorders (NCT04226963). Results: The conducted analysis showed that among people suffering from hypertension there is a higher increase in systolic blood pressure (RR) after infusion 2 (p = 0.004) than among people who do not suffer from hypertension. Patients with hypertension have a higher increase in diastolic RR compared to those not suffering from hypertension . Among the subjects with diabetes mellitus, significant differences occurred for infusions 2 (p = 0.020), 7 (p = 0.020), and 8 (p = 0.035) for heart rate (HR), compared to subjects without diabetes mellitus. A higher increase in diastolic RR was noted in the group of subjects suffering from diabetes mellitus (p = 0.010) compared to those who did not. In the hyperlipidemic patients studied, a significantly greater decrease in HR after infusion 5 (p = 0.031) and systolic RR after infusion 4 (p = 0.036) was noted compared to nonpatients. People after a stroke had significantly higher increases in diastolic RR after infusions 4 (p = 0.021) and 6 (p = 0.001) than those who did not have a stroke. Patients suffering from epilepsy had a significantly greater decrease in systolic RR after the 8th infusion (p = 0.017) compared to those without epilepsy. Limitations: The study may be underpowered due to the small sample size. The observations apply to inhomogeneous TRD population in a single-site with no blinding and are limited to the acute administration. Conclusions: This study supports evidence for good safety and tolerability profile for short-term IV ketamine use in TRD treatment. However, risk mitigation measures are to be considered in patients with metabolic and cardiovascular comorbidities. Several safety concerns arise with ketamine infusions in treatment-resistant depression (TRD). Sequalae observed are cardiovascular factors with a prominent focus on arterial hypertension ,2,3,4. AThe literature data represents the correlation between oral, intranasal esketamine and intravenous ketamine ,2,3,7, aThe aim of this study is to review blood pressure measurements in course of the treatment of resistant depression in patients with somatic comorbidities.The study population selection has been described in detail elsewhere ,9. BriefOnly medically stable, adult inpatients aged 18–90 were enrolled to study. None of the patients suffered from psychotic symptoms in course of the disease. Some patients significantly affected by somatic illness continued current medication during ketamine treatment. The exclusion criteria included a history of uncontrolled medical conditions, a previous adverse reaction to ketamine, active substance use  including alcohol and cannabis, pregnancy, or breastfeeding.All subjects gave written informed consent to participate in the study. The study was carried out in accordance with the latest version of the Declaration of Helsinki (NKBBN/172-674/2019) and Registered as NCT04226963.The study design was discussed in detail elsewhere ,9. BriefU test was utilized. For within-subject and groups analyses the Kruskal–Wallis tests were conducted. α = 0.05 was adopted as the level of significance for the purposes of this analysis.The primary outcome of interest was change in Systolic RR and Diastolic RR from preinfusion to highest postinfusion measurement explored post hoc in database registry. The analyses were conducted using statistical software the IBM SPSS Statistics 25.0. For sociodemographic variables and the occurrence of diseases and treatment, frequency analyses were carried out with Fisher’s exact test. When assessing the statistical significance between dichotomous groups, the Mann–Whitney Due to the small sample size nonparametric tests were used and inequities among groups analyzed were used for the analysis for discrete and continuous variables.Demographic and clinical characteristics of the study population is presented in Using the Mann–Whitney U test, the mean-term blunt changes in HR and RR were compared with each other due to the use of a given type of medication. The results are presented in Overall, blood pressure elevations were observed in patients with comorbid: arterial hypertension, diabetes mellitus (DM), hyperlipidemia, and stroke history. Significant RR elevations were transient and observed at various points of time with no stable pattern, attributable to specific comorbidity or timepoint.p = 0.004) than among people who do not suffer from hypertension. A similar situation occurred for diastolic RR after one infusion (p = 0.038)—patients with hypertension have a higher increase in diastolic RR compared to those not suffering from hypertension.The conducted analysis showed that among people suffering from hypertension there is a higher increase in systolic RR after infusion 2 (p = 0.020), 7 (p = 0.020) and 8 (p = 0.035) for HR. These subjects obtained a significantly higher increase in HR compared to subjects without DM. A higher increase in diastolic RR was noted in the group of subjects suffering from DM (p = 0.010) compared to those who did not.Among the subjects with DM, significant differences occurred for infusions 2 (p = 0.031) and systolic RR after infusion 4 (p = 0.036) was noted compared to nonpatients.In the hyperlipidemic patients studied, a significantly greater decrease in HR after infusion 5 (p = 0.021) and 6th infusion (p = 0.001) than those who did not have a stroke.People after stroke had significantly higher increases in diastolic RR after 4th infusion (p = 0.017) compared to those without epilepsy.Patients suffering from epilepsy had a significantly greater decrease in systolic RR after the 8th infusion  . It is oThe methodological strength of our study was to strengthen the point regarding the tolerability and general safety of the administration of the drug and that result being in support with some previous ketamine studies mentioned above.The key study limitations include small sample size and lack of randomization with the intervention blinding. Thus, it may be underpowered, and its results shall be treated with caution as the observational design does not warrant comparative or causative conclusions. The observations apply to treatment-resistant depression and include both, MDD and bipolar depressed patients with a proportion of subjects diagnosed with somatic comorbidities and concomitant medication. Thus, the study population is inhomogeneous and represents subjects attending the tertiary-reference center. All safety and tolerability findings shall be replicated in a larger sample exposed to the intervention across the long-term study design. Although specific safety observations may apply to TRD patients presenting clinical response pattern, this study sample did not warrant such analysis that may be particularly worth consideration in future safety studies in larger samples.This study supports evidence for good safety and tolerability profile for short-term IV ketamine use in TRD treatment in subjects with stable somatic illness. However, risk mitigation measures are to be considered in patients with metabolic and cardiovascular comorbidities. The abatement of elevated HR and RR was observed in time of the treatment with no sequelae nor harm. The side effects are mild or moderate, well-tolerated and transient as all of them cease within 4 h post administration. No exacerbations of cardiovascular, metabolic or seizure related conditions were observed.