Malignant hypertension (hypertensive emergency), is an extreme elevation of blood pressure under certain conditions that can lead to organ damage and other serious consequences. It is a common condition that affects about one in three Americans, according to the Centers for Disease Control and Prevention. An elevation of systolic blood pressure above 180 mmHg and diastolic blood pressure above 120 mmHg is considered a hypertensive emergency. This article addresses the case of a 61-year-old female patient who presented to the ER with a semicomatose and gasping condition and response to painful stimuli with an unclear voice. She also had unstable vital signs, with a blood pressure of 370/200 mmHg, a pulse rate of 115, a respiratory rate of 22, and a pulse oximetry of 96%, but no fever. Her son provided a brief history and reported that a stressful condition had occurred at home one hour before; she had begun to scream and been brought to the ER by ambulance in the condition described above. Cardiac monitoring and an electrocardiograph were performed and indicated a normal condition besides the unstable vital signs. Oxygen was administered via a nasal cannula with 20 mg of intravenous hydralazine, and the patient’s blood pressure improved progressively. Moreover, she regained consciousness with no end-organ damage. A hypertensive emergency is usually associated with end-organ damage, such as heart, kidney, eye, or brain damage. However, in this case, despite the extreme elevation of her blood pressure, the patient suffered no organ damage. It is essential to manage the extreme elevation of blood pressure as soon as possible and monitor the patient for consequences. Hypertension is the most common condition in the United States. It affects one in three American adults, according to the Centers for Disease Control and Prevention . Blood pWhen blood pressure exceeds 120/80 mmHg, several readings reveal hypertension. Different levels of blood pressure occur: level one is considered normal, while level two indicates that a patient is at risk of prehypertension when his or her systolic blood pressure is between 120 mmHg and 129 mmHg and diastolic blood pressure is below 80 mmHg. Various evaluations consider blood pressure above 130/80 mmHg a hypertensive condition [Clinical historyA 61-year-old female patient presented to the ER with a semicomatose and gasping condition. She was holding her right hand over the right side of her chest and responded only to painful stimuli with an unclear voice. Her son provided a brief history and reported that a stressful condition had occurred at home an hour before; she had been arguing with one of her family members for about 30 minutes, which had initiated her presentation. Her son also reported that she had been moving her right arm and chest erratically and screaming during the ambulance ride. Upon their arrival at the ER, the paramedics also offered a brief history. They could not report accurate vital signs from their ride to the hospital, stating that the patient’s blood pressure could not be read due to a device error; her other vital signs had included a respiratory rate of 24, heart rate of 126, and pulse oximetry of 94%. The paramedics had administered oxygen via a nasal cannula and set an intravenous line in the ambulance.After her son and the paramedics supplied their information, the patient was attached to the cardiac monitor, which immediately rendered no signs of cardiac ischemia via electrocardiography Figure . A physiThe vital signs recorded were surprising since, while the patient had no fever, her blood pressure was 370/191 mmHg, respiratory rate 22, heart rate 115, and pulse oximetry 95%. Immediate verification of her blood pressure revealed the same reading. A decision to administer 20 mg of intravenous hydralazine and monitor her vital signs under the highest care was made. The first ampule of hydralazine was administered, and after five minutes, the patient’s blood pressure dropped to 330/182 mmHg. The second ampule of hydralazine was then administered, and after another five minutes, her blood pressure dropped to 300/180 mmHg. Finally, the decision to administer 40 mg of hydralazine in two dosages ten minutes apart was made. The patient’s blood pressure dropped to 220/160 mmHg; she began to regain consciousness gradually, with no gasping, and her right arm movement subsided. Her vital signs indicated a heart rate of 118, a respiratory rate of 20, and unchanged pulse oximetry. Another electrocardiograph rendered no ischemia. However, five minutes after the last dose of hydralazine, another ampule was administered in response to unchanged blood pressure since the previous reading; the patient’s blood pressure then dropped to 171/130. She began to feel better and wanted to know what had happened to her. She was alert to time, place, and persons a few minutes later.The patient’s current vital signs were as follows: blood pressure of 170/128 mmHg, respiratory rate of 17, heart rate of 119, and pulse oximetry of 94% on room air. She received 50 mg of oral metoprolol and provided a full history. She had been on 10 mg/day of lisinopril for the last five years for hypertension, and she denied having any chronic diseases such as diabetes mellitus, asthma, stroke, angina, and liver or kidney problems. Repeated physical, neurological, cardiac, pulmonary, and gastroenterological examinations were normal. Her blood pressure dropped to 150/100 mmHg 20 minutes after the latest reading. Her vital signs then revealed a heart rate of 105, respiratory rate of 17, and pulse oximetry of 95%. Computer tomography rendered normal findings and no signs of a stroke , pons, and midbrain, decreases the efferent sympathetic activity, which finally leads to bradycardia and vasodilation when the arterial baroreceptors respond to vessel wall distention by increasing the afferent impulse activity.A hypertensive emergency is a true medical emergency that requires prompt treatment to reduce blood pressure and prevent organ damage. The pathophysiology is not well understood; nevertheless, the failure of normal autoregulation and an abrupt rise in systemic vascular resistance are often the first steps in the disease process. An increase in systemic vascular resistance occurs with the release of vasoconstrictors from the vessel wall. Incremental pressure changes in the vessel lead to endothelial damage. Local intravascular activation of coagulation cascade releases more vasoconstrictors, and fibrinoid necrosis of small blood vessels. If this process is not prevented as soon as possible, further vascular injury, tissue ischemia, and autoregulation dysfunction occur .The risk factors for hypertension include age (the most important one), race (African Americans are more vulnerable), family history, obesity, alcohol, diet, a sedentary lifestyle, and stress . While tStress is now a major predicament, whether it is related to environmental or psychological factors, as both can trigger a hormonal change in the body. The initial response to stress begins in the amygdala, which receives input from various brain centers, including visual and auditory systems. In other words, when an individual experiences a critical situation, data is transmitted to the amygdala, which interprets that information and sends it to the hypothalamus; the hypothalamus then communicates with the rest of the body via the autonomic nervous system to control vital signs such as breathing, blood pressure, heart rate, and the dilation or constriction of blood vessels. The autonomic nervous system is divided into sympathetic (fight-or-flight response) and parasympathetic (rest or digest) systems. The activation of the sympathetic nervous system during emotional stress ultimately sends an impulse to the adrenal medulla to release catecholamines, including epinephrine and norepinephrine, which both lead to an increase in vital signs such as elevated blood pressure, tachypnea, and tachycardia. If the stressors persist, the surge in catecholamines also persists, resulting in more damage to the vascular endothelium and worsening the condition . These cThe first organ that a hypertensive emergency affects is the kidney, which suffers from ischemia and activates the renin-angiotensin-aldosterone system (RAAS). The condition therefore worsens due to the further elevation of blood pressure. In addition to the activation of the RAAS, other factors such as endothelin, vasopressin, and catecholamines play a vital role in the pathogenesis of hypertensive emergency .The goal is to find any organ damage  and attempt to prevent the progression as fast as possible. The patient could present with shortness of breath, chest pain, confusion, coma, vomiting, or vision changes. A physical examination should initially focus on any cardiac symptoms, such as gallops, murmurs, and S3 sounds; a lung examination on rales; and a neurological examination on seizures. Moreover, a mental status funduscopic examination should exclude papilledema and other conditions. Monitoring the patient’s vital signs is an important step. Indeed, the patient should be managed in the ICU under high care and supervision ,13.First, lowering the patient’s blood pressure should be done within minutes by lowering the mean arterial pressure by up to 25% in the first thirty minutes and if the patient remains stable then further lowering can be done over the next hour. Attaching the patient to a cardiac monitor is a crucial step in blood pressure management . Once thA hypertensive emergency usually presents with elevated blood pressure and end-organ damage, including heart, eye, kidney, and brain damage. Remarkably, the current case presented with the usual elevated blood pressure but without end-organ damage, which makes it a unique case to report. The patient was successfully treated with hydralazine and suffered no complications, including stroke and myocardial infarction.


Our findings suggest that Parkinson’s disease and osteoarthritis are the main predictors independently associated with a history of falls in patients admitted to the geriatric ward, although the influence of some factors may be underestimated due to the tendency of not taking the history of falls in very frail, functionally dependent and bedridden individuals.Falls are a serious health problem in older adults. A limited number of studies assessed their multifactorial nature in geriatric ward patients. The aim of this study is to explore health, functional and nutritional correlates of experiencing fall(s) in the previous year by older inpatients. A cross-sectional study of patients admitted to the department of geriatrics was conducted. A “faller status” was defined based on positive history of falls in the previous 12 months. Health, functional and nutritional factors associated with falls were evaluated, and multivariable logistic regression analysis models were built. A total of 358 patients (median age 82 (IQR 76–86) years, 77.9% women) were recruited, 43.9% of whom reported falls. The “fallers” presented with a significantly higher number of chronic diseases, higher prevalence of Parkinson’s disease, peripheral arterial disease, chronic osteoarthritis, more frequently reported urinary incontinence and were dependent on others for daily living activities. They had significantly worse results for the assessment of gait, balance and frailty status. The Mini Nutritional Assessment-Short Form scores and the mean value of serum albumin were significantly lower in the fallers’ group. Parkinson’s disease (OR = 2.82, CI—1.07–7.45;  Falls are a major health problem in older adults. A high percentage of the geriatric population experienced a fall each year ,2. FallsMany intrinsic and extrinsic factors can contribute to or cause falls. The intrinsic factors include gait and balance disorders, cognitive deterioration, abnormal nutritional status, orthostatic hypotension and different medical conditions such as Parkinson’s disease, stroke and its consequences or chronic osteoarthritis, among others ,6,7,8,9.The aim of the study was to assess clinical health, functional and nutritional characteristics associated with the history of pre-hospitalization falls in geriatric inpatients, taking into account the multifactorial nature of this “geriatric syndrome” . To the Our study is a secondary analysis of the data collected across the cross-sectional study on frailty and multimorbidity in patients of the department of geriatrics  . All conThe analysis included patients who—alone or represented by a guardian—answered the question about the occurrence of falls in the last 12 months. Participants who confirmed such incidents were treated as having a “faller” status, and those who denied them as “non-fallers”.Sociodemographic characteristics included age, gender, place of residence . History taking included information on 15 chronic diseases  or stroke, chronic obstructive pulmonary disease, diabetes or prediabetes, neoplasm, dementia, parkinsonism, chronic osteoarthritis, osteoporosis and chronic renal disease), drug for treatments taken before hospitalization that could influence the risk of falls (antihypertensive drugs: angiotensin converting enzyme inhibitors (ACE-Is)/ angiotensin II receptor blockers (ARBs), beta-blockers, calcium channel blockers, diuretics, α1-blockers; digoxin; lipid lowering drugs; antidepressants: selective serotonin reuptake inhibitors (SSRI); neuroleptics: in general and quetiapine separately; pro-cognitive medications: memantine, acetylcholinesterase inhibitors (AChE-Is), benzodiazepines (BDA); non-steroidal anti-inflammatory drugs (NSAIDs)) and hospitalizations in the last 12 months. Information obtained from the patient was verified by an interview with his or her guardian, by a thorough clinical examination, and by a review of all of the patient’s medical records available.The functional profile of a patient was created based on the results of comprehensive geriatric assessment routinely conducted at the department. Risk of recurrent falls was assessed with previously validated tests—the Performance-Oriented Mobility Assessment (POMA)  and the Systolic and diastolic blood pressure was measured at admission. Orthostatic hypotension occurrence was assessed with active standing test performed by a physiotherapist in the morning on the second day of the patient’s hospital stay. After a resting period of 10 min, blood pressure was measured electronically  on the non-dominant arm with the patient lying down. The patient was then asked to stand up, and the blood pressure was measured again during the first and the third minute after standing . If the Data on vitamin B12, serum sodium, creatinine, albumin, and hemoglobin levels was extracted from patients’ medical records. Renal function was assessed with glomerular filtration rate—GFR, counted using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula .2. Anemia was diagnosed if the hemoglobin level was below 8.7-mmol/ L in men and below 7.5-mmol/L in women. Patients with BMI ≥ 30 kg/m2 were classified as obese, and with BMI < 24 kg/m2 as being at risk for malnutrition. Malnutrition was also suspected if the MNA-SF score was below 8. Dynapenia (or probable sarcopenia) was derived from the handgrip strength and diagnosed in men if grip strength was lower than 27 kg and in women if it was lower than 16 kg [Multimorbidity was defined as the co-occurrence of 5 or more diseases of the 15 listed above. Polypharmacy was defined as 5 or more drugs taken. Severe frailty was defined as a CFS score of 6 or 7 . Orthostan 16 kg . It was 2 tests or Fisher’s exact test, as appropriate, while the independent samples Student’s t-test and the Mann–Whitney U test were used to compare the distribution of continuous variables. It was followed by a multivariable logistic regression including all predictors with a p-value less than 0.2 and without significant multicolinearity effect. The variance inflation factor was used to identify correlation between independent variables and the strength of that correlation. Missing values were omitted and statistics in such cases were calculated for the adequately reduced groups. A p-value of less than 0.05 was regarded as significant.The IBM SPSS Version 18 Software suit  and STATISTICA 13.3 software package  were used to analyze the data collected. The Shapiro–Wilk test was used to assess the distribution of variables. Data were presented as means (M) and standard deviation (SD) for normally distributed continuous variables, as medians (Me) and interquartile range (IQR) for not normally distributed ones and the number of cases and percentage for categorical variables. Proportions were compared using χThe source study was approved by the Ethics Committee at the Medical University of Bialystok (no R-I-002/305/2013). All procedures performed in the study were in accordance with the ethical standards of the Medical University of Bialystok research committee and with the Helsinki declaration and its later amendments. The study can be classified as a study of ‘usual practice’. All study participants gave their informed consent to participate in it.A total of 358 (86.1%) patients of 416 hospitalized during the study period—or their guardians—answered the question about the occurrence of falls in the last 12 months and were included in the analysis . Falls ip = 0.02), but not in the percentage of multimorbidity. The percentage of some diseases was significantly higher in the fallers group: Parkinson’s disease , peripheral arterial disease  and chronic osteoarthritis , but the percentage of dementia, hypertension, ischemic heart disease, history of myocardial infarction, congestive heart failure, TIA/ stroke, diabetes, osteoporosis and chronic kidney disease was not substantially different in both groups. The median number of medications taken, and the percentage of polypharmacy also did not significantly differ. We did not notice any dissimilarities in the frequency of taking any type of medication. Only in the case of quetiapine, the difference was on the verge of statistical significance . Median systolic and diastolic blood pressure value at admittance and percentage of orthostatic hypotension were similar in fallers and non-fallers. The groups did not differ in median levels of vitamin B12, serum sodium, serum creatinine, hemoglobin and in mean value of GFR. The percentage of anemia patients was also not significantly different in both groups.The characteristics of the study groups—fallers and non-fallers—are presented in p = 0.03). The handgrip strength did not differ significantly between fallers and non-fallers, although such a difference was observed in men. Despite that, no difference was observed in the percentage of patients with dynapenia, as well as those classified as severely dynapenic between fallers and non-fallers. The medium level of frailty status classified with the CFS was significantly higher in fallers , but the groups did not differ significantly in the percentage of patients assessed as severely frail. The mean BMI as well as percentages of patients with BMI below 24.0 kg/m2 and with BMI above 30 kg/m2 were not significantly different in fallers and non-fallers. The mean value of serum albumin was notably lower in fallers: 39.0 ± 4.0-g/L vs. 39.5 ± 4.0-g/L in non-fallers, p = 0.03, but the groups did not differ significantly in the percentages of patients at risk of malnutrition according to the MNA-SF score.Similar percentages of fallers and non-fallers were hospitalized in the last year . The Barthel index, the Duke OARS and the MNA-SF scales scores were significantly lower in the fallers’ group, whereas the AMTS and GDS scores were not materially different. Urinary incontinence was reported significantly more frequently in the fallers’ group. The gait speed, the POMA, and the TUG results were significantly worse in the fallers’ group and the percentage of patients with gait speed ≤0.8 m/s was significantly higher  were not included in the logistic regression after testing for correlation with other variables and for their multicollinearity effect. The handgrip variable was introduced into the regression model, although it did not meet criteria (p = 0.22) because when it was separated by sex, it did it. Significantly higher odds for faller status was observed only for Parkinson’s disease  and osteoarthritis .A direct multivariable logistic regression analysis was carried out on faller status as outcome and 21 predictors: age 75+, multimorbidity, cardiac heart failure, peripheral arterial disease, history of stroke/TIA, Parkinson’s disease, chronic osteoarthritis, POMA, Barthel Index, IADL score, gait speed, CFS status, urinary incontinence, MNA-SF score, albumin value, vitamin B12 level and taking certain medications  . A few vN = 265) = 32.90, p < 0.047, indicating that the characteristics, as a set, reliably distinguished between fallers and non-fallers. An overall prediction success rate in logistic regression constituted 64.2%, with 60.2% of fallers and 67.9% of non-fallers predicted correctly.A test of this model against a constant-only model was statistically reliable, χ  increased the risk of falls, but it was not observed in our study ,12,33,34U-shaped association observed between BMI and the risk for falls, with the nadir between 24.5 and 30 kg/m2 [Several studies suggested that the nutritional status and BMI should be evaluated when assessing the risk for falls in older age. Systematic review and meta-analysis confirmed a 30 kg/m2 . We did Parkinson’s disease was the most significant variable independently associated with falls in our research. It corresponded with the results achieved by other authors . The mosContrary to our expectations and to the results of a number of studies,  our reseAlbeit the assessment of the risk of falls is an important element of the comprehensive geriatric assessment and the question on falls in the last 12 months should be asked at the beginning of the screening, as many as 13.9% of patients hospitalized in the study period or their guardian, were not asked about or were unable to answer this question. This fact could have been caused by the possible assumption that patients with significantly reduced mobility did not experience falls although the results of a number of studies contradicted this presupposition . A similThe study has got some limitations that ought to be emphasized. First of all, because of the temporal relationship of fall incidence with baseline medical information, we can say that the study identified potential factors associated with falls, but not actual “predictors” of falls, and the word “predictor” should be treated as a mathematical concept used in regression analysis, rather than as a factor determining the occurrence of a phenomenon. Additionally, as it was underlined above, the study was conducted not in a random sample from the general population, but in a convenient sample of patients admitted to the geriatric ward, therefore, the results can be generalized for patients of similar settings only. Prospective population-based studies should be conducted to explore our findings more thoroughly and overcome these limitations. As our study was based on the secondary analysis of data previously collected, some pieces of information were limited, as indicated in tables. Moreover, the nonparticipant group differed significantly from the study group in various important characteristics. This could also have had an influence on the final results.In summary, the study revealed that falls were a common problem among geriatric ward patients and affected up to 43.9% of them. Parkinson’s disease and osteoarthritis were the main independent predictors connected with the significantly higher odds for being a faller before admittance to the hospital. Sarcopenia and some other previously confirmed risk factors for falling were not connected with a faller status in geriatric ward patients, although their influence may be underestimated due to the tendency of not taking the history of falls experienced in very frail, functionally dependent and bedridden individuals.


Objective: We sought to clarify the interface pressure (IP) when using a tubular elastic bandage (TEB) and examine the possibility for TEBs to provide IPs comparable to those provided by anti-thrombotic stockings.Materials and Methods: In 40 healthy patients, IPs were measured at the level of calf at its maximum diameter (C) and transition of the medial gastrocnemius muscle into the Achilles tendon (B1) while a single or double layer of TEBs (17.5 cm in circumference) were applied with the patient in a supine position.Results: Including both the C and B1 levels, circumferences and IPs showed a good correlation . The IP obtained with a single layer of TEB at the C level  was higher than that at the B1 level . When double-layer TEB was used, the IP at B1 level increased to 18 (14–23) mmHg (p<0.001 vs. single layer).Conclusion: Considering the characteristics of TEBs and using a single or double layer appropriately, creating a pressure profile mimicking that of an anti-thrombotic stocking seemed to be feasible when using a TEB. ATS are known to cause skin irritation and/or uncomfortable feeling, and, more seriously, can damage soft tissue and/or peripheral nerves. These complications are considered to be caused mainly by improper fitting and/or application technique. However, this may not be simply because of the lack of experience of nurses and/or patients themselves. Postoperative leg sizes in the patients who have undergone vascular or orthopedic surgery can vary greatly depending on the severity of postoperative inflammation and/or edema. Bandages can fit legs of any size and shape, but maintaining a proper interface pressure (IP) is difficult, with the guideline recommending daily re-measurement of leg sizes and refitting of ATS whenever necessary, however, this would lead to excessive economic costs and work overload for staff. For these reasons, the nurses at our institute started to use tubular elastic bandages (TEBs) instead of ATS. Indeed, TEBs are less costly and easier to apply than ATS. Moreover, their thick fabric is beneficial to avoid medical device-related pressure ulcer. However, they are not designed to generate graduated compression to increase venous blood flow as demonstrated by Sigel et al. and Lawrence et al., i.e., 18 mmHg at the ankle and 14 mmHg at the calf. Since the IPs obtained TEBs have not been studied well, we investigated IPs obtained when using TEBs and discussed whether TEBs could provide IPs mimicking those provided by ATS.At the same time as some controversies existing, with anti-thrombotic stockings (ATS) still being considered to reduce the risk of venous thromboembolism in postoperative patients,This prospective study was approved by the Institutional Review Board of Yamaguchi University Hospital . All patients provided signed, informed consent before enrollment. The TEB evaluated in this study was an Elutube® , which consists of 84% cotton, 12% polyester, and 4% polyurethane, because Elutube® has already been adopted and utilized in our institute. In this study, size E, which fits medium-sized calves (not defined by measurements) was used. The circumference of the TEB in its original shape is 17.5 cm. The study patients comprised 40 healthy volunteers with a median age of 38  years. The characteristics of the patients and their right legs are summarized in Firstly, two air pack-type sensors were attached to the medial aspect of the right leg, one at the level of the calf at its maximum diameter (C) and another at the level of the transition of the medial gastrocnemius muscle into the Achilles tendon (B1) in each patient (Results are expressed as the median (range) or count, unless otherwise indicated. In order to classify the leg size fit for ATS, we used the brochure provided by the manufacturer . The Mann–Whitney U-test was used to test differences in IPs obtained in different positions. The Wilcoxon signed rank sum test was used to test differences in IPs between single- and double-layer TEBs. The correlations between IPs and circumferences were tested using a linear regression analysis. Statistical analyses were performed using JMP 11.0 . A p-value <0.05 was considered significant.The correlations between leg circumferences and IPs in a supine position are shown in  increased from 5 to 7 mmHg (p<0.01) when a double layer of TEB was used.The IPs obtained using TEBs in various settings are listed in  On the other hand, IPs at the C level were higher than 14 mmHg for M- and L-size legs.Median IPs according to leg size based on the fit of the ATS are demonstrated in The main findings in this study were as follows: 1) there was a significant linear correlation between IPs obtained using TEB and circumferences, 2) the IP increased approximately 1.3 times by doubling the layer of TEB, and 3) a pressure profile mimicking that of ATS might be created using TEBs in legs of a certain size. where, if the TEB is doubled only below the calf, then a pressure gradient mimicking ATS might be created in S-size legs. Considering the fact that certain prophylactic effects of ATS to prevent venous thromboembolism could be expected in such conditions, and also considering that the National Institute for Health and Care Excellence guideline recommends the use of stockings producing a calf pressure of 14–15 mmHg to prevent venous thromboembolism in in-hospital patients, which requires a pressure of 14–18 mmHg at the ankle according to the British Standard, the pressure profile required to prevent venous thromboembolism itself may need to be revised.As expected, the simple application of either a single or double layer of TEB did not produce a pressure gradient as recommended to increase venous return. Namely, the IP was higher at the C level than that at the B1 level. Interestingly, Bowling et al. reported that the desired pressure gradient for ATS was achieved in only 14% of legs, and a positive pressure gradient from the calf to ankle was observed in approximately 23% of legs,In this study, the correlation between the circumference, i.e., the degree of stretching of the TEB, and IP was linear at the C level, while there was no such correlation at the B1 level. In results that might be interpreted as the correlation at each level representing a different phase of hysteresis, this is probably because we used linear regression analysis for each level. Another possible explanation for this result is “floating” of the TEB at the B1 level because the B1 level is recessed between the calf and ankle and because the degree of depression varies widely depending on the leg shape.Since this study was a single-center study that included a limited number of patients, reaching a definitive conclusion is difficult. The validity of the pressure profile of ATS is generally determined using the IP at the ankle level. However, we could not find an appropriate place to attach the sensor around the ankle in which little flat and non-bony places could be found. This might have prevented the obtaining of conclusive results. Since there are a wide variety of commercially available TEBs with different sizes and made of different materials, the current results may not be generalizable; therefore, the circumference-pressure relationship needs to be clarified for each TEB. Furthermore, because the pressure profile may not the only factor determining anti-thrombotic properties, validity of the use of TEBs instead of ATS should be tested in future clinical trials.The IP achieved using TEBs linearly correlated with calf circumference, and using double-layer TEB increased the IP by up to 1.3 times. Using these characteristics, it seems feasible to create a pressure profile mimicking that of ATS using TEBs.


There are doubts among anesthesiologists on the use of the Laryngeal Mask Airway (LMA) in nasal surgeries because of concerns about the occurrence of blood leakages to the airway. We hypothesized that the use of LMA-Supreme (LMA-S) in nasal surgery is comparable with endotracheal tube (ETT) according to airway protection against blood leakage through the fiberoptic bronchoscopy, oropharyngeal leakage pressure (OLP), heart rate (HR), mean arterial pressure (MAP), and postoperative adverse events.The present study was conducted in a prospective, randomized, single-blind, controlled manner on 80 patients, who underwent septoplasty procedures under general anesthesia, after dividing them randomly into two groups according to the device used (LMA-S or ETT). The presence of blood in the airway  was analyzed with the fiberoptic bronchoscope and a four-point scale. Both groups were evaluated for OLP; HR; MAP; postoperative sore throat, nausea, and vomiting; dysphagia; and dysphonia.p = 0.004; distal trachea, p = 0.034). Sore throat was detected less frequently in the LMA-S group at a significant level in the 2nd, 6th, and 12th hours of postoperative period; however, other adverse events were similar in both groups. Hemodynamic parameters were not different between the two groups.In the fiberoptic evaluation of the airway postoperatively, less blood leakage was detected in both anatomic areas in the LMA-S group than in the ETT group  # NCT03903679 on April 5, 2019.This trial is registered at the US National Institutes of Health ( For many years, the endotracheal tube (ETT) has been accepted as the standard method for airway safety . High prThe LMA has many advantages over the ETT, such as having no direct contact with the tracheal mucosa, no need for direct laryngoscopy during inserting, and less adverse events such as lower frequency of coughing and decreased oxygen saturation during emergence, and lower incidence of sore throat in adults . In receThe LMA-S is one of the second-generation semi-rigid and elliptical LMAs; it can be easily and quickly inserted without placing fingers in the patient’s mouth, and it does not include latex. These second-generation models were designed to provide higher sealing pressures than the LMA-Classic. In addition, they have a duct for facilitating early identification of regurgitation prior to aspiration and also helping gastric decompression . There aBlood leaking from the nasopharynx to the hypopharynx in nasal surgeries contaminates the vocal folds and the tracheobronchial tree. We hypothesized that the LMA-S will reduce the blood leakage to the glottis/trachea and distal trachea. The primary outcome of this study, which was conducted on septoplasty cases, was to compare the effectiveness of the LMA-S and the ETT in protecting the airway against blood leakage using fiberoptic bronchoscopy. The secondary outcome of this study was to evaluate oropharyngeal leakage pressure (OLP); hemodynamic response, including HR and MAP; and postoperative adverse events.www.ClinicalTrials.gov (# NCT03903679). We conducted a prospective, randomized, single-blind, and controlled clinical study with 80 adult patients undergoing septoplasty surgery at Inonu University Hospital, Malatya, Turkey. This study was prepared in accordance with the Consolidated Standards of Reporting Trials (CONSORT) [This study was approved by the Local Ethics Committee (Protocol no: 2018/165) and registered at CONSORT) .n = 40) or ETT (n = 40) group; randomization (1:1) was based on a computer generated random numbers table, using MedCalc v. 16 statistical software for Windows . The patients who agreed to participate voluntarily were told about the features of both airway devices to be used in airway management. The patient wasn’t told which device was to be used. Patients was blinded by this method. At the same time, the nurses who had the task of evaluation in the study in PACU and the related service were blinded by not being informed about the airway device used in the operation.This study was planned as a randomized prospective study. Patients were randomly assigned to either LMA-S  I-II).In the preoperative anesthesia evaluation, patients with scores higher than ASA II and patients who had severe respiratory, hepatic, or renal dysfunction; neurology and/or psychiatry disorders; an allergy to anesthesia drugs, a body mass index (BMI) over 30; predictors of a difficult intubation ; or a history of gastroesophageal reflux or hiatal hernia were excluded from the study.The general anesthesia was standardized for all patients. Standard monitoring consisting of noninvasive blood pressure (NIBP), pulse oximetry (SpO2), electrocardiogram (ECG) were applied to the patients who were admitted to the surgery room. Following this stage, preoperative oxygenation was performed with 100% oxygen for 3 min (min).− 1 intravenously (IV) + remifentanil 3 μg.kg− 1 IV in both groups, and no myorelaxants were used. After the patients lost consciousness and following adequate mandibular relaxation, the LMA-S was inserted using a single-hand rotation technique with the cuff lubricated. The back side of the cuff was lubricated with a water-soluble gel , and the cuff of the mask was fully deflated before insertion. Airway management was performed by the same anesthesiologist, who had at least 5 years of experience. Cases in which the airway devices was not performed successfully after the second trial were excluded from the study.Anesthesia induction was carried out with propofol 2.5 mg.kgThe LMA-S size was chosen according to body weight in accordance with the manufacturer guidelines . After the insertion of LMA-S, if a leak sound occurs with gentle manual ventilation, a larger sized LMA-S was used which is in accordance with daily clinical practice , 12.2O was adjusted to the ETT cuff pressure of 20 cm H2O/1 manometer  [Cuffed endotracheal tubes with internal diameters of 7 mm and 8 mm were used for female and male patients, respectively. The LMA-S intracuff pressure of 60 cm HKingdom) . SuccessKingdom) .2 concentration of 35–45 mmHg. Anesthesia was maintained in all patients with sevoflurane mixture of FiO2 0.5 and air. The depth of anesthesia was monitored using the Bispectral Index . BIS sensors were placed in the right and left frontal areas under the hairline and covered with tape to prevent exposure to light. MAC value of Sevoflurane was titrated so that the BIS value was between 40 and 60 during operation. In addition, 0.1–0.3 μg/kg/min IV remifentanil infusion was used.After successful airway management, volume-controlled mechanical ventilation  was initiated at a tidal volume of 8 ml/kg and a respiratory rate of 12 breaths/min; then, the respiratory rate was adjusted to maintain an EtCOThe primary outcome of the present study was to evaluate tracheal blood leakage in patients, who underwent septoplasty and whose airway patency was maintained by the LMA-S or the ETT, using a fiberoptic bronchoscope. At the end of the surgeries, a 3.5 mm fiberscope  was used to examine blood leakage through both airway devices . In the patients for whom an ETT was used, the posterior oropharynx was aspirated carefully at the end of the surgeries; after extubation, the presence of blood around the distal area of the ETT cuff was examined. To evaluate the presence of blood , a four-point scale was used  . Blood l2 flow was set to 3 L/min in the flowmeter, and the expiratory valve was closed. To prevent bias, one researcher covered the airway device so that the airway device type was not visible; then, another researcher checked the peak pressure value as soon as the first researcher heard an oropharyngeal leak sound, confirming that the pressure remained constant (manometer stability test) [2O, the expiratory valve was opened, and the test was ended. MAP and HR were measured immediately before anesthesia induction and at the 5th, 15th, 30th min of perioperatively and 5th min after the extubation and airway placement were confirmed.The secondary outcome of the study was to evaluate OLP; hemodynamic response, including HR and MAP; adverse events, including sore throat, nausea, and vomiting; dysphagia; and dysphonia. OLPs were measured for the LMA-S and the ETT when the head was in a neutral position. The Oty test) . This vaIn the 24-h postoperative period, sore throat, nausea, vomiting, dysphagia, and dysphonia were recorded at the 2nd, 6th, 12th, and 24th hours. Sore throat was defined as continuous pain felt independently from swallowing, evaluated using a numeric rating scale (NRS) between 0 and 10. According to the NRS, the sore throat score was evaluated as “0-1 none; 2-4 mild; 5-7 moderate; and 8-10 severe” . A 4-poiThe patients who opened their eyes with stimuli and had regular spontaneous breathing, a respiratory rate of 12–20/min, and an oxygen saturation larger than 95% were extubated and taken to the recovery room. The patients were transferred to the Otorhinolaryngology ward when they achieved a modified Aldrete’s score of nine or greater , indicating recovery sufficient for the patient to be transferred from Postoperative Care Unit (PACU) to the ward . All pathttp://biostatapps.inonu.edu.tr/WSSPAS/).A type I error  0.05, strength of the test (1-beta) 0.9, effect size 0.71 for the amount of blood in the primary output variable airway (glottis/trachea), and the alternative hypothesis (H1) were employed to calculate the minimum sample size. Subsequently, the minimum sample size was determined to be 40 for each group and 80 patients in total in order to find a significant difference [P < 0.05 was considered as significant. IBM SPSS Statistics version 25.0 for Windows was used for the statistical analysis.Quantitative data were expressed as mean with standard deviation and median (min-max) values depending on the variable distribution, and qualitative data were summarized as frequency (percentage) for the related variables. Normality distribution was assessed using the Shapiro Wilk test. Quantitative data was analyzed using the independent samples t-test and the Mann Whitney U-test, where appropriate. Qualitative data was analyzed with the Pearson chi-square or the Fisher’s exact test, where appropriate. A value of A total of 80 patients were included in this study. A flow diagram is presented in Fig. p = 0.004). The blood leakage in the distal trachea was significantly lower in the LMA-S group than in the ETT group (p = 0.034). OLP was 21.60 ± 3.74 cmH2O in the LMA-S group and 22.88 ± 5.52 cmH2O in the ETT group; there was no statistically significant difference between the groups (p = 0.577). Clinical outcome variables by airway type are presented in Table The blood leakage in the glottis/trachea was significantly lower in the LMA-S group in the ETT group (p = 0.003). There was no significant difference between the groups at other time points. The HR of the patients in the two groups at various time points are presented in Table p = 0.029). There was no significant difference between the groups at other time points. The MAP of the patients in the two groups at various time points are presented in Table p = 0.003, p = 0.017 and p < 0.001, respectively).Heart rate was significantly lower in the LMA-S group at 15 min after intubation than in the ETT group p = 0.00. There wp = 0.057). Nausea, vomiting, dysphagia, and dysphonia were similar in both groups. The postoperative adverse events are presented in Table There were no differences between the groups in terms of having a sore throat at the 24th postoperative hour p = 0.07. NauseaIn this study, in which LMA-S and ETT use was compared in terms of tracheal blood leakage and adverse events in septoplasty cases, the blood leakage in the LMA-S group was statistically less than in the ETT group; this was determined by examining the airway for the presence of blood with a fiberoptic bronchoscope.Many anesthetists and otolaryngologists are concerned about using the LMA due to concerns that blood leakage from the posterior to the hypopharynx during nasal and endoscopic sinus surgery could contaminate the vocal folds and the tracheobronchial tree, causing laryngospasm and bronchospasm. Therefore, for such operations, the ETT has been the first choice for airway safety. In the literature, there are studies comparing LMA and ETT use in nasal surgeries , 19. Al-In septoplasty cases, the LMA-S avoids blood leakage to the glottis and the trachea, with its high sealing effect in the oropharynx, by surrounding the supraglottic and glottic area . With thp = 0.004); distal trachea: LMA-S: 4 cases (10%), ETT: 11 cases (27.5%), p = 0.034). Unlike Kaplan et al., we found significantly less blood in both the glottis/trachea and the distal trachea in the LMA-S group. The reasons for the differences between the two results may be, first that our study examined only septoplasty cases, while Kaplan et al. included septoplasty, endoscopic sinus surgery, and combined septoplasty/endoscopic sinus surgery cases in their study. Second, in our study, the intracuff pressure was applied as 60 mm H2O in the LMA-S and 20 H2O in the ETT, but Kaplan et al. did not report any information on which intracuff pressures they used in the airway devices. Therefore, differences in cuff pressures may have affected the results. In many studies in which the LMA and the ETT were compared without using fiberoptic bronchoscopes in patients who underwent nasal and sinus surgeries, it was concluded that the LMA provided better airway protection [Kaplan et al. conducted a study in which 74 patients, who underwent septoplasty or endoscopic sinus surgery, were compared in terms of ETT and LMA-Classic use; they reported that the presence of blood in the glottis/trachea level was at a less significant level in the LMA-Classic group than in the ETT group . Howeverotection . Therefo2O in 99 cases in which the LMA-S was used with an intracuff pressure of 60 cmH2O [2O) in 123 cases, OLP was measured as 26, 20, and 18 H2O, respectively [2O in LMA-S and 22.8 in ETT, and did not differ between the groups. In summary, the OLP values in these other studies are consistent with our OLP values.Oropharyngeal leakage pressure is a gas leak occurring around the airway device. In general, the verification of the position of the airway device shows the success of positive-pressure ventilation and the degree of airway protection. It is also used to evaluate the effectiveness of different airway devices . Seet et60 cmH2O . In anotectively . In our 2O; they reported no significant differences between the LMA-S and other airway devices in terms of postoperative sore throat [2O as a reference. Barreriera et al. compared LMA-S and ETT use in their study and found that the incidence of sore throat was significantly higher in the ETT group using a ETT cuff pressure of 25–30 mm cmH2O [p = 0.003, p = 0.017 and p < 0.001, respectively). Therefore, we believe that the LMA-S causes fewer sore throats at appropriate intracuff pressures in septoplasty cases than the ETT.Postoperative sore throat is among the pharyngolaryngeal adverse events that commonly occur after general anesthesia, decreasing patient satisfaction and causing prolonged hospital stays. In addition to the direct trauma of the rigid materials that are inserted in the upper airway, the physical tension caused by the laryngoscopy, tube size, gender, surgery type, and cuff pressures may cause postoperative throat complaints after tracheal intubation , 27. In e throat . For thimm cmH2O . SimilarOur study had some limitations. First, in the ETT group, the presence of blood at the vocal cord level was evaluated visually by the presence of blood on the cuff after extubation, since it was not possible to assess it with a flexible bronchoscope. Secondly, the amount of bleeding in the airway could not be measured due to technical difficulties of aspiration and the risk of undesirable airway reflexes .As evident in our findings, we have determined that the LMA-S is superior to the ETT in protecting the airway against blood contamination and reducing postoperative sore throat associated with general anesthesia in septoplasty surgeries. We also believe that the LMA-S may be a more reliable and better alternative to the ETT for airway management in septoplasty surgeries.


An algorithm derived from machine learning uses the arterial waveform to predict intraoperative hypotension some minutes before episodes, possibly giving clinician’s time to intervene and prevent hypotension. Whether the Hypotension Prediction Index works well with noninvasive arterial pressure waveforms remains unknown. We therefore evaluated sensitivity, specificity, and positive predictive value of the Index based on non-invasive arterial waveform estimates. We used continuous hemodynamic data measured from ClearSight (formerly Nexfin) noninvasive finger blood pressure monitors in surgical patients. We re-evaluated data from a trial that included 320 adults ≥ 45 years old designated ASA physical status 3 or 4 who had moderate-to-high-risk non-cardiac surgery with general anesthesia. We calculated sensitivity and specificity for predicting hypotension, defined as mean arterial pressure ≤ 65 mmHg for at least 1 min, and characterized the relationship with receiver operating characteristics curves. We also evaluated the number of hypotensive events at various ranges of the Hypotension Prediction Index. And finally, we calculated the positive predictive value for hypotension episodes when the Prediction Index threshold was 85. The algorithm predicted hypotension 5 min in advance, with a sensitivity of 0.86  and specificity 0.86 . At 10 min, the sensitivity was 0.83  and the specificity was 0.83 . And at 15 min, the sensitivity was 0.75  and the specificity was 0.75 . The positive predictive value of the algorithm prediction at an Index threshold of 85 was 0.83 . A Hypotension Prediction Index of 80–89 provided a median of 6.0  minutes warning before mean arterial pressure decreased to < 65 mmHg. The Hypotension Prediction Index, which was developed and validated with invasive arterial waveforms, predicts intraoperative hypotension reasonably well from non-invasive estimates of the arterial waveform. Hypotension prediction, along with appropriate management, can potentially reduce intraoperative hypotension. Being able to use the non-invasive pressure waveform will widen the range of patients who might benefit.Clinical Trial Number: ClinicalTrials.gov NCT02872896.The online version of this article (10.1007/s10877-020-00463-5) contains supplementary material, which is available to authorized users. The association between hypotension and serious complications and mortality in non-cardiac surgical patients is well established –7. ThereRecently, an algorithm  based on machine learning was developed which predicts intraoperative hypotension  with a sensitivity and specificity of 88%  and 87%  15 min before a hypotensive event. The area under the receiver operating characteristics curve was 0.95  . DevelopAdvances in non-invasive hemodynamic monitoring now allow arterial pressure waveforms to be estimated from a finger cuff –16. But For this post hoc analysis, we used hemodynamic data measured by noninvasive finger cuff monitors  in patients enrolled in a randomized trial of continuous noninvasive blood pressure monitoring during noncardiac surgery. The trial was approved by the Cleveland Clinic Institutional Review Board (IRB # 16-845) and written informed consent was obtained from all subjects participating in the trial. The trial was registered before patient enrollment at clinicaltrials.gov  . We enroPatients were excluded if the attending anesthesiologist determined that invasive arterial monitoring was needed. Patients were also excluded when there was more than a 10% discrepancy in preoperative MAP between the arms, or if the expected duration of surgery exceeded 2 h.The detailed trial protocol has been published . BrieflyThe continuous blood pressure monitor was properly positioned and all patients also had a cuff on opposite arms for intermittent oscillometric measurements. In the unblinded group, information from the continuous monitor was available to clinicians in addition to the usual oscillometric values. In the blinded group, blood pressure management was based only on intermittent oscillometric blood pressure monitoring per routine; information from continuous monitors was not available to the clinicians but recorded for analysis purposes. Oscillometric measurements were typically obtained at 5-min intervals, but clinicians were free to select any interval and to change it as conditions warranted. Clinicians were asked to minimize the amount and severity of hypotension < 65 mmHg MAP. However, the study protocol did not specify any particular approach. Clinicians were thus free to use any type and amount of intravenous fluids, whatever dose of vasopressors and inotropes they cared to and to adjust the inhalational concentration and intravenous anesthetic drugs as necessary.The Hypotension Prediction Index was not available to either group and was calculated post hoc. But hypotension management and thus algorithm performance metrics might be influenced by the availability of continuous arterial pressure and the early treatment in the unblinded group. We therefore separately evaluated HPI performance in unblinded and blinded patients, as well as in the entire cohort.The Hypotension Prediction Index is based on an algorithm that estimates the likelihood of a hypotensive event in the near future. The HPI algorithm takes arterial pressure waveform as the input, then extracts various waveform features, then together with the patient demographics , it computes an index value that ranges between 0 and 100: the larger the value, the more likely and the sooner a hypotensive event will occur. For this study, raw arterial waveform data from our previous study , togethePositives and negatives need to be defined for a receiver operating characteristic (ROC) analysis. We defined positive samples as data points exactly ‘t’ minutes  prior to a hypotension event, where a hypotensive event is defined as MAP ≤ 65 mmHg for at least 1 min. A negative sample was selected from each non-event segment of 30-min duration, where a non-event segment was at least 20 min from any hypotensive events and had MAP > 75 mmHg. The HPI model used in this noninvasive analysis was identical to the invasive HPI model developed previously . SensitiIn this analysis, we compared actual occurrences of hypotensive events to the predicted rate in 15 min and separately in the blinded, unblinded, and combined cohort. For every data point in a given HPI range, a 15-min forward search window was used to locate a hypotensive event. The percentage of all data samples with a hypotensive event compared to the total number of samples in the HPI bin was the rate of hypotension for that bin.Positive predictive value of dynamic algorithms like HPI provides incomplete information because PPV does not take into account the continuous nature of monitoring . A challWe tried to mitigate false-positive events by identifying rapid increases in MAP that were potentially consequent to clinical interventions. Specifically, we defined rapid mean pressure increases as > 5 mmHg in 20 s or > 8 mmHg in 2 min from a baseline MAP < 75 mmHg based on Hatib et al.  analysisWe calculated the positive predictive value (PPV) at an HPI threshold of 85. We selected an HPI threshold of 85 since the current commercial implementation includes an alarm at this value. True positives were all data samples with HPI value above 85 and a hypotensive event within 15 min in the future. False positives were all data samples with HPI value above 85 but without a hypotensive event within 15 min in the future. PPV was calculated as the ratio of true positives to all data points with HPI value above 85. We assumed rapid increases in blood pressure were true positives only when there was supportive evidence in the medical record, and eliminated other blood pressure increases from the analysis.All statistics were performed with MATLAB . Repeated measurents from same subjects were evlauated  by bootstrapping method , where aFour patients enrolled in the underlying trial did not receive the allocated intervention and 11 others had incomplete waveform data. Consequently, a total of 305 of patients were included in this analysis, with an average age 60 ± 9 years, weight 98 ± 28 kg and height 171 ± 10 cm. The incidence and severity of hypotension are characterized by various way in Table Figure Figure The positive predictive values of the algorithm were similar in the blinded and unblinded groups. We thus present results for the entire population at an HPI threshold of 85. The positive predictive value prediction was 0.83  when rapid increases in blood pressure after HPI reached 85 were considered to be true positives only when there were supportive clinical interventions in the electronic record, and other rapid increases, presumably due to surgical manipulations, fluid boluses, change in anesthetic level, etc. were excluded from the analysis altogether..Our primary result is that the Hypotension Prediction Index, which was developed and validated from invasive arterial waveforms, works reasonably well with non-invasive arterial pressure waveform estimates. Given that the vast majority of noncardiac surgical patients are monitored non-invasively, our findings markedly broaden the range of patients who might benefit.The non-invasive ClearSight system used in our investigation gives reliable estimates of arterial pressure even in highly dynamic situations such as during induction of anesthesia  and clamPositive predictive value of dynamic algorithms like HPI provides incomplete information because PPV does not take into account the continuous nature of monitoring and possible interventions . Clinicamax [Clinicians use a wide variety of hemodynamic measurements and experience to anticipate intraoperative blood pressure changes. Factors related to surgical procedures, anesthetic drugs, and advanced hemodynamic parameters when available all guide clinicians to manage blood pressure. Stroke volume variation –22, pulsmax , 30, andmax . All helIn summary, the Hypotension Prediction Index, which was developed and validated with invasive arterial waveforms, predicts intraoperative hypotension reasonably well from non-invasively measured arterial blood pressure waveforms. Being able to use non-invasive pressure waveforms will widen the range of patients who might benefit.Electronic supplementary material 1 (JPG 51 kb) HPI behavior prior to a hypotensive event; A. All events, thick line is the mean, B. Mean and standard deviation. HPI, hypotension prediction indexBelow is the link to the electronic supplementary material.


The frequency of laughter has been associated with cardiovascular disease and related biomarkers, but no previous studies have examined association between laughter and changes in blood pressure levels. We sought to identify temporal relationships between frequency of laughter in daily life and systolic and diastolic blood pressure changes in participants from 2010 through 2014.Participants were 554 men and 887 women aged 40–74 years who answered self-administered questionnaire quantifying frequency of laughter at baseline. We measured participant blood pressure levels twice using automated sphygmomanometers for each year from 2010 to 2014. The associations between laughter and changes in blood pressure over time were analyzed using linear mixed-effect models.P = 0.05). Changes in blood pressure associated with infrequent laughter  were evident in men without antihypertensive medication use over 4 years  and men who were current drinkers at baseline . No significant difference was found between frequency of laughter and systolic  and diastolic  blood pressure changes in women.There was no significant difference in blood pressure according to frequency of laughter at baseline in either sex. Men with frequency of laughter 1 to 3 per month or almost never had significantly increased systolic and diastolic blood pressure levels over the 4-year period (time-dependent difference: 0.96 mm Hg (95% confidence interval [CI], −0.2 to 1.8; Infrequent laughter was associated with long-term blood pressure increment among middle-aged men. In 1976, Norman Cousins, a sufferer of ankylosing spondylitis, made the joyous discovery that 10 minutes of genuine belly laughter allowed him to sleep without pain for at least 2 hours. He subsequently adopted laughter as a treatment for his disease.8 Reduced mental stress may contribute to reduced activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system,9 as well as improve vascular endothelial function10 and heart rate variability.11 All of these effects may in turn reduce blood pressure levels.12 A previous study showed that the mean value of salivary cortisol concentration, a surrogate marker of mental stress, declined after the participants watched a comedy, and this value was particularly lower in both men and women who laughed everyday compared with those who laughed less often.8The frequency of laughter in everyday life is associated inversely with mental stress.7,13,14 no previous studies have examined the association between the frequency of laughter and blood pressure levels, an important risk factor for cardiovascular disease. If the beneficial impact of laughter on blood pressure levels is confirmed, psychological interventions to increase the frequency of laughter may contribute to the prevention of cardiovascular disease.Although various mechanisms have accounted for the association between laughter and cardiovascular disease and related biomarkers,a prior hypothesis that lower frequency of laughter may lead to incremental increases in blood pressure levels. We aimed to identify the temporal relationship between the frequency of laughter in daily life and blood pressure levels over 4 years. Since lifestyles  and social psychological factors are largely different between men and women,15 we carried out sex-specific analyses.Therefore, in this longitudinal study, we examined the effect of laughter on blood pressure levels in the general population. We sought to examine our 16–18 Annual cardiovascular risk surveys have been conducted between mid-November and mid-December since 1981.16,17 The study subjects were residents aged 40–74 years who participated in the annual health checkups from 2010 through 2014 in the CIRCS.The participants were the residents of Kyowa, a rural district of Chikusei City, Ibaraki Prefecture, Japan. The Kyowa community is included in the community-based part of the Circulatory Risk in the Community Study (CIRCS).In 2010, a baseline self-administered questionnaire quantifying the frequency of laughter was administered to 1,710 Kyowa residents  aged 40–79 years old. We excluded 269 participants who had a history of cardiovascular disease (stroke and coronary artery disease) or were missing information on the frequency of laughter, age, or sex at the baseline. As a result, 1,441 participants (554 men and 887 women) remained eligible for the study from the baseline.Furthermore, we separately analyzed participants with and without antihypertensive medication use between 2010 and 2014 and conducted the stratified analysis according to the baseline drinking status. Antihypertensive medication use was defined as “yes” in any of annual surveys between 2010 to 2014.In the questionnaire, we asked participants, “How often do you laugh out loud in your daily life?” to measure their frequency of laughter. Respondents could choose one of four possible answers: “almost every day”, “1 to 5 days per week”, “1 to 3 days per month”, or “almost never”. In this study, the categories of “1 to 3 days per month” and “almost never” were combined because only 36 participants (25 men and 11 women) answered “almost never”. We chose “almost every day” as the reference category.P < 0.001).19 In addition, no regional or seasonal differences were found in the frequency of laughter among Japanese men and women.20 Therefore, the questionnaire on laughter is reliable and generalizable.The 1-year test–retest reliability of the questionnaire was assessed in a previous study of 2,680 men and women aged 30–74 years  on their right arms once a year from 2010 to 2014.From the baseline, 1,441 participants (554 men and 887 women) remained eligible for this study. The numbers of participants for subsequent annual follow-ups were 713 (49.5%) for all four follow-ups, 225 (15.6%) for three follow-ups, 157 (10.9%) for 2 follow-ups, 148 (10.3%) for 1 follow-up, and 198 (13.7%) for no follow-up. We included these 198 participants who were lost to follow-up in the analyses.2). Socks and light clothing were included when measuring height and weight. Waist measurements were made at the umbilical level and clothes were removed at the time of measurement. Each participant was interviewed to determine their usual weekly alcohol consumption in “go” units, a traditional Japanese unit of volume equivalent to 23 g of ethanol. Smoking status and history were also determined in the interview, as well as the present daily number of cigarettes smoked. Histories of hypertension, stroke, coronary heart disease, and use of antihypertensive medication were also collected during the interview.We calculated participant body mass index (BMI) by dividing weight (kg) by the square of height (mLow-density lipoprotein (LDL) cholesterol (mg/dL), high-density lipoprotein (HDL) cholesterol (mg/dL), blood glucose levels (mg/dL), and factors related to cardiovascular disease were measured at the annual health examination. Fasting glucose ≥5.55 mmol/L (100 mg/dL), non-fasting glucose ≥7.77 mmol/L (140 mg/dL), HbA1c level ≥6.5%, and/or diabetes treatment were defined as hyperglycemia.To measure participants’ mental health, we asked, “Do you feel stressed in your work or daily life?” and offered the following response options: “all of the time”, “much of the time”, “a little”, or “almost never”. We also asked, “Have you had little interest or pleasure in doing things in the past month?” and “Have you felt depressed or hopeless in the past month?”, to which participants responded with “yes” or “no”.This study was approved by the ethics committees of the University of Tsukuba , Osaka University , and Ethics Review Board of Juntendo University’s Faculty of Medicine (2016091), and the institutional review boards of the Osaka Center for Cancer and Cardiovascular Disease Prevention (26-rinri-1). In accordance with Japanese ethical guidelines, we provided participants with information about our study at the survey sites and informed them of opt-out opportunities. All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.We obtained informed consent for the use of existing data from representatives in communities, but not from each research participant since the current study is the secondary use of the data obtained for public health practice on cardiovascular disease prevention in local communities. However, participants were given the option to withdraw their consent. If the participant(s) did not clearly decline consent, their consent was granted in the present study.22:ijy represents the systolic and diastolic blood pressure levels for individual i taken at time j; β0 is the overall intercept; βp is the effect of the frequency of laughter, considered as constant across time; βT represent respectively the intercept and the slope of the linear relationship between the systolic and diastolic blood pressure levels and time at which the outcome was measured; and βPT is the effect of laughter frequency on the slope describing the linear relationship between blood pressure levels and time (blood pressure changes per year). Coefficients for this model were estimated by maximum likelihood using the SAS MIXED procedure and specifying a compound symmetry structure for the covariance matrix.22–25Age-adjusted means and proportions of various lifestyle and psychological factors were tested using analysis of covariance and by conducting chi-square tests of baseline characteristics. To examine the effect of changes in the frequency of laughter on changes in blood pressure over time, we analyzed the data using mixed effects modeling, the commonly accepted method for dealing with longitudinal data, which accounts for correlations among measurements taken from the same individual. In the present study, we used the following model (SAS MIXED procedure)2) from 2010 to 2014. Covariate measurements were assessed at study baseline. When the frequency of laughter was missing, we used available measurements closest in time when the frequency of laughter was assessed. To assess the potential modifying effects of baseline age and change in age on the relation of the frequency of laughter with blood pressure levels over time, we ran regression models that included cross-product terms for interaction between age and change in age with the frequency of laughter along with the main-effects.The covariates included baseline age, time (the difference in age between the baseline and the time at which the outcome was measured), presence of stress at the baseline , presence of declining interest and depressed mood before the baseline (yes or no), participants’ baseline occupational status , smoking status from 2010 to 2014 (yes or no), drinking status from 2010 to 2014 , antihypertensive medication use from 2010 to 2014 (presence or absence of medication), and BMI  was considered statistically significant, except for a P value <0.10 in the interaction analysis according to previous study.25,27We used SAS software version 9.4  for all analyses. A Table P = 0.05) and diastolic blood pressure  compared with men with the frequency of laughter ≥1 day/week. In this group, mean systolic blood pressure at the baseline in 2010 was 130.7 mm Hg and increased to 134.1 mm Hg in 2014. Mean diastolic blood pressure was 75.9 mm Hg at the baseline and increased to 78.9 mm Hg in 2014. In women, the mean systolic and diastolic blood pressure did not change over the 4 years in any group.Table P = 0.09) and diastolic blood pressure  over time. In this group, mean systolic blood pressure at the baseline in 2010 was 129.8 mm Hg and increased to 134.3 mm Hg in 2014. We found a similar association for diastolic blood pressure (75.4 mm Hg at the baseline and 78.6 mm Hg in 2014). However, no significant difference in blood pressure change was evident according to the frequency of laughter in men with antihypertensive medication use and in women with or without antihypertensive medication use.Table Sex-specific changes in systolic and diastolic blood pressure over time according to the frequency of laughter in everyday life by baseline drinking status are shown in In this study, we found no significant difference in systolic and diastolic blood pressure levels according to the frequency of laughter at the baseline. However, men who replied that they laughed “1 to 3 days per month” or “almost never” had significantly increased systolic and diastolic blood pressure over the 4-year period compared to those who answered that they laughed “almost every day” or “1 to 5 days per week”. We found no significant change over time for either systolic or diastolic blood pressure in women. The effect of the frequency of laughter on blood pressure increment was more evident in men without antihypertensive medication use during the study period and men with current drinking status at the baseline.8,28 The relationship between laughter and mental stress has been documented in previous intervention studies. A randomized controlled trial was conducted in Korean breast cancer patients using a four-session therapeutic laughter program (n = 31) to examine the effect of mental health status  compared with control patients (n = 29).29 Each therapeutic laughter session was a 60-minute class of laughing in rhythm with clapping, laughing for a long time, laughing with the whole body, laughing in various ways, and laughing together with dance routines. In that trial, participants showed significantly lower anxiety, depression, and stress levels after the first laughter session, which remained thereafter.29 Another Iranian randomized controlled trial with the laughter therapy program  found a significant increase in general health scores (P = 0.001) and a decrease in somatic symptoms scores (P = 0.001), as well as insomnia and anxiety scores (both P = 0.001).30A plausible mechanism for the association between the frequency of laughter and blood pressure may be through the effect of mental stress.31 The trial participants watched a 30-minute comedy or documentary on separate days, which led to the brachial artery flow mediated dilation (FMD), a marker of endothelial function, increasing significantly after watching a comedy and reducing after watching a documentary.31 Reduced FMD was associated with higher systolic and diastolic blood pressure levels,32 which is a known predictor of future cardiovascular events.33Another mechanism for the association between the frequency of laughter and blood pressure levels may be through the improvement of vascular endothelial function. A cross-over trial of 17 apparently healthy adults (23–42 years of age) investigated the relationship between laughter and vascular function.14,34 In our longitudinal study, however, the lower frequency of laughter at baseline was associated with the overtime increase in systolic and diastolic blood pressure among men. Our study is the first to find longitudinal association between infrequent laughter and blood pressure increases.Previous studies found no association of the laughter frequency with the prevalence of hypertension at baseline.26 Only 9% of women were current drinkers; thus, the association between infrequent laughter and blood pressure increment was unlikely to appear.We found no significant association between the frequency of laughter and blood pressure changes in women. One of the explanations for the lack of association for women may be much lower means level of systolic and diastolic blood pressures at the baseline in women than in men, which made it difficult to detect any effect of laughter on blood pressure changes. Another explanation may be the effect modification by alcohol consumption on the association between laughter and blood pressure changes. The significant positive association between infrequent laughter and blood pressure increment was confined to current drinkers in men probably because alcohol consumption increases blood pressure levels which may likely detect that association or because of unknown reasons.A strength of the present study is a prospective study with a large sample size to identify the association between the frequency of laughter and blood pressure levels over a period of 4 years. Most of the subjects (86.3%) had more than one blood pressure measurement between 2010 and 2014. Moreover, there was no significant difference in baseline characteristics, including the frequency of laughter and baseline blood pressure levels, between subjects who had more than one blood pressure measurement and those who only had the baseline blood pressure measurement (not shown in tables). Therefore, the withdrawal from the follow-up was unlikely to affect the results.19,35 we did not collect the information on education status, income, or other socioeconomic factors other than occupational status as potential confounders, so we could not rule out the possibility of residual confounding. Fourth, we could not consider the effect of positive emotions other than laughter, such as contentment, amusement, and optimism due to the lack of data. Lastly, the effect of infrequency laughter on blood pressure increment was more evident in men without antihypertensive medication use during the study period. However, the respective samples with antihypertensive medication use for the frequency of laughter of “1 to 3 days per month” or “almost never” were unlikely to have enough statistical power to detect any significant effects. Statistical power with alpha 5% using a MIXED model was 68% for a time-dependent difference of systolic blood pressure and 57% for that of diastolic blood pressure.The present study has several limitations. First, the frequency of daily laughter was evaluated using a single self-reported question. It is possible that the perceived frequency of laughter differs from actual frequency. Second, we only had information regarding declined interest, feelings of subjective stress, and depression at the baseline. Therefore, we could not consider changes in the negative emotional status from 2011 to 2014 in the analyses. Furthermore, all the answers to questionnaire were self-reported and we used a single simple question rather than scores about negative emotions, such as self-perceived mental stress, depressed mood, and declined interest. We also lacked objective data on negative emotions. Third, although previous studies showed that higher income and high social participation were significantly associated with higher frequency of laughter,In conclusion, the present longitudinal observational study suggests that infrequent laughter leads to the increment of blood pressure levels during a 4-year period among middle-aged men. Future studies should investigate whether psychological interventions are useful for preventing or controlling hypertension in men who laugh infrequently.


Cardiovascular diseases, including ischemic heart disease, are the most common causes of morbidity and death in the world, including Serbia, as a middle-income European country. The aim of the study was to determine the costs of preventive examinations for ischemic heart disease in active-duty military personnel, as well as to assess whether this was justified from the point of view of the limited health resources allocated for the treatment of the Republic of Serbia population. This is a retrospective cost-preventive study which included 738 male active-duty military personnel, aged from 23 to 58. The costs of primary prevention of ischemic heart disease in this population were investigated. Out of 738 subjects examined, arterial hypertension was detected in 101 subjects . Average costs of all services during the periodic-health-examination screening program were €76.96 per subject. However, average costs of all services during the periodic-health-examination screening program for patients with newfound arterial hypertension and poorly regulated arterial hypertension were €767.54 per patient and €2,103.63 per patient, respectively. Since periodic-health-examination screening program in military personnel enabled not only discovery of patient with newfound arterial hypertension but also regular monitoring of those who are already on antihypertensive therapy, significant savings of €690.58 per patient and €2,026.67 per patient can be achieved, respectively. As financial resources for providing health care in Serbia, as a middle-income country, are limited, further efforts should be put on screening programs for ischemic heart disease due to possible significant savings. Cardiovascular diseases (CVDs), including ischemic heart disease (IHD), are the most common causes of morbidity and death in the world, but with especially high prevalence in low- and middle-income countries (LICs and MICs) . MoreoveDespite earlier beliefs that AH is not significantly prevalent in young people, it was shown that in the population aged between 20 and 40 years, one in eight adult people has high blood pressure . UnfortuTherefore, the aim of this study was to determine the costs of preventive examinations for IHD in the active-duty military personnel, as well as to assess whether this was justified from the point of view of the limited health resources allocated for the treatment of the Republic of Serbia Army military personnel.This is a retrospective cost-preventive study, performed from September 2018 to July 2019, which included 738 male active-duty military personnel of the Serbian Army, aged from 23 to 58, examined only once during the regular 1-year follow-up.For the categorization of the level of blood pressure, the average value of all three measurements was used and the information of AH treatment over the last 4 weeks if the person has already taken antihypertensive therapy. According to the 2018 European Society of Cardiology and European Society of Hypertension Guidelines, the examinees were classified according to the values of blood pressure into the following categories: normal blood pressure (systolic blood pressure/diastolic blood pressure: <139/<89 mmHg) and hypertension (systolic blood pressure/diastolic blood pressure: >140 and/or >90 mmHg) , 18.The costs of primary prevention of IHD of professional military personnel were investigated. This examination included biochemical analyses , body measurements , blood pressure and pulse rate values, color Doppler echocardiography, and specialist examination, here as preventive procedures.Data on expenditures were presented as the sum of total costs for all subjects. They were also presented as an average cost per subject, average cost per patient with newfound AH, and average cost per patient with newfound and poorly regulated AH. The criteria for poorly regulated AH were values over 140 and/or 90 mmHg during this preventive examination, although they were already on antihypertensive therapy, according to their medical records.The principles of ICH Good Clinical Practice were strictly followed, and ethical approval no. 151/2019 (05/11/2019) from the Ethics Committee of the Military Medical Academy was obtained for the study protocol.ex officio subject of the regular systematic examinations.This study is part of the research project of the Ministry of Defense of the Republic of Serbia entitled “Primary prevention of IHD of professional military personnel and civilians employed in the Army of the Republic of Serbia.” The aim of this project is to implement modern principles of CVD prevention in the part of the population that is an The data were analyzed using the Statistical Package IBM-SPSS, version 26.0. Categorical variables (subjects with or without AH) were presented as frequency and were analyzed using the chi-square test.AH (>140 and/or >90 mmHg) was recorded in 101 subjects out of 738 examined . HoweverAll expenditures of services performed during the periodic-health-examination screening program which involved 738 male active-duty military personnel in the Republic of Serbia amounted to €56,798.1 . The larThe average cost of all services during the periodic-health-examination screening program in active-duty military personnel in the Republic of Serbia  was €76.ex officio subject of the regular systematic health examinations. In this paper, we report the costs of preventive examinations for IHD in the active-duty military personnel, from the point of view of the limited health resources allocated for the treatment of not only this population but the whole Serbian population as well. In addition to the expanded type of laboratory tests performed, special attention was paid to the values of arterial blood pressure, since AH, as a risk factor for CVDs, was at first place and drove the most death from 2009 to 2019 in Serbia , as MIC situated in the Balkan region , 7. Largn Serbia . Accordin Serbia , 23. Litn Serbia . In thisn Serbia . The conn Serbia . High len Serbia , 20. A dn Serbia , 25.In addition to the health care status of the military personnel, reduction of the health care costs is also very important for each national army force. In our study, the average cost of all services during the periodic-health-examination screening program was €76.96 per subject. However, the average costs of all services during this program for patients with newfound AH and poorly regulated AH were €767.54 per patient and €2,103.63 per patient, respectively. The economic aspects of AH are very important for the implementation of prevention and therapy of modern principles, in both the civilian and military sectors . The higEpidemiological burden with chronic NCDs, like CVDs, together with a population which is much older means that difficulties in financing health care will be very serious even for the richest countries, such as nations of the OECD, BRICS, and the Group of Seven (G7) nations –34. DiffThe results of our study enabled us not only to discover the patients with newfound AH but also to regularly monitor those who were already on antihypertensive therapy and detect significant savings of €690.58 per patient and €2,026.67 per patient, respectively. These results encourage us to continue our research, in order to assess the cardiovascular outcomes in our examinees after a longer period of follow-up, as well as the costs not only for prevention but also for the treatment of conditions resulting from numerous risk factors for CVDs in our military personnel. Moreover, 19.51% of the examined military population had AH, while that value in the general population in Serbia accounted for about 27–28% –23. HoweThe limitation of our study refers to the fact that blood pressure during the periodic health examination of military personnel was registered only once, although the measurements were repeated three times. However, these blood pressure checks in each person have already been performed once a year, in previous years, and will be done regularly in the future. Additional laboratory tests and specialistic examinations were introduced, and costs of preventive examinations for IHD were determined. Moreover, the prices of each service provided are shown, as well as savings achieved as a result of early detection of high blood pressure, as well as of constant monitoring of those individuals who are already on therapy.The average cost of all services during the periodic-health-examination screening program for IHD in active-duty military personnel in the Republic of Serbia was €76.96 per subject. However, these examinations enabled not only discovery of the patients with newfound AH but also regular monitoring of those who were already on antihypertensive therapy, and significant savings from €690.58 per patient to even €2,026.67 per patient, respectively, were achieved. Taking into account the very limited financial resources for providing health care in Serbia, as a MIC, in both the civilian and military sectors, further efforts should be put on screening programs for IHD in both populations, due to possible significant savings.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Ethics Committee of the Military Medical Academy. The patients/participants provided their written informed consent to participate in this study.NRat and RS: conceptualization. NRat and NRan: methodology. VP and MP: software. NRat, VDS, ZS, MJ, and NRan: formal analysis. VP, MP, ZS, and NRat: investigation. RS, NRat, VDS, and NRan: writing—original draft preparation. RS, NRat, VDS, MJ, and NRan: writing—review and editing. NRat: project administration. All authors have read and agreed to the published version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.