Chest physiotherapy (CPT) is a care that increases the mobilization of several structures from both muscle and subcutaneous tissue. We planned to investigate the effect of classic CPT on pain, fatigue, satisfaction, and hospital length of stay (LOS) in patients undergoing off-pump coronary artery bypass graft (CABG).  This study was a randomized controlled trial that conducted on 50 patients undergoing elective off-pump CABG. The patients have been randomly divided into two groups; in the group A (n=25) patients received physiotherapy at a single session of classic CPT, 4 times during 2nd to 5th days for 15 minutes in every session, in the group B (n=25) patients had not protocol of this exercise therapy (control).  The average age of all participants was 62.08 ±9.08 years. Of the 50 patients, 33 (66%) was male. Classic CPT significantly decreased pain (P=0.04), hospital LOS (P=0.010) and could increase in patients’ satisfaction (P<0.001). However, it had no considerable effect on fatigue (P=0.725).  According to our findings, classic CPT could improve postoperative care after off-pump CABG surgery Coronary artery bypass graft (CABG) surgery is common cardiac surgery in the world that has both early and late surgical complications compares to other operations . SternalA double-blind randomized clinical trial was conducted on 50 patients undergoing CABG. The procedure is shown in After receiving the written informed consent from patients, they participated voluntarily for off-pump CABG, at Afshar Cardiovascular Surgery Center of Yazd, Iran. Certain cardiothoracic surgeon performed all of the operations. We included only those who gave written informed consent and were medically able to participate in MT postoperatively from March 5, 2016, through April 3, 2016.Patients post off-pump CABG were similar in the inclusion criteria. Patients were excluded from the study if they met the criteria as follow: (a) history of cardiac and thoracic surgery; (b) chronic pain syndrome; (c) prolonged bleeding during hospital stay (more than 200 cc per hour); (d) psychiatric disorders; (e) history of chest trauma and deformity.Eligible participants (n=50) were randomly allocated to the CPT or control group. The participants were divided into two groups; Patients in the group A (n=25) received physiotherapy at a single session of classic CPT 4 times during second to the fifth day for 15 minutes in every session.In the group B (n=25) patients had not protocol of this exercise therapy (control).To perform random allocation, a block of four was applied. Each patient in a block assigned to letters A, B, C, and D. The possible groups that could assign to CPT group were AB, AC, AD, BC, BD, and DC. Then one number from 1-6 was selected at random, for assigning to CPT group; for instance, if number 5 was selected, number 2 would be allocated to the control group.The study was a double-blind trial; so, the participants were unaware of the intervention they had received. The two groups were in separate rooms to avoid possible cross-talking between them. After collecting the data, the secondary blinded researcher measured outcomes. The blinded researcher was not aware of the group of patients whether they were in the control group or CPT group.The data collected using a two-part questionnaire. The first part included items about the demographic information of the participants , and the presence of hypertension (HTN), diabetes mellitus (DM), and hyperlipidemia (HLP)). Also,pre-operation data such as the number of vessels which were involved before the surgery that were single vessel disease (SVD), two-vessel (2VD), and three-vessel (3VD) coronary artery disease were recorded.Part two included a self-report Questionnaire to evaluate the patients’ quality and degree of pain, fatigue and satisfaction.The patients were asked to fill in a questionnaire and rate their pain, fatigue and satisfaction from 0 to 10 . On the fifth day and before discharge, the questionnaire was filled again to determine the patients’ score finally. Pain, fatigue, and satisfaction were measured at the baseline and the end of the intervention period.Patients were received follow-up care and stabled for one day in intensive care unit (ICU) after surgery. After the first postoperative day, they were transferred to the heart ward.Thus CPT sessions must be started from the second postoperative day and only after transfer of the patients to the ward. In order to homogenize the two groups, four 15-minute sessions were determined as quiet time in days 2-5 after surgery. To preventing entering confounding factors, all of the processes of intervention was performed by a just one physiotherapist familiar with methods of physiotherapy in cardiac surgery patients. Selection of the methods of physiotherapy was on a patient-oriented basis; individualized to each patient .The position could be affected by many factors such as the ability to move, tubing and medical equipment connected to the patient and the patient’s preference. After being in the right situation, in the second part, physiotherapist tries to perform gentle and relaxant exercises to reduce anxiety and tensions of the patient. Movements of the shoulder joint  an example of the relaxant movements. This movement is beneficial after heart surgery specially in patients with a long time motionless on the bed. In the third part of each session, the physiotherapist tries to apply MT methods to help patients. These methods are according to the physiotherapist’s knowledge and opinion and due to the patient’s medical condition, the patient’s signs and symptoms as well as the patient’s tolerance. Hence, deep tissue massage, trigger point therapy, neuromuscular techniques, myofascial release, acupressure, some Swedish massage techniques, manual lymphatic drainage, and reflexology were selected. The physiotherapist would attempt not to push, pull or hit the regions which were very close or on the surgical incisions, and they avoid inflicting of physical forces on the patient’s sternum region (due to the mid-sternotomyduring operation). All techniques could be performed in other parts of the body such as the head, neck, shoulders, arms, hands, back, and legs based on the patient’s request. During the second to fourth days after surgery, to unify intervention in intervention and control groups, three 15-minute sessions entitled (silence time) for patients in the control group was considered that the patient was lying on the bed no physical activity. Also, after discharge and at follow-up period, the patients will benefit from standard medical care , it was recommended that patients should comfort on a bed in a low-light environment, every week for thirty minutes.Local Medical Ethics Committee of Shahid Sadoughi University of Medical Sciences (SSU) approved the study proposal with the ID number: 746/G/T.Moreover, this clinical trial registered in the Iranian Registry of Clinical Trials (IRCT) and allocated a unique code IRCT2016010925913N1. All of the participants signed the written informed consent.The data were analyzed by SPSS16 software. Regarding demographic information of participants, descriptive statistics  were calculated. The ANOVA and Chi-square tests were used for analyzed variables and to evaluate the difference between groups. A P-value< 0.05 was considered as significant.In this study, 50 patients who underwent elective off-pump CABG were enrolled.The average age of all participants was62.08 ±9.08 years. In the control group, 40% (10) were female, and 60% (15) were male, and 28% (7) were female, and 72% (18) were male in the CPT group. Totally, 33 patients (66%) were male and 17 patients (34) were female. Of all the participants who were studied in this survey, 30% had DM, and 60% suffered from hypertension (HTN). In addition, 48% of them had hyperlipidemia (HLP), and 30% of them were cigarette smokers (CS). From all the participants, 6% were SVD, 34% with 2VD, and 60% with 3VD coronary artery disease . AccordiOn the other hand, patients who were massaged for 15 minutes complained of less pain in the 2-5 days after surgery. The mean score of pain was 1.56 in the CPT group at the final level, and it was lower in comparison with the control group (3.04).Although, CPT had no considerable effect on fatigue. The mean score of fatigue was 1.28 in the CPT group, and it was approximately close to the score in the control group (1.84).There was no statistical relationship between the CPT and fatigue (P=0.725) . AccordiThe aim of this study was to deal with the effect of CPT on pain, satisfaction, fatigue and hospitalization in post-CABG patients. In this clinical trial, CPT had considerable positive effects on pain relief after CABG. Satisfaction was another important factor that could be used as an indicator of quality of life, which has been much considered in patients following major surgeries these days. At last, shorter duration of bed rest in hospital after CABG was a better way to reduce hospital costs and common complications of surgery (e.g. thromboembolism); moreover, patients often had more emotional supports and better remission when they were discharged as soon as possible.Pain, fatigue, and anxiety are common complications after surgery. All of these factors may compromise treatment and quality of life following surgery; therefore, decreasing pain scales may improve outcomes after surgery. According to our hypothesis, performing physiotherapy on an area could increase its circulation. Therefore, there would be more oxygen provided for the tissue by increasing the red blood cell count. It also increases the immune system function in the area by providing more immune factors. These two can remove pathogenic factors and relatively heal wounds and alleviate pain -16.et al. carried out research on 70 patients undergoing breast surgery to determine the effect of foot massage on post-operative pain and found that this therapeutic method in breast surgery patients was effective in postoperative pain management [Ucuzal M nagement . Jane annagement , 19.et al. 2013 reported better mood in 72 patients post CABG after 4 sessions of massage therapy per day. These patients were 18-75 years old [Also, Tarja claimed that, there was a negative relationship between massage therapy and pain in patients who were admitted in ICU . Interesears old . Also, Sears old .et al. showed that CPT can minimize hospital LOS in patients hospitalized in the ICU [Castro AA  the ICU . Nowaday the ICU , 25, pai the ICU , chronic the ICU , knee os the ICU , musculo the ICU , open-ab the ICU  and incrSince close monitoring is necessary for patients after CABG operation, CPT could be helpful to reduce their chest pain in the department of cardiovascular surgery in Iran. However, patients often want to stay in hospital as short time as possible; therefore, postoerative CPT may partly meet their needs.The authors declare that there is no conflict of interests regarding the publication of this article.


Aging, an irreversible and unavoidable physiological process in all organisms, is often accompanied by obesity, diabetes, cardiovascular diseases, sleep disorders, and fatigue. Thus, older adults are more likely to experience metabolic symptoms and sleep disturbances than are younger adults. Restricted feeding (RF) is a dietary regimen aimed at improving metabolic health and extending longevity, as well as reorganizing sleep-wake cycles. However, the potential of RF to improve metabolic health and sleep quality in older adults who are known to show a tendency toward increased weight gain and decreased sleep is unknown. To elucidate this issue, aged mice were assigned to an RF protocol during the active phase for 2 h per day for 2 weeks. Sleep-wake cycles were recorded during the RF regime in RF group and control mice. At the end of this period, body weight and blood biochemistry profiles, including blood glucose, cholesterol, and enzyme activity, in addition to dopamine concentrations in the brain, were measured in the RF group and age-matched controls. RF for 2 weeks improved the metabolic health of aged mice by reducing their body weights and blood glucose and cholesterol levels. At the beginning of the RF regime, sleep decreased in the dark period but not in the light period. After stable food entrainment was achieved (7 days post-RF commencement), the amount of time spent in wakefulness during the light period dramatically increased for 2 h before food availability, thereby increasing the mean duration of awake episodes and decreasing the number of wakefulness episodes. There was no significant difference in the sleep-wake time during the dark period in the RF group, with similar total amounts of wakefulness and sleep in a 24-h period to those of the controls. During the RF regime, dopamine levels in the midbrain increased in the RF group, pointing to its potential as the mechanism mediating metabolic symptoms and sleep-wake regulation during RF. In conclusion, our study suggested that RF during aging might prohibit or delay the onset of age-related diseases by improving metabolic health, without having a severe deleterious effect on sleep. The circadian system, which is driven by both an internal circadian clock and external environmental signals, controls the timing of feeding, and sleep-wake cycles . Food scAging is a complex and unavoidable process, which is accompanied by a series of comorbid conditions, including sleep loss, fatigue, metabolic syndrome, and diabetes . With inad libitum feeding, where an animal has unrestricted access to food, restricted feeding (RF) is a dietary regime involving fasting for specific periods, which restricts energy intake and appears to reduce body weight  were purchased from the Experimental Animal Center of Anhui Province . All the mice were maintained under a 12-h light/dark cycle (lights on at 08:00 and off at 20:00) and had access to food and water  100 lux . All ani 100 lux .The surgical procedure for implanting the EEG/EMG electrodes was as described previously . Using aad libitum throughout the study period (All the mice were kept under a 12-h light/dark cycle (lights on at 08:00 and off at 20:00). After recovery from the EEG/EMG electrode implantation surgery and an acclimation period for 3 days in sleep recording chambers, the mice were allowed free access to food and water for four consecutive days during which EEG/EMG signals were collected as baseline data. The mice were then divided into two groups (an RF group and a control group), and the protocols were applied for 14 consecutive days. The RF group had access to food only for 2 h each day. The same experimenter provided food at 20:00 (lights off/dark period) each night for 14 nights, taking care not to disturb the animals via the use of a low-intensity red light  and remoy period . The bodFourteen days after recovery from the surgery, each mouse was connected to a cable with a slip-ring for sleep recording in a chamber. This allowed the animal to move freely, without any restrictions during the sleep recordings. All the mice were habituated to the recording cable in a chamber for 3 days before the recordings. The EEG/EMG signals were collected at a sampling rate of 128 Hz , amplified, and the data were stored on a local computer using Vitalrecorder software . The EEG/EMG data were then scored offline in consecutive 4-s epochs into three vigilance stages: awake, REM sleep, or NREM sleep , in accordance with previously established criteria . After ag for 10 min, 4°C. The serum samples were then transferred into sterilized tubes for the biochemistry assay. Serum biochemistry profiles, including electrolytes, glucose, amylase, and lipase, were measured using a preloaded Chem 17 CLIP using a Catalyst One analyzer  following the manufacturer’s instructions.At the end of the study, blood samples were collected from the two groups between 19:00 and 19:30. The blood samples were collected in a sterilized tube after cardiac puncture . All theg, 10 min, 4°C). The supernatants were then collected. Dopamine concentrations in the striatum and midbrain were measured using a commercially available dopamine ELISA kit  in accordance with the manufacturer’s instructions.At the end of the study, all the mice were euthanized and decapitated between 19:00 and 19:30. Striatum and midbrain samples were immediately removed and preserved in ice. They were then homogenized (10% w/v) with phosphate-buffered saline  and centrifuged  at 4°C until sunk to the bottom. The brains were then frozen and coronal slices 30 μm thick were obtained using a freezing microtome .During the staining procedure, all the brain slices were kept at room temperature. The brain sections were incubated with the primary antibody for c-Fos  overnight. The sections were then rinsed with 0.01 M PBS six times and incubated with biotinylated secondary antibody  for 90 min. All the tissue sections were treated with avidin-biotin complex  for 60 min, and immunopositive cells were visualized black by reaction with 3,3-diaminobenzidine with nickel . After rinsing with PBS, the slices were mounted, dried, dehydrated by ethanol and xylene, and cover slipped. Images were obtained using a BX53 microscope .t-test. A two-way repeated-measures analysis of variance, followed by Tukey’s post hoc test was conducted to compare body weight changes. In all cases, a value of p < 0.05 was taken as the level of statistical significance.All the results are expressed as the mean ± SEM. Time-course changes in the durations of the sleep-wake stages in the control and RF groups were compared using a two-sided Student’s p < 0.01, p < 0.01, Food intake in the control group remained unchanged during the study . In contp < 0.01, p < 0.01, To determine whether RF improved metabolic symptoms in aging mice, we measured and compared serum biochemical parameters in the control and RF groups. Blood glucose and cholesterol levels significantly decreased in the RF group as compared with those in the control group  as compared with that in the control group  increased, thereby increasing the mean duration of awake episodes. There was no significant difference in the amount of wakefulness, NREM sleep, and REM sleep during the dark period in the RF group as compared with that in the control group. During the RF regime, dopamine levels in the midbrain increased in the RF group, suggesting that dopamine transmission in the midbrain might contribute to increased wakefulness during food anticipation.The incidence of many chronic diseases, including sleep disorders, obesity, cancer, and neurodegenerative disorders, has increased in the aged population . PharmacWe also found that RF improved cardiometabolic symptoms by lowering blood glucose levels and cholesterol levels in aged mice. Previous studies showed that time RF maintained glucose homeostasis  and lowead libitum, there were no significant differences in the sleep-wake rhythms of the two groups. After the start of the RF protocol, both NREM and REM sleep decreased in the dark period but not in the light period in the RF group as compared with that in control group. Stable food entrainment was achieved in the RF group around 7 days after the commencement of the RF protocol. At this point, wakefulness, characterized by an increased mean duration of wakefulness and a decreased number of wakefulness episodes, dramatically increased during the 2-h period before food availability. We found no significant difference in the sleep-wake cycles in the RF and control groups during the 10-h light (08:00–18:00) and dark periods (20:00–8:00). During RF days 7–14, the sleep-wake profiles in the RF group during each 24-h period were similar, without any significant difference in the mean duration and number of wakefulness, NERM sleep, and REM sleep episodes or any significant difference in the total amount of wakefulness. In contrast, previous studies showed that caloric restriction and fasting increased the amount of wakefulness in rats, with longer term food deprivation (>7 days) causing sleep to become fragmented  in the RF group compared to that in the control group. Our findings are in accordance with those of studies on wild-type mice and diabetic mice, in which the authors reported that homeostatic regulation of sleep and wakefulness remained intact during an RF protocol .Previous studies showed RF increased c-Fos protein expression in the dorsomedial nucleus, lateral hypothalamus (LH), perifornical area, and tuberomammillar nucleus, which indicated that FAA may be regulated by networks distributed throughout the brain or that more essential nuclei controlling FAA remain to be unidentified . The dopIn addition to dopamine, several other neurotransmitters regulate food intake and sleep and are therefore thought to regulate FAA . PharmacAt present, there is little consistency in RF protocols in animal studies. For example, in many animal studies on RF, food was provided during the inactive period when animals spend more time sleeping. In other studies, food was provided during the active period. Moreover, the feeding window has also varied from 2 to 8 h per day in different animal studies . An inapThe present study has some limitations. As sleep-wake cycles vary with age and gender , one limIn summary, food restriction in aged mice had a profound impact on body weights, blood glucose and cholesterol levels, and amylopsin and lipase activities. In addition, RF changed the sleep-wake profiles of the mice, with an increase in the mean duration of wakefulness and a decrease in the number of wakefulness episodes. Food restriction also influenced sleep and wakefulness quality during the 2-h period prior to food availability. Our results indicate that RF during aging may prohibit or delay the onset of age-related diseases by improving metabolic health, without severe deleterious effect on sleep. They also suggest that RF could be a novel, non-pharmacological intervention to prevent metabolic disorders in the elderly population.The original contributions presented in the study are included in the article/The animal study was reviewed and approved by the Animal Care and Use Committee of Anhui Medical University.QX, Y-XX, and M-KZ conceived and designed the study. Y-XX, G-YL, H-QB, S-CW, W-HC, and G-JC carried out the experiments. QX, G-YL, P-PZ, and QJ analyzed the data. C-BG, M-KZ, G-HC, D-FZ, and QX wrote the manuscript. All authors contributed to the study and approved the final version.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Despite improvements in renal replacement therapy (RRT) for end-stage renal disease (ESRD), it continues to have serious negative impacts on quality of life (QOL) and emotional status. This study determines the association between demographic characteristics and the negative emotional states of depression, anxiety, and stress in Saudi Arabia. A comparative cross-sectional study was conducted in the Eastern Region of Saudi Arabia. Convenience sampling was used to recruit participants comprising hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (Tx) patients. They completed the Short Form-36 Survey and the Depression, Anxiety, Stress Scale (DASS). The physical component summary (PCS) score was similar for HD (41.7) and PD (41.5), but higher among Tx (45.2). The mental component summary (MCS) score was similar between HD (48.0) and Tx (48.8), but lower in PD (42.3). The majority of patients in all groups had normal levels of depression, anxiety, and stress. Overall, the study found that PCS was higher among Tx patients compared to HD and PD, while MCS was higher among HD and Tx patients than PD patients. Most patients' levels of depression, anxiety, and stress were within the normal range. Those findings will provide policymakers and health managers with the significant factors which can affect the QOL of dialysis and Tx patients. Chronic kidney disease (CKD) caused 1.2 million deaths in 2020 and was the twelfth leading cause of death worldwide . ConsequQuality of life is a substantial indicator of welfare, which helps in health planning by shaping care priorities and the effectiveness of healthcare interventions . QOL is “An individual's perception of their position in life in the context of the culture and value systems in which they live and relate to their goals, expectations; standards and concern and this include six domains; physical health, psychological status, level of independence, social relationship, environmental features, and spiritual concern” .QOL research is important in evaluating the outcome of any intervention in chronic diseases. ESRD effectively incurs disability for patients and fundamentally changes their lives, leading to reduced QOL . It is aSince dialysis and Tx are life-prolonging and not curative treatments, they affect many patients' psychological health status. Depression and anxiety are the most commonly reported mental problems, and psychological factors have a negative influence on patients' QOL –15. A syAlDukhayel  carried In a cohort study in Japan which is part from the Dialysis Outcomes and Practice Patterns Study (DOPPS), the study found that QOL among dialysis patients is lower than that of patients who undergo kidney Tx . AccordiDetermine the level of QOL for ESRD patients undergoing dialysis or kidney Tx in Saudi ArabiaDiscover the prevalence of negative emotional states of depression, anxiety, and stress for ESRD patients undergoing dialysis or kidney Tx in Saudi ArabiaIdentify the association between QOL, DASS, and demographic characteristicsQOL is an important outcome measure in the assessment of chronic diseases. It measures physical and social functioning, and perceived physical and mental well-being. The importance of QOL in ESRD patients is manifest in the clinical outcome of the disease and its treatments. Moreover, evaluating the demographic characteristics of patients can help health practitioners and planners to improve management for ESRD patients and their treatment, to improve their QOL. There may be significant limitations on patients' QOL. Most studies on QOL and ESRD have been done abroad, and QOL studies on Saudi patients are limited. To address these research gaps, the current study aimed to do the following:A comparative cross-sectional study was carried out in the Eastern Region of Saudi Arabia. There were 21,068 patients diagnosed with ESRD in 2019 in Saudi Arabia, of whom 19,522 were treated with HD, while the remainder (1546 patients) received PD. In the eastern region in 2019, 2,416 patients received HD and 300 received PD, while there were 204 transplant patients . PatientThe population sample consisted of all patients diagnosed as ESRD and treated with HD, PD, or Tx. Convenience sampling was utilized, with the following inclusion criteria: all participants aged 18 years or older, on dialysis or Tx for more than 3 months prior to the survey date  , 30.G∗Power software. With an estimated effect size of 0.25, and alpha was 0.1 among three predictors for analysis of variance (ANOVA) [The data were collected form HD patients in their unit which has 105 machines utilized by 218 patient who frequently on hemodialysis treatment two or three times per week. The unit is part from a public central hospital. In the PD unit which includes 33 patients, the patients are having their PD procedure through using an APD machine at home, and they should have frequent visits to the unit for medical evaluation and to collect their supplies and medicine. The Tx center is part of a specialist hospital and provides kidney transplants to the region with about 200 surgeries annually. The data were collected by face-to-face interviews while patients were on dialysis or waiting for their routine visit to collect medicine or blood test as a follow-up visit. The face-to-face interview was conducted to consider illiterate and weak patients. In addition, to give more explanation to them depend on their education level and mental health which will help in improve the quality of data. The minimum required sample size was calculated as 213 patients using  (ANOVA) .The 36-Item Short Form Survey (SF-36) is a standard questionnaire used for many purposes. It is a short-form health survey with 36 questions, and it is one of the most widely used measures of health-related QOL , with a The Arabic version of the Depression, Anxiety, and Stress Scale (DASS) was designed to measure the level of the negative emotional states of depression, anxiety, and stress . The DASThe study protocol was approved by the Institutional Review Board (IRB) at the university where the study was carried out. Participants' written permission was obtained by means of an informed consent form before data collection, including assurance that their participation was entirely voluntary and would not affect the care they received, and that their data would be maintained confidentially, available only to the research team. The data collection was started after ethical clearance was secured. SPSS was used to determine frequencies and percentages for demographic data and the DASS and the difference between groups. The mean and standard deviation (SD) were used to present QOL, and SF-36 software was used to calculate the score of QOL.The majority of the patients were male, married, educated to grade 9–12, and nonsmokers in the three studied treatment categories. Their mean ages were 49.1, 40.4, and 43.2 years old for HD, Tx, and PD patients, respectively. Dialysis hours per session were 4 for HD patients and 9 for PD patients. For Tx patients, the mean time since kidney transplantation surgery was 33.3 months, with a median of 22.5 months. The length of the period on dialysis for HD and PD was 44.7 and 24 months, respectively .QOL for PCS and MCS were calculated. The PCS score was similar for HD (41.7) and PD (41.5), but higher among Tx (45.2). The MCS score was similar between HD (48.0) and Tx (48.8), but lower in PD (42.3). On the DASS scale, for depression level, the majority of patients had a normal level of 57.1%, 73.9%, and 50.0% for HD, Tx, and PD, respectively. Anxiety was normal among the majority of patients in HD (60.0%), Tx (72.8%), and PD (55.0%). Additionally, stress was within the normal range for all categories of patients: HD (55.0%), Tx (62.0%), and PD (40.0%) .p value 0.004); patients with education levels G9–12 (compared to illiterate ones)  and higher than BSc ; and employed patients (compared to retirees) . For Tx, higher PCS was reported for unmarried patients (p=0.05), patients with G9–12 , and smokers (p=0.048). For PD, the PCS score was also higher among smokers (p=0.022)  .This current study found that PCS was higher in Tx patients compared to their HD and PD counterparts, while MCS was higher among HD and Tx patients compared with those receiving PD. In HD, PCS was higher among males, patients with an education level of G9–12, and those in employment. For Tx, PCS was higher among unmarried patients, those with G9–12, and smokers. For PD, the PCS score was higher among smokers. In the DASS scale, most patients' levels of depression, anxiety, and stress were within the normal range.This study confirmed that PCS was higher in Tx patients compared to those receiving HD and PD. Also, MCS was higher among HD and Tx patients compared with PD patients. These results corroborate previous studies in a single center in Sichuan Province, China, and in a multi-center in China and Trinidad and Tobago –36. A 10Although no single treatment provides a complete cure for the studied factors, transplant patients seem to function more normally, and one of the benefits of transplantation is to offer a state of health similar to what patients had before the onset of the disease . A possiThe results of this study showed that in Tx patients, PCS was higher among the unmarried, patients with G9–12, and smokers. In HD, PCS was higher among males, patients with educational levels G9–12, and those in employment. For PD, the PCS score was higher among smokers. Correspondingly, the results from a multinational study reported that factors associated with reduced QOL included being female, having a lower educational level, and being single . In JordA multinational study found that married patients experienced better QOL . FurtherThe justification of worse outcomes for women may be that they are a vulnerable group with chronic disease since they have different psychosocial perspectives on life compared with men according to multinational study . DespiteWith regard to the DASS scale, most patients' levels of depression, anxiety, and stress were found to be within the normal range, in line with a study by , who fouFinally, the current study had several important limitations that need to be considered. The sampling setting limits the generalizability of the findings to other areas or settings. Additionally, the cross-sectional design does not evaluate changes in QOL over time. Furthermore, the limited number of PD participants does not help us in carrying out regression analysis for this group.This study was designed to determine the level of QOL in relation to the negative emotional states of depression, anxiety, and stress for ESRD patients undergoing dialysis or kidney Tx.This study found that PCS was higher in Tx compared to HD and PD, while MCS was higher among HD and Tx than for PD patients. In HD, PCS was higher among males, patient with an education level of G9–12, and working patients. For Tx, PCS was higher among unmarried, G9–12, and smoking patients. For PD, the PCS score was higher among smokers. In the DASS scale, most patients' levels of depression, anxiety, and stress were within the normal range.These findings have significant implications for understanding the QOL among patients on ESRD. It is expected that findings from this study will provide health care managers and policy developers with significant information about the impact of dialysis and its treatment on patients' QOL and help identify patients' needs, as well as particularly vulnerable patient groups. An implication of this study is the possibility that the findings provide direction for hospital decision makers on the areas that could be improved to ensure better QOL among patients. This research allows managers to better understand the relation between QOL and other variables. This will enhance awareness of pertinent risk outlines, to help administrators address such factors.The present study extends knowledge about QOL among patients on ESRD. A key strength of the present study was the inclusion of the three modalities at the same time for the same area, to be a basis for comparison. More research is required to develop a deeper understanding of the complexity of QOL in ESRD and its longitudinal changes over time.


The study aimed to build and validate practical nomograms to predict overall survival (OS) and cancer-specific survival (CSS) for patients with synovial sarcoma (SyS).A total of 893 eligible patients confirmed to have SyS between 2007 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided into the training cohort (n = 448) and validation cohort (n = 445). Clinically independent prognostic and important factors were determined according to the Akaike information criterion in multivariate Cox regression models when developing the nomograms with the training cohort. The predictive accuracy of nomograms was bootstrapped validated internally and externally with the concordance index (C-index) and calibration curve. Decision curve analysis (DCA) was performed to compare the clinical usefulness between nomograms and American Joint Commission on Cancer (AJCC) staging system.Two nomograms shared common indicators including age, insurance status, tumor site, tumor size, SEER stage, surgery, and radiation, while marital status and tumor site were only included into the OS nomogram. The C-index of nomograms for predicting OS and CSS was 0.819 (0.873–0.764) and 0.821 (0.876–0.766), respectively, suggesting satisfactory predictive performance. Internal and external calibration curves exhibited optimal agreement between the nomogram prediction and the actual survival. Additionally, DCA demonstrated that our nomograms had obvious superiority over the AJCC staging system with more clinical net benefits.Two nomograms predicting 3- and 5-year OS and CSS of SyS patients were successfully constructed and validated for the first time, with higher predictive accuracy and clinical values than the AJCC staging system regarding OS and CSS. Synovial sarcoma (SyS) is a rare malignancy that most commonly occurs in adolescents and young adults, accounting for about 6%–9% of the soft tissue sarcomas . SySs ofBecause of the rarity of this tumor, to date, there is no perfect model for survival outcome prediction. Tumor-node-metastasis (TNM) staging system of the American Joint Commission on Cancer (AJCC) has long been a generally accepted formula for predicting prognosis of malignancies and represents the gold standard classification method for SyS . NeverthPrognostic nomograms are graphic and quantitative models with high precision and forecasting ability, and they have been developed in clinical practice to evaluate survival for several cancers –8. CompaThe Surveillance, Epidemiology, and End Results (SEER) database collects the demographics, clinicopathological, and survival data of various cancer patients from population-based cancer registries in the USA, providing a favorable source to investigate rare tumors . In thisPatients diagnosed with SyS between 2007 and 2015 were identified from the SEER database and included in our study. The inclusion criteria were as follows: 1) International Classification of Diseases for Oncology third edition (ICD-O-3) histology code for SyS was not otherwise specified (9040/3), spindle cell (9041/3), epithelioid cell (9042/3), and biphasic (9043/3); 2) SyS was confirmed as the first and only primary malignancy by histology; 3) Patients were older than age 18 years; 4) Clinical and pathologic features were complete and detailed; 5) The follow-up was active with known outcomes. Patients whose diagnostic information could only be derived from a death certificate or autopsy report, as well as those who died within 1 month since initial diagnosis, were excluded. All the included patients were randomly allocated to the training cohort  and validation cohort . Institutional review board approval was not required in our study, since the SEER database is publicly available for researchers worldwide. Our accession ID to the SEER database was 10165-Nov 2017.Age, sex, race, marital status, insurance status, tumor size, pathology, histologic grade, SEER stage, chemotherapy, radiotherapy, surgery, survival months, vital status, and causes of death for each patient were extracted from the SEER database. The races included white, black, and others . Marital status was described as married or unmarried, while insurance status was described as Any Medicaid, insured, or uninsured. Tumor size was a continuous variable and converted to categorical variable according to optimal cutoffs, which were determined by X-tile program, a favorable software to determine optimum cut point value . The tumor primary site was described as head and neck, trunk, thorax and pleura, extremities, or others. Cancer stages recorded according to the 6th AJCC stages were regrouped according to the 7th edition. OS and CSS were determined as the primary endpoints of our study. Survival time (in months) was calculated as the interval from diagnosis to death from any cause (OS) or death from SyS (CSS).The training cohort was used to build the nomograms. The univariate Cox regression analysis was used to determine factors associated with survival. Then, variables significantly associated with survival in univariate analysis were subsequently subjected to the multivariable Cox regression analysis. Finally, using the minimum value of Akaike information criterion (AIC), the backward stepwise process was used to stop rule for the multivariable Cox regression analysis and select the independent prognostic factors that strikingly contributed to patients’ survival for the constructions of the nomograms, and those factors were integrated to construct the nomograms for 3- and 5-year OS and CSS.The validations of the nomograms were conducted both internally (training cohort) and externally  using C-index and calibration curve. To minimize the overfitting bias, the nomograms were subjected to 1,000 bootstrap resamples in both validations. Predictive performance was examined using the concordance index (C-index), which was analogous to the area under the curve (AUC) but more suited to censored data . The valDecision curve analysis (DCA), a new algorithm, was performed to assess the clinical usefulness of nomograms that predict survival . The besrms, cmprsk, rcorrcens, and DecisionCurve. All statistical tests were two-sided, and P value <0.05 was statistically significant.All statistical analyses were performed by R software (version 3.3.0). The R packages used in our study included A total of 893 eligible SyS patients diagnosed between 2007 and 2015 in the SEER database were included in our analysis. The flowchart of the patient selection process was shown in In the univariate analysis, age, marital status, insurance status, pathology type, tumor site, tumor size, surgery, radiotherapy, and SEER stage were found to be significantly associated with both OS and CSS Table 2.Regarding internal validation, the C-index for the nomograms to estimate OS and CSS in the training cohort was 0.819 (0.873–0.764) and 0.821 (0.876–0.766), respectively. As for external validation, the C-index for the nomograms to predict CSS and OS was 0.816 (0.865–0.767) and 0.831 (0.889–0.772), respectively. The results of C-index all demonstrated that our nomograms were suitable for SyS patients. The calibration curves of OS and CSS nomograms in the training and validation cohorts were shown in ), with all between-group P values <0.001. Similar distinction was also observed in the validation cohort. The results indicated that our nomograms had more accurate and robust predicting power than the traditional AJCC staging system.Additionally, we made a comprehensive comparison between SyS nomograms for predicting OS/CSS and the current 7th AJCC staging system. In the training cohort, our nomograms yielded minimum AIC values along with maximal log-likelihoods and C-indexes for both OS and CSS compared with the AJCC stages Table 5).After addressing the model accuracy, DCA was performed to render clinical usefulness to the nomograms using the training cohort and generalize it to the validation cohort. The nomogram had high potential for clinical application in predicting CSS and OS of SyS patients because of their wide and practical range of threshold probability through total survival of 3 or 5 years in both cohorts. When further comparing with the current AJCC staging system, our nomograms still had superiority over the AJCC staging system for the fact that more clinical net benefits were obtained in a rather wide range of threshold probabilities when using the nomograms than those when using the AJCC stages  inhibitors or anti-angiogenic agents, and the detailed information of chemotherapy and surgery, were not taken into consideration in our study, since they were unavailable in the SEER database. Third, there was no other independent database available to validate our nomograms externally, hence we used the same retrospective dataset to establish and validate the nomograms. As we know, external validation with independent data was required to evaluate whether it was applicable for another patient groups. And to further refine our nomograms, prospective validation with independent patients was warranted.In conclusion, for patients with SyS, we developed and validated the first two nomograms that estimated 3- and 5-year OS and CSS by using population-based data. These nomograms showed more accurate predictive performance and clinical usefulness than the AJCC staging system for predicting CSS and OS. However, performing further external valuation with other independent patients is still warranted.The raw data supporting the conclusions of this article will be made available by the authors without undue reservation.The experiments were approved by the Ethics Committee of Zhongshan Hospital, Fudan University.ZW and YZ: conceptualization, investigation, methodology, project administration, writing—review, editing, and supervision. ZS and LC: data curation, formal analysis, investigation, methodology, and writing—review. LL and WL: methodology, validation, writing—review, and editing. All authors have read and approved the article.The present study was supported by the Science and Technology Planning Project of Xiamen, Fujian Province, China .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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Objective: Deep brain stimulation (DBS) has shown promising outcomes as new therapeutic opportunities for patients with treatment-resistant depression (TRD) who do not respond adequately to several consecutive treatments. This study aims to systematically review and conduct a meta-analysis on the efficacy and safety of DBS for TRD.Method: The literature was comprehensively reviewed using Medline, Google scholar, Cochrane library, Embase, and World Health Organization International Clinical Trials Registry Platform until January 2019. The studied outcomes included response, remission, recurrence, and adverse events (AEs) rates, and were reported as the rate ratio (RR) or pooled estimate with a 95% confidence interval (95% CI). Heterogeneity was measured by an I-square test and a sensitive analysis.Results: A total of 17 studies involving 7 DBS targets were included. For efficacy, DBS treatment was statistically beneficial for TRD, and the response, remission, and recurrence rates were 56% (ranging from 43 to 69%), 35% (ranging from 27 to 44%), and 14% (ranging from 4 to 25%), respectively. However, only two randomized-controlled trials (RCTs) considered the invalidity of DBS . For safety, the AEs rate was 67% (ranging from 54 to 80%). The AEs were common and moderate, but the problems related to suicide and suicidal ideation should not be underestimated.Conclusion: These findings suggest that DBS for TRD is considered promising, which should be confirmed by well-designed and large sample studies. Future basic research and comprehensive clinical trials are needed to reach better understanding on the mechanisms of action and optimal targeted structure. From 1990 to 2017 the number of incident cases of depression worldwide increased by 49.86% with 25,8 million in 2017   constructed the corresponding search strategies in the Medline, Google scholar, Cochrane library databases, Embase and World Health Organization International Clinical Trials Registry Platform up to January 2019. The search results from the databases were obtained using the terms “deep brain stimulation” OR “DBS” AND “depression” OR “depressive disorders.” We searched for eligible studies by scanning the abstracts from the original articles and screening the list of references for relevant publications. Additionally, other references were manually scanned from relevant reference reports and clinical trial websites. Only eligible studies that met the predefined criteria were input into a bibliography management system.For accuracy and completeness, two reviewers (JM and KZ) independently checked the full articles and extracted the information corresponding to the characteristics of the study population, the details of the surgery, the outcome measures, and the adverse events. We recorded the data, including the Hamilton Rating Scale for Depression (HRSD), Montgomery-Asberg Depression Rating Scale (MADRS), adverse events, suicidal ideation and suicide, in each target location. Discrepancies were resolved by discussion and consensus. Cochrane tools were not used to assess the quality of the included studies, because most were open-label studies.A meta-analysis was conducted to calculate the studies outcomes, including the response, remission, recurrence and adverse events rate, using Stata software (version 13.0). A 50% or greater improvement from the baseline score to end of treatment on a depression rating scale  was defined as the clinical response. A clinical remission was defined as a score on a depression rating scale within the normal range . The adverse effects were evaluated by examining the proportion of adverse events.During the systematic searching based on the searching strategies, 374 references from the electronic databases and eight additional records from other resources were identified and the last searching was performed on January, 30, 2019. After screening stage where the titles and abstracts of the retrieved records were reviewed, 360 records were excluded due to duplication or non-relevant content . Of the I2 = 73.6%, p < 0.0001*), using a random model , using a fixed model. According to the results of the meta-analyses, the pooled estimate was 0.32 (95% CI = 0.25–0.39)  .I2 = 0.0%, p = 0.383), using fixed model. According to the results of the meta-analyses, the pooled estimate was 0.14 (95% CI = 0.04–0.25)  .I2 = 76.8%, p < 0.0001*), using a random model. According to the results of the meta-analyses, the pooled estimate was 0.67 (95% CI = 0.54–0.80)  . Of the To assess the statistical heterogeneity for response, remission and AEs rate, funnel plots  were genWe reduced the bias in our study as much as possible. We used reasonable search strategies, and the contribution of three independent authors contributed to reducing the sampling bias. In addition, we used explicit and rigid inclusion criteria, independent searching and a sensitivity analysis to contribute to the reduction of selection bias. Moreover, no funding source influenced the reporting bias. However, almost all the included studies were open-label studies, which will inherently result in bias indicated by an asymmetry in funnel plots.Currently, DBS therapy is still in the stage of exploration and cannot be used as a recommended intervention. Most patients with TRD, who undergo DBS treatment, also receive antidepressant treatment, psychotherapy and other neuromodulation therapies, according to the 2016 guidelines by the Canada Network for Mood and Anxiety Treatment (CANMAT) for management of major depressive disorder (MDD) in adults , suggesting that this treatment might be considered as promising. On the other hand, the AEs rate was common (67%) and moderate, which can be resolved by the corresponding therapy. However, suicide and suicidal ideation still occurred in the patients who received this treatment. Two studies (Dougherty et al., The exact mechanism of DBS is unknown and studies are ongoing on this regard. Some studies have demonstrated that the gamma oscillations inhibition and the facilitation of theta-gamma coupling by DBS is probably mediated by activation of inhibitory circuits in SCG and the enhancement of plasticity in the frontal cortex (Sun et al., During the last decade, several studies have utilized anatomical and functional neuroimaging modalities to investigate the neurobiology of depression (Holtzheimer and Mayberg, There are several limitations in this study. The specificity of the DBS surgery and the relevant ethical issue attributes to the difficulty of performing high quality and large sample RCTs. We, therefore, performed this meta-analysis using the rates to obtain a more reliable conclusion by pooling rates from multiple studies. In addition, the study implementation, patient characteristics, and different sample sizes also contribute to the bias. However, we illustrated the clinical heterogeneity by performing a sensitivity analysis. Further studies should refine the methodology, investigate the optimal targets structures and stimulation parameters, and maximize the consistency of outcomes measurement to make comparisons feasible. Moreover, it is of extreme importance to analyze the exact network effects to understand the neurobiological mechanisms.We concluded that the DBS treatment had good prospects. However, the problem of the reported adverse events is worth paying attention to and resolving, because it could lower the quality of life. Further basic scientific research is needed to search for more optimal brain structures to modulate the neural circuits and to investigate the mechanisms of underlying the DBS treatment.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.KZ and XX designed the topic and reviewed the manuscript. LS, JZ, WH, CZ, YW, CL, BZ, and XW collected the references and did the statistical analysis. JM and YLW wrote the manuscript. All authors contributed to the article and approved the submitted version.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.


Introduction: Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus which has not been identified previously in humans. The disease leads to respiratory problems, systemic disorders, and death. To stop the virus transmission, physical distancing was strongly implemented, including working and school from home (WFH & SFH). The limitation altered daily routines and needs advanced to adapt. Many have felt uncomfortable and this could have triggered anxiety symptoms. This study aimed to evaluate the proportion of significant anxiety symptoms and its association with COVID-19-related situations in an Indonesian context during the initial months of the pandemic.Methods: An online community survey was distributed through social media and communication platforms, mainly WhatsApp, targeting people >18 years old in Indonesia. Anxiety symptoms were assessed using Generalized Anxiety Disorder-7 (Indonesian Version). Demographical data and information on social situation related to the COVID-19 pandemic were collected. The proportion of clinically significant anxiety symptoms was calculated and the association with demographic and social factors was assessed using chi square test (χ2) and logistic regression for multivariate analysis.Results: Out of 1215 subjects that completed the survey, 20.2% (n = 245) exhibited significant anxiety symptoms. Several factors, such as age (AOR = 0.933 CI 95% = 0.907–0.96), sex (AOR = 1.612 CI 95% = 1.097–2.369), medical workers (AOR = 0.209 CI 95% = 0.061–0.721), suspected case of COVID-19 (AOR = 1.786 CI 95% = 1.001–3.186), satisfaction level of family support (AOR = 3.052 CI 95% = 1.883–4.946), and satisfaction level of co-workers (AOR = 2.523 CI 95% = 1.395–4.562), were associated with anxiety.Conclusion: One out of five Indonesian people could have suffered from anxiety during the COVID-19 pandemic. The riskiest group being young females, people who had suspected cases of COVID-19, and those with less satisfying social support. Nevertheless, health workers were found to have a lesser risk of developing anxiety. Accessible information and healthcare, social connection, supportive environment, and mental health surveillance are important to prevent bigger psychiatric problems post-pandemic. Coronaviruses are a group of viruses with a single-stranded RNA structure. Some of the subtypes are known to affect humans, most of which cause mild infections in the upper respiratory tract of immunocompetent individuals –3. Some In order to minimize the coronavirus infection rates, governments and health authorities of countries worldwide, including Indonesia, have implemented large-scale social restriction measures for various communal activities, including changes in the systems of labor and school from home largely starting as of April 2020 . Short-tThe mental problems that might be found during a pandemic can be summarized into: (1) stress and anxiety for self and family health, e.g., being transmitted to or transmitting the disease to family or society , 12; (2)Based on a study in Basque, Spain, anxiety was experienced by all ages, although younger people showed greater stress compared to older people . AnxietyIndonesia Basic Health Research 2018 data showed that about 9.8% of the population has mental and emotional health problems  and higher  levels. Socio-economic status was classified into low to lower-middle income and upper-middle to high income groups according to the gross national income classification by the World Bank. All the respondents were also asked about their implementation of working from home and social restriction policy  during the pandemic, current health status of the respondents and their families regarding COVID-19, and their access to related information, such as physical and mental health guidance. The information sources were differentiated into online media, offline media, and direct information from family or friends.Health status regarding COVID-19 was classified according to the World Health Organization case definition as follows: healthy individual, suspect case, probable case, and confirmed case. A suspect case of COVID-19 applies to individuals who (1) experience acute respiratory illness (fever and at least one respiratory symptoms); (2) have traveled to, or have a residency history in a local transmission area or contact history with confirmed or probable cases during the last 14 days before symptoms onset. A probable case is a suspect case who has obtained inconclusive laboratory test results. A confirmed case is defined as a person who has a confirmed laboratory test result of a COVID-19 infection.Several questions were aimed to investigate the respondents' behavior changes during the pandemic, along with satisfaction level toward support from family, friends, and colleagues using a single question for each item. Behavior changes were measured on a yes or no scale. Satisfaction toward support system was classified into satisfied and not satisfied. Family members in an Indonesian context are considered not restricted to the nuclear family  but also include extended family members, such as grandparents . The resThe level of anxiety was assessed using the Indonesian version of Generalized Anxiety Disorder-7 (GAD-7). It is a self-report anxiety screening tool for adults (aged 18–95 years old) which was originally developed by Spitzer et al. . This inPrevalence of anxiety disorders was estimated based on the proportion of respondents with clinically significant anxiety. Furthermore, we evaluated if socio-demographic characteristics, access to health information, social restriction practice, health status (COVID-19 infection), and social support had associations with the occurrence of anxiety. Univariate logistic regression was first performed to evaluate the unadjusted association between each factor and anxiety disorder. The statistically significant factors (p < 0.05) from the univariable analyses were then evaluated using a multivariate logistic regression. Data analysis was performed using SPSS IBM version 25.n = 884, 72.8%) and 1,026 (84.4%) had finished a higher educational level. Respondents mainly came from the western part of Indonesia, including those who lived in DKI Jakarta, West Java, and Banten, and belonged to the upper-middle to high income socio-economic level.Of the 1,215 respondents included in this study, 245  exhibited clinically significant anxiety. The general characteristics of the respondents are shown in n = 739) were working from home at the time of the survey and most of them were implementing the social restriction policy. A majority of respondents had access to physical health information regarding COVID-19 , yet only half of them  received related mental health information. Most respondents reported to be healthy  and only a few  had family members with suspected cases of COVID-19. The survey showed that respondents felt satisfied with the support they received from family, friends, and colleagues , with a balanced number of both females and males, and with only 10.2% who had completed higher education .Similar findings were found in other online studies in Indonesia. The psychosocial aspect of the pandemic also had a majority of female respondents , 26, eveOur findings on anxiety were higher when compared to several studies before the COVID-19 pandemic, including the national number from Indonesia Basic Health Research in 2018 which stated that 9.8% of the adult population had mental and emotional problems . When coSeveral factors have been identified to play a role in the increase of anxiety during the outbreak, as stated by the World Health Organization (WHO) . First, This study also analyzed several factors that could be associated with anxiety level among the general population. Female gender was significantly associated with anxiety in this study. A study from Megatsari et al.  also fouMarital status was found to be significantly associated with anxiety during the COVID-19 pandemic in the univariate analysis of this research. Unmarried  status was found to increase the risk of anxiety in our study. These findings were in accordance with previous findings –51. As mOur findings also showed that lower educational level was significantly related to anxiety at the bivariate level, however it was found to not be significantly related at the multivariate level. This is different to what was shown in previous studies –58, althOur study showed that occupational status was not related to the occurrence of anxiety. However, multivariate analysis described that a healthcare worker was not more anxious than the unemployed. This might be associated with the amount of exposure to COVID-19-related information. They were confident in knowing and managing the symptoms, as well as in prevention practices. In contrast, the unemployed group may not have sufficient knowledge and skills to manage the risk due to lack of exposure , 59.In our study, level of income, which could be included in the material factor, was not significantly related to anxiety in the multivariate analysis. This could be due to the fact that our survey was conducted during the initial period of the large-scale social restriction implementation; therefore, people still thought that the circumstance was only temporary. The huge economic loss had not been felt yet as the businesses had just been shut down for a short period . In spitIn the present study, the majority of respondents were working from home and executing social restriction measurements. Anxiety may also have resulted from the impact of COVID-19 containment measures. Implementation of quarantine and social restriction policy leads to decreased social interaction which consequently increases loneliness. A study in China at the peak of the pandemic showed that home quarantine was part of the psychosocial stressors that were significantly associated with the development of anxiety and depression . SeveralOur study also showed that dissatisfaction toward support from family, friends, and co-workers was associated with anxiety. This observation is in line with the study conducted by Ni et al.  which shThe study also showed that younger age was related to clinically significant anxiety. This finding corresponds with several studies about COVID-19 and anxiety that showed that the younger population  tended to have more anxiety compared to their older counterparts , 67, 70.This study also revealed that the health status of respondents was related to anxiety. However, data on the anxiety level of patients suspected to have COVID-19 were scarce. One study showed that prevalence of anxiety in suspected cases was not significantly different from the confirmed cases . On the This research provided important information that can help develop public policy for managing the COVID-19 pandemic or create a mitigation plan for a disaster/pandemic in the future. The high proportion of anxiety proves that it has been a crucial issue during the pandemic. Proper and continuous measures must be implemented to ensure optimum functioning of society, particularly within high-risk populations . To prevent mental health issues during and post-pandemic, people will need access to information and healthcare, availability of psychosocial support including social connectedness, and a supportive environment.One in five people affected by the COVID-19 pandemic in Indonesia may have suffered from anxiety. Based on our findings, the factors associated with anxiety were younger age, female sex, suspected case of COVID-19, and less satisfying social support. Psychosocial support with the emphasis on accessible information and healthcare services, social connection, and a supportive environment in households as well as workplaces, are thought to be important. Nevertheless, health workers were found to have a lesser risk of developing anxiety. Further study on anxiety among people without access to digital technology and diverse age group populations  is suggested to fully understand the matter. Furthermore, surveillance regarding the long-term effects of the COVID-19 pandemic on mental health is also needed.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Medical Research Ethics Committee from Faculty of Medicine Universitas Indonesia (KET-375/UN2.F1/ETIK/PPM.00.02/2020). The patients/participants provided their written informed consent to participate in this study.TW, GA, and HD were responsible for the study concept and design. TW, GA, HD, BM, NW, AP, EH, KM, and HC contributed to data or analysis tools. GA, BM, NW, AP, EH, KM, RI, FK, and TW collected the data. GA, BM, HC, EH, and KM performed the data analysis. GA, BM, HC, EH, and KM wrote the manuscript. AS, CU, TW, and HD provided critical revision of the manuscript for intellectual content. All authors critically reviewed and approved the final version of the manuscript submitted for publication.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.


Out-of-pocket (OOP) payments are perceived as the most regressive means of health financing. Using the panel-data approach and region-aggregated data from Statistics Poland, this research investigated associations between socio-economic factors and OOP health spending in 16 Polish regions for the period 1999–2019. The dependent variable was real (inflation-adjusted) monthly OOP health expenditure per person in Polish households. Potential independent variables included economic, labour, demographic, educational, health, environmental, and lifestyle measures based on previous research. A set of panel-data estimators was used in regression models. The factors that were positively associated with OOP health spending were disposable income, the proportions of children (aged 0–9) and elderly (70+ years) in the population, healthcare supply (proxied by physicians’ density), air pollution, and tobacco and alcohol expenditure. On the other hand, the increased unemployment rate, life expectancy at age 65, mortality rate, and higher sports participation were all related to lower OOP health spending. The results may guide national strategies to improve health-care allocations and offer additional financial protection for vulnerable groups, such as households with children and elderly members. Sustainable financing of health services is a subject of major concern throughout the world . HealthcHealth financing involves not only raising adequate financial resources to fund the health system, but also doing so in a way that increases equity and access for all . The maiIn Poland, a European Union (EU) member state with a population of 38 million, health insurance contributions (an earmarked payroll tax) are the major source of public healthcare funding, accounting for over 60% of total current spending on health and close to 90% of public health expenditure. Households’ OOP payments were the second-largest source of health financing, accounting for 22.6% of the current spending on health in 2017, more than in most of the developed countries . This imComprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals as well as to examine a health system’s performance towards financial protection for citizens. A considerable number of studies have been carried out to identify and quantify the determinants of healthcare expenditure at the macro level. The roles of socio-economic, geographic and environmental, lifestyle, and macro-economic factors are well-documented in determining health and healthcare expenditures . HoweverThus, this paper examined the social and economic factors associated with OOP health expenditures in Poland; for this purpose, we relied on panel-data regression and aggregated household data from 16 Polish regions and for the period 1999–2019.The paper is organized as follows. This background sets the stage for empirical analysis. The second section provides a literature review on the topic. The third section describes data and methods applied. The fourth section delivers empirical results on factors associated with OOP health spending. The fifth section discusses our results, while the sixth and seventh sections conclude the paper and provide policy implications from our analysis.OOP payments for health are known as an inherently regressive source of financing, meaning that poor households face a higher relative burden of OOP payments than households with higher income . Out-of-The existing literature on determinants of OOP health expenditure at the micro level , has focused extensively on studying the issue in a single country setting, typically using survey data. At the micro level, OOP health payments are defined as “spending on consultations, medicines and tests, and additional payments related to the treatment, and are net of any reimbursement that patients have received or expect to receive from their health insurance programs” . The aimStudies in different countries found that poorer individuals and households have lower absolute OOP expenditures on healthcare than well-off households, but the relative proportion of healthcare expenditure to total expenditures or income is significantly higher among poorer households ,21. HousAt the macro level, indicators of macro-economic profiles such as growth in gross domestic product (GDP) and foreign debt, government fiscal capacity, the inflation rate, and unemployment rate have been examined as the most important possible determinants of OOP health expenditures. Applying national health accounts estimates for 191 countries, Musgrove et al.  examinedhttps://bdl.stat.gov.pl/BDL/start (accessed on 2 December 2021). This database collects regional datasets from a variety of Statistics Poland research, including household surveys, regional accounts, prices, education, population, and environmental issues. The Local Data Bank is Poland’s largest database on the economy, society, and environment, offering more than 40,000 statistical measures thematically grouped. The data are collected for all statistical localities, including gminas, powiats, and voivodships. The advantage of this databank is the cross-regional uniformity of the data collection process and completeness of data for particular variables.The study used aggregated regional data extracted from an online database of Statistics Poland, Local Data Bank—n = 16 regions; t = 21 years, 1999–2019) with no missing data; therefore, the panel was balanced. The research period was chosen based on the availability of data; earlier or more recent figures were unobtainable.We used the regionally aggregated data, and the regions of interest were voivodships; there are 16 regions of this level in Poland, with a population ranging from 0.9 to 5.4 million people. There were 336 observations for all variables  monthly out-of-pocket health expenditure per person in Polish households. The figures used for constructing this outcome measure come from representative household budget surveys with a sample of about 37,000 households, representing 0.3 percent of households in Poland. For the purpose of inflation adjustment in this variable, we used the country-level consumer health price index as reported by the Local Data Bank database. Based on previous systematic reviews, a set of potential independent variables (IVs) was developed, including economic, labour, demographic, educational, health, environmental, and lifestyle measures ,5. Real In the estimated models, all variables apart from those expressed as percentages were transformed into natural logarithms.We based our model building on study focus, previous research, and statistical properties of models constructed. Stata 14  was usedTertEdu and LowEdu with a correlation coefficient of –0.87 and both proxying education level). Instead, we selected one of such competing variables by estimating a separate model with each of these variables included and choosing the one with the lowest Bayesian information criterion (BIC) value. This choice was used for the following sets of variables: (1) Unempl and EmpRate; (2) Pop0_4 and Pop0_9; (3) LE_0 and LE_65; (4) Mortality, MortCancer, and MortCardio; (5) Gas, Gas-CO2, SO2, and Nox. This led to 96 (2 × 2 × 2 × 3 × 4) combinations of IVs and 96 potential initial models.Our initial approach was to include variables from all categories of factors potentially affecting OOP health spending as categorized in We estimated one- and two-way fixed effects models (FEMs) in each of these potential initial models to decide whether year dummy variables should be included in the specification . This was done by testing the hypothesis that the coefficients of all year dummy variables were not different from zero. FEM was used because this approach is appropriate if a focus of analysis is on a specific set of entities and inference is restricted to the behaviour of these units. In contrast, the random-effects model applied if we randomly drew some individuals from a large population . BecauseIncome; Doctors; Clinics; VisitPr; Unempl or EmpRate; Pop0_4 or Pop0_9; Pop70+; TertEdu or LowEdu; PopDens; LE0 or LE65; Mort or MortCancer or MortCardio; Gas or Gas-CO2 or SO2 or Nox; Sport; and TobAlc. In backward elimination, those variables with p-values higher than a chosen threshold of α = 0.1 were excluded one by one, starting from the IV with the highest p-value, and the order of exclusion was determined by a decreasing p-value. In this step, the FEM approach was also used and the minimization of the BIC value was a criterium to choose the model with a final set of IVs.Among 96 potential initial models, the model with the lowest BIC value was chosen as a starting point for further backward elimination (which is preferred over forward selection ) of IVs.This model was also subjected to an analysis of the potential presence of heteroscedasticity, cross-sectional dependence, and autocorrelation, and if any of these were found, remedial estimation approaches were used. Finally, to test the robustness of our estimates, we employed a set of alternative panel-data estimators suitable to our panel structure and potential problems stemming from heteroscedasticity, cross-sectional dependence, and autocorrelation. In particular, fixed-effects regression with Driscoll–Kraay robust standard errors ,52 was o-pocket payments for healthcare in Polish regions using 5-year interval figures for the period analysed. The average per capita OOP spending was 43.3 PLN in 1999, and it increased to 58.65 PLN in 2019 with an average annual growth rate of 1.9%. However, this increasing trend was not uniform across the period; the figures show that in 2004 and 2014, real OOP health spending decreased compared to the previous year shown in the table  in several regions. In fact, in 2014 a majority of voivodships were characterised by lower levels of real household health spending than 5 years before.Hexp variable in the period investigated varied from 11.4% in 2002 to 17.8% in 2010–2011, and this variation was notably higher than the respective coefficient for disposable income  for the A more detailed analysis of OOP health dynamics is provided in the 2 = 0.919 (Income) was associated with a 0.63-percent increase in OOP health spending. Therefore, according to this finding, healthcare funded by OOP spending is considered a necessary  good. Considering healthcare variables , only the density of physicians was included in the final specification. A 10-percent increased availability of doctors (Doctors) was associated with 1.8-percent higher health spending. No such effect was identified for the accessibility of outpatient clinics. Moreover, our findings show that the price of a specialist private visit did not translate to changes in OOP health expenditure.The model was well-fitted to empirical data with adjusted R = 0.919 , and thiUnemploy) was related to 0.01 lower OOP expenditure. On the other hand, demographic variables  have a very strong effect on health expenditure; a 1-percentage point higher share of population at age 0–9 (70 and over) would result in 4.9-percent (8.5-percent) increased health spending. Considering population health status, the results are ambiguous. Higher life expectancy at age 65 (LE_65) was associated with lower health spending , meaning that in the regions where people enjoy longer life, health expenditure is substantially lower. However, when it comes to the mortality variable , the negative sign of its coefficient was unexpected because greater mortality here is associated with lower spending on health.The effect of the labour market situation on household health spending is significant but very modest; a 1-percentage point higher unemployment rate (2 (Gas) significantly affected higher OOP expenditure, but this effect was modest (elasticity of 0.07). Finally, the model shows that lifestyle choices were related to household spending on health. The regions characterised by higher expenditures on tobacco and alcohol (TobAlc) were the ones where people also spent more on health (elasticity of 0.17). Moreover, a proxy variable for physical activity (Sport) was negatively associated with OOP spending; however, this effect was not strong (elasticity of −0.09).Gas pollutant emissions per 1 kmWe applied three other panel data estimators to test the robustness of our econometric estimates: (Model S1) Prais–Winstein regression with correlated panel corrected standard errors; (Model S2) feasible generalized least squares in the presence of AR(1) autocorrelation within panel and cross-sectional correlation and heteroskedasticity across panels; as well as (Model S3) Baltagi and Wu  fixed-efIncome) was hardly affected by the three alternative estimators ). The coefficient of doctors’ density (Doctors) was also similar in sensitivity scenarios  compared to the BS (0.18); however, this variable was only weakly significant in model S3. In general, the results obtained with the Baltagi and Wu [Doctors, Unemploy, Gas, and Sport also proved to be significant only with p < 0.1. Moreover, health status  and tobacco and alcohol spending (TobAlc) were insignificant in this specification. Still, the estimates of the other two sensitivity models (S1 and S2) were very similar to the BS and our findings were clearly supported by these model specifications.The elasticity of income , average OOP spending per capita decreased compared to the previous year in almost all (12–13) of 16 regions . This trIn general, in the period investigated, the average annual growth rate for income was notably higher  than the corresponding growth rate for OOP (1.9%). This suggests that healthcare financed through household spending has characteristics of a necessity  rather than a luxury. This finding is evidently supported by the estimate of income elasticity from our panel-data regression. According to the model, the income elasticity of OOP health expenditure in Polish regions was 0.63, and this estimate was highly significant and stable in the sensitivity analysis (0.56–0.60). Therefore, Polish households increased their health spending by less than a unit in response to a unit increase in disposable income.Improved access to health services was previously recognized as a factor contributing to rising healthcare expenditure . When thIn terms of the labour market, a 1-percentage-point rise in the unemployment rate is associated with a 0.01 percent decrease in OOP expenditure; therefore, this effect—although significant—is irrelevant. The linkage between healthcare spending and employment could be explained by the fact that healthcare is not a luxury but a necessity. Similar studies conducted in EU and OECD countries reported that unemployment has a positive effect on OOP spending because unemployed people lose their insurance coverage and thus have to deal with OOP expenses in order to meet necessary healthcare needs . This meThe regression estimates discussed above present a coherent picture; all the coefficient signs are in accordance with a priori expectations. However, the findings are not that clear when it comes to health status measures used in our model. The negative and significant effect of longer life expectancy is expected because if people enjoy better health, they also require less healthcare, and, as a consequence, their resulting OOP spending is lower. This process, however, is not reflected in our estimate of mortality; the coefficient of this variable is negative, despite the fact that we would anticipate it to be positive since higher mortality reflects worse health and, perhaps, more OOP spending. This is not the case here and this contradictory finding is difficult to explain on the basis of only the regression results. This variable might reflect the impact of technological progress on health spending  and Furthermore, air pollution appears to be associated with higher OOP spending on health. This suggests that poor air quality in Poland  leads toLifestyle behaviours are major determinants of health and accordingly have an impact on healthcare needs and spending. The associations between healthcare expenditure growth and lifestyle-related factors, including alcohol and cigarette consumption, calorie intake, sugar consumption, obesity, and physical activity, were proved by a number of studies performed in OECD countries at the macro level ,66. As eVisitPr) used is based on a single price only , and this definitely oversimplifies the real variation in healthcare prices. Moreover, our outcome variable was based on self-reported spending, making it prone to typical bias associated with survey data, e.g., participants’ inability or aversion to report precise and reliable data. Similarly, life expectancy or mortality rates are also not perfect measures of health status, as they do not explicitly account for morbidity dimension or quality of life. Thirdly, it should be recognized that the results of this analysis were context-specific and their generalization to other settings might not be appropriate. Particularly, Poland has quite a substantial share of OOP spending compared to other developed countries, and this possibly means that the mechanisms behind factors associated with OOP might be different here than in, for example, Western European countries. Furthermore, the present COVID-19 pandemic situation might have important implications for OOP health spending that were not taken into consideration in our study. This limitation results from data constraints; statistics on a set of variables used were not obtainable for the period from 2020 onwards. Therefore, the pandemic effect on OOP spending shall be investigated in the future, once more recent data is available.Before we conclude, we shall acknowledge the limitations of our analysis. First, because we used aggregated data, our results are at risk of ecological fallacy, meaning that the relationships observed at the regional level might not reflect household behaviour appropriately. Aggregated data also more often result in confounding bias and cross-level bias. These kinds of bias call for caution in interpreting the findings; however, such an approach is common in the literature, and numerous previous studies based on aggregated data were useful in disentangling relationships between socio-economic factors and health spending. Second, some of the variables we used are imperfect proxies for phenomena they are intended to illustrate: e.g., the price variable  are significant positive predictors of OOP payments. Additionally, we opened a new debate on research into other determinants of OOP payments. Particularly, we identified healthcare (financed from OOP) to be a necessity rather than a luxury good. In addition, we observed a modest supplier-induced demand effect and identified the importance of environmental and lifestyle factors for household health expenditure. Our findings also suggest further research to explore the relationship between health status and OOP spending.One of the main objectives of the national and international health policy is to replace OOP payments with more equitable sources of funding. In this context, analysis of the determinants of OOP payments is of great importance in order to identify problems associated with the accessibility and affordability of healthcare and to devise effective health policies to manage such payments. Based on these findings, several policy implications can be drawn in order to protect Polish households from the negative effects of OOP spending. The study suggests the need for considering a wider range of factors that are positively associated with OOP health spending  by policy makers while designing and implementing policies to increase financial protection for the Polish population. The findings can guide national policies toward enhancing allocations to healthcare and providing further financial protection for vulnerable populations, including households with elderly members and children.


Plummer-Vinson syndrome (PVS), the triad of dysphagia, iron-deficiency anemia (IDA), and esophageal webs, is a relatively rare disease entity that is mostly observed in the Caucasian populations of Scandinavia and North America. As these regions have become more developed with improved nutrition, PVS is now more commonly seen in the developing regions of the world.Helicobacter pylori (H. pylori) gastritis on upper endoscopy. She improved with dilation of the web in the esophagus and treatment of H. pylori. Identifying the possibility of this syndrome in clinical practice and the association between H. pylori and PVS, especially given recent changes in its epidemiology, is important given the patient population in Hawaii and the Pacific.We present the case of a 29-year-old Pacific-islander woman who presented with progressive dysphagia and IDA and was found to have an esophageal web and  Plummer-Vinson syndrome (PVS) is a rare syndrome characterized by the triad of dysphagia, iron-deficiency anemia (IDA), and proximal esophageal webs, which are thin membranes that may develop across the lumen of the esophagus -3. It waModern-day epidemiological data about the incidence and prevalence of PVS is not widely available. A single population-based study in the 1960s in South Wales reported the prevalence of post-cricoid webs was between 8.4% and 22.4% in women with dysphagia, while no webs were identified in men .PVS is most common in middle-aged women, which accounts for almost 90% of cases -3. The hHelicobacter pylori (H. pylori) gastritis on EGD.The initial management of PVS involves iron and B-complex supplementation. In most cases, iron therapy alone results in the improvement of symptoms . MoreoveA 29-year-old Pacific-islander (Chuukese) woman with no past medical history presented to the GI clinic for evaluation of dysphagia. She started having progressive difficulty swallowing nine months before the evaluation, mainly for solid food. She lost 78 pounds in three years. She also reported heartburn, intermittent chest and throat pain, and nausea but denied vomiting, abdominal pain, diarrhea, constipation, or bloody stool. She visited the emergency room one week prior for fatigue and was diagnosed with microcytic anemia.H. pylori chronic gastritis, and increased intraepithelial lymphocytes in the duodenum.In the GI clinic, physical examination was unremarkable, including an abdominal exam. Initial laboratory studies were significant for microcytic anemia with a hemoglobin of 11.1 g/dL and a mean corpuscular volume (MCV) of 78.6 FL. Otherwise, the white blood cell count (WBC), platelet count, kidney function test, and liver function test were normal. Iron studies were consistent with IDA with a total iron level of 25 ug/dL, low saturation, high iron-binding capacity, and ferritin level of 8 ng/mL. A barium esophagogram was performed and revealed no abnormalities. Therefore, the patient underwent an EGD, which revealed a stricture from an esophageal web in the proximal esophagus  for treatment of PVS has been reported from all parts of the world but was initially concentrated in Northern European countries ,2,13. CuDysphagia is the most common presenting symptom of PVS, resulting from luminal stenosis and esophageal dysmotility. It is often low-grade, intermittent, and painless. The progression of dysphagia is slow and can take several years . PatientH. pylori infection impairs iron absorption as a result of chronic gastritis, which causes gastric hypochlorhydria and subsequent impaired iron uptake and an increase in iron loss, potentially leading to IDA. One case report from Japan described successful therapy of PVS with endoscopic dilation and eradication of H. pylori infection [Although the pathogenesis of PVS is unclear, there are several proposed mechanisms, including nutritional deficiency , genetic predisposition, and an autoimmune process ,3. It isnfection .Barium esophagram is the most sensitive diagnostic test to detect esophageal webs. However, it can be unrevealing, and therefore endoscopy is required to make the diagnosis. Endoscopy should be done cautiously as the web is usually detected close to the upper esophageal sphincter and thus can be missed or ruptured during the passage of the endoscope ,2. The first step in the management of PVS is to clarify the etiology of the IDA by excluding other causes, such as celiac sprue, malignancy, or hemorrhage. The initial management of PVS involves iron and B-complex supplementation ,15. In oPVS has an excellent outcome; however, it can be associated with an increased risk for upper GI tract cancers. There have also been reports of gastric cancer. Thus, regular follow-up with endoscopic surveillance for this premalignant condition is recommended even after the resolution of symptoms ,3,11,12.H. pylori infection, and thus evaluation of patients with PVS should also include testing for and treatment of H. pylori. Further studies are needed to clarify the association between H. pylori and PVS, and perhaps this may be the origin of iron deficiency in PVS and the association between PVS and gastric malignancy. The diagnosis of PVS requires a high clinical suspicion. Thus, for any patient with dysphagia and IDA, PVS should be on the differential diagnosis as it carries an increased risk of upper GI malignancies and responds well to treatment with iron supplementation and esophageal dilation.PVS is a rare finding among Pacific islanders. Our patient was a young Chuukese woman, which is not the usual demographic of PVS patients. Our case provides a fresh new perspective on the etiology of PVS and its possible link to