The COVID-19 outbreak has placed substantial pressure on the medical systems worldwide. This study aimed to investigate the influence of the prepandemic vs. pandemic period on the activity of the Vascular Surgery Unit of a large emergency hospital in Eastern Europe. We performed a retrospective review of the vascular surgery cases admitted, comparing the statistics from the two time periods. We examined data of a total of 1,693 patients over the two periods. We report a 34.51% decrease in the surgical procedures performed during the pandemic period, with a disproportionate 80.6% decrease in the number of cases admitted with a diagnosis of venous insufficiency diagnosis and an increase of 67.21% in the number of patients admitted with acute arterial ischemia. Furthermore, individuals not classed as emergencies were delayed or denied surgical care. The number of nonurgent procedures conducted by our Vascular Surgery Unit decreased significantly, whereas the number of emergency surgeries increased. COVID-19′s effect is projected to have a long-term impact on how surgical treatments are provided in Romania. The declared epidemic of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), also known as COVID-19, has disrupted the normal operations of the global healthcare system , with liOnce the number of cases began to rise, certain restrictions also affected medical activity, such as reducing the number of surgical procedures, delaying programmed operations, and deciding to admit emergencies only , 8. It wNumerous publications revealed the effects of the pandemic on the activity of specific clinics dealing mainly with chronic pathologies, such as head and neck surgery, otorhinolaryngology, bariatric surgery, orthopedic surgery, cardiac surgery, plastic surgery, cardiology units, nephrology units, oncological clinics, and special transplant facilities –23.The Vascular Surgery Unit of The County Hospital Târgu-Mureș is the only one of this type in the county. It also provides specific vascular emergency care for five other counties. The leading chronic pathologies admitted to the clinic are peripheral artery disease (PAD), chronic venous insufficiency (CVI), symptomatic carotid stenosis, and patients with end-stage chronic kidney disease for arteriovenous fistula (ESKD). The acute pathologies include acute ischemia of the upper and lower limb, arterial trauma, and ruptured aortic aneurysm –32.As for many other departments in the hospital, the pandemic took a toll on the care provided to the patients. The characteristics of the procedures performed changed, as did the addressability, and the overall structure of the activity shifted toward supporting the emergency system and prioritizing acute strategies vs. elective surgery.This study aims to compare the pandemic interval 1 June 2020 to 30 November 2021 with the prepandemic period of 1 June 2018 to 30 November 2019 and analyze the effects of the pandemic on vascular surgery activity.This is a retrospective study analyzing the pandemic effect on the surgical activity of the Vascular Surgery Unit operating inside the Emergency County Hospital Târgu-Mureș, Romania, by comparing the pandemic period 1 June 2020 to 30 November 2021 with the same prepandemic time frame 1 June 2018 to 30 November 2019. The Vascular Surgery Unit was found in 2019, covering the territory of 250 km and a population of approximately 1.7 million people in Central Romania.The number of patients admitted over the two time periods was selected from the computerized database of the Emergency County Hospital Târgu-Mureș by age, gender, diagnosis, type of surgical operation, and the number of hospitalization days.Throughout the pandemic course, the unit was involved in emergency cases of both COVID-19 and non-COVID-19 patients.via Fogarty thrombectomy/embolectomy, and acute arterial trauma patients. Due to fewer performed procedures, patients undergoing lumbar sympathectomy, post-traumatic reconstructions, and excision of infected prosthetic grafts were grouped under the label “other procedures.” We excluded from the study candidates for extra-anatomical procedures, outpatients, patients treated conservatory, recipients of minor amputations , and patients presenting with acute limb ischemia solved by thrombolysis or mechanical thrombectomy, as these procedures are not performed in the unit. Also, the abdominal aortic aneurysm patients were excluded due to the small number of open repair procedures performed in the unit.Our cohort included PAD patients of any Leriche–Fontaine stage  who wereThis study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Ethics Committee of Târgu-Mureș Emergency County Hospital (no. Ad. 31750/7 December 2021).t-test or Mann–Whitney U-test as appropriate for two-group comparisons. Categorical variables were compared with the χ2-test. All p-values are two-tailed, with p < 0.05 considered statistically significant. Statistical analysis was performed using SPSS for Windows version 22.0 .Data are presented as the mean ± SD if normally distributed and median (Interquartile range) if nonparametrically distributed. Differences between groups were tested using a two-tailed Student's Among the surgical procedures performed in the Vascular Surgery Unit are saphenous stripping or RFA, vascular access procedures, infrainguinal and aortoiliac revascularization, carotid surgery, major amputations, endovascular treatment of various stenosis, and Fogarty thromboendarterectomy for acute limb ischemia.p < 0.0001), followed by symptomatic carotid stenosis (p < 0.0001), STG IV Fontaine PAD patients (p < 0.001), and patients with CLI (p = 0.001). Moreover, no significant difference was observed between the two periods regarding ESKD patients (p = 0.66) and STG III PAD patients (p = 0.79). All other diagnoses had a significant decrease during the pandemic period, as shown in A number of 1,693 patients were admitted to our clinic over the two periods, with a decrease of 34.51% in the performed surgical procedures during the pandemic period . However, there was a statistically increased number of ALI cases (p = 0.0003) and a decrease of patients from other counties during the pandemic (43.41% vs. 27.17%. p = 0.0003).The addressability was analyzed based on the residential county of the patients. Although we recorded decreases in the numbers of patients referred to us both from the local Mures county and from neighboring counties, addressability from the neighboring counties decreased proportionally more. We recorded statistically significant differences between the prepandemic and pandemic periods, with a percentual increase of patients from the local county , gender distribution , or hospitalization day   .p < 0.0001) and amputation (p < 0.0001) in COVID-19 patients. Moreover, a substantial increase in the number of hospitalization days (p = 0.0001), ICU admission (p < 0.0001), and deaths (p < 0.0001) was detected in COVID-19 patients. Furthermore, in terms of gender distribution, significantly more women were admitted during the pandemic period (p < 0.0001)  admissions, and mortality rates are presented in  0.0001) .p < 0.0001). In terms of the average age, only patients with symptomatic carotid stenosis (p < 0.0001) and patients who benefited from endovascular treatments (p < 0.0001) have been reported to be younger during the pandemic period. Fewer days of hospitalization have been recorded for carotid thrombendarteriectomy (p < 0.0001), upper and lower limb embolectomy (p = 0.01), suprainguinal revascularization (p < 0.0001), infrainguinal revascularization (p < 0.0001), and endovascular treatment (p < 0.0001) during the pandemic period. However, the number of days spent in the hospital was higher regarding amputations (p = 0.001), as shown in The statistics show no significant differences in the number of surgical procedures performed in the two periods. The only procedure that has grown tremendously is carotid thrombendarteriectomy (Furthermore, the number of in-patients admitted each month was analyzed. A significant decrease was registered during the pandemic, with one exception: in May, the same number of patients were admitted in both periods, in 2020–2021, during the pandemic, and in 2018–2019. The decreases in the number of patients were 76.19% in December 2020, compared to the corresponding month of 2018, followed by 73.91% in November 2021, compared to 2019, and 63.93%decrease in September 2021, compared to 2019 .An overall decrease in surgical procedures was experienced throughout the pandemic, significantly affecting chronic pathologies such as CVI and the initial stages of PAD. Due to the alarming infection rate, lockdowns were established everywhere. Nationally, the first lockdown was initiated on 24 March 2020. All chronic admittances were canceled, and all surgical activity was redirected toward emergencies. Therefore, the Vascular Surgery Unit experienced a significant increase in the number of patients diagnosed with symptomatic carotid stenoses eligible for endarterectomy, patients with ALI of the upper and lower limb, and patients with ischemia-induced trophic disorders of such amplitude that a major amputation was required. We believe that the thrombotic effect of the virus may have influenced the more significant number of acute ischemia.The number of patients presenting with lower stages of PAD and CVI decreased. Also, except for amputation patients, the hospitalization days were reduced for all categories of patients admitted to minimalize hospital contact and decrease the risk of infection with COVID-19.Schuivens et al., in a paper on the effect of the pandemic on peripheral artery disease patients, recorded an increase of major amputations, with an incidence of 42% in 2020, compared with 18% in 2019 and 15% in 2018 . In a paMiranda et al. analyzed the activity of the Vascular Surgery Clinics of nine tertiary hospitals, comparing the lockdown period 18 March–17 May and the immediately following period when the restrictions were withdrawn, 18 May–31 December, with the corresponding periods in 2019. The results were a decrease of the procedures by 64% compared to 2019, whereas in the following period, there was only a 14% decrease compared to 2019. According to their study, venous pathology recorded the highest decrease, followed by endovascular procedures and aortic aneurysm repair. The only procedure registering an increase in the number of interventions during the pandemic was amputation, which increased by 7% .As shown in As the virus was spreading and the severe cases of SARS-CoV-2 were accumulating, Infectious Diseases, Pulmonary Diseases, and then Intensive Care Units were filling up, and organization measures were necessary. Some units were transformed into COVID-19 hospitals, taking care of this pathology alone. The Vascular Surgery Unit is the only of this kind in the county, so it had to provide care for both COVID-19 and non-COVID-19 pathologies. A whole wing was transformed into a COVID-19 facility in the County Hospital, with a dedicated COVID-19 Operating Room.Apart from the lockdown periods, medical activity was continuously affected. New protocols were elaborated, and the 1.5–2 m distance between the patients in the wards had to be respected. The chronic, ambulatory patients who needed clinical follow-up were evaluated respecting two patients per hour regulations. These measures affected the waiting period and the regular flux schedule. The COVID-19 pandemic affected medical activity globally, causing a decrease in the addressability of chronic cases and increased referred emergencies.As some of the tertiary units around the county were entirely transformed into COVID-19 facilities, a significant number of patients were addressed to nearby vascular surgery units. On the other hand, some of these patients with chronic pathologies were reluctant to travel to another county, leading to unavoidable delays in treatment. In the prepandemic period, the addressability from other counties to our vascular surgery unit was greater than that during the pandemic, explainable by the restrictions and limitations to travel and the redirecting of the cases to the nearest vascular center.Another interfering issue worth mentioning is the staff redistribution: many trainées were reassigned to the COVID-19 units to help general practice, making it harder to maintain the same rhythm and disrupting their vascular surgical training.The strong point of this paper is the study of the whole pandemic course. We analyzed its effect on the number of patients and the hospitalization days for each pathology and procedure in our service. The limitations of the study are the relatively small number of patients from a single center, mainly men, making extrapolation difficult. Multicentric, retrospective studies are required for better accuracy of the results and a more extensive overview of the national impact of the pandemic on the healthcare system.The SARS-CoV-2 pandemic was a worldwide public health problem affecting all areas of medical interest. Our Vascular Surgery Unit was also influenced by the pandemic changes in the healthcare system, suffering a significant decrease in the number of performed non-urgent procedures and increasing the number of emergencies attended. It is questionable whether the increase in the number of amputations during the pandemic was due to the forceful delaying of the chronic pathology or simply because the addressability of this type of emergency has grown.


Hepatocellular carcinoma (HCC) remains a global medical problem. Programmed cell death protein 1 (PD-1) is a powerful weapon against many cancers, but it is not sensitive to some patients with HCC. We obtained datasets from the Gene Expression Omnibus (GEO) database on HCC patients and PD-1 immunotherapy to select seven intersecting DEGs. Through Lasso regression, two intersecting genes were acquired as predictors of HCC and PD-1 treatment prognosis, including HAMP and FOS. Logistic regression was performed to build a prediction model. HAMP had a better ability to diagnose HCC and predict PD1 treatment sensitivity. Further, we adapted the support vector machine (SVM) technique using HAMP to predict triple-classified outcomes after PD1 treatment in HCC patients, which had an excellent classification ability. We also performed external validation using TCGA data, which showed that HAMP was elevated in the early stage of HCC. HAMP was positively correlated with the infiltration of 18 major immune cells and the expression of 2 important immune checkpoints, PDCD1 and CTLA4. We discovered a biomarker that can be used for the early diagnosis, prognosis and PD1 immunotherapy efficacy prediction of HCC for the first time and developed a diagnostic model, prognostic model and prediction model of PD1 treatment sensitivity and treatment outcome for HCC patients accordingly. Liver cancer, as one of the four main causes of cancer-related death all over the world, has brought heavy human and economic burdens to society ,2. HepatAlthough the diagnosis and treatment techniques of liver cancer have developed in recent years, early detection and monitoring are still obscure ,5,6. CurAs to therapies, while immunotherapy has played an extremely important role in the treatment of many tumors in recent years, clinical studies of immune checkpoint inhibitors (ICIs) in liver cancer have continued to emerge ,14. PD-1With the rapid development of genomics, proteomics, and metabolomics, as well as the discovery and application of PCR amplification and sequencing technology, liquid chromatography-mass spectrometry metabolomic analysis technology, and quantitative proteomics technology, the search for more accurate and effective markers in the early screening of liver cancer has become a high point of research. This study tries to identify novel biomarkers for the early diagnosis, prognosis and prediction of PD-1 immunotherapy sensitivity and development with respect to new medicines. With detection or monitoring, not only can the biomarkers facilitate early detection, but also screen suitable HCC patients and predict their prognosis . Furtherhttps://www.ncbinlm.nih.gov/geo/, accessed on 2 February 2022), which is based on the GPL19965 platform and contains a total of 24 samples, all of which were treated with PD-1 immunotherapy, and they were classified as 6 with partial remission (PR), 10 with stable disease (SD) and 8 with progressive disease (PD) according to the treatment efficacy. The raw data on the “Liver Tumor” criterion were downloaded from GSE14520 based on the GPL571 platform, and 43 samples were availa2015013052@stu.gzucm.edu.cnble, of which 22 were tumor samples and 21 were normal samples. The patients back ground data was showed in With the search criteria of “PD-1 Receptor” and “Liver Neoplasm”, the dataset GSE140901 was obtained from the Gene Expression Omnibus (GEO) of NCBI  was calculated to assess the discriminatory ability of the prediction models. It should be highlighted that the nomograms of the critical factors were created separately for visualization in this study. Nomograms are able to visualize the results of regression analysis and allow for a more intuitive presentation of multiple indicators that combine to diagnose or predict disease risk or prognosis. Meanwhile, this study also plotted survival curves using the Kaplan–Meier (KM) method by using individual overall survival times (OS) as an outcome variable for the GSE14520 and GSE140901 datasets, separately, and performed a logrank test to compare significant differences in survival curves, aiming to screen genes that specifically affect the prognosis of PD-1 treatment.The support vector machine (SVM) algorithm is capable of mapping the categorized data to a higher dimensional feature space with certain fault tolerance conditions based on an appropriate kernel function and classifying the data by constructing an optimal classification hyperplane in this space. This algorithm is suitable for small sample, nonlinear, high-dimensional data classification problems, with high reliability in its prediction, stability and generalization ability, and it is widely applied to processing classification problems and regression analysis. However, the model built in this study incorporates only one feature variable and does not require an SVM algorithm for high-level processing data; compared with logistic regression, SVM is more suitable for small-scale data sets. Moreover, SVM is better for handling nonlinear relationships; therefore, it is feasible for us to model with the SVM algorithm. The present study segmented the GSE140901 dataset into three categorical outcome variables on the basis of post-treatment efficacy, constructing prediction models of pivotal genes screened from 1.3 by SVM and assessing them through the subject working characteristic curves.https://www.cancer.gov/aboutnci/organization/ccg/research/structural-genomics/tcga, accessed on 2 February 2022). The patients’ background for TCGA can be found in https://www.Rproject.org, accessed on 2 February 2022) and its powerful data analysis capabilities and box plotting in the “ggplot2” R package, we compared the expression levels of the pivotal gene in normal versus HCC tissues, as well as in different tumor stages. The expression differences between HCC and normal tissue samples were identified with a p-value of <0.05.To provide a further test of the actual value of the pivotal gene in clinical samples, we downloaded liver cancer and its normal samples from the TCGA database , disease-specific survival (DSS) and progression-free interval (PFI) were deemed to be indicators to explore the correlation between pivotal gene expression and HCC patient prognosis. When it concerned survival analysis, the Kaplan–Meier method and logrank test were deployed.https://cibersort.stanford.edu/, accessed on 2 February 2022) and the R software packages “ggplot2” and “ggpubr”. As a final step, we separately evaluated the co-expression of the pivotal gene with PDCD1 and CTLA4 in HCC using Spearman correlation coefficients, which are the target genes of two well-recognized anticancer miracle drugs.What is more, the correlations between the pivotal gene and the 24 immune cells’ infiltration levels in HCC were assessed using CIBERSORT .The two pivotal genes identified in Setting HAMP as an independent variable, we constructed an SVM model utilizing the e1071 package and applied a lattice parameter search function to find the best cost value. When cost = four, we constructed the best support vector machine model, and the performance of the model was assessed using multi-category ROC curves . Meanwhile, the model also had good discriminative performance in the prognostic multiclassification .Based on the TCGA data, by comparing the expression levels of HAMP in normal samples with those of HCC samples, it was obvious that the expression level of HAMP was significantly reduced in HCC tissues A. This cp < 0.05)  B. DSS is < 0.05) D.p < 0.001) and CTLA4 (p = 0.004). Immunotherapy targets mainly included CD274, PDCD1, and CTLA4. CD274 correlation was calculated as cor = 0.066, p = 0.203 > 0.05, so it was not included. Moreover, CD8, T-cell failure, tumor-associated fibroblasts (CAF), and tumor-associated macrophages (TAM) markers belonged to tumor microenvironment markers and were not in our scope of concern.From the results of CIBERSORT, it appeared that for HCC, the level of immune cell infiltration was remarkably correlated with HAMP expression to a great extent, except for Tcm . MeanwhiIn the present study, firstly, we attained two crossover genes, HAMP and FOS, by differential gene extraction and lasso regression analysis. Next, to pick a more valuable biomarker, we employed logistic regression to build prediction models using HAMP and FOS as independent variables. Combining the results of ROC curve and nomogram, we concluded that HAMP has a better ability to diagnose HCC and predict PD-1 treatment sensitivity. As a further step, we constructed the SVM model of HAMP to predict the three-stage outcome after PD-1 treatment in HCC patients, which had good classification ability. In addition, we performed external validation by using TCGA data, which revealed that the expression level of HAMP was significantly reduced in HCC tissues and was significantly elevated in the early stage of HCC, suggesting an important role of HAMP in the early diagnosis of HCC. More notably, we found that HAMP was significantly and positively correlated with the expression of 18 major immune cell infiltrates and 2 important immune checkpoints, PDCD1 and CTLA4. This finding lays a foundation for HAMP to guide the immunotherapy of HCC, which could be beneficial for clinical precision treatment and saving medical resources.Hepcidin antimicrobial peptide (HAMP), a liver-produced protein-coding gene, is the master regulator of iron homeostasis maintenance , and it Of more interest, however, is that this study further examines the predictive role of HAMP in assessing the sensitivity and prognosis of patients with HCC to PD-1 therapy, which is of great significance both in terms of improving effective clinical treatment rates as well as saving healthcare resources. PD-1 immunotherapy serves to increase the antitumor activity of T cells in the body by relieving the suppression of immune function, which is mediated as a result of the combination of PD-1 and PDL-1, thus providing a killing and suppressing impact on cancer cells . In someThe main inadequacy of this study was that the superior prognosis of HAMP was not as well captured in the OS and PFI of patients with HCC. Regarding this point, we speculated that it was due to a high number of missing follow-ups in the extracted patient data; thus, the time of death of these patients was not precisely estimated. In addition, the cause of HCC is still not understood, due to the limitation of data sources.In a nutshell, this investigation suggested whether HAMP could be considered a new biomarker for diagnosing early-stage HCC and used to predict the sensitivity and prognosis of PD-1 immunotherapy, in addition to orienting the development of new drugs.


The aims of this study were (1) to develop a comprehensive risk-of-death and life expectancy (LE) model and (2) to provide data on the effects of multiple risk factors on LE. We used data for Canada from the Global Burden of Disease (GBD) Study. To create period life tables for males and females, we obtained age/sex-specific deaths rates for 270 diseases, population distributions for 51 risk factors, and relative risk functions for all disease-exposure pairs. We computed LE gains from eliminating each factor, LE values for different levels of exposure to each factor, and LE gains from simultaneous reductions in multiple risk factors at various ages. If all risk factors were eliminated, LE in Canada would increase by 6.26 years for males and 5.05 for females. The greatest benefit would come from eliminating smoking in males (2.45 years) and high blood pressure in females (1.42 years). For most risk factors, their dose-response relationships with LE were non-linear and depended on the presence of other factors. In individuals with high levels of risk, eliminating or reducing exposure to multiple factors could improve LE by several years, even at a relatively advanced age. The health impact of risk factors at the individual level is often measured in terms of absolute risk of disease occurrence or mortality over a specified time period. Risk prediction models, such as the Framingham equations , have beA less common but potentially useful alternative to disease-specific risk prediction is to assess the impact of risk factors in terms of all-cause mortality or life expectancy (LE) . Trends Another approach to assessing the impact of risk factors is to develop a “synthetic” model which utilizes data from many sources to combine information on mortality and relative risks associated with multiple diseases . This apCHARM is a computer program that estimates LE and risk of death from specific conditions based on a person-specific risk profile . Model pEstimation of LE starts with the specification of the age and sex of the individual, and the values of the risk factors . For each risk factor, the exposure-specific RR was calculated relative to the country-specific mean exposure for continuous factors and prevalence-weighted relative risk for categorical factors. Dose-response functions included continuous exponential and more flexible interval risk functions for continuous exposures, and ordinal, nominal, and dichotomous functions for categorical exposures . The oveTo obtain the effect of changes in a risk factor on LE at any age, we developed an  lagged model, which assumes a gradual change in risk following a change in exposure. In this model, we assumed an exponential decay process, with the half-life parameter specific to each exposure-disease pair . TechnicWe used data from the 2016 and 2017 GBD studies (GBD 2016 and GBD 2017) to obtain age/sex-specific deaths rates for 270 diseases, including residual categories for comprehensiveness , populatIn this study, we used mortality and risk factor exposure data for Canada. We analyzed the effects of 51 out of 60 risk factors available in the model. Five factors that apply to children only and four factors that do not cause death were excluded. We computed LE gains from eliminating each factor, LE values for different levels of exposure to each factor, and provided an example of gains in LE from simultaneous reductions in multiple risk factors at various ages for a person with a complex risk factor profile. To assess model performance, we compared LEs for 40 and 60-year-old males and females according to smoking and body mass index (BMI) between our model and the Mortality Population Risk Tool implemented in the Project Big Life calculator developed by Manuel et al. and based on a Canadian cohort  ,29. We aLife expectancy at birth (LE0) in Canada in 2017 was 79.61 years for males and 83.74 for females. The difference in LE between males and females diminished with age and by age 90, it was less than one year. In The greatest difference in LE0 for males was from eliminating smoking (2.45 years), followed by high systolic blood pressure (SBP) (1.51 years), high body mass index (BMI) (1.43 years), high low-density lipoproteins (LDL) cholesterol (0.98 years), and high sodium intake (0.80 years). For females, the greatest difference was for SBP (1.42 years) followed by smoking (1.26), BMI (1.25), LDL (0.84), and sodium (0.68). The effect of eliminating alcohol drinking was 0.21 years for males and −0.02  for females. Increasing physical activity to 4500 MET-min/week would, on average, improve LE0 by 0.17 and 0.21 years for males and females, respectively. Many of the factors studied had a very small impact on LE0 (0.01 years or less), mainly due to relatively low population levels of exposure in Canada, such that the average person (not a person exposed) would not gain much from removing these factors. These include most chemical exposures at work and some environmental factors . The combined effect of improving all 51 risk factors from the current average to the optimal level (adjusted for mediation) was 6.26 years for males and 5.05 years for females , resultiFor most risk factors, the relationship between exposure and LE0 was non-linear . For exaWe evaluated the impact of 7 metabolic factors . Of thos2.5 levels around 300 μg/m3 associated with a reduction in LE0 of more than 2 years. Very high levels of radon exposure also had a significant impact on LE0. Among the environmental and occupational factors, a high level of exposure to asbestos was associated with a 1.04-year reduction in LE0 in males and 0.85 years in females . Work exIn In the standard instantaneous (no lag) effect model, conditional LE at a given age following a change in exposure is the same as the LE of a person who has never been exposed. In the lagged model, we assume a gradual change in risk according to an exponential decay process, with a half-life parameter specific to each disease-exposure pair. In the no-lag model, quitting smoking at age 50 in our example (a person who has smoked 10 cigarettes/day since age 20) would produce gains of 3.18 and 4.23 years in males and females, respectively . A more The impact of changing the level of a risk factor may depend on the levels of other factors, as shown in In Comparisons of LEs according to the number of cigarettes and BMI between CHARM and the Big Life calculator are shown graphically in In In this report we described a novel risk and LE model based on GBD data and provided estimates of the LE impact of 51 risk factors. For many of the factors studied, including most occupational and some dietary factors, these are the first published estimates of their impact on LE. When we set all risk factors to their optimal values, life expectancy at birth for Canada increased to 85.87 for males and 88.79 for females. In males, the greatest impact on LE0 could be gained from eliminating smoking, followed by high SBP, high BMI, high LDL cholesterol, and several dietary risks. In females, the greatest impact would be achieved from optimizing SBP, followed by smoking, BMI, LDL, and dietary factors. The effect of changing a given risk factor was often non-linear and depended on the levels of other factors. Reducing exposure to multiple factors resulted in potentially large gains in life expectancy, even at a relatively advanced age. Our model development process has been described briefly in the methods section. A detailed, technical description of the model and the interactive computer program we have developed are given in Our model generally assumes that risk factors do not interact in their effect on RR, except for mediation effects. We did not incorporate interactions between risk factors because the required data were not available from the GBD and the knowledge base to justify this is not sufficiently robust at this time . HoweverTo accommodate mediation effects, we applied two models. In estimating the individual  effect of each factor, without specifying other factors, we used a model without mediation. For example, the effect of BMI in Our results can be compared with published LE effects of selected exposures from cohort-based models. In one of the first studies of the impact of smoking , LE of hThe association of diet with life expectancy and all-cause mortality has been controversial . ImplausPrevious research on physical activity (PA) found a strong impact on all-cause mortality, but few studies provided data on LE ,40. Lim Additional empirical evidence of CHARM’s validity is provided in Differences in the estimates of risk of death from CVD between CHARM and SCORE were generally smaller than differences observed among established cohort-based models . On averCHARM is a comprehensive, interactive risk and life expectancy model that provides estimates for a large number of diseases (270) and risk factors (60). Previously, Lim and colleagues developed a multi-disease mortality risk calculator using GBD data, but their model included only 12 risk factors . Unlike most published risk calculators based on statistical prediction models developed from cohort studies, CHARM is a synthetic model that uses all available, up-to-date data from a wide range of sources, collected, processed, and analyzed by the GBD. Cohort-based models are rarely fully representative of the underlying geographical population. Furthermore, parameters from a single cohort study are usually considered less reliable and less generalizable than those from a meta-analysis of many studies. Moreover, data from cohort studies are limited to a set of variables measured in those studies , may not collect data repeatedly over time, and may not be publicly available, which makes the model less transparent and verifiable. In addition, models developed from a cohort study may be difficult to update if the study has been discontinued or extensive new data collection and analyses are needed. In contrast, the relative risks and dose-response relationships underlying our estimates are publicly available, easily updatable, and based on meta-analyses of epidemiological studies carefully evaluated for potential biases and adjusted for confounding and mediation ,27. The All results presented in this paper are based on mortality and exposure data for Canada. Therefore, our LE estimates are not strictly applicable to other countries. However, since the relative risk functions are considered by the GBD to be the same for all countries, the relative effects on LE should be generalizable to other populations, especially other high-income countries. Caution is required when applying our data to low and middle income countries because the impact of risk factors on mortality may depend on access to health care. Nonetheless, replacing current parameters with a parameter database for any other country would be straightforward.A limitation of our model is that data for some factors that affect LE were not available. Specifically, we did not have risk functions for social determinants of health, genetic factors, and pre-existing conditions, as well as some environmental factors . Although these factors are generally unmodifiable, their inclusion in future versions of the model may improve the accuracy of predictions. A limitation of any model are potential inaccuracies in the data-derived parameters. This applies mainly to relative risk functions, derived from epidemiological literature, and the lag parameters. Some parameters derived from studies elsewhere may not apply to Canada. There may also be inaccuracies in exposure distribution data. Although uncertainty intervals for these parameters are available from the GBD, our model currently does not provide uncertainty intervals for LE or risk estimates. Therefore, similar to data from other published models, our estimates should be regarded as approximations and treated with caution. Finally, while LE is an important indicator of population health, a measure that reflects both quantity and quality of life, such as health-adjusted life expectancy (HALE) , would aPrior studies of the impact of risk calculators on the uptake of preventive measures by individuals have produced mixed results ,43,44,45Personalized prevention has been advocated for many years but despite significant progress in risk prediction for specific diseases, the data and tools needed to support large-scale applications of risk models across all diseases and risk factors have been lacking. In this report we estimated the effects of 51 risk factors on LE, derived from a new model that utilizes GBD data on mortality, risk factor distribution, and relative risk functions for 270 diseases. As such, the model is a synthesis of current epidemiological knowledge in a format suitable for immediate implementation. Limitations of the model notwithstanding, we hope this tool, and the data it generates, can assist patients and their doctors in making difficult choices between different options for risk factor modification.


AimThe current study aims to evaluate and compare the efficacy of light-cured calcium hydroxide and a fourth-generation calcium silicate cement  as indirect pulp capping (IPC) materials in patients with deep carious lesions.Materials and methodsA total of 28 patients were randomly divided into two groups (n=14). Group A was managed by light-cured calcium hydroxide, while group B was treated with TheraCal LC . Clinical examination was conducted to check for postoperative pain, tenderness, and neural sensibility, and radiographical examination was conducted to check for periodontal ligament space widening, presence of calcific barrier, and periapical radiolucency at patient recall of 21 days, three months, and six months. Primary and secondary outcome variables were based on clinical and radiographical success rates noted at six months’ follow-up.ResultsSuccess rate for light-cured calcium hydroxide group at follow-up came out to be 0% at 21 days, 85.71% at three months, and 92.85% at six months. The success rate for TheraCal LC group came out to be 0% at 21 days, 92.85% at three months, and 100% at six months. The overall success rate for IPC procedure was 89.28% at three months’ follow-up and 96.42% at six months’ follow-up for both groups. The difference was statistically non-significant at the end of three and six months’ follow-up.ConclusionWithin the limitations of our study, it was concluded that TheraCal LC can be used alternatively with light-cured calcium hydroxide in IPC, with a predictability of similar success outcome in patients with deep carious lesions. Indirect pulp capping (IPC) is a treatment modality that aids in sustaining pulpal vitality by facilitating healing/repair  of traumIPC agent is placed at the affected site with an objective to form "dentin‑like matrix" (reactionary/reparative dentin). This helps in repairing the "dentin‑pulp complex." There is stimulation of dentinal sclerosis, which results in formation of reparative dentin . Also, tCalcium hydroxide (CH) is taken as the gold standard among all the pulp capping agents that are used. Its use was first put forward by Zander . There iOn the basis of the chemical properties and composition of calcium silicate cement, TheraCal LC is classified as a fourth-generation calcium silicate-based material . It is aOnly a few clinical trials have been conducted so far, determining the clinical efficacy and successful outcome of light-cured CH or TheraCal LC as IPC agents in permanent teeth with deep caries. Hence, there is a requirement for more studies on these two materials. The objective of our study was to evaluate clinically postoperative pain, tenderness, and neural sensibility, and to check radiographically periodontal ligament (PDL) space widening, periapical radiolucency, and the presence of calcified barrier using intraoral periapical radiograph (IOPA). This evaluation was carried out at follow-up interval of 21 days, three months, and six months after IPC with light-cured CH and TheraCal LC in permanent teeth with deep carious lesions. The other objective of the study is the comparison of the efficacy of these two materials as IPC agents.This article was previously presented as a meeting abstract at the 12th IFEA WEC 202One on August 8, 2021.Study designThis randomized, parallel-group trial was carried out in the Department of Conservative Dentistry and Endodontics, Sharad Pawar Dental College and Hospital, Sawangi (Meghe), Wardha, India. It got its approval from the Institutional Ethics Committee of Datta Meghe Institute of Medical Sciences (Deemed to be University) (Ref No.- DMIMS(DU)/IEC/Dec-2019/8562) and was registered at Clinical Trial Registry-India as CTRI/2020/03/023808. Study participants were recruited from the patient group that reported at the Outpatient Department, where they were explained the significance of IPC. Before their enrolment in the clinical trial, participants were explained the potential risks and the expected benefits of treatment procedure. Informed consent was taken prior to the commencement of the treatment procedure. Confidentiality related to the participants was maintained. Sequence generation for the usage of the two materials was done by computer-generated randomization. Centralized allocation of the materials was done for the study. The reporting of the trial has been done according to CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials  + p2(1-p2)] / (p1-p2) 2The sample size was 14 in each group. Therefore, a total of 28 samples were required.Treatment protocolA detailed case history was taken, and the patients were thoroughly examined both clinically and radiologically. Local anesthesia (2% lignocaine HCl with epinephrine) was administered to prevent unpleasantness of sensitivity during caries removal. There was reduction of postoperative pain or sensitivity as well. The sample tooth was isolated with a rubber dam. Using a slow-speed round bur, the superficial caries layer was removed. Disinfection of cavity was done with 2% chlorhexidine  followed by irrigation with saline. The rest of the soft caries present in the deep layers was removed carefully with a spoon excavator. Disinfection of the rest of cavity was done by irrigation with 3% NaOCl  with the help of a syringe. The cavity was rinsed with saline to get rid of the excess NaOCl. The cavity was dried using cotton pellets . Pulp caIn the light-cured CH  group, CH was placed at the exposed area followed by its curing. Similarly, in the TheraCal LC  group, the agent was placed on the affected site and cured. Type II glass ionomer cement  was used as a base. Following this, a direct composite restoration  was undertaken. Finishing of the final restoration was done to attain a smoother surface to decrease plaque aggregation and to prevent discoloration of the restorative material  Figure . After fFollow-up and outcome measuresThe tooth was examined clinically to evaluate postoperative pain, tenderness, and neural sensibility, and radiographically to assess PDL space widening, presence of calcified barrier, and periapical radiolucency at a follow-up interval of 21 days, three months, and six months. On the basis of outcomes of evaluation of primary and secondary variables, at follow-up intervals, the clinical and radiographical success rate was determined. A successful primary outcome was indicated by the presence of calcified barrier at the restored site. A successful secondary outcome was defined by the absence of postoperative pain, tenderness on percussion, and positive response to neural sensibility tests, with absence of any radiographical signs of PDL space widening and lack of periapical radiolucency. The experience of pain by participants was scored using visual analogue scale (VAS) before and after the procedure .Patients were recalled for follow-up at the intervals of 21 days, three months, and six months postoperatively. During this session, they were assessed clinically for postoperative pain using VAS. Assessment of tenderness was done by vertical percussion of the restored tooth. Endo-Ice  was used for cold test in order to evaluate neural sensibility.Also, for assessing the tooth radiographically, periapical radiograph was recorded during these follow-up intervals. Evaluated parameters were presence/absence of PDL space widening, presence/ absence of periapical radiolucency, and the presence/absence of calcified barrier formation below the restoration. Radiographical assessment of group A at different time periods of follow-up is depicted in Figures  Statistical analysisDescriptive and analytical statistics had been done. The normality of data distribution had been analyzed using the Shapiro-Wilk test . As data followed normal distribution, parametric tests were utilized for analyzing the data. Fisher's exact test was applied for dichotomous variables such as tenderness on percussion, neural sensibility, PDL space widening, presence of calcified barrier, periapical radiolucency, and success rate.The one-way analysis of variance (ANOVA) test was utilized for the parameter of pain for checking the mean differences between the groups at different time period, and "post hoc Tukey’s HSD (honestly significant difference) test was used to compare the difference between two groups. The level of significance was set at less than 0.05 using two-tailed analysis. Statistical analysis was conducted using SPSS  Version 24.0 (IBM Corp.).A total of 26 patients were screened for the study, of which five were excluded because their age did not meet the age limit criteria. Therefore, only 21 participants were kept in the trial. They gave us the required sample size of 28 teeth. They were randomly allocated to the light cure CH group (group A) and the TheraCal LC group (group B), i.e., 14 teeth samples in each group. Among the teeth types, 10.7% comprised anterior teeth, 17.85% comprised premolars, 28.57% comprised first molars, 25% comprised second molars, and 17.88% comprised third molars.At the end of three months, 12 out of 14 teeth and 13 out of 14 teeth exhibited calcific barrier formation in the light-cured CH group and the TheraCal LC group, respectively. By the sixth month, 13 out of 14 teeth and all 14 teeth displayed calcific barrier in the light-cured CH group and the TheraCal LC group, respectively  at follow-up was found to be 0% at 21 days, 85.71% at three months, and 92.85% at six months. The success rate for the TheraCal LC group was found to be 0% at 21 days, 92.85% at three months, and 100% at six months Table .The overall success rate for IPC procedure was 89.28% at three’ follow-up months and 96.42% at six months’ follow-up for both groups. The difference was statistically non-significant at the end of three and six months’ follow-up.Treatment of reversible pulp injury is the main aim of indirect IPC. After caries removal, the thin layer of dentin remaining between the prepared cavity and the pulp chamber is lined with a protective covering to prevent any further injury to the pulp and to facilitate its healing and repair. The type of treatment strategy has a key function in determining the success of vital pulp therapy. It includes the operative procedure undertaken to remove the pulpal irritant, controlling infection, and placement of a protective barrier for isolation of pulp/dentin from further injuries . Also, tCa(OH)2 was introduced as a "remineralizing agent" for vital pulp therapy in 1930. It aids in the production of reparative dentin in the treated site by releasing Ca+ and OH- ions. The calcium ions form a gradient that stimulate the aggregation of undifferentiated cells of the pulp. Along with this, there is activation of stem cells. An alkaline condition is created. This type of environment is bacteriostatic and triggers the action of alkaline phosphatase and bone morphogenic protein‑2 (BMP‑2). This favors the production of calcific nodules. Calcium ions thus help differentiate and mineralize pulp cells ,21. AddiIn our study, it was found that TheraCal LC has a slightly better outcome as compared to light cure CH group, with a success rate of 100% and 92.85%, respectively, at the end of six months’ follow-up. The difference was statistically non-significant at the end of three and three months’ follow-up.A few limitations were present in the study. The follow-up carried out in the study was up to six months. This was a short period to determine the success rate of IPC . Also, nThe objective of restoring deep carious lesions is the preservation and maintenance of pulp vitality after it has been subjected to events such as trauma, carious process, or mechanical insults due to iatrogenic errors. IPC is a technique that aids in preserving a vital pulp and restoring it to its healthy state. Within the limitations of the study, as per our observation, it was concluded that TheraCal LC can be used alternatively with light-cured CH in IPC, with a predictability of similar successful outcome in patients with deep carious lesions. In the quest of search for better materials for IPC, continuous developments in the field of conservative dentistry had led to invention of newer pulp capping agents. These agents play a significant role in maintaining vitality of pulp tissue, thus preventing more invasive intervention for the tooth.


This study aimed to compare profiles of coping among females with thyroid disorders and females from a healthy control group regarding depression levels and body image anxiety. We also wanted to check whether subjectively experienced Covid-19-related psychological distress moderated the above-mentioned association in both groups of participants.The study sample comprised 564 females, of which 329 were diagnosed with a thyroid disease and 235 formed the healthy control group. Participants filled out paper-and-pencil or online versions of psychometric questionnaires to assess coping strategies, depression, and body image anxiety.In general, we observed higher depression intensity and a higher level of body image anxiety among females with thyroid diseases than among the healthy control group. Latent profile analysis revealed adaptive vs. maladaptive coping profiles from both study samples. Depression symptoms were significantly higher if coping was maladaptive in both the clinical and control groups. Still, there were no significant differences in body image anxiety between participants with adaptive and maladaptive coping profiles. Covid-19-related distress did not moderate the link between coping profiles, depression, and body image anxiety in either group.Greater focus should be placed on the role of body image in females struggling with thyroid diseases. Bodily therapy may help these patients to cope better with co-occurring thyroid diseases and mental disorders, whose relationship is still not fully understood. Thyroid diseases constitute a global health problem and are associated with substantial deterioration of physical and psychosocial quality of life among sufferers [see reviews and meta-analyses: nervous affectations and myxedema madness, have been used to underscore common-knowledge observations pointing to frequent mood swings, irritability, and worries among people suffering from thyroid diseases. Currently, the prevalence of mood and anxiety disorders in thyroid diseases accounts for up to 60% of anxiety disorders and even 70% of cases of depression [Investigations of the link between thyroid dysfunction and psychopathology go back almost 200 years in medicine ,9. Severpression ,11. Althpression ,13. Attepression –16. Dayapression  underlinpression . In our Although a considerable amount of research has provided solid evidence that coping matters concerning how people deal with stressful life events [see meta-analysis: The final variable of interest was subjective body image anxiety . TraditiThe study had two aims. First, we wanted to determine whether we could observe different profiles of coping among females with thyroid disorders and females from the healthy control group concerning depression level and body image anxiety. Second, we wanted to check whether both samples’ subjectively experienced Covid-19-related psychological distress moderated the relationship between coping profiles, depression, and body image anxiety. To the best of our knowledge, there are no studies conducted with females with thyroid disorders that might be useful as a direct source of research hypotheses in relation to this unique study design, particularly with a control group. Therefore, we mainly employed an exploratory approach in our study. However, based on existing studies within a similar methodological framework but conducted on different samples of participants see ,27, we fHypothesis 1. We expected that, in general, females with thyroid diseases would score higher on depression and state and trait body image anxiety compared to females in the control group.However, the picture of these differences may be modified if coping is included in our analysis. More specifically, we hypothesize that adaptive and maladaptive coping profiles (see Measures section) may be found among the participants. Adaptive coping profiles will be negatively associated with the intensity of depression and body image anxiety (on both the state and trait levels). The opposite trend will be observed in maladaptive coping profiles.Hypothesis 2. We expected that the aforementioned relationships between coping profiles, depression, and body image anxiety would be moderated by subjectively experienced Covid-19-related psychological distress.Firstly, the characteristics of the sample in the current study were calculated in order to verify if the two main groups differ and how it limits the conclusions. Next, distributions of analysed interval variables were assessed with the use of measures for skewness and kurtosis. The clinical group and the control group were compared in terms of body image anxiety and depression with the use of independent samples t-test. Then, Latent Profile Analysis was conducted to extract distinct profiles of coping. The participants with extracted coping profiles were compared in terms of body image anxiety and depression separately in the clinical group and the control group also with the use of independent samples t-test. To assess if Covid-19 distress was a moderator of the relationships between coping style and body image anxiety and depression a hierarchical regression analysis with focus on interaction effects was applied.This was a cross-sectional, comparative study design with two study groups: clinical and control. Female participants from the clinical group, i.e. with thyroid disorders were recruited from the Department of Gynecological Endocrinology at the Medical University of Warsaw and the Endocrinology Clinic of the Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw. The participants from the clinical sample completed paper-and-pencil questionnaires. The control group was recruited via social media platforms and completed the study measures online. In this study, we included a control group as we wanted to compare the way of coping with stress in health and disease during the Covid-19 pandemic with a particular focus on depression and body image anxiety in this matter. For the clinical sample, the eligibility criteria were being 18 years or older and having a medical diagnosis of thyroid disorder, which was screened by medical doctors working in the hospitals where the research was conducted. The inclusion criteria for the control sample were 18 years or older and declaring no chronic illness. The study occurred between September 2021 and February 2022; a time described as the "fourth wave" of the Covid-19 pandemic in Poland.All procedures performed in this study were per the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. All groups voluntarily participated in the study and written informed consent was obtained from all the study participants. The local ethics committee approved our study.Stress-coping strategies were evaluated using Carver’s Brief COPE inventory  adapted We used the Centre for Epidemiological Studies Depression Scale CES-D;  adapted We used the state and trait versions of the Physical Appearance State and Trait Anxiety Scale PASTAS;  adapted We used a short but reliable operationalization of Covid-19 distress based on other studies published prior to the commencement of our research e.g., . We askeParticipants in the study comprised 564 women aged 18–82 , 329 of whom were diagnosed with thyroid diseases (58.3%) and 235 of whom formed the control group (41.7%). Most participants in both groups were in a stable relationship, had a secondary or higher education, and were regularly employed. Their financial status was medium or good. Most lived in cities with over 100,000 inhabitants. Most of those in the clinical group were diagnosed with hypothyroidism. The treatment period ranged from just diagnosed to 52 years . Most participants from the clinical group experienced dry skin, tiredness, weight gain, and nervousness.To start verifying Hypothesis 1, participants from the control group were compared in terms of body image anxiety and depression separately from participants in the clinical group. The results are presented in The intensity of body image anxiety, both as a state and as a trait, and the level of depression were significantly higher in the clinical group.The main analysis was based on a Latent Profile Analysis LPA; . This waProfile 1) and a group with maladaptive coping (Profile 2). Adaptive coping was more prevalent in the clinical group. It was present in 181 participants in the clinical group (55.0%) and 78 participants in the control group (33.2%). According to the Pearson’s chi-square test of independence, the relationship between group membership and coping style profile was statistically significant, χ2(1) = 26.29, p < .001.The extracted classes included a group of participants with adaptive coping (Profile 1) and participants with the maladaptive coping profile (Profile 2) were separately compared in terms of body image anxiety and depression in the clinical group and the control group. The results are presented in To verify Hypothesis 1, participants with the extracted adaptive coping profile (r(233) = .22, p < .001, and trait, r(233) = .16, p < .001, but it was not significantly related to body image anxiety in the clinical group for either state, r(326) = .04, p>.05, or trait, r(326) = .02, p>.05. Finally, BMI did not correlate with depression in the clinical group, r(326) = .03, p>.05, or in the control group, r(233) = -.01, p>.05.For the mean values of body image anxiety, both state and trait were higher when coping was maladaptive in the control group. However, there were no significant differences in body image anxiety between participants with adaptive coping and participants with maladaptive coping in the clinical group. Depression symptoms were significantly higher if coping was maladaptive in both the clinical and control groups. In the control group, BMI was positively related to body image anxiety for both states, t-test, the difference was statistically significant, t(562) = -4.74, p < .001, meaning that the level of Covid-19 distress was significantly higher in the clinical group. Second, we conducted a regression analysis separately for the clinical and control groups. The interaction effects between coping style and the Covid-19 level of stress intensity were not statistically significant. This applied to models in which the explained variable was body image anxiety as a state in the control group, B = -.03, t = -.42, p>.05, body image anxiety as a trait in the control group, B = -.08, t = -1.14, p>.05, depression in the control group, B = -.03, t = -.45, p>.05, body image anxiety as a state in the clinical group, B = .01, t = .22, p>.05, body image anxiety as a trait in the clinical group, B = .04, t = .76, p>.05, and depression in the clinical group, B = -.01, t = -.09, p>.05. Therefore, no moderation effects were detected.To verify Hypothesis 2, a hierarchical regression analysis was carried out. The interaction effects between coping style and the Covid-19 level of stress intensity were used as indicators for moderation. First, to provide context for the interpretation of potential interaction effects we compared the mean level of Covid-19 psychological distress between the two groups of participants. The mean level of Covid-19 psychological distress in the clinical group was 3.54, with a standard deviation of 1.06. The mean level of Covid-19 psychological distress in the control group was 3.10, with a standard deviation of 1.08. According to the value of an independent samples The results of our study were consistent with our first hypothesis. We observed higher depression intensity and a higher level of body image anxiety (in both state and trait dimensions) among females with thyroid diseases than among the healthy control group. We also extracted adaptive vs. maladaptive coping profiles from both study samples, as shown in enduring somatic threat model of posttraumatic stress disorder of Edmondson [Our findings have important implications for the psychological functioning of females with thyroid dysfunction as operationalized by body image. Several authors have observed relatively impaired psychosocial well-being and poor quality of life among females with thyroid disorders compared to healthy controls ,41. Nevedmondson . AlthougConcerning depression, maladaptive coping was a significant predictor of depressive symptoms in both groups. Still, as with body image anxiety, depression was not linked to BMI in either group. Engum et al.  argued tOur second hypothesis was not confirmed. The intensity of Covid-19-related distress did not moderate the relationship between coping profiles, depression, and body image anxiety either in the clinical sample or in the control group , and its focus on an understudied variable in this illness, namely, body image anxiety. However, we should also note several limitations. First, due to organizational reasons, our clinical sample was heterogeneous in terms of thyroid disease diagnoses and stages of the disease. We also controlled for a relatively low number of clinical markers because the main focus was on psychological functioning. Second, because of organizational difficulties, our control group of healthy females was not entirely similar in terms of their various sociodemographic factors. Third, the cross-sectional design of this study precludes causal interpretations of the observed findings.Despite these limitations, our study addresses significant research gaps in the literature on psychological functioning among females struggling with thyroid diseases. It indicates, in particular, that a greater focus is required in healthcare programs for these patients on their body image and related dysfunctional emotions and cognitions. Perhaps bodily therapy could help these patients to cope better with mental disorders co-occurring with thyroid diseases, whose relationship is still not fully understood. More specifically, various programs have been created over several years to shape a positive body image, creating analogous interventions focusing on clients’ strengths and resources in different clinical and non-clinical samples . ConcernS1 Dataset(XLSX)Click here for additional data file.


Frailty, disability, and polypharmacy are prevalent in nursing home (NH) residents, often co-occurring with multimorbidity. There may be a complex interplay among them in terms of outcomes such as mortality. Aims of the study were to (i) assess whether nursing home residents with polypharmacy (5–9 medications) or hyperpolypharmacy (≥10 drugs), have an increased risk of death and (ii) whether any association is modified by the co-presence of frailty or disability.Cohort study with longitudinal mortality data including 4,023 residents from 50 European and 7 Israeli NH facilities  in The Services and Health for Elderly in Long Term care (SHELTER) cohort study. Participants were evaluated with the interRAI-LongTerm Care assessment tool. Frailty was evaluated with the FRAIL-NH scale. Hazard ratio (HR) of death over 12 months was assessed with stratified Cox proportional hazards models adjusted for demographics, facilities, and cognitive status.n = 2,002) were on polypharmacy, and 24.3% (n = 979) on hyperpolypharmacy. Frailty and disability mostly increased risk of death in the study population . Among non-frail participants, multimorbidity  and hyperpolypharmacy  were associated with higher risk of death. Among frail participants, no other factors were associated with mortality. Polypharmacy and multimorbidity were not associated with mortality after stratification for disability.1,042 (25.9%) participants were not on polypharmacy, 49.8% (Frailty and disability are the strongest predictors of death in NH residents. Multimorbidity and hyperpolypharmacy increase mortality only in people without frailty. These findings may be relevant to identify patients who could benefit from tailored deprescription. The most frequently used definition  assess whether nursing home residents with polypharmacy (5–9 medications) or hyperpolypharmacy (≥10 drugs), have an increased risk of death and (ii) whether any association is modified according to the presence of frailty or disability and multimorbidity.This longitudinal cohort study is a secondary analysis based on data from the Services and Health for Elderly in Long Term care (SHELTER) study . The SHEParticipants were randomly selected among older adults residing in participating NHs at the beginning of the study and those admitted in the 3 month enrolment period following the initiation of the study, based on their willingness to participate in the SHELTER study.The original aim of the SHELTER study was to validate the use of the interRAI-LongTerm Care assessment tool (InterRAI-LTCF) as a methodology to assess provision of care in NH in Europe All participants were evaluated by trained assessors with the InterRAI-LTCF, which includes more than 350 elements, covering sociodemographics, clinical items about physical and cognitive status, and clinical diagnoses. The tool also collects information about clinical signs, symptoms, diseases, and treatments .Ethical approval for the study was obtained in all countries according to country-specific agreements, on the behalf of the ethical committee of the Catholic Unviersity of the Sacred Heart, approval number P/220/CE/2009. Residents were invited to take part in the study and were free to decline participation. Written informed consent was obtained from participants, or their legal guardian, to participate in the study.F = fatigue, R = resistance, A = ambulation, I = incontinence, L = weight loss, N = nutritional approach, H = help with dressing. The overall score ranges from 0 to 14. Frailty was defined as score equal or >8 at the FRAIL-NH scale. In the paper that describes thoroughly the process of codfication, FRAIL-NH codification and application has been demonstrated to be a reliable indicator of frailty compared to a comprehensive geriatric assessment for nursing home residents in the SHELTER population  Hierarchy scale . The ADLInformation on medications was collected at baseline assessment using the dedicated InterRAI-LTCF section according to their Anatomical Therapeutic and Chemical code. Polypharmacy was defined as concurrent use of 5–9 medications and hyperpolypharmacy was defined as the concurrent use of 10 or more drugs .Covariates were assessed through specific items from the InterRAI-LTCF. Cognitive status was assessed with the Cognitive Performance Scale (CPS) . This scParticipants were followed over 1 year during their residence in the nursing homes and all deaths were recorded. No information regarding causes of death was gathered. Time to death was considered as the date of the first assessment until the date of death. An extra record was made in case of discharge from the facility and cases were censored at this date. In survival analyses, death for any cause was considered as the outcome and discharge from the facility as censoring events. For remaining participants, time was censored at 12-months.post-hoc for normally distributed variables, while chi-square and post-hoc Z-test were used for dichotomous variables. A two-tail p-value < 0.05 was considered significant.Baseline characteristics (mean and standard deviation or number and percentage) of participants were compared between frail and non-frail participants using analyses of variance and Tukey R2 was 0.678, suggesting collinearity between the two scales. On the contrary, no collinearity was detected for multimorbidity and polypharmacy . Hence, two different models to assess differences in mortality according to polypharmacy status were performed: the first one exploring frail and non-frail patients, the second one exploring patients with and without disability in the ADLs. Survival curves were plot through Kaplan–Meier methodology and the Log-Rank test was used to assess difference among survival curves. Shared frailty Cox proportional hazard regression models were used to evaluate the effect of polypharmacy on time to death in both frail vs. non-frail patients and those with and without disability, while accounting for potential random effect due to data clustering within NHs (Collinearity was tested according to Pearson correlation coefficient and Variance Inflation Factor (VIF). A VIF > 10 indicates severe collinearity. For FRAIL-NH and ADL Hierarchy scale, that share 3 items , VIF was 4.1 and Pearson's thin NHs . Potentin = 1,042, 25.9%) of participants were not on polypharmacy regimen, while a half  were on polypharmacy and a quarter  were on hyperpolypharmacy. Laxatives, antiulcer medications, psychotropic drugs , and diuretics were the most common classes prescribed in the study population.At baseline, from the initial sample of 4,156 participants, 133 (3.2%) were excluded due to missing data, leading to a final sample of 4,023 participants. The sociodemographic and clinical characteristics of participants have been described for the overall study population and according to the number of medications used . The meap < 0.001). Dementia and poor cognitive status were inversely associated with being on polypharmacy or hyperpolypharmacy (p < 0.001). The proportion of residents with disability (ADL score 5–6) was comparable among polypharmacy groups (p = 0.147). On the contrary, frailty was less common in participants on polypharmacy (46.2%) or hyperpolypharmacy (44.1%) compared to the group of those taking <5 drugs (51.6%) (p = 0.002).Comorbidities such as Parkinson's disease, stroke, heart failure, and cancer were more common among patients on polypharmacy or hyperpolypharmacy compared to those who were not. Multimorbidity was more common in participant on polypharmacy (42.8%) or hyperpolypharmacy (52.9%) than people taking 0–4 drugs (27.9%)  participants died during follow-up and 262 (6.5%) moved out of the nursing home and were censored. Overall the incidence rate of death in the study population was 0.21 persons/year. In this longitudinal study of older nursing home residents, we found that hyperpolypharmacy and multimorbidity both increase the risk of death, but only in people without frailty, even after adjustment for demographics, facilities, comorbidities, and cognitive status. Person without frailty who had multimorbidity had 35% increased risk of death compared to those without multimorbidity. There was a 29% increased mortality risk in people with hyperpolypharmacy compared to those without polypharmacy, within the non-frail stratum.Chart review of patients in the last year of life suggest that there is a continued prescribing of futile medications . HoweverFrailty is associated with short-term mortality also in older people without multimorbidity  and disaFuture research is needed to replicate our findings and identify mechanisms behind the results –28. IndeOn the other hand, NHs resident could ondergo other interventions in order to ameliorate their health outcomes, besides deprescribing. That is why it is worth it to thoroughfully assess nursing home patients both with and without frailty: one randomized control study found that an outpatient intervention with Comprehensive Geriatric Assessment (CGA) may both delay the progression of frailty and may contribute to the improvement of frail patients in older persons with multimorbidity . A CGA sIn the current study we defined frailty with the FRAIL-NH, although there are a large range of definitions and tools in the literature . FRAIL-NIn conclusion, among nursing home residents in the SHELTER study multimorbidity and polypharmacy increased the risk of death only in people without frailty. This may be relevant for planning which vulnerable older people should be targeting for deprescription. However, more research is needed to verify whether these findings are replicated in other health care settings and to identify the mechanisms behind the difference in the risk of negative health outcomes and death according to frailty status.graziano.onder@unicatt.it.All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author. Requests to access these datasets should be directed to The studies involving human participants were reviewed and approved by Ethical Committee of the Catholic Unviersity of the Sacred Heart, approval number P/220/CE/2009. The patients/participants provided their written informed consent to participate in this study.Study concept and design: EV and RL. Acquisition of data: GO. Analysis and interpretation of data: EV, RL, and KP. Preparation of the manuscript: MZ, EV, KP, and RL. Revision of the manuscript: LS, AC, DFi, MD, DFu, and MC. All authors contributed to the article and approved the submitted version.


To determine the relationship between pubertal timing and quality of life (QOL) in children and adolescents and to provide a basis for QOL intervention in pubertal children in the future to promote good adaptation and healthy physical and mental development of children.The survey was conducted in one county using a stratified cluster sampling method. The five physiological change items of the Puberty Development Scale (PDS) were used to assess the timing of puberty in students. Compared to students of the same age and the same sex, students who scored higher than the mean + standard deviation (SD) of individual developmental scores were defined as an early pubertal timing group. A 39-item QOL Scale for Children in Puberty was used to assess the QOL of the respondents. Multiple linear regression models were fitted separately for boys and girls.Of the 7223 students, 3754 (51.97%) were boys and 3469 (48.03%) were girls. The prevalence of early pubertal periods was 16.07%. The total QOL score in the early pubertal timing group (137.16 ± 18.67) was significantly lower than in the normal (on time) group (142.02 ± 17.98) and the late group (142.76 ± 18.35) . A multiple linear regression model showed that early pubertal timing was a risk factor for QOL (P < 0.0014), compared with normal and late pubertal timing.The early pubertal timing was associated with poorer QOL in children and adolescents. More attention should be paid to children with early pubertal timing in intervening children’s QOL during pubertal development. Future longitudinal studies are needed to confirm the association between pubertal timing and QOL.https://doi.org/10.1265/ehpm.22-00159.The online version contains supplementary material available at  Adolescence is a gradual transition from childhood to adulthood, during which individuals undergo dramatic changes in physical, functional, sexual, endocrine, psychological, and behavioral aspects , 2. AdolThere are subjective and objective methods for assessing pubertal timing. The subjective assessment method mainly uses the PDS to measure the degree of pubertal development, and then calculates the overall or mean value of the scale, using the percentile method or the rank rating method to determine whether the pubertal timing is early, on time, or late –8. The oThere are many adverse effects of early pubertal timing on children’s physical and mental health. Previous studies have shown that early pubertal timing has been associated with depression, low self-esteem, and other mental health problems –15, as wAccording to the World Health Organization, QOL is determined by physical health, mental state, level of independence, social relationships, environmental factors, and personal beliefs . For chiIn conclusion, the early pubertal timing has adverse effects on children’s health and development, which in turn may affect QOL. The complex relationship between the timing of puberty and QOL in children and adolescents has not been adequately studied in China. In this study, the PDS was used to assess the timing of puberty in children and adolescents, and the Quality of Life Scale for Children in Puberty , 28 was A multistage cluster sampling method was used to select 11 schools in the QiJiang district, Chongqing, China. First, the QiJiang district, Chongqing, was selected as the survey site. Second, five middle schools and six primary schools were selected from this district. Finally, 3 to 8 classes from each grade from the third to sixth grade of primary schools and seventh to ninth grade of middle schools were selected, and all students in the classes studied were included as participants. When investigating, each class had one or two investigators. Before the start of the survey, the investigator explained the purpose and content of the survey and the precautions for filling in the questionnaire. We also explained the concept of puberty to the third grade students. Although third grade children are outside the pubertal period, the correct knowledge and attitude toward puberty will help children to pass through this stage more smoothly. Guideline for Health Education in Primary and Secondary Schools, issued by Ministry of Education of the People’s Republic of China in 2008, mentioned that three to four grade students should learn about growth and adolescent health, including the human life cycle such as birth and development, and the functions of the main organs of the body of children and adolescents . MoreoveThe following information was collected from the students using a self-administered questionnaire: age, gender (boy/girl), without siblings (yes/no), boarding school student (yes/no), left-behind children (yes/no), family financial situation (good/moderate/poor), physical condition (good/moderate/bad), self-reported physique , and academic performance (good/moderate/bad). In China, left behind children usually refer to minors under the age of 16 whose parents are working outside the home or one of them is working outside the home and the other has no guardianship ability.The timing was measured using the PDS with five items –8. The PIn this study, the QOL Scale for children in puberty was used. All elements were derived mainly from the Inventory of Subjective Life Quality for Children and Adolescents (ISLQ) , CAQOL , and theStatistical analysis was performed using SPSS . Demographic characteristics of the different genders were analyzed using the chi-square test or the t test. The QOL score between groups with different characteristics was assessed with an F or t test. Multiple linear regression models were fitted separately for boys and girls. In the total model, the QOL score and the scores of the four subscales were used as dependent variables, demographic characteristics as covariates, and the timing of puberty as independent variables. The trichotomous variables were transformed into dummy variables, and the focus category of concern was used as a reference. Because we performed four hypothesis tests for nine factors on the same data, resulting in an increased probability of Type I errors, the Bonferroni method was used to correct α. Therefore, for linear regression, the α was approximately 0.0014 (0.05/36), and for other analyses, the α was 0.05. All analyses were performed using two-sided tests.χ2 = 30.747, P < 0.001). Regarding the self-reported physique, the rate of thin physique in boys was higher than in girls . Girls showed a poorer academic performance than boys .  participants were boys and 3469 (48.03%) were girls. The average age of the boys and girls was 11.49 ± 2.01 and 11.50 ± 2.05 years, respectively. Of the boys, 53.60% were left-behind children, and of the girls, 53.56% were left-behind children. Boys reported a higher rate of good physical condition than girls . The mean QOL score in the early pubertal timing group (137.16 ± 18.67) was significantly lower than in the normal group (142.02 ± 17.98) and the late group (142.76 ± 18.35) . The QOL scores of boys were slightly higher than those of girls . Students with a good financial situation, good physical condition, self-reported normal physique, and good academic performance had higher QOL scores.  and in the late group . After adjusting for covariates, the associations between the early pubertal timing group and the normal group  and the late group  remained significant.As shown by the unadjusted linear regression model, the QOL scores were lower in both boys and girls in the early pubertal timing group than in the normal group , good physical condition , normal physique , good  and moderate  academic performance in boys and girls. Furthermore, older age was associated with lower QOL scores in girls .  and the social dimension . Students in the late group had significantly higher scores in the physiological dimension , the mental dimension , and the social dimension  in boys. Among the girls, the students in the normal pubertal timing group had significantly higher scores in the physiological dimension , mental dimension , and social dimension ; students in the late group also had significantly higher scores in the physiological dimension  and social dimension  and had significantly lower scores in the pubertal dimension . Additionally, students with good physical condition had significantly higher QOL scores in the total scale and in the specific domain subscales than students with poor physical condition. , which was lower than that in students aged 11–16 years in Hunan Province (19.1%)  but closAdditionally, we found that physical condition and academic performance also have a significant association with the QOL of children and adolescents. Children with better academic performance receive more attention and care from parents, teachers, and classmates. They have a better sense of life at home, at school, and among their peers. Furthermore, students with better academic performance may have a stronger ability to learn and acquire correct knowledge, which is conducive to the formation of correct cognition in these children. Children with poor physical health, who suffer from symptoms of illness or discomfort, naturally have poor QOL. When studying the relationship between QOL and factors of interest, these confounding factors (such as academic performance) need to be taken into account in order to draw more accurate conclusions.In interpreting our results, some caveats should be noted. First, we adjusted for α in the linear regression analysis, which may have resulted in us missing some meaningful results. Second, this study used at subjective assessment method (the PDS) to determine pubertal timing, which can differ from an objective assessment method . Thirdly, the reliability, validity, and acceptability of QOL Scale for children in puberty hadn’t been confirmed for 8-year-old children. As for this present study, the measurement has shown good reliability in 8-year-old children. The Cronbach’s alpha of the total scale was 0.877, and 0.781, 0.773, 0.841 and 0.614 for each subscale, respectively. During the survey, we found that the major of 8-year-old children could complete the scale with high quality. It indicates that the scale is acceptable for 8-year-old students. The validity of this scale in 8-year-old children need to be verified in the future. Finally, the study was a cross-sectional study and causality cannot be established with this study design.The early pubertal timing was associated with poorer QOL in children and adolescents. Future longitudinal studies are needed to confirm the association between pubertal timing and QOL. Measures should be taken to improve the QOL of children with early pubertal timing to promote good adaptation and healthy physical and mental development of children.


Cervicogenic headache (CEH) is a secondary headache caused by lesions of the cervical spine and surrounding soft tissues. Cervical muscle dysfunction may be related to the onset of CEH. However, whether cervical muscle stiffness changes in patients with CEH has not been well studied. The purpose of this study was to explore changes in superficial cervical extensor muscle stiffness in patients with CEH using shear wave elastography (SWE).In this study, 19 patients with CEH and 20 healthy controls were recruited. Superficial cervical extensor muscle stiffness was obtained from SWE, and the SuperLinear SL10-2 MHz linear array probe in the musculoskeletal muscle mode was chosen as the transducer. Regions of interest in the trapezius (TRAP), splenius capitis (SPL), semispinalis capitis (SCap), and semispinalis cervicis (SCer) were manually segmented. Correlations between superficial cervical extensor muscle stiffness and visual analog scale (VAS) scores, age, and body mass index (BMI) were analyzed using Pearson's correlation. Receiver operating characteristic (ROC) curve was used to investigate the diagnostic ability of superficial cervical extensor stiffness for CEH.p < 0.05). Increased stiffness was also observed in SCer on the non-headache side of patients with CEH compared to healthy controls (p < 0.01). In patients with CEH, SCer stiffness was positively correlated with VAS scores , but no correlation was found between other muscles and VAS scores (p > 0.05). The areas under the curve of TRAP, SPL, SCap, and SCer in diagnosing CEH were 0.766, 0.759, 0.964, and 1.000, respectively.Superficial cervical extensor muscle stiffness on the headache side of patients with CEH was higher than that on the non-headache side and in healthy controls (Increased stiffness was observed in the superficial cervical extensor muscles on the headache side of patients with CEH. SCer stiffness was correlated with headache intensity in patients with CEH and may provide clues for the diagnosis of CEH. Cervicogenic headache (CEH) is a common secondary headache caused by lesions of the cervical spine and surrounding soft tissues. The prevalence of CEH has been reported to be 0.4–2.5% in the general population  and as hLesions of the cervical extensor muscles may be related to the onset of CEH. The cervical extensor muscles are the basis for maintaining normal function of the cervical vertebra. The cervical extensor muscles include the trapezius (TRAP), splenius capitis (SPL), SCap, semispinalis cervicis (SCer), and multifidus  from theShear wave elastography (SWE) is a non-invasive, quantitative, and real-time imaging of soft tissue stiffness, which is considered to be more objective and reproducible than compression sonoelastography . SWE useIn this study, SWE was used to study superficial cervical extensor muscle stiffness in patients with CEH and in healthy controls. The shear elastic modulus of TRAP, SPL, SCap, and SCer was quantitatively measured. In addition, we investigated the factors that may be associated with superficial cervical extensor muscle stiffness and explored the diagnostic ability of superficial cervical extensor stiffness for CEH.A total of 19 patients with unilateral CEH were recruited for this study from the Department of Rehabilitation Medicine of Weifang People's Hospital between June 2021 and October 2021, and another 20 healthy volunteers with matched age and gender were recruited as a control group. Patients with CEH were diagnosed by a neurologist (SYZ) with more than 30 years of experience. This study was approved by the Local Ethics Committee, and all patients were fully explained about this study and were given informed consent.Inclusion criteria for patients with CEH were based on the International Classification of Headache Disorders-3 (ICHD-3). These criteria included clinical or imaging evidence of a lesion within the cervical spine or soft tissues of the neck, known to cause headache. Any headache fulfilling the following standards or evidence of causation was demonstrated by at least two of the following: firstly, the headache has a temporal relationship to the onset of the cervical disorder; secondly, the headache can be significantly relieved as the cervical spondylosis improves or subsides; thirdly, the cervical range of motion is reduced and the headache is significantly worsened by provocative maneuvers; and fourthly, the headache is abolished following diagnostic blockade of a cervical structure or its nerve supply. Patients with CEH aged 16–55 years without cognitive impairment were included in this study. Exclusion criteria included combination with other types of headaches, a previous history of severe head and cervical trauma or cervical surgery, cervical congenital malformation, osteoporosis, cervical vertebra fracture, bone destruction, patients with mental or psychological disorders unable to cooperate with the examination, pregnant women, and patients after treatment such as massage, physiotherapy, and muscle relaxants.Inclusion criteria for healthy controls were 16–55 years of age, with no history of CEH and cognitive impairment. Exclusion criteria included other types of headaches, a previous history of severe head and cervical trauma or cervical surgery, cervical congenital malformation, and pregnancy.Before measuring stiffness, we measured the headache intensity with the visual analog scale (VAS)  in the CThe subjects were lying prone, with their shoulders in abduction and external rotation, hands overlapped under the forehead and the chest supported by a pillow to make the neck in a neutral position. The stiffness of the muscles on the left and right sides of the back of each subject's neck was measured. Muscle stiffness was measured by shear wave ultrasound elastography , and a SL10-2 MHz linear array probe in the musculoskeletal muscle mode was chosen as the transducer, with a shear elastic modulus up to 180 kPa. Ultrasound was performed by a sonologist (YNY) who had 5 years of experience in musculoskeletal ultrasound and was blinded to the information of subjects. The measured shear elastic modulus values were expressed in kPa, the larger the shear elastic modulus value, and the greater the muscle stiffness.v2, where ρ is the muscle density and v is the speed of the shear wave propagating in the muscle tissue . Independent samples t-test was used to compare age and BMI between patients with CEH and healthy controls. Correlations between cervical extensor muscle stiffness and VAS scores, age, and body mass index (BMI) were analyzed using Pearson's correlation. The diagnostic ability of the stiffness of TRAP, SPL, SCap, and SCer for CEH were determined by performing receiver operating characteristic (ROC) curve analysis. A two-tailed p < 0.05 was considered significant.In this study, all statistics were performed with Statistical Product and Service Solutions . Numerical data were presented as mean ± standard deviation (SD), and the Shapiro–Wilk test was used for normality test. One-way analysis of variance (ANOVA) was used for comparison of muscle stiffness between the different groups, and the least significant difference (LSD) test was used for p = 0.227) and BMI (p = 0.888). The mean VAS score in patients with CEH was 5.21 ± 1.13 (range 3–7)  and 20 age-matched healthy controls (10 men and 10 women) were included in the analysis. The mean age of patients with CEH and healthy controls was 27.47 ± 8.38 (range 16–44) years and 24.60 ± 5.92 (range 16–40) years, respectively. The mean BMI of patients with CEH and healthy controls was 21.75 ± 2.65 (range 17.3–26.8) and 21.63 ± 2.74 (range 17.6–25.8), respectively. There were no statistically differences between the two groups for age (nge 3–7) .p < 0.001). Compared to healthy controls, the stiffness of TRAP, SPL, SCap, and SCer was significantly increased in the headache side of patients with CEH (p < 0.01). Significantly increased stiffness in SCer was found on the non-headache side of patients with CEH compared to healthy controls (p < 0.01)  . In addir = 0.481, p = 0.037). No correlation was found between stiffness and VAS in TRAP , SPL , or SCap  , SPL , SCap , or SCer . No correlation was found between stiffness and BMI in TRAP , SPL , SCap , or SCer . Similarly, no correlation was found between superficial cervical extensor muscle stiffness on the non-headache side and VAS, age, or BMI.In patients with CEH, headache side stiffness and VAS scores were positively correlated in SCer (= 0.455) . There wThe ROC curve analysis showed that the area under the curve (AUC) of TRAP, SPL, SCap, and SCer were 0.766, 0.759, 0.964, and 1.000, respectively . The senIn this cross-sectional study, we found that the stiffness of all the examined superficial cervical extensor muscles was higher on the headache side of patients with CEH than on the non-headache side and in healthy controls. The stiffness of SCer on the non-headache side of patients with CEH was also increased compared to healthy controls. In patients with CEH, the stiffness of SCer was positively correlated with VAS scores. There was no correlation between the stiffness of lateral TRAP, SPL, SCap, SCer, and age or BMI. Measured muscle stiffness had fair combined sensitivity and specificity in the diagnosis of CEH, and the stiffness of SCer had the best diagnostic ability to distinguish patients with CEH from healthy controls. The results were consistent with the manifestations of cervical lesions and their soft tissues in patients with CEH. Our study provided evidence that superficial cervical extensor muscle stiffness was increased in patients with CEH, with data supporting the clinical findings of increased cervical muscle stiffness in patients with CEH.In vitro animal studies showed that type I fibers were harder than type II fibers  and migraine, making them difficult to distinguish. It has been found that the stiffness of TRAP, SPL, SCap is significantly greater in patients with TTH and migraine than in healthy controls , 43, butOur study has several limitations. Firstly, although SWE is performed at a specific vertebra level and in a standard position from the spinous process, intramuscular variations may make the data to have a small extent of variability , 44. SecIn conclusion, our study found significantly increased stiffness in the superficial cervical extensor muscles of patients with CEH. The stiffness of the superficial cervical extensor muscles, especially SCer, has a fair diagnostic ability for CEH. Whether the stiffness of the superficial cervical extensor muscles is related to the severity of CEH remains to be studied.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 Medical Ethics Committee of Weifang People's Hospital. The patients/participants provided their written informed consent to participate in this study.LZL, YNY, SYZ, XZY, and JCF developed the study concept and design. LZL, YNY, and JCF collected clinical and imaging data and analyzed and interpreted the data. PWG, CFX, and XG analyzed the data. SYZ and XZY designed and revised this manuscript. LZL wrote the first draft. All authors critically reviewed this manuscript, contributed to this article, and approved the submitted version.This study was supported by grants from the Weifang Health Commission Fund Project (wfwsjk-2021–161).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.