Distilleries are among the most polluting industries because ethanol fermentation results in the discharge of large quantities of high-strength liquid effluents with high concentrations of organic matter and nitrogen compounds, low pH, high temperature, dark brown color, and high salinity. The most common method of managing this wastewater (distillery stillage) is to use it for soil conditioning, but this requires thickening the wastewater and may cause soil pollution due to its high nitrogen content. Therefore, treatment of distillery stillage is preferable. This review discusses individual biological and physico-chemical treatment methods and combined technologies. In addition, special attention is paid to valorization of distillery stillage, which is a valuable source of polysaccharides and volatile fatty acids (VFAs), as well as natural antioxidants, including polyphenols and other bioactive compounds of interest to the pharmaceutical, cosmetic, and food industries. New directions in improvement of valorization technologies are highlighted, including the search for new eutectic solvents for extracting these compounds. Such technologies are essential for sustainable development, which requires the use of management and valorization strategies for recovery of valuable compounds with minimal disposal of waste streams. Alcohol is considered a basic material for a number of industries, e.g., the chemical, pharmaceutical, cosmetics, beverage, food, and perfume industries, and the number of alcohol distilleries is increasing worldwide . In 2005Currently, alcohol production is based on the use of non-waste agricultural substrates, such as cereals, potato starch, molasses from sugar beet, beetroot, and fruits . EthanolSaccharomyces cerevisiae [Four stages of alcohol production in distilleries embrace feed preparation, fermentation, distillation, and packaging . The feerevisiae , which crevisiae . In geneDistillery stillage may pose a serious environmental concern since it pollutes the water sources in several ways. First, the dark-colored stillage can block out sunlight, inhibiting photosynthesis and reducing the oxygenation of the water, which is detrimental to aquatic life . Second,Due to the production of a large amount of wastewater  of very high organic loads , 20, disThe pollution of distillery stillage depends on the quality of the substrates and the unit operations used for alcohol production, which means that the characteristics of stillage can differ between distilleries , 25. ForThe discharge of wastewater produced by distilleries has become increasingly restricted as the requirements of environmental regulations have become more stringent and as understanding grows regarding the negative effects of seasonal discharges of water containing high nutrient and organic loadings into water courses . Numerou3/ha), the use of distillery stillage is harmful to plant growth and soil properties, but its application at lower doses (125 m3/ha) significantly improves the sprout, growth, and yield of dry land plants, due to its content of nutrients . Moreover, the combined application of distillery stillage and natural organic compounds  is suitable under dry land conditions [Distillery stillage can be considered a pollutant, but it has also been used in agriculture. For this application, distillery wastewater is potentially valuable, but it also poses problems and has negative effects on the environment. At high doses  can be used separately for the treatment of distillery stillage, but because this kind of wastewater has high concentrations of organic pollutants, in most cases, a combination of both is used.Anaerobic digestion is a natural process in which anaerobic microorganisms utilize organic matter and transform it to biogas, which makes this treatment more attractive than aerobic treatment. The process is conducted by a comprehensive ecosystem in which physiologically different groups of microorganisms function and interact with each other. A number of microorganisms are involved in anaerobic digestion, including acetic acid-forming bacteria (acetogens) and methane-forming archaea (methanogens). The anaerobic digestion can treat high-strength distillery stillage more effectively than aerobic treatment because it degrades concentrated wastewater, produces a small amount of sludge, requires less energy, and produces economically valuable bioenergy (biogas) . The by-3/kg. The process should be carefully controlled by first operating at a low loading rate (4–8 kg COD/(m3 day)) to ensure successful startup, and then, when removal efficiency is over 90%, increasing the loading rate up to even 30 kg COD/(m3 day) is possible. On the basis of these results, we can deduce that the distillery stillage is a potential source for the production of biogas, and that anaerobic digestion is a reliable solution for the treatment of this type of effluents.Anaerobic processes in the treatment of distillery stillage have been used in various reactor technologies. UASB reactors have been reported to be particularly successful in the treatment of highly polluted effluents. This technology is attractive because the reactors do not require mechanical mixing and enable recycling of biomass sludge. According to Wolmarans and De Villiers , UASB teBecause anaerobic bacteria are capable of transforming distillery stillage, which is rich in organic compounds, into biogas, anaerobic digestion is highly advantageous for the treatment of such effluent. The process demands less energy input and also very low nutrient load. Generation of energy can reduce operational costs to a large degree as compared with energy-intensive aerobic processes .Although the key disadvantage of the aerobic processes for the treatment of distillery stillage is high energy consumption, these processes are widely used because of their high efficiency and ease of use. They are applied both as a pretreatment and as a final treatment .Bacillus bacteria (thermophilic and mesophilic) was used. In the case of stillage from maize, the removal of COD was 82.6%, but from rye residues, COD elimination was 84.6% [A large number of microorganisms  can be used for treatment of distillery stillage in aerobic conditions. Filamentous fungi can be considered important phenolic-degrading organisms, as they frequently grow on wood, utilizing lignin as a carbon source , 41. Oneas 84.6% . Reportsas 84.6% . The sysas 84.6%  used an Currently, study is focused on the combination of anaerobic and aerobic techniques for effective removal of pollutants from distillery stillage. Kapdan et al.  obtainedPhysico-chemical methods of distillery stillage treatment combine physical and chemical processes, in which the first process leads to the removal of suspended materials and the second to the elimination of soluble COD. Such processes involve coagulation/flocculation, electrocoagulation, adsorption, advanced oxidation, and membrane treatment .4·5H2O at optimum pH of 6. It was shown that this coagulant ensured 91% of COD removal and 85% of color removal. COD and color removal increased as the dosages of coagulant were increased from 20 to 60 mM, but above this limit, increasing the dosage did not increase the percentage of COD removed. The treatment of distillery stillage by coagulation/flocculation led to COD removal of 55, 60, and 72% and color removal of 83, 86, and 92%, respectively, with the use of 60 mM aluminum chloride, 60 mM iron chloride and 30 mL/L of poly-aluminum chloride [Coagulation is a process of agglomeration of suspended particles present in wastewater by inorganic coagulants, such as sulfates and chlorides of iron, aluminum, or copper, or bioflocculants . Prajapachloride .Chemical coagulation is an efficient pretreatment process when used before biological or membrane treatment processes or used as a final polishing treatment to eliminate non-biodegradable organic matter from by-products from distillery industry . The disin situ production of insoluble suspension which can remove the pollutants from the wastewater by coagulation. In surface complexation mode, the pollutant acts as a ligand to chemically bind hydrous iron or aluminum. In electrocoagulation, direct current is used [Electrocoagulation is a complex, effective alternative to chemical coagulation process for the treatment of COD-rich wastewater. Electrocoagulation is based on the electrolytic dissolution of metals like iron or aluminum and  is used .2, distance between electrodes of 1 cm, and pH of 6 gave the highest COD removal of 79.09%.Electrochemical treatment of rice grain–based distillery effluent using an iron electrode has been studied by Prajapati and Chaudhari  who inveThis method has severe limitations due to the consumption of large amounts of electricity . Other dAdsorption on activated carbon (AC) is employed for the elimination of color and specific organic pollutants. The efficiency of adsorption technology depends on adsorbent pore volumes, which affect the reactions between the adsorbate and adsorbent, the nature of the adsorbent, and the type of activating agent and activation conditions . AC is r2/g. Almost complete decolorization was obtained with 70% of the diluted sample. Lalov et al. [Bharagava and Chandra  reportedv et al.  investigv et al.  comparedThe main disadvantage of adsorption for the treatment of distillery wastewater is high operational costs  and the 2O2 by Fe2+ ion under acidic conditions. The electrochemically active organic compounds react with oxygen, which consequently leads to mineralization of color components and bioresistant fractions present in distillery stillage [Fenton process, oxidation, ozonation, and wet oxidation are advanced oxidation processes that can be used to treat distillery wastewater. Fenton process is based on generation of hydroxyl radicals (•OH) with extremely high oxidation potential, through catalysis of Hstillage .Solar photo-Fenton oxidation process showed a significant removal of COD, dissolved organic carbon (DOC), and color by 70.0 ± 3.3, 53.0 ± 3.7, and 75.0 ± 2.2%, respectively . In an eThe highest efficiency of the treatment of distillery stillage with the use of advanced oxidation can be obtained with the combination of these processes with other methods. Ozone oxidation after aerobic treatment of distillery stillage eliminates most of the degradable organic compounds. The un-decomposed phenolic compounds and organic matter remaining after the aerobic treatment can be completely oxidized by ozone .2), and H2O2 concentration (50 to 500 mg/L) on the removal of COD and color. The results showed that 100% of color and COD removal could be achieved by ozone-electrocoagulation process with an energy consumption of 5.7 kWh/m3 during four hours of reaction time. Hadavifar et al. [Ramana et al.  studied r et al.  carried r et al. . Howeverr et al. .Membrane processes are considered the most reliable technologies for the treatment of wastewater originating from different industries. These are physical processes that separate the feed stream into permeate and retentate, in which particles are separated on the basis of their molecular size and shape, with the use of specially designed semi-permeable membranes. Although there are a number of different methods of membrane treatment, the most suitable for the treatment of distillery stillage is pressure-driven membrane filtration. The application of microfiltration (MF) and ultrafiltration (UF) for the treatment of distillery wastewater to produce water suitable for reuse in the bioethanol industry has been studied by Vasić et al. . The eff3 day). Up to 41% COD removal and up to 87% suspended solid retention were obtained. Because of high mixed liquor suspended solids of 10–12 g/L and long solids retention time, the low molecular weight compounds were degraded, whereas the high molecular weight compounds comprising the color imparting melanoidins remained unaffected. Similarly, high molecular weight compounds were not degraded when MBR operation was supported by powdered activated carbon (PAC) when treating sugarcane molasses based distillery wastewater [3 day)) was possible. Moreover, PAC addition increased the critical flux by 23%, which prolonged the period between membrane cleaning.For the treatment of distillery effluents, the combination of membrane techniques and biological treatment was used. For example, Satyawali and Balakrishnan  operatedstewater . HoweverThe thermal treatment of highly polluted wastewater from distilleries is considered an economical and effective supplement to the anaerobic digestion and oxidation processes. Heating the stillage at high temperatures (160–250 °C) results in large amounts of organic substrate in the form of solid precipitates. This charred solid stillage has a high heating value (17–24 MJ/kg) and could be easily separated by filtration and then dried .Currently, numerous full-scale plants that use thermal treatment are operated. Combustion of distillery stillage is gaining interest. The treatment relies on the utilization of stillage as a fuel source. Direct combustion of distillery stillage is more effective if the stillage is pre-dried (to less than 55% moisture content). However, the technology is currently expensive, particularly when applied in small to medium size industries. The most prevalent challenge is the high energy requirement for the pre-drying stage and the treatment of toxic gas emissions .The distillery stillage can be dried using hot air (180 °C), which leads to generation of a dry powder  . The powTable In general, for the processing complex wastewater such as distillery stillage, the integrated application of many techniques is very practical and promising ; combiniDespite very high efficiency of organic compounds and color removal, the use of membrane filtration is restricted by membrane cost and high energy consumption for operating the pumps. The greatest effort is put into searching both for new membrane materials that will decrease membrane fouling, thus giving optimal permeate flux and maximal pollutant rejection, and for energy sources that will minimize the cost. For example, Lapišová et al.  investigApart from physico-chemical processes of stillage treatment, the use of microalgae seems to be a method that will be developed in the future . This is2 [To valorize distillery stillage, valuable and/or bioactive compounds can be extracted from it. Depending on the raw material used for fermentation, the composition of the stillage varies, as do the substances that can be recovered from them, i.e., polyphenolic compounds, polysaccharides, or volatile fatty acids (VFAs). In the fermented liquor, the content of bioactive substances is influenced by genetic factors, environmental factors, atmospheric conditions, exposure of substrates to stress, and the technological processes used . Therefo2  or water2  are used2 . Conside2 . ExtractPhenolic compounds are commonly found in plants. They have an important role in their growth, development, and reproduction and protect the plants against pathogens and predators. The polyphenol compounds are the most abundant antioxidants and include flavonoids  and nonflavonoids  . MoreoveThe most common method for the recovery of polyphenols is extraction. The main organic solvents for recovery of polyphenols are acetone and ethyl acetate or alkyl alcohols, e.g., methanol, ethanol, and propanol or their mixtures . The finLibrán et al.  determinTo increase the efficiency of polyphenol recovery, chemical substances were used to support ethanol extraction. Ross et al.  conducteIn addition, physical processes for increasing the extraction of polyphenols from distillery stillage have been tested. Microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE) are gaining increasing acceptance owing to their benign character and the high effectiveness of recovery of various substances. The rapid penetration of microwaves into the solid leads to the generation of heat inside the solid and a rise in temperature. The heating is uniform, which accelerates extraction. UAE offers several advantages such as low cost, versatility, and ease of deployment  and may In the light of recent studies, researchers should focus on extraction with the use of eutectic solvents. Eutectic (low-melting-point) mixtures are liquids formed from natural substances. For example, organic acids , polyols , and salts  belong to this group. Currently, these liquids attract attention as green extraction media because they are characterized by reduced toxicity, ease of preparation and use, and low cost . UAE of The recovery of phenolic compounds from wine residues was also conducted with the sequential processes of centrifugation, MF, UF, and nanofiltration (NF) . This coPolysaccharides are low-cost materials and have many applications mainly in the food industry. Some function as emulsifiers and surface active agents, and many are used as simple thickeners. They can be classified as viscosity-increasing agents and as gelling agents. Some polysaccharides are used to the preparation of dextran and pullulan and rare sugars .Giacobbo et al.  recovereGiacobbo et al.  investigIn addition to biogas production, recovery of VFAs from industrial wastewater is another method of making wastewater treatment economically attractive. These substances can be produced by elimination of the methane-forming phase of anaerobic digestion/fermentation . VFAs ar2 equivalent, are 3.3 t/t [Although VFAs can be produced by processing petrochemicals, this leads to serious negative health and environmental effects. Greenhouse gas emissions from acetic acid production in the petrochemical industry, calculated as CO 3.3 t/t . Distill 3.3 t/t . To cond 3.3 t/t . The opt 3.3 t/t . Therefo 3.3 t/t , 124; a  3.3 t/t . Martine 3.3 t/t  used aciZacharof and Lovitt  used memTable The approach of conversion of organic wastewater, such as distillery stillage, into valuable materials and energy, defines the biorefining concept as one of the elements of sustainable development. This so called waste bio-refinery is in fact a method of waste valorization . HoweverExpansion of distillery industry in the world made it necessary to develop effective technologies for the treatment of distillery stillage. Due to the presence of difficult-to-degrade compounds, physico-chemical, biological, and thermal treatment processes, such as aerobic and anaerobic biological treatment, coagulation/flocculation, electrocoagulation, adsorption, advanced oxidation, membrane processes, and evaporation/combustion, have been explored during recent years to address the demands of environmental regulations. It has been documented that for effective degradation of organic matter, particularly in terms of water reuse, a comprehensive treatment that involves several sequential technologies should be employed. Apart from this, much attention is paid to development of membrane treatment and particularly to exploring new membrane materials that will decrease membrane fouling, thus giving optimal permeate flux, to optimizing energy demand and to valorization of retentate.As it was presented through this review, distillery stillage is a source of valuable substances such as polyphenols, polysaccharides, and VFAs. The methods of their recovery, according to the biorefinery concept, have been overviewed, indicating the need to focus on the selectivity, purity, and stability of the recovered compounds. However, in the light of recent studies, future research should include the searching for biodegradable, reusable, and non-toxic solvents for effective extraction of these bioactive compounds. Hence, the investigations of the use of deep eutectic solvents for valorization of distillery stillage still remains a considerable challenge.


To investigate the epidemiology and in-hospital mortality of veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) in Mainland China throughout 2018.Patients supported by ECMO from 1700 tertiary hospitals in 31 provinces from January 1 to December 31, 2018, were selected from the National Clinical Improvement System database.The 1700 included hospitals had 2073 cases of ECMO in 2018, including 714 VV and 1359 VA ECMOs. The average patient age was 50 years (IQR 31–63), and 1346 were male. The average hospital stay was 17 days (IQR 7–30), and the average costs per case was $36,334 . The three provinces with the highest number of ECMO cases were Guangdong, Beijing, and Zhejiang; the southeast coastal areas and regions with higher GDP levels had more cases. Overall in-hospital mortality was 29.6%. Mortality was higher among patients who were male, over 70 years old, living in underdeveloped areas, and who were treated during the summer. Mortality in provinces with more ECMO cases was relatively low. The co-existence of congenital malformations, blood system abnormalities, or nervous system abnormalities increased in-hospital mortality.Mortality and medical expenses of ECMO among patients in China were relatively low, but large regional and seasonal differences were present. Risk factors for higher in-hospital mortality were older age, male sex, in underdeveloped areas, and treatment during the summer. Additionally, congenital malformations and blood system and nervous system abnormalities were associated with in-hospital mortality. Extracorporeal membrane oxygenation (ECMO) was first used in neonates in the 1970s. ECMO has been widely used to treat various types of acute cardiogenic shock and respiratory failure among adults in whom conventional life support has failed. In recent years, an increasing number of patients with severe conditions have benefited from ECMO . Extracohttps://ncisdc.medidata.cn/login.jsp) was designed to collect detailed ICU-level data. In 2018, the front page information of patient medical records from 1700 tertiary hospitals was first included in this database. We screened all the available information of ECMO-supported patients who were included in the database and conducted a summary analysis. This work provides a detailed nationwide epidemiological study of ECMO and its associated mortality based on real-world data in Mainland China and provides information to support and improve the use of ECMO.The database of the National Clinical Improvement System (NCIS) of the National Health Commission of the People’s Republic of China  diagnosed with ECMO in the discharge diagnosis; (2) operation code of ECMO, 39.6500; (3) catheterization for ECMO noted in the surgical section; and (4) support, monitoring, or replacement of ECMO noted in the surgical section. At the same time, we searched the database for the incidence and type of complications, and whether the prone position was used during ECMO support.For all the ECMO patients, we collected all information including sex, age, place of residence, diagnosis at discharge, date of hospitalization, discharge date, hospitalization costs, and in-hospital mortality. We then identified the type of ECMO support received by the included patients. If not clearly recorded, the type of ECMO support was determined according to the main diagnosis and operation site. For example, catheterization of the femoral and internal jugular veins was categorized as veno-venous (VV) ECMO; catheterization of the femoral vein and femoral artery or internal jugular vein and femoral artery was categorized as VA ECMO. VV ECMO was determined for patients with a primary diagnosis of acute respiratory failure, and VA ECMO for patients with cardiogenic shock or cardiac arrest.We classified patients by age as follows: less than 14, 14–20, 21–30, 31–40, 41–50, 51–60, 61–70, and older than 70 years. The 31 provinces/municipalities/autonomous regions of Mainland China were included in this survey .China is divided into seven geographic regions: Central China, North China, East China, South China, Northwest China, Northeast China, and Southwest China. According to its geographical regions and economic development levels, China is also divided into three economic zones: southeastern coastal areas, central inland areas, and western remote areas. The level of gross domestic product (GDP) in China can be divided into high-, middle- and low-GDP regions eTable .Four seasons were distinguished: spring is from March to May, summer from June to August, autumn from September to November, and winter from December to February.The costs are expressed in USD, and the exchange rate between RMB and USD was based on the standard of January 1, 2018 (1 USD to 6.5063 RMB).t test. Non-normally distributed data are presented as the median and interquartile range (IQR) and were analyzed using the non-parametric Mann–Whitney U test. Categorical variables are expressed as number and percentage and were compared with the chi-square test or Fisher’s exact test. Univariate and multivariate logistic regression analyses were performed successively to determine independent risk factors for in-hospital mortality, considering all variables with P < 0.05 in the univariate analysis as significant. The results are expressed as the P value and odds ratio (OR) with the 95% confidence interval (CI). IBM SPSS 23.0 software was used for all statistical analyses .Normally distributed data are expressed as the mean and standard deviation and were compared using Student’s The NCIS database included front page information of 79,668,156 patients admitted to the 1700 tertiary hospitals of Mainland China in 2018, and a total of 2073 ECMO procedures were conducted, including 1359 (34.4%) VA and 714 (65.6%) VV ECMO procedures . The median hospitalization cost of ECMO was $36,334 , and VV cost less than VA ECMO , and 1346 were male, accounting for 64.9%. Children under 14 years accounted for 11.4%, and most patients were between ages 41 and 70. There were significant differences in the age composition between the VA and VV ECMO groups. Most patients who received VA ECMO were 51–60 years old (40.7%) and most who received VV were 41–50 or 61–70 years old (40.6% together). The median length of hospital stay was 17 days , with a significant difference between VV and VA ECMO , and VV ECMO was mainly conducted in winter and spring . The mortality differed slightly according to age group, with a higher rate among patients between age 14–20 years and those over 70 years; the lowest mortality rate was among those aged 30–40 years (Table We found large differences in in-hospital mortality for ECMO patients in different provinces, with the highest mortality reaching 53% and the lowest being 15% Fig. . The higThe in-hospital mortality of ECMO patients across the seasons also varied. In spring and summer, the number of ECMO cases was lower and the mortality relatively higher, while in autumn and winter, the number of ECMO cases was higher and the mortality relatively lower eFigure . MortaliUsing the baseline data and comorbidities of ECMO patients, we performed Cox multivariate analysis to elucidate the risk factors of in-hospital mortality. ECMO performed during the summer, patients aged over 70 years, and male sex were independent risk factors for higher in-hospital mortality. Congenital malformations, blood system diseases, and neurological diseases were also independent risk factors. Residing in areas with middle-GDP levels was a protective factor Table .Table 3The most common complications during ECMO treatment were hemorrhage, infection, and mechanical complications. The proportion of bleeding complications was as high as 23.2%. Infection complications occurred in 15.1% of patients receiving ECMO, with bloodstream infection accounting for 9.6%. The incidence of ECMO-related mechanical complications was 2.2%, including blockage, accidental decannulation, and hemolysis. There were some differences in the types and incidence of complications among the different regions and among the ECMO centers (eTable We also determined the number of patients treated with VV ECMO combined with the prone position. In provinces with more than 25 cases of VV ECMO, the average proportion of patients treated in the prone position was 39.5%, and the highest was 83.3% eTable .This is the first detailed nationwide epidemiologic study of ECMO and its associated mortality based on medical front page data in Mainland China. The data obtained in this study are authentic and can well reflect the current use and in-hospital mortality of ECMO.Previous statistics in China  have shoOur data showed that the average length of hospital days on ECMO was 17 days, which is similar to that of other countries . Unlike Lack of data on diagnoses and the severity of illness in the medical front pages database. In terms of indications for ECMO, acute myocarditis, acute coronary disease, acute respiratory distress syndrome, and other reversible diseases are common, which would greatly reduce mortality. However, using the present dataset, we could not distinguish the specific primary disease of patients; therefore, additional data are needed for further analysis. At the same time, waiting for organ transplantation with ECMO support is not currently an indication in China.Fewer ECMO complications. Bleeding, infection, and mechanical complications were much lower in our data than those reported by some countries, especially bloodstream infections , 17–19. More stringent indications. ECMO is not fully covered by national insurance at present; therefore, ECMO candidates are thoroughly evaluated by clinicians, which potentially led to selection bias. Furthermore, family members may be reluctant to authorize this procedure. We found that the median age of ECMO patients was 50 years, and fewer than one third were over 60. In Germany, 50% of ECMO patients in 2014 were over 60 . NumerouA high level of care. The establishment and maintenance of ECMO reflects the overall medical level of a hospital, which is highly valued by clinicians and hospital managers. For VV ECMO patients, the proportion of patients treated in the prone position might be as high as 30%, and this might be greater than 80% in certain centers. This more aggressive and advanced treatment could also reduce the mortality rate.Dying at home. The traditional preference of many Chinese people is to die at home. Some patients without hope of further treatment would choose not to die in the hospital. This information is not reflected in the front page of medical records, but it might be reflected in the ECMO mortality rate.The mortality varied among patients who received ECMO. ELSO data from 2002 to 2012  showed tAs to additional study findings, the risk of in-hospital mortality was significantly increased in patients older than 70 years, which is consistent with the conclusions of several studies , 5, 7. SThis is the first study of ECMO based on objective data in Mainland China. Although the data are objective and detailed, some limitations remain that are directly related to the structural features of the database used. First, the disease categories were not sufficiently detailed to distinguish the survival rate for specific diseases after ECMO support. In the future, further division according to different disease types will help to clarify the effect of ECMO treatment and its most appropriate uses. Second, Smith and El Sibai both found that the treatment duration of ECMO was significantly correlated with in-hospital mortality , 3, 7. WECMO technology is developing rapidly in Mainland China, but a large gap remains in comparison with other countries. From the data analysis, in-hospital mortality was relatively high in older male patients, patients from less-developed areas, and in those treated during the summer. The presence of congenital malformations and abnormalities of the blood and nervous systems also showed increased in-hospital mortality. The large regional and seasonal differences could be because ECMO development in China is uneven. China is in the early stages of ECMO use. Therefore, standardized ECMO training and treatment procedures should be established in China to further improve the use of ECMO.Additional file 1: eTable 1 regional division of China.doc.Additional file 2: eTable 2 the number of ECMO cases and in-hospital mortality in all provinces in mainland China.doc.Additional file 3: eTable 3 the number of ECMO cases and in-hospital mortality in different months.Additional file 4: eTable 4 ECMO related complications in 7 geographical regions of China.Additional file 5: eTable 5 ECMO related complications in provinces with more than 50 cases.Additional file 6: eTable 6 The number and proportion of patients treated with prone position in the provinces with more than 25 cases of VV ECMO.Additional file 7: eFigure 1 Supplement 2 Flow chart of enrollment. ECMO extracorporeal membrane oxygenation; VV veno-venous; VA veno-arterial.Additional file 8: eFigure 2 the number of ECMO cases and in-hospital mortality in different months ECMO extracorporeal membrane oxygenation; VV veno-venous; VA veno-arterial.


Liver cirrhosis has been known to be associated with increased intestinal permeability (IP); however, little is known about the modification of IP after liver transplantation (LT). The present study was aimed to assess IP after LT and evaluated its association with laboratory tests and clinical parameters, as well as with the development of infections.51Cr-EDTA).LT recipients were consecutively enrolled and compared with an equal number of patients with liver cirrhosis and healthy subjects. IP was assessed by urinary excretion of chromium-51 ethylenediaminetetraacetic acid  vs. 2.07% (1.57–2.42), p<0.0001], and comparable to that in the cirrhotic patients . 51Cr-EDTA excretion was not associated with clinical variables, the type of immunosuppressive therapy, donor-related factors, comorbidities and incidence of infections .The median LT recipients show an increased IP, similar to that in patients with liver cirrhosis. However, it is not associated with a high risk of infections. Further investigations into the pathogenesis of this persistent impairment of the intestinal barrier are warranted. Liver cirrhosis has been reported to be associated with an increase in the intestinal permeability (IP) . Portal Increased IP is associated with bacterial translocation and systemic inflammation, which together play a crucial role in the development of liver disease complications, such as hyperdynamic circulation, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome . These mLiver transplantation (LT) is the most effective treatment for end-stage liver disease and associated complications . As a chThe present study investigated the IP in LT recipients and evaluated its possible correlation with laboratory tests, immunosuppressive treatment and post-LT clinical outcomes.Due to difficulties in carrying out a longitudinal enrollment in the population of cirrhotic patients before and after LT, we decided perform a study with cross-sectional design. Patients who had previously undergone LT and consecutively evaluated at the Liver Transplant inpatient and outpatient clinics of the Fondazione Policlinico Agostino Gemelli IRCCS in Rome were included in the study (recruitment period: January 2011-December 2015). Age-matched cirrhotic patients  and healthy individuals, selected among the patients’ family members and the medical staff, served as control groups.For all the subjects included in the study, the following exclusion criteria were adopted: treatment with antibiotics (including rifaximin), probiotics, prebiotics, proton pump inhibitors and laxatives during the last month; diseases involving the gut ; significant alcohol consumption in the last six months (>21 standard drinks on an average per week in men and >14 standard drinks on an average per week in women). Furthermore, LT recipients showing the signs of cirrhosis according to histological and/or clinical findings  were excluded.51Cr-EDTA) assay. All LT recipients were also subjected to laboratory examinations as well, including liver function tests ; body mass index (BMI), type of immunosuppressive drug regimen, Child-Pugh and model for end-stage liver disease (MELD) scores before LT, alcohol intake before LT, and previous history of hepatocellular carcinoma (HCC) were also recorded. Follow up data concerning the occurrence of infections (within 6 months since IP assessment) were registered.The IP was assessed by performing the chromium-51 ethylenediaminetetraacetic acid  and was conducted in accordance with the principles of the Declaration of Helsinki. All patients gave their written informed consent to participate in this research protocol.51Cr-EDTA assay, as described by Bjarnason and Peters  - 1.The absorption of 51Cr-EDTA into the bloodstream is directly related to the level of IP and is poorly affected by bacterial degradation in the case of small intestinal bacterial overgrowth. In normal subjects, 1% to 3% of the orally administered dose of 51Cr-EDTA gets absorbed from the gastrointestinal tract .It was higher than that reported in the healthy controls , but similar to that in the cirrhotic patients . In the subgroup of cirrhotic patients, We unexpectedly observed that IP was still elevated after LT; therefore, we tried to investigate whether the time elapsed since LT could have influenced this result. IP was measured at a median time of 6.6 (1.2–32.8) months after LT. In particular, 13 patients had undergone LT within three months since IP assessment, 10 within 12 months and 12 for more than 12 months. However, no significant correlation was observed between the time interval since LT and IP  or donor-related factors such as age (0.195 p = 0.27) or graft steatosis (p = 0.26).There was no significant correlation between age, BMI, laboratory parameters or MELD score before LT and red Figs  and 4. WThe second aim of the study was to explore the association between IP and infection episodes in the LT group.51Cr-EDTA excretion in these patients .Eight patients presented an episode of bacterial infection . However, we did not observe an increased LT is considered the best treatment for end-stage liver disease; however, at present, its effects on IP have remained unknown. The present study demonstrated that altered IP could not be recovered to normality after LT, irrespective of the time elapsed since LT.To date, only two small studies , 12 haveIn both studies, the investigators reported an increased ratio of lactulose and L-rhamnose urinary excretion, a marker of permeability of the small intestine. Furthermore, Parrilli et al. reported a reduced urinary excretion of L-rhamnose, suggesting a selective alteration of transcellular permeation. Moreover, this study group explored the gastroduodenal permeability by measuring the urinary sucrose excretion, which was found to be normal.Therefore, data available so far are based on the use of sugar probes and reflect the permeability of the proximal part of the gastrointestinal tract. Furthermore, these studies made no comparison with the pre-LT setting, making it difficult to hypothesize the effect of LT on IP.51Cr-EDTA urinary excretion. Indeed, compared to lactulose, L-rhamnose and sucrose, 51Cr-EDTA is not metabolized along the gastrointestinal tract and therefore reaches the colon in an unaltered form. We found that LT recipients have an increased IP compared with that in healthy subjects. Interestingly, a comparison of LT recipients with a group of cirrhotic patients, most of whom showing moderate or severe impairment of liver function, revealed no significant difference. Notably, we excluded patients with post-transplant liver cirrhosis, and clinical data highlighted better liver function tests in LT recipients than in cirrhotic patients. Therefore, this finding suggests that the altered IP in patients with liver cirrhosis could not be improved by LT.In the present study, we investigated for the first time the permeability of the small and the large intestine of LT recipients by measuring the urinary excretion of To assess the effect of the time interval elapsed since LT on IP, we included in this study patients at different post-LT periods. However, we failed to find any significant correlation between IP and time elapsed since LT. This may reflect an irreversible modification of the gut barrier, which cannot be restored by the improvement in the liver function. Notably, this observation was in line with the results previously obtained in both the early (mean 16 days)  and the Although these results may suggest that the permeability of the whole intestine gets irreversibly damaged by liver cirrhosis and is not improved by LT, it is well-known that LT is considered an effective treatment for portal hypertension, a factor involved in the pathogenesis of increased IP in patients with cirrhosis .Therefore, we further explored possible factors that could be responsible for the observed alteration of IP in LT recipients.It has been previously demonstrated in rats , 15 and Among the other investigated factors, we did not find any significant correlation between donor-related factors, comorbidities, clinical and laboratory parameters, alcohol consumption or history of HCC before LT and IP.51Cr-EDTA excretion and occurrence of infections. This result raises several considerations. Although we found a similar increase in the IP in both cirrhotic patients and LT recipients, this did not seem to have any clinical relevance after LT. A similar result was reported by Vogt et al. and Benjamin et al. [Finally, we assessed if the alteration of IP could have a role in increasing the risk of infections in LT recipients. There was no relationship between n et al. , 17, whon et al. . The conn et al. , 20. Conn et al. , 7. In c51Cr-EDTA excretion. This method has already been used to test IP in patients with liver cirrhosis [The present study had certain limitations. This was a cross-sectional design, as it is difficult to perform a longitudinal study in the LT setting, owing to multiple confounding factors in both the waiting list period and the post-LT period  and the need for a long period of follow-up. Furthermore, we included patients at different post-LT periods; however, there was no influence of the time elapsed since LT on IP values, supporting our results to be reliable. Moreover, we selected to measure IP by assessing irrhosis . AlthougIn conclusion, LT recipients show an IP comparable to that of patients with liver cirrhosis; however, the lack of IP improvement after LT seems to have poor clinical relevance. Further studies are required to assess the impact of immunosuppressive drugs on IP and the functional implications of our findings, especially with respect to the systemic inflammatory response.


The present study aimed at extending the work on individual differences, in the relationship between personality traits and the cortisol response, by examining the interaction effects of sex and the role category of Italian adolescent elite dinghy sailors. Seventy athletes completed a self-reported questionnaire including socio-demographic data, information about the role played on board (helmsmen or bowmen) and the Big Five Questionnaire-2. Salivary cortisol samples were collected at 30 min after awakening the day before competitions. Main findings from bivariate correlations showed positive associations among cortisol levels, extraversion and consciousness in both male and female bowmen groups. The moderation and moderated moderation analyses further indicated (1) a three-way interaction effect in the relationship between extraversion and salivary cortisol, (2) a marginal significant three-way interaction effect in the relationship between neuroticism and salivary cortisol, and (3) no other personality dimensions were significantly predictive of the outcome variable. Our results provided evidence not only about sex differences, but also about the role played on board by the sailors in the linkages between personality traits and the biomarker of the trait component of HPA axis functioning. An increasing number of studies investigated the individual differences in psychological and physiological responses to stressors and challenging environments. Among psychological factors, personality constructs, rather than environmental factors, have been proposed as major variables in identifying and impacting on biomarkers of stress-sensitive biological systems, such as the hypothalamus-pituitary adrenal (HPA), as indexed by the cortisol response. Indeed, based on theoretical arguments and research showing the substantial heritability of personality , previouThe personality construct has generally been analyzed by the following psychological models: Model of psychosocial characteristics, Model based on Rumination and Emotional Inhibition, Eysenck’s biopsychological model and the Five Factor Model FFM; . The lasA further complex matter concerns the effects of sex on HPA functioning, within the above mentioned associations; different sex patterns were reported to be close to significance only in women , whereasExtroversion, indicating individuals who enjoy being with people and are full of energy, contrary to introverts who are less involved in social activities and tend to keep to themselves, is the second well-investigated trait in relation to HPA functioning, although inconclusive results have been yielded. No association was found between extraversion and the variability in early morning salivary cortisol levels  and betwIn light of the inconsistency of these results, the current research sought to examine the individual differences in the relationships between personality traits and the salivary cortisol in adolescent elite sailors. According to the authors’ knowledge, the relevance of this research is that the psycho-physiological profile of dinghy sailors has not yet been empirically analyzed. Only Manzanares Serrano and colleagues distinguished, although theoretically, bowmen’ and helmsmen’ profiles: the former are more extrovert and the latter more determined and introverted with higher levels of self-control . ConsequThe sample was composed of 70 sailors , with 27 in the under 16 category (15–14 years) and 43 in the under 19 category (16–18 years), all participants of the Italian Youth Two Crew Members Dinghy Classes Championship, held in Bari, Italy, in September 2019. Exclusion criteria were the presence of any form of contraception and a menstrual cycle outside the range of 28 ± 1 days. The cultural and the socioeconomical background of the athletes was homogenous. The research proposal was submitted to the Italian Sailing Federation Committee for approval. In addition, the Regional Committee for Medical and Health Research Ethics approved the study, which was conducted in accordance with the Helsinki declaration. Since most of the athletes were under the legal age of consent, only their attorney/legal representative provided written informed consent for participation. All results were treated anonymously.All the data were collected the day before the competitions. Initially, a questionnaire was applied, containing information regarding sailors’ practical experience: dinghy class, role on board, and years of practicing.Saliva collection and cortisol assays were performed as previously described . Brieflystrongly agree) to 5 (strongly disagree). In the current research, alpha coefficients ranged from 0.81 to 0.83.To assess the sailors’ personality characteristics, the Big Five Questionnaire-2 BFQ-2,  was usedDescriptive statistics and zero-order correlations between the variables of interest were applied to the total sample, sex, and sailor roles on board. Age, sex, roles, and salivary cortisol differences for the variables’ scores were analyzed using independent samples t-tests.via the moderators, were considered significant if 95% bootstrap confidence intervals from 10,000 bootstrap samples did not include zero. Single moderation models were first conducted to test whether the influence of each personality trait (X) on cortisol levels (Y) was moderated by sailing category and sex   . To thisctively)  and the ctively) .The physical and technical variables analyzed in this study are shown in p = 0.068), which did not reach significance, probably because of the small sample size (n = 70) included in the analysis.The impact of athletes’ personality on the biological trait models of stress reactivity was indexed by cortisol reactivity. The total and detailed awakening cortisol analyses are shown in t(68) = −2.053, p = 0.047, where females obtained higher mean scores (M = 88.92) in comparison to males (78.48). On the other hand, when considering the role, sex effects emerged in the mean scores of consciousness in helmsmen, t(68) = −2.568, p = 0.017, a category in which females obtained higher mean scores (M = 88.75), compared to males (M = 77.61).With regard to the total sample, sex differences emerged only in the mean scores of openness to experience, t(68) = −2.065, p = 0.046, among sailors. Bowmen obtained higher mean scores (M = 4.50) in comparison to helmsmen (M = 3.86). When considering this effect within sex groups, significant differences were observed in the mean scores of cortisol levels, t(35) = −3.565, p = 0.002, and consciousness, t(35) = −2.638, p = 0.014: male bowmen obtained higher scores compared to male helmsmen in both variables of interest . No significant differences emerged within female bowmen and helmsmen.Moreover, sailing role effects were also examined in the total sample. Significant differences emerged in the mean scores of cortisol levels, b = 0.142, t(32) = 2.596, p = 0.014 with a 95% CI of 0.031 to 0.252, the magnitude of the moderation by sailing role of the effect of extraversion on cortisol, depended on the sex category. The effect of extraversion on cortisol was positive, but the difference of this effect between helmsmen and bowmen was stronger in female bowmen. This moderated moderation accounted for 10% of the variance in support of the cortisol levels. With regard to the traits of agreeableness, consciousness, and openness to experience, both models indicated no significant direct effect or interaction effect in the relationship with cortisol levels, whereas the association between neuroticism and cortisol levels was moderated by sailing role  = 2.204, p = 0.034 with a 95% CI of 0.004 to 0.105) and by the product of the two moderators  = −2.228, p = 0.033 with a 95% CI of -1.419 to -0.690). Finally, in this relationship a three-way interaction effect was close to being significant  = 1.998, p = 0.0543 with a 95% CI of -0.002 to.226), thus indicating a slight significant moderated moderation of sailing role, by sex category. The positive relationship between neuroticism and salivary cortisol tended to be stronger in female bowmen. The three-way interaction is plotted in The current study examined the individual differences in the relationships between personality traits and the trait components of HPA axis functioning, i.e., the awakening cortisol, in a sample of adolescent elite sailors. Moreover, given the lack of empirical evidence for the different psychological profiles of helmsmen and bowmen, this investigation sought to fill this gap by exploring whether the different roles played by these athletes could moderate the linkages between personality traits and awakening cortisol levels. It was also explored whether sex could influence the moderated associations. With regard to the trait components of HPA axis functioning, we found evidence that cortisol awakening levels were not significantly influenced by the physiological response of the training load imposed on the athletes, with respect to age, sex, and years of practicing. Notably, we might speculate that cortisol awakening levels are positively influenced by the role played on board. However, these findings posit the possibility that such a different response detected in both helmsmen and crew members were consistent with the different training loads, related to the role. Our findings further corroborated those studies that showed significant relationships of awakening cortisol levels with extraversion  and neurIn alignment with some other studies , extraveWhen looking at neuroticism, findings corroborated the significant trend of elevated cortisol levels, that is, higher levels of neuroticism were positively associated with higher baseline levels of cortisol . Such a Other important information from the current research, concerned the hypothesized positive relationship between cortisol and neuroticism, which was yielded in the bowmen’s category. As such, the empirical evidence took a first step in addressing sport research e.g.,  in the eThe current research examined the psycho-physiological profile of adolescent elite sailors by focusing on individual differences in the relationships between personality traits and the salivary cortisol response. To this purpose, two models were tested: in the former model sailing role and sex were computed simultaneously when considering the linkages between personality traits and cortisol levels; whereas, in the latter model, the function of the conditional effects between personality traits and sailing role by sex was taken into account when considering the effect of personality traits on cortisol response. In summary, these findings suggested that the effect of extraversion on cortisol was positive in female bowmen. Likewise, the effect of neuroticism on cortisol tended to be marginally significant and positive in female bowmen. No other personality traits were significantly predictive of cortisol levels. Therefore, our results extended the knowledge on previous contrasting findings, shedding light on the importance of sex differences and the role of adolescent dinghy sailors, when examining the relationships between personality trait and the HPA system.The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by Regional Committees for Medical and Health Research Ethics. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.GC and LM: conceptualization, LM: methodology and formal analysis. FC, GM, AV, and RP: investigation. LM and MS: writing-original draft preparation. LM and MS: writing-review and editing. MS: supervision. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Background: Scanty data exist on the integration between the analgesic effect of opioids, dose changes, and adverse events in cancer patients. Methods: To provide further information on this issue, we analysed data on 498 advanced-stage cancer patients treated with strong opioids. At baseline and three visits , pain intensity, oral morphine-equivalent daily dose, and the prevalence of major adverse events were measured. The proportion of responders (pain intensity decrease ≥30% from baseline) and non-responders, as well as of patients with low or high dose escalation, was calculated. Results: Pain intensity strongly decreased from baseline (pain intensity difference −4.0 at day 7 and −4.2 at day 21) in responders, while it was quite stable in non-responders (pain intensity difference −0.8 at day 7 and −0.9 at day 21). In low dose escalation patients , daily dose changed from 52.3 to 65.3 mg; in high dose escalation patients (17.6%), it varied from 94.1 to 146.7 mg. Among responders, high dose escalation patients experienced significantly more frequent adverse events compared to low or high dose escalation patients, while no differences were observed in non-responders. Conclusions: The response to opioids results from the combination of three clinical aspects, which are strongly interrelated. These results provide some thoughts to help clinical evaluations and therapeutic decisions regarding opioid use. Opioids are considered the most effective drugs to relieve severe cancer pain, as indicated by several guidelines and recommendations ,2,3. TheIn general, analgesia is not a constant outcome but tends to vary among patients and time ,5. GivenPersonalised, interventional, and multimodal management, aiming to give an exhaustive approach to all factors influencing pain, must be carefully considered. Moreover, facing poor analgesia, the clinician tends to apply a compensatory increase in the opioid dose. This choice may give a temporary benefit that often disappears over time. Indeed, prolonged and continuous use of opioids, with a compensatory increase of dose, produces two types of neuroadaptation that interfere with opioid ability to provide analgesia . The firWe carried out this analysis with the aim of evaluating the analgesic responses in advanced-stage cancer patients treated with strong opioids over a period of treatment of three weeks and describe the course of the treatment in terms of analgesic effect, required doses, and AEs. This is a post-hoc analysis from a randomised, open-label, longitudinal, phase IV clinical trial ,19 on adThe eligibility criteria and study details are described in the original study publication . BrieflyThe study consisted of six visits, including the baseline visit and five follow-up visits at days 3, 7, 14, 21, and 28. At each visit, pain intensity (PI) was assessed as average pain intensity (API) experienced by the patient in the previous 24 hours by means of a numeric rating scale, from 0 (no pain) to 10 (worst imaginable pain). Moreover, at each visit, the prescribed opioid daily dose, expressed in OMEDD, was recorded. Moreover, the main opioid-induced AEs were also assessed using the Therapy Impact Questionnaire [For this analysis, only the baseline visit and those at days 7, 14, and 21 were considered since we aimed to evaluate the role of the administered opioids with the associated dosages after one week of treatment. The visit at day 28 was not considered since 166 patients dropped-out for different reasons . Pain intensity difference (PID) between baseline and each subsequent visit was calculated and used to classify patients as responders  or non-responders , based on Farrar’s criteria [Original study approval was obtained by the review boards of each centre, and patients gave their written informed consent.t-test. The profile of safety was analysed according to the combination of analgesic response (responders and non-responders) and dose escalation , and logistic regression models were used to estimate the odds ratio (OR) of AEs for high dose escalation patients as compared to low dose escalation patients, among responders and non-responders. The Breslow–Day test was used to detect heterogeneity of OR estimates between responders and non-responders. All the analyses were carried out with the SAS Software, version 9.4 .Mean and standard deviation (SD) and absolute and percentage frequencies were used to describe continuous and categorical variables, respectively. Trends in API, PID, mean dose, and high dose escalation over time (from days 7 to day 21) were tested using linear regression models. Moreover, differences across responders and non-responders were evaluated by independent samples p-value for trend: 0.002), from −4.0 to −4.2 in responders , and from −0.8 to −0.9 in non-responders .p-value for trend <0.001) and according to dose escalation status .p-value: 0.049; day 14: 84.1 vs. 68.9 mg, p-value: 0.004; day 21: 93.5 vs. 76.4 mg, p-value: 0.015).Mean dose and the prevalence of high dose escalation patients according to analgesic response (responders or non-responders) are reported in The prevalence of the six most frequent AEs according to the analgesic response and dose escalation over time is reported in The initial assumption of our study was that the assessment of the response to prolonged treatment with opioids was based on three variables: the achieved analgesia, the change of dose, and the opioid-induced AEs. Each of these variables was considered separately and then correlations between them were made. With reference to analgesia, the percentage of responders varied between 74% and 81% across the subsequent visits, and pain intensity in responders decreased by an average of 4 points. On the other hand, the percentage of non-responders ranged from 26% to 19% and pain intensity in non-responders diminished less than one point. From these data, it emerged, once again, that satisfactory analgesia was not always achieved [The daily dose of opioids on average tended to increase over time in the whole population. Low dose escalation patients were between 73% and 82% depending on the visit time. The difference in dose between low dose escalation and high dose escalation groups was quite impressive: at day 21, high dose escalation patients were prescribed a more than two-fold higher dose than low dose escalation ones. Responders received a significantly lower dose of opioids, their dose increased by an average of 50% in 21 days, and among them, the percentage of high dose escalation ranged from 16% to 22%. Conversely, non-responders were given higher opioid doses, with an increment of about 80%, and among them, high dose escalation proportion ranged from 26% to 39%. The trend was particularly critical in this last group of patients since the dose increase did not correspond to a better analgesic effect.When we considered the prevalence of the six most common opioid-induced AEs according to the combination of opioid analgesic effect and dose escalation, we found that responders with high dose escalation experienced more frequently all AEs, except vomiting. In addition, AEs were significantly more frequent, especially at the beginning of treatment (at days 7 or 14). No substantial differences in the prevalence of AEs were observed over time in non-responders, regardless of dose increase. The results that emerged in this analysis can provide useful indications for the clinical evaluations and therapeutic decisions for cancer patients with pain. First, in each patient, pain intensity should be measured at each visit, and the analgesic response should be considered positive if pain decreases by at least 30% compared to the baseline value . MoreoveSecond, the dose increase over time should also be measured. The opioid dose is often increased due to the failure of the analgesic effect. It is necessary to understand to what extent the increase can be considered normal. The cut-off between low dose escalation and high dose escalation is a daily increase of 5%. Although this value has been empirically calculated , it remaThird, AEs and safety profiles should be assessed along all the care path. A simple tool, like the Edmonton Symptom Assessment System , based oFourth, a “time factor” should be considered. The response to opioid treatment is a dynamic and evolving process. Analgesia, dose, and tolerability change over time, differently in each patient. The speed of these changes is important and depends on the disease, the duration of treatment, and the prognosis. For example, a rapid dose increase can be accepted in a terminal patient where the primary goal is reducing suffering, but it becomes problematic when the disease is chronic, not advanced, and requires intercurrent cancer treatments other than long-term opioid treatment. In the latter case, frequent changes in a short time can be critical and require rapid and competent evaluation and decision-making processes. Possible solutions include the dose reduction of the opioid if analgesia does not worsen, or the co-treatment with non-opioid analgesic drugs, or, alternatively, an opioid switch .The main strength of this study consists of the original idea of considering the response to opioids not only in terms of the obtained reduction in pain but also as the combination of various aspects relevant in determining the outcome and duration of the therapy. Previous studies that evaluated opioid treatment outcomes showed only a measure of positive responses, based on pain reduction by ≥30% . Also, iThis analysis indicates that the clinical response to opioids results from the combination of three clinical aspects , which are strongly interrelated, plus the “time factor”. The time factor should be evaluated in pharmacological and clinical terms. Some changes in the opioid response are related to the adaptive behavior of the drug used, such as the onset of tolerance or opioid-induced hyperalgesia. In other cases, the variations of cancer pain and its multimorphic nature in the course of the disease influence the response . Consequ


Body dysmorphic disorder consists of excessive concern with minimal appearance defects, which causes functional impairment. Its prevalence is estimated to range from 5% to 35% of dermatological patients, especially adult women with esthetic complaints.To investigate the prevalence and factors associated with dysmorphic disorder in female dermatological patients, in a public institution in Brazil.This was a cross-sectional study involving adult women attended at a public dermatological service in Brazil. Participants underwent a demographic survey, in addition to a screening form for body dysmorphic disorder (Body Dysmorphic Disorder Examination [BDDE]). The presence of dysmorphic disorder (BDDE > 66 points) was assessed among the participants according to demographic covariates and psychological problems, through logistic regression.A total of 223 women were evaluated. The BDDE showed high internal consistency (Cronbach’s α = 0.90). It is noteworthy the high prevalence of psychological problems and the fact that over one-third (38%) of the sample presented a high degree of dissatisfaction with their image. The prevalence of dysmorphic disorder was 48% among women with esthetic complaints and 30% among the others (p < 0.01). Lower family income (OR = 2.97), history of domestic violence (OR = 3.23), search for dermatological care due to an esthetic complaint (OR = 2.05), and suicidal ideation (OR = 4.22) were independently associated with the occurrence of body dysmorphic disorder.This was a single-center study of a non-randomized sample from public service.Body dysmorphic disorder is prevalent among female dermatological patients; it is associated with traumatic psychological experiences, lower income, affective disorders, and demand for esthetic care. It is essential to recognize the diagnosis in order to treat such patients and refer them for appropriate psychiatric treatment instead of trying to satisfy their esthetic demands. Body dysmorphic disorder (BDD), or dysmorphophobia, is defined as an excessive and pathological concern with minimal or nonexistent defects in appearance. BDD differs from normal concerns because it causes important functional impairment to the individuals, decreasing their quality of life, distancing them from daily activities, and taking up a lot of their time. Examples of BDD include anorexia, concern with muscle definition, and aspects related to esthetic complaints, such as open pores, facial asymmetry, wrinkles, and discreet spots.3vs. 0.7% to 2.3% of the control population. A higher prevalence is observed among adult women (76% of cases) (25 − 40 years) and patients who report esthetic complaints.12BDD is quite prevalent among plastic surgery and dermatology patients. It is estimated to affect between 4.5% to 35.2% of dermatological patients, BDD is underdiagnosed in dermatology, and its psychosocial aspects have been receiving greater focus in recent decades.The Body Dysmorphic Disorder Examination (BDDE) is a specific instrument for assessing BDD, developed in 1996 and translated into Brazilian Portuguese in 2008.This study aimed to explore the prevalence and variables associated with BDD in female dermatological patients in a Brazilian public institution.This was a cross-sectional study involving adult women attended at the public dermatological service of UNESP . The research was approved by the ethics committee (No. 969.426) and all participants signed an informed consent form. Women in care at the psychiatric clinic or those with evident cognitive impairment were excluded.There was no randomization of the inclusion of the participants, who were approached consecutively after medical care at dermatological outpatient clinics with esthetic complaints, in order to adequately represent this category and allow comparisons between the strata of the sample.The participants underwent a standardized demographic survey regarding age, phototype, medical or psychiatric diagnosis, educational status, and family income, in addition to the BBDE questionnaire. The sum of the scores of the BDDE items varies from 0 to 168 points, with higher scores indicating greater dissatisfaction with body image. There is no accepted scale for categorizing patients; however, scores equal to or greater than 66 points indicate a high degree of dissatisfaction with appearance. Its internal consistency was assessed by Cronbach's alpha coefficient.Dermatological complaints were classified as esthetic or non-esthetic by a qualified dermatologist (H.A.M).BDD was defined as BDDE scores > 66, and assessed according to the behavior of demographic and psychological covariates using a logistic regression model. Only the covariables that maintained significance (p < 0.05) in the final model were maintained in the multivariate model. The size of the effect was estimated by the odds ratio (OR) of the regression and its 95% CI. For the multivariate analysis, the missing data (< 5% per variable) were estimated using the multiple imputation technique, with ten iterations.The sensitivity analysis of the results was performed from the perceptual map by multiple correspondence analysis.Sample design calculation was based on a pre-test with 100 participants. The prevalence of BDD, up to 15 covariates (including dummy variables) indicated that a minimum of 80 cases of BDD was needed to conduct the analysis, thus requiring up to 220 participants.Data were analyzed using the IBM SPSS v. 25 software. A p-value ≤ 0.05 was considered significant.A total of 223 women were evaluated. There was no refusal to participate or difficulty in filling out the questionnaire, and the BDDE showed adequate internal consistency, with Cronbach's alpha coefficient = 0.90 (95% CI: 0.88 − 0.92).The dermatological diseases sampled are listed in The perceptual map  of the variables explained 33% of the variance of the complete model and is shown in The skin is the main organ of social contact, and body appearance can represent concepts such as health, well-being, youth, fertility, and success. In a range of cultures, good-looking individuals are more likely to get better grades at school, to be hired for a job, to receive higher salaries, and to be seen as better, smarter, and healthier.Medical care (plastic or esthetic) is part of the concept of health and disease, due to the damage to well-being that can be inflicted by the appearance. However, the perception of body image is deeply dependent on individual subjectivity, and can be influenced by cultural, economic, social, religious, and psychological experiences of each individual.24Self-image disorders greatly influence the search for skin and body care, which should alert medical professionals  to this demand, which has no correlation with the physical status of the condition.The evaluation of the participants' statements demonstrates the diversity of meanings that patients associate with body appearance: beauty, self-esteem, disgust, appearance of being older than their actual age, shame, calling attention, strangeness, rejection, failure. In the case of BDD, considering the behavioral strategies used, there is a predilection for escape or avoidance behaviors in relation to events in which their appearance can trigger aversive feelings, which promotes social isolation and favors the onset of affective disorders. Furthermore, patients with BDD have a frequent history of coercive educational practices, low social skills, great appreciation of appearance by people with whom they lived during childhood, and unpleasant events related to the part of the body with which they were concerned.e.g., depression) and anxiety.31A controlled study with magnetic resonance imaging in eight women with BDD revealed morphometric changes in the caudate nucleus and a higher volume of white matter, similarly to what happens in obsessive compulsive disorder.The study has limitations related to sampling in a public institution and the lack of randomization of the sample; however, the high frequency of esthetic complaints by the sampled patients may allow a certain inference for private dermatological activity, where this practice is more usual. Likewise, there was no obstacle to the internal comparative analysis of the subgroups.Dermatologists should be aware of the high prevalence of BDD, especially in adult women with esthetic complaints, who present affective disorders or use of psychotropic drugs. The implemented procedures and treatments are unlikely to achieve satisfaction. This is primarily because skin complaints can result from the somatization of internal conflicts, and reveal a desire for change or permanent personal dissatisfaction, which can indicate psychological problems and result in suicidal ideation.In dermatology, BDD is not only linked to dissatisfaction with treatments, but also to the urgency of its results (treatment overdose) and intolerance to adverse effects. The increase in longevity and the availability of technologies for skin and body care result in greater demand for esthetic care by the population. Careful selection of patients and procedures should lead to better levels of satisfaction and well-being.BDD is prevalent among female dermatological patients; it is associated with traumatic psychological experiences, lower income, affective disorders, and demand for esthetic care. It is essential to recognize the diagnosis in order to treat such patients and refer them to the appropriate psychologic or psychiatric treatment instead of trying to satisfy their demands.FAPESP (no 2015/04592-5).Mariana Mathias Morita: Approval of the final version of the manuscript; drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the literature; critical review of the manuscript.Maira Renata Merlotto: Approval of the final version of the manuscript; drafting and editing of the manuscript; collection, analysis, and interpretation of data, intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.Cássia Lopes Dantas: Approval of the final version of the manuscript; design and planning of the study; collection, analysis, and interpretation of data; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the manuscript.Fernando Henrique Olivetti: Drafting and editing of the manuscript; collection, analysis, and interpretation of data; critical review of the manuscript.Hélio Amante Miot: Statistical analysis; approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; obtaining, analyzing, and interpreting the data; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.None declared.


Considering only the dcSSc patients, TE-ILD and GGOs correlated with the ESSG index (r = 0.5 p = 0.009), while fibrosis grade correlated with disease duration and systolic pulmonary artery pressure. In conclusion, our data suggest that GGO correlates with DA, while fibrosis may be a sign of disease damage. The quantification of pulmonary involvement using the Wells score can be a useful tool for assessing the appropriate treatment in SSc patients.Interstitial lung disease (ILD) is the main cause of death in systemic sclerosis (SSc) patients. Usually, patients have lung involvement characterized by ground glass opacities (GGOs), but honeycombing (HC) is also possible. The Wells score is a semi-quantitative index, which is able to assess ILD by distinguishing its main components. The aim of this work is to evaluate the Wells score in relation to the disease activity (DA) index. We enrolled 40 consecutive SSc-ILD patients . All patients were evaluated by the European Scleroderma Study Group (ESSG) index, high-resolution computed tomography, transthoracic echocardiogram, pulmonary function tests (PTSs), and nailfold videocapillaroscopy for the number of microhemorrhages (NEMO) score. In our study, the total extent of ILD (TE-ILD), fibrosis and GGOs correlated with dyspnea ( Systemic sclerosis (SSc) is a connective tissue disease characterized by vasculopathy, Raynaud’s phenomenon (RP) and fibrosis that involves skin and internal organs.Pulmonary involvement is the primary cause of death in SSc patients . InterstIn this view, the quantification of the disease, and above all, of its potentially reversible feature (GGOs), can be very useful in the clinical management of these patients. Several indexes have been studied for ILD-SSc, however, computer-aided quantification has difficulty in distinguishing the two main components of ILD. On the contrary, the Wells score, despite its semi-quantitative design, is able to produce a quantification of the total extent of ILD (TE-ILD) and a proportion of GGOs and fibrosis (HC) in ILD-SSc .Therefore, the purpose of this study is to quantify pulmonary involvement by means of this score in a cohort of systemic sclerosis patients, looking for any correlation with disease activity (DA) and clinical features.We enrolled 40  consecutive patients, with a diagnosis of SSc according to the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria , who preClinical assessment was performed according to the European Scleroderma Study Group (ESSG) criteria ,14, whicFor the radiological assessment, all patients underwent a HRCT with a thickness ranging between 0.625 and 1.25 mm. The presence of GGO and HC, as well as the description of prevalent patterns, were performed by experienced pulmonologists and radiologists according to the current guidelines . The quaThe nailfold videocapillaroscopy (NVC) was performed during the visit, by two clinicians. The nailfold capillaries of all fingers of both hands, excluding thumbs, were examined in each patient using a videocapillaroscopy with a 200× magnification lens. Four consecutive 1 mm fields for a total extension of 4 mm in the middle of the nailfold were examined. The derived digital images were then stored and analysed using dedicated software . Each NVC was classified as “early”, “active” or “late” according to the method proposed by Cutolo . In addiGeneral blood tests were also carried out for the complete blood count, ESR, C-reactive protein, creatinine, creatine phosphokinase, complement fractions C3 and C4, antinuclear antibodies in indirect immunofluorescence, extractable nuclear antigen antibodies with a commercial ELISA kit comprising SSA, SSB, anticentromeric antibodies (ACA), anti-topoisomerase I autoantibodies (Scl70), anti-Sm and anti-ribonucleoproteins.To complete the clinical assessment, the patients also underwent a transthoracic echocardiogram to obtain an estimation of systolic pulmonary artery pressure (SPAP) and pulmonary function tests, including DLCO. Both these tests were performed by expert operators independent of this study. DLCO was preferred to Forced Vital Capacity for its better sensitivity and for its inclusion in the ESSG criteria ,12,20,21A statistical analysis was performed by standard procedures using IBM SPSS Statistics for Windows, Version 20.0 . A D’Agostino–Pearson test was performed in order to evaluate their distribution. Since the values obtained did not appear to have a normal distribution, we used non-parametric tests to compare these variables with other categorical or ordinal variables taken into account in the study, (Mann–Whitney U test and Spearman’s test were used for correlation).This study was conducted according to the Helsinki Declaration, updated to the latest version , and a written informed consent was obtained from all of the enrolled patients.We enrolled 26 dcSSc and 14 lcSSc patients. The general features of these patients are reported in p = 0.03) and a referred worsening of the cardio-pulmonary function and dyspnea (ΔCP) (p = 0.01). Considering ILD features separately, both fibrosis and GGOs were higher in patients with ΔCP . However, we did not find any correlation between the quantification of ILD involvement and the ESSG index.The TE-ILD was higher in patients with high ESR  and with ΔCP (p = 0.03 and 0.009). No correlation was found between the early form of SSc and DA, mRSS, SPAP or DLCO. In the longstanding form, TE-ILD, fibrosis and GGOs were higher in patients with an elevation of ESR . We also found a significant correlation between the grade of fibrosis and SPAP .When we considered the disease duration, and taking into account the early form, both TE-ILD and GGOs were higher in patients with scleredema . In this group of patients, TE-ILD was higher in patients with ΔCP (p < 0.0001), while patients with an elevation of ESR had higher amounts of GGO (p = 0.04). We also found correlations between the ESSG index and both TE-ILD and GGO (r = 0.45 p = 0.02 and r = 0.5 p = 0.009). Fibrosis correlated with disease duration (r = 0.4 p = 0.04) and with SPAP (r = 0.46 p = 0.02)  . DetaileNo significant results were found in patients with lcSSc.NVC scores were not associated with lung involvement in both the disease subsets.ILD is one of the most important clinical challenges for both rheumatologists and pulmonologists in the management of SSc patients. Although the NSIP pattern is prevalent, HC areas are not uncommon, and the UIP pattern is the second most prevalent.In our study, population ILD was associated with the worsening of respiratory symptoms (ΔCP) and higher levels of ESR. The lack of correlation between mRSS and TE-ILD could be explained by an independent progression of skin thickening and fibrosis, in accordance with what has been observed by Shand et al. .In our study, the ESSG DA score was not associated with the TE-ILD in the overall cohort. This data could be explained by the presence of lcSSc patients, in which the pulmonary involvement is significantly lower than what was observed in dcSSc patients. In fact, ACA  appears to be protective for a clinically severe pulmonary involvement, whereas the anti-Scl70 antibody is associated with a faster and more severe evolution of ILD . Indeed,To confirm this, taking into account only dcSSc patients, the ΔCP and scleredema were associated with the presence of a higher amount of HC, GGO and TE-ILD, and the ESSG DA score was associated with TE-ILD and the amount of GGOs (the latter associated with high ESR), while fibrosis correlated with DD and SPAP. The association between fibrosis and DD could be explained by a progression from GGO to HC, and therefore fibrosis can be an expression of the lung disease severity , rather than of DA. On the other hand, although SSc is obviously able to produce vasculopathy with a direct pathogenic mechanism, the association of fibrosis and a higher level of SPAP could be explained by an indirect mechanism linked to the loss of the interstitial space of the lung. This mechanism may be similar to what is expected in idiopathic pulmonary fibrosis (IPF) . On the The NEMO score should be mentioned, as it is of high interest. This is a validated NVC index that is able to predict, in an easy way, DA in SSc. NVC demonstrated good performance in the follow-up of SSc patients and could be useful for selecting patients for whom a more aggressive immunosuppressive treatment is appropriate. However, in our study, NEMO was not related with any parameters of lung involvement in our patients. This data can be explained by the small cohort of patients involved, but also for an intrinsic limit of the score. Probably NEMO is more sensible when recognizing vascular and cutaneous features rather than pulmonary DA. It should be taken into account that in the ESSG DA index, pulmonary DA is poorly explored: the respiratory items are DLCO <80% of the predicted (weight 0.5 out of 10) and ΔCP (weight 2 out of 10). Both these conditions can be secondary to pulmonary artery hypertension, rather than ILD, reflecting a vascular involvement.A fascinating topic is also the quantification of lung involvement in SSc. An objective evaluation of ILD can be useful for both clinical and research purposes. Actually, the majority of clinical trials on ILD-SSc use pulmonary function tests (PFTs) as a surrogate primary outcome, but the performance of these parameters is often burdened by a concomitant condition in SSc  . A numbeThe aim of our work was to evaluate the clinical significance of the two main features in ILD-SSc (GGOs and HC) and therefore we preferred a semi-quantitative score. However, interesting methods were recently reported by Bocchino M et al. . The autHowever, HRCT quantification seems to be a promising tool, and it is reasonable to imagine that future clinical trials in ILD-SSc will consider it as a possible primary outcome.Finally, the study has some limits due to the limited number of patients enrolled, and the good but not absolute inter-reader agreement in the semi-quantitative evaluation of ILD-SSc. However, the extensive clinical and instrumental assessment, as well as the correlation with DA, could highlight the value of a different approach in the management of ILD-SSc.Our study shows that in dcSSc patients, high disease activity scores are associated with a high proportion of ILD and GGOs, but not fibrosis. Possible predictors of lung involvement in these patients are the presence of scleredema, high ESR and ΔCP. These data can be useful, not only in recognizing active lung disease in SSc patients, but also in selecting patients for whom an aggressive immunosuppressive treatment can be useful. In this view, the lack of association between disease activity and fibrosis can be useful. In reality, at the moment, the treatment of ILD-SSc has produced conflicting results, despite the large number of compounds studied . The lac


With an estimated > 800,000 suicide-related deaths and potentially several attempts for each death in the world. The purpose of this study was to determine the epidemiological characteristics of self-poisoning with pesticides within the Jiangsu province in China.Suicide rate was calculated the Routine Surveillance System by Jiangsu Provincial Center for Disease Control and Prevention, stratified by gender, age and region, combined with socioeconomic and agriculture-related factors to investigate trends in suicide over the study period. A logistic regression model was used to investigate the associations between pesticide types and pesticide-related deaths.p < 0.001). Suicide using organophosphate and carbamate insecticides was most common, with 10,303 reported cases accounting for 42.02% of all suicides.In recent years, Jiangsu Province has witnessed a decrease in pesticide self-poisoning cases and consequent deaths. Among all suicides by deliberate ingestion of pesticides, the proportion of cases were mainly in the age 40, accounting for 3.43% of all cases with pesticide suicide. The proportion of suicide due to pesticide poisoning in females was markedly higher than that in males (For national responses to be effective, the characteristics of pesticide suicides should be comprehensively investigated for the formulation of corresponding prevention strategies. At present, more pesticide suicide prevention policies for the elderly people and women should be implemented, and stronger pesticide management policies should be implemented for rural areas. Suicide is a universal incident, with an estimated 800,000 suicide-related deaths reported worldwide in 2016. On average, the annual worldwide suicide rate is 10.5 per 100,000 individuals . Among tSuicides in China account for 26% of the global suicide statistics. Suicide is the fifth leading cause of death in the country, along with injuries, poisoning and falls. China is an agricultural and developing nation with a large number of rural inhabitants. In rural areas, higher rates of suicide are predicted relative to urban areas . IntensiSuicide is a serious public health problem but preventable with timely, evidence-based, and often low-cost interventions. For national responses to be effective, a comprehensive multisectoral suicide prevention strategy is warranted. From this viewpoint, we investigated the characteristics of 24,602 pesticide-based suicides in China’s Jiangsu Province over the past 13 years in the current study. Our findings offer a scientific basis for developing effective intervention measures as well as preventive strategies.The reporting system database contained information obtained from health institutions, hospitals and community healthcare centres. Pesticide poisoning data were acquired through the routine surveillance system of Jiangsu CDC Usage of the database was approved by CDC of Jiangsu. Jiangsu is one of the richest agricultural provinces in China and has the highest GDP per capita of Chinese provinces and second-highest GDP of Chinese provinces, after Guangdong. The Engel coefficient is the proportion of family income that is spent on food . Engels’China is an agricultural and developing nation with a large number of rural inhabitants. After the announcement of No. 322 of the Ministry of Agriculture at the end of 2003, the use of highly toxic pesticides in Jiangsu Province showed an obvious downward trend. By 2007, five highly toxic pesticides such as methamidophos and parathion-methyl were basically stopped selling. The amount of pesticide sold decreased at an average rate of 2% per year from 2006 to 2018 Fig. . AccordiAll participants  were diagnosed by specialists at different levels in the hospital according to the correlated national diagnostic criteria. The pesticide poisoning report cards contained vital information, such as patient age, sex, region and other diagnostic results. Among the poisoning records obtained through the ICD-10 code (T36.0-T65.9), all records from January 1, 2006 to December 31, 2018, listed a disease diagnostic code for at least one pesticide toxicity effect . For our study, all doctor specialists were briefly trained on judging and reporting suicide. The information of suicidal deaths gathered at the county CDCs were then forwarded on a monthly basis to the provincial CDC. For those suicidal deaths that were not recognized by any health agency, our mortality registry system allowed the village treasurers, who collect fees for each burial or cremation and are aware of all the deaths in the village, to notify the township health agency or the county CDC. Pesticide deaths included those who died before admission and those who failed treatment after admission.t-test for continuous data. Based on the significance level of equality of variance, one-way ANOVA or Welch F test was applied to compare mean values. Heat maps showing correlation between pesticide suicides and socioeconomic and agriculture-related factors were generated by Heml 1.0 (hemi.biocuckoo.org). We used logistic regression model to analyze the association between pesticide suicide deaths (vs no deaths) and pesticide types. The dependent variable was pesticide suicide deaths (vs no deaths). Confounding factors controlled in the multivariate analysis are age, sex, and different types of pesticides. Logistic regression models are presented as odds ratios (OR) and 95% confidence intervals (CI). P values < 0.05 were considered statistically significant.The total population of Jiangsu Province from 2006 to 2018 was 78.69–80.5 million. Rural population of Jiangsu Province from 2006 to 2017 was 36.82–25.08 million. The incidence of pesticide self-poisoning was calculated per 1,000,000 population. Detailed statistical analyses on the sociodemographic variables of pesticide self-poisoning were conducted. Data were compiled in the statistical package for social sciences (SPSS) software, version 20.0, and analyzed by application of Mann-Whitney U or Student’s P > 0.05).From 2006 to 2018, a total of 24,602 cases of self-poisoning through pesticides were reported in Jiangsu Province. In 1991 cases, the individuals died, leading to a fatality rate of 8.09%. We observed a general decline in the number of self-poisoning cases and deaths with pesticides, in particular, from 2007 to 2014 , as illustrated in Fig. p < 0.001). From a geographical viewpoint, the proportion (%) of self-poisoning with pesticides in the northern areas of Jiangsu  were as high as 58.01, 21.16% in the middle areas  and 20.83% in the southern areas , as shown in Fig. In total, 9353 male and 15,249 female suicides by intentional ingestion of pesticides were recorded. The proportion of pesticide-induced suicides in females  was significantly higher than that in males   as shown in Fig. p < 0.001).A large proportion of pesticide self-poisoning cases 80.23%) was identifiable in the age range of 15–64 years . Logistic regression analysis was employed to assess the association between pesticide-related deaths and different types of pesticides to a more precise extent, additionally adjusting for confounding factors . Since 2007, the GDP per capita, Divorce rate had increased and % population in farming, Pesticide sold , % Engel coefficient, Unemployment rate had decreased, and the number of pesticide suicides has dropped by 76.77%. But since 2014, the number of suicides has declined steadily, so we need to find a new key point to reduce the self-poisoning with pesticides.In the current study, we investigated pesticide self-poisoning cases and consequent deaths in Jiangsu, China, over a 13-year interval. Our data indicated that while Jiangsu province has witnessed a decreasing trend in self-poisoning with pesticides from 2006 to 2018 (p < 0.001). The higher number of self-poisoning cases in females may be due to low intent suicidal behaviour [Globally, the male suicide rate is three times higher than that of females , 17. Howehaviour . Self-poehaviour , 19. Traehaviour . The proehaviour . ConsequAccording to age, the proportion of suicides were highest in people aged 65 years or older for both men and women worldwide and lowest for people aged less than 15 years. However, age and sex patterns also changed from one region to another . In somePrevious research has shown that the incidence of self-poisoning with pesticides quarterly in a year due to season-specific agricultural activities, with high the proportion of suicides correlating with availability of pesticides during the farming season , 25. Conp < 0.001). Organophosphate and carbamate insecticides, such as T60.0X2, were the most commonly used agents, which could be attributed to their prevalent domestic use for controlling mosquitoes and other insects [Our study showed that suicide induction with organophosphate and carbamate insecticides was the most common with a total of 10,303 cases, which accounted for 42.02% of all cases. Overall, insecticides were the main agents utilized for self-poisoning . The case-fatality rate using organophosphate and carbamate insecticides was significantly higher than those with other pesticides ( insects . Althoug insects . Studies insects . Method  insects . This coWith the increase of GDP per capita, the number of suicides had decreased, showing that people’s suicide had a strong negative correlation with per capita GDP. That is, increasing per capita GDP was a key point to reduce pesticide suicide. In addition, the strong correlation between the % population living in households involved in farming and pesticide suicide indicated that pesticide supervision was still weak in agricultural cultivation areas, and it was necessary to improve supervision. Furthermore, there was a strong positive correlation between the decline in cases of pesticide suicide and the decline in pesticide sold, especially since the ban on highly toxic pesticides in 2007, the number of deaths from pesticide suicides had decreased significantly. In addition, there is a weak correlation between the unemployment rate and self-poisoning with pesticides, which coincides with the fact that the main population of pesticide suicides in China is still concentrated in rural area. The unemployed in China are mainly concentrated in urban areas . This phSuicide prevention strategies focusing on mental disorders may not be the most effective approach for rural China. The government should formulate appropriate policies for the actual situation of local pesticide usage for suicides. First, mental health education in areas with large agricultural populations, such as northern Jiangsu, should be improved. Second, better care for the elderly, who present with the highest the proportion of pesticide suicide, is an essential step. Third, the most important and effective strategy is to increase the management of pesticides and community interventions during the farming season, as well as to screen impulse-related personality, which should effectively reduce the number of impulsive suicide attempts. Finally, there was a need to strengthen the management of pesticides, because the second largest the proportion of pesticide suicide was mainly caused by unspecified pesticides.Limitations of the study include the limited geographical scope of the sample, which is mainly concentrated in Jiangsu Province, China. Therefore, we are not able to represent the overall situation of pesticide suicide in China and the factors affecting pesticide suicide. Besides, since some pesticide suicide surveys were conducted after the suicide, it is not clear whether the types of pesticides used in the surveys are the same as the suicide. This may also cause recall bias.Suicides can be avoided if crucial measures are taken to avert them. For national responses to be effective, the characteristics of pesticide suicides should be comprehensively investigated for the formulation of corresponding prevention strategies. Although the self-poisoning with pesticides cases and deaths has been decreasing year by year, the elderly and women have always been the main groups of suicides. At present, more pesticide suicide prevention policies for the elderly people and women should be implemented, and stronger pesticide management policies should be implemented for rural areas.