There were no other significant changes within or between the groups. The recruitment rate was 46%, the retention rate was 75%, and the ability to collect outcome measures was 80% at baseline and 64% at follow-up. Based on the results, it is possible to, after adjusting the protocol, conduct a full RCT.Although hip fractures are common and severe, there is insufficient evidence concerning which type of rehabilitation is most beneficial. The primary aim of this three-armed pilot study was to investigate any difference in outcome after hip fractures between and within groups in terms of balance, everyday activities, and health-related quality of life (HRQoL) following different home rehabilitation interventions. Further aims were to study feasibility and to suggest, if necessary, adjustments to the protocol for a future full randomized controlled trial (RCT). In total, 32 persons were included in this study. The intervention groups underwent the HIFE program with or without an inertial measurement unit, while the control group underwent standard rehabilitation. Within- and between-groups differences in outcomes and feasibility outcomes in terms of recruitment and retention rates were analyzed, and the ability to collect primary and secondary outcomes was assessed. Balance, measured as postural sway, showed no significant improvement in any group. All three groups improved in functional balance ( By 2050, around 8 million hip fractures are expected to occur per year ,2. This A hip fracture increases a person’s fear of falling and, thus, restricts activity . MoreoveOne type of rehabilitation program is the High-Intensity Functional Exercise (HIFE) program, which contains exercises for balance, progressive strength training, and functional exercises. The HIFE program was developed for frail older adults with lower limb problems at different functional levels living in a nursing home. It is designed to help them improve balance, lower-limb strength, and mobility in their own home . Using aIn the Medical Research Council (MRC) framework for designing and evaluating complex interventions in health care, feasibility studies constitute important steps to inform further full-scale testing, e.g., by performing an RCT . FurtherThe primary aim of this pilot and feasibility study was to investigate the feasibility of an RCT in terms of the rates of recruitment, retention, and adverse events, as well as regarding outcome data collection. A further aim was to study outcome differences after hip fractures regarding balance, everyday activities, and health-related quality of life across groups following different home rehabilitation interventions. Furthermore, if found necessary, suggested adjustments to the protocol could be made to conduct a full randomized controlled trial (RCT).A three-armed pilot study was designed. Two intervention groups were included, namely, (1) participants following the HIFE program and (2) participants following the HIFE program, with the addition of data collection using a wearable device measuring body position and movement, and (3) a control group. The design of this study has been published in a detailed study protocol . The stuThe study was performed in Malmö, the third largest city in Sweden, with approximately 330,000 inhabitants. Every year, about 700 individuals are admitted and treated for a hip fracture at Skåne University Hospital in Malmö [The inclusion criteria were being hospitalized, treated for a hip fracture, and in need of home-based rehabilitation. The exclusion criteria were (1) not being able to read and understand Swedish, (2) having major neurological diseases impacting walking and balance, and (3) having a diagnosed cognitive disease or severe cognitive impairment affecting the ability to perform exercises or use the wearable device, which was assessed by a physiotherapist.Those fulfilling the inclusion criteria were informed about the study after hospital discharge by a physiotherapist (PT). Written informed consent was provided by those agreeing to participate.A cluster randomization procedure was applied, a 6-based cluster, thus giving each cluster 2 participants to each intervention arm. Sealed envelopes were used. The numbers were randomly drawn by a person that had no contact with the participants or the researcher.All participants received an individually tailored intervention in either one of the intervention groups (HIFE) or the control group (standard rehabilitation). In all three groups, home visits by the physiotherapist were included. At these home visits, exercises were added or adjusted when needed.Intervention group 1: This group followed the HIFE program, and other exercises were added when needed. The HIFE program consists of 5 training categories depending on the individual’s level. In every category, several exercises are included . To selewww.infonomy.com) , which they wore 24 h a day until the end of the rehabilitation period . The PT omy.com) . The IMUThe equipment used in HIFE was step boards, chair cushions (5 cm height minimum), weighted belts (1 kg), soft pads, mattresses, balls, bean bags, belts with handles, and chairs without arm support; all equipment was portable. Progression for each exercise could, for example, be achieved by providing less assistance or softer surfaces or by increasing the load of the weight belt. Control group: Participants were offered individually tailored standard rehabilitation, which included walking and functional exercises . The intrecruitment rate, calculated as the percentage of individuals who agreed to be in the study among those who were qualified; retention rate, calculated as the percentage of individuals who completed the intervention; the ability to collect data, calculated as the percentage of completed collected data at baseline and follow-up; and adverse events, which is the number of harmful or negative events that may have influenced the study procedure. It was decided that, if the majority of feasibility measures was rated as low and there was no possibilities to adjust the protocol in order to raise the measures from low to acceptable or high, the full RCT would not be performed.Feasibility was the main outcome measure and measured by means of Patient-related outcomes were balance-measured as postural sway, functional balance, functional independence in everyday activities, and health-related quality of life (HRQoL). Measures of postural sway, especially in the medio-lateral direction, have been shown to be indicators of future falls . ResearcHRQoL was evaluated using the EQ-5D . It consAn IMU measures linear acceleration and rotation. The study used 2 different types of IMUs, one for intermittent measurements of postural sway and one for continuous measurements of body positions and movement. The IMU that measured postural sway was used in all 3 groups to measure postural sway in the anterior/posterior and medio/lateral directions at baseline and follow-up. During the measurements, the IMU was attached to the back, and the participant stood still for 30 s. An IMU attached to the back has shown an equally good ability to discriminate between different conditions in postural sway as other placements . A largeBefore the data collection, all health care personnel involved in hip fracture rehabilitation in Malmö municipality were trained in the HIFE program and in using the IMU device. Several workshops were held with the participation of leaders from the rehabilitation unit and technicians who developed the IMU device. After the data collection was completed, a final workshop was held to obtain information from the involved physiotherapists regarding the feasibility of the study.Data on primary and secondary outcomes were collected at baseline, together with participant characteristics , by the PT. Data on outcomes were also collected at the end of the rehabilitation period. The responsible PT also took notes in case there were deviations from the protocol or withdrawal from the study.n = 43 in each arm was required for the full RCT. To conduct the pilot study, 20% was needed, which meant 9 individuals in each group.A previous study was used to calculate statistical power . From thThe data were not normally distributed, and due to the small sample sizes, the difference in the primary and secondary outcomes between the 3 groups was analyzed using the Kruskal–Wallis test. To measure within-group differences, the Mann–Whitney U test was used. No adjustment for the number of comparisons was conducted, as all the variables were analyzed independently. Following the CONSORT statement, on-treatment analyses were applied. SPSS version 28.0 was used .A total of 32 participants were included in the study, 25 women and 7 men aged between 56 and 95 years of age (Md 85 years), during the period of January 2021 to June 2022. A total of 10 persons had had a hip arthroplasty, 19 had had intramedullary nail fixation, and 3 had had other surgical treatments. A total of 22 persons used cardiovascular medication, 4 used psychotropic medication, 2 used anticonvulsants, and 22 used other medication. Pain medication in relation to the hip fracture was used by 24 persons.Among the 32 persons included in the study, 11 were randomized to intervention group 1 (HIFE program), 10 were randomized to intervention group 2 (HIFE program + IMU), and 11 were randomized to the control group . In totan = 5) and hospitalization (n = 2). At baseline, 80% of the primary and secondary outcomes were collected (n = 32) , (PSOEAP and PSOEML = 68%), (PSCEAP and PSCEML = 53%), and at follow-up, the corresponding figure was 66% (FBG and BI =78%), (EQ5D index and EQ5D VAS = 75%), (PSOEAP = 59%), (PSOEML and PSCEAP = 56%), (PSCEML = 53%) (n = 25).In total, there were 61 qualified participants for the feasibility study. The recruitment rate was 52%, and the retention rate 78% at the primary follow-up assessments. Seven participants dropped out of the study. The reasons for drop out were unknown reasons , functional independence in everyday activities (BI) , and quality of life (EQ5D index) . There were significant changes in intervention group 2 and in the control group for EQ5D VAS (p = 0.036 and p = 0.018) but not in intervention group 1 (p = 0.262). There were no significant differences in postural sway within any group (p > 0.05)  (intervention group 1  > 0.05) .p > 0.05) between the three groups , but there may be several reasons for it not being higher. Those who experience hip fractures are often frail with multiple comorbidities, e.g., cognitive impairments, which may affect their ability to participate in the study . PotentiThe retention rate was 78%, which may be due to the individually tailored interventions. Due to loss of mobility and high age, it is important that interventions after hip fracture meet the individual needs and personal prerequisites required to enhance motivation and, therefore, improve outcome . In totaThe decision that a full RCT is feasible to perform was made after discussions in the team concerning the possibilities of adjusting the protocol in a way that recruitment and abilities to collect outcomes at follow-up could be more efficient. In particular, the decision to collect data on postural sway more frequently, together with position and mobility data from the body-worn IMU, may improve the ability to truly individualize rehabilitation.Firstly, there were some problems when collecting data on postural sway with the IMU device. The device did not show when it was fully charged, and, therefore, it sometimes turned out to be uncharged at the time of data collection. Moreover, the instructions for standardizing the measuring procedure were not clear enough, which limited our results on postural sway. Moreover, due to the lack of data on compliance rate, we did not know if the intervention groups received more training sessions than the control group or the compliance rate. We did not have information regarding the pre-fracture function of the participants.In this study, we lack qualitative information about how the participants and the PT perceived the intervention. The User Satisfaction Evaluation Questionnaire (USEC) is designed to be answered by a user of technology. In our study, the physiotherapists were the users, but the final workshop with the physiotherapists revealed that they considered USEC to be irrelevant, and, thus, they had not filled it in. Therefore, there were no data from USEC to analyze. We consider the RCT design and the individualized but controlled exercise program as strengths of this study since the program was easy to adjust to each individual’s progression.The results of this pilot and feasibility study show that a full RCT is feasible and can be conducted after adjustments to the protocol. The adjustments include changing to a two-armed RCT, adding two measurements and excluding one, and modifying the instructions and handling of the IMU when measuring postural sway. The result also shows no gain in terms of balance, everyday activities, and health-related quality of life after hip fracture for the group randomized to the HIFE rehabilitation with or without an IMU compared to the control group.


To compare the long-term nutritional status, reflux esophagitis and anastomotic stenosis, between total gastrectomy (TG) and proximal gastrectomy (PG).Patients who underwent PG or TG in this single institution between January 2014 and December 2016 were included in this study. The inclusion and exclusion criteria were defined. One-to-one propensity score matching (PSM) by the demographic and pathological characteristics was performed to compare the long-term outcomes between the two groups. The primary endpoint was long-term nutritional status, and the second endpoints were reflux esophagitis and anastomotic stenosis. Long-term nutritional status was valued by percentage of body mass index (%BMI), body weight, and blood test including total protein, prealbumin, hemoglobin and total leukocytes.Totally 460 patients received PG or TG in our institution for the treatment between January 2014 and December 2016 and according to the inclusion and exclusion criteria 226 cases were included in this study finally. There was no significant difference as to nutritional status in the end of first 5 years after PG or TG. While reflux esophagitis and anastomotic stenosis were significantly higher in the PG group than in the TG group . Overall survival rates were similar between the two groups after PSM . The rate of carcinoma of remnant stomach after PG was 3.5% in this group of patients.TG should be more aggressively recommended for the similar nutritional status, significantly lower reflux esophagitis and anastomotic stenosis, and free of carcinoma of remnant stomach compared with PG. Gastric cancer remains the fifth most frequently diagnosed cancer and the third most common cause of cancer-related death worldwide, especially in Eastern Asia, Eastern Europe, and South America –3. The eMany studies had been conducted to compare the nutritional status of patients underwent PG or TG for the early EGJ cancer, and the results were controvesial –12. In aFurthermore, the hotly debated nutrition state was only one aspect to be concerned after PG or TG, life quality was also very important to those long-time survivors. Reflux esophagitis, anastomotic stenosis and carcinoma of remnant stomach made many patients suffered much. Many studies reported that the reflux symptoms after PG was prevalent, and one of which found that the reflux rate can be as high as 48% within 5 years, and if assessed by the LA grade or Visick grade classification reflux esophagitis was much more severe in the PG group than the TG group , 13, 14.However, these studies were limited to early gastric cancer, and the long-term nutritional status, reflux esophagitis and anastomotic stenosis of those patients who survived more than 5 years were rarely studied across all gastric cancer stages. In the present study, we tried to make clear this question by the data of our single institution.In total, 2890 gastric cancer patients underwent gastrectomy at the Cancer Hospital Chinese Academy of Medical Sciences, from January 2014 to December 2016, and 460 patients who received PG or TG were included in this study. The inclusion criteria for this study were as follows: proximal or total gastrectomy; pathologically diagnosed as primary gastric adenocarcinoma; no other malignant tumor history; regular follow-up and received blood test in this institution every 3 months in the first 2 years after surgery and every 6 months in the next 3 years. The excluding criteria: Those patients who refused to answer the questionnaire were excluded.Treatment methods for all patients were decided by a multidisciplinary treatment (MDT) group including at least radiologists, pathologists, medical oncologists, and surgeons, according to the preoperative assessment of contrast-enhanced chest–abdomen–pelvis computed tomography, upper gastrointestinal endoscopy and other examinations. Patients with clinical TNM stage III received 2-4 cycle neoadjuvant chemotherapy with SOX regimen. The criteria for choosing type of surgery were mainly based on the “Japanese gastric cancer treatment guidelines (ver. 4)”. According to the guidelines, the selection criteria for EGJ cancer surgery are as follows: PG: Tumor size ≤ 4cm, cT1 and lymph node metastasis ; cT2 or above and lymph node metastasis . TG: Clinically node-positive (cN+) or T2–T4a tumors. PG was performed in a resection region of standard D2 lymphadenectomy except No. 5 and 6 group lymph nodes and the digestive tract reconstruction was accomplished by gastro-esophagectomy. TG was performed in a resection region of standard D2 lymphadenectomy, and the reconstruction of digestive tract was achieved by Rox-en-Y esophagojejunostomy. Additionally, all patients with TNM stage II-III were recommended for postoperative adjuvant chemotherapy administrated by the physician.PSM analysis was conducted using a logistic regression model and the following covariates: age, sex, body mass index (BMI), tumor size, histological type, pathological TNM stage. Among them, sex, age, BMI, and tumor size were nearly matched, and the P value > 0.2 was set as nearest match; pathological TNM staging was set as a binary variable, which were I-II and III-IV, respectively. Finally, the Borranmm type and the pathological TNM staging were matched exactly one-to-one. The clinicopathological characteristics, short-term and long-term complications and long-term life status including long-term nutritional outcomes, recurrence and survival, were compared between the PG and TG groups after PSM.The primary endpoint was the long-term nutritional status, and the second endpoints were reflux esophagitis and anastomotic stenosis. Long-term nutritional status was valued by percentage of body mass index (%BMI), body weight, and blood test including total protein, prealbumin, hemoglobin and total leukocytes.Each of the follow-up data including BMI, weight and hematological indicators at each time of follow-up were calculated based on the preoperative data and took the percentage value into analysis. Postoperative complications were graded according to the Clavien–Dindo (CD) classification of surgical complications, and those events which were grade II or higher were included into analysis . Reflux www.r-project.org ) was used for all statistical analyses. Chi-square tests for categorical variables and the Student’s test for unpaired data for continuous variables were performed to compare clinicopathological characteristics between the two groups. A p value of <0.05 was regarded as significant. Survival rates were calculated by the Kaplan–Meier method. In addition, the SVA package function Combat was used to remove the batch effect of laboratory items if the detection method changed over the years.R version 4.1 software . In addition, the grade C or D reflux esophagitis judged by the LA classification in PG group was significantly higher than TG . Similarly, reflux esophagitis assessed by the Visick grade in PG group was also higher than TG group (p < 0.001). Besides, significant difference was also observed in the rates of anastomotic stenosis between the PG and TG groups .Postoperative %Weight and %BMI changes were shown in Totally, 71 of 226(31.4%) patients relapsed after surgery. Among them, 24 were in the PG group and 47 were in the TG group, the difference was significant (P<0.05) Table 5.Finally, 78 people in the PG group and 78 people in the TG group were matched by PSM 2. The 5As reported, the incidence of EGJ cancer increased in recent decades , 19. ForPostoperative %BMI is the most important indicator of postoperative nutritional status because postoperative malnutrition is one of the most common disturbs experienced by patients undergoing gastrectomy. In our study, we found that %BMI were basically similar in the PG and TG groups as a long-term result. Similarly, Cho et al.  also fouFurthermore, there were no differences among the two treatment groups in our study in terms of postoperative nutritional transitions, consistent with previous reports of EGJ cancer, which reported that nutritional status indicators including hemoglobin, total protein, and total leukocyte count for EGJ cancer, were not significantly different between PG group and TG group within three years after surgery , 14. BesHowever, a few reports have reported that TG resulted in worse postoperative %BMI changes and long-term nutritional status than PG , 25, 26.For postoperative complication assessment, some retrospective studies have reported that the incidence of anastomotic stenosis and reflux esophagitis in the PG group was significantly higher than that in the TG group , 13, 22,In the present study, overall postoperative survival rates were comparable between the PG and TG groups after PSM, while TG used to be thought as the standard surgical method of advanced EGJ cancer for better survival and lower recurrence , 22, 27 The present study has several limitations. Firstly, the analysis was based on retrospective data collected at a single institution and included a relatively small number of patients. Due to the retrospective nature of this study, a selection bias existed between the PG and TG groups. While the selection bias in this study might not be so important as other studies focused on survival, the present study concerned on those who survived more than 5 years. Secondly, only the Visick symptom grade and LA classification were used for grading postoperative esophageal reflux. In fortunately, all of the patients received endoscopy examination every year after surgery, and the diagnosis of reflux esophagitis was credible. Finally, although the reconstruction methods of digestive tract included several kinds such as traditional esophageal-gastrostomy, JI, ET and overlap, traditional method took the predominant, and the study endpoint was still comparative between PG and TG.In conclusion, TG should be more aggressively recommended for the similar nutritional status, significantly lower reflux esophagitis and anastomotic stenosis, and free of carcinoma of remnant stomach compared with PG.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.SD and XZ contributed to study conception and manuscript writing and data analysis. SD, XZ, SW, MW, YW, and CS contributed to data collection. YX, CW, SW, MW and CS contributed to clinical treatment and diagnosis. All authors contributed to the article and approved the submitted version.This work was supported by CAMS Innovation Fund for Medical Sciences (CIFMS No. 2016-I2M-1-001 and No. 2016-I2M-1-007) and National Natural Science Foundation of China (81972314).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The neurological academic field is an illustrative example of persistent gender-related disparities reflected in compensation, funding, leadership, promotion, publishing, and recognition. Several studies indicate that neurology is one of the most underrepresented specialties with female physicians as first authors, but also has one of the highest gender payment gaps. Neglecting the role of women in academic leadership positions hinders the visibility and recognition of research and leadership in multiple sclerosis (MS). Increasing diversity within academia has positive effects, such as widening focus and expanding the plurality of research outputs. The gender gap and visibility of female MS clinicians and researchers remains an unexplored research topic in our country despite the rising number of female neurologists.This study aims to establish the gender distribution between researchers and clinical neurologists in multiple sclerosis in Colombia and raise awareness about gender disparities in this area.We applied a cross-sectional survey study of Colombian neurologists and neurology residents currently members of the Colombian Neurology Association. Mean and standard deviation (SD) were used for quantitative variables and frequency for qualitative variables. To evaluate the influence of gender, logarithmic regression was used. Data were analyzed in SPSS 26.n = 135, 67.2%). All the Colombian regions were represented in the survey. Of those surveyed, 31.5% (n = 64) had an interest in demyelinating diseases and MS, of which 46.8% (n = 30) were female. Of the women with MS training, only 50% (n =5) had more than three publications as the first author of a scientific article compared to men . After adjusting the number of publications by gender, there were no significant differences between men and women . However, only 16.6% (n = 5) of women had a visible academic, leadership, or teaching position compared with men 75.7% (n = 25). When adjusting the salary income by gender, we found a statistically significant difference between women and men . Women in MS earned between USD 2,500 and 3,800 per month; while men earned between USD 3,800 to 5,070.A total of 201 participants agreed to complete the survey, most of whom were female (Despite a higher number of female neurologists trained in MS in Colombia, our data suggest considerable differences and gender gaps with regard to diverse opportunities at the academic, salary promotion, leadership, teaching, and recognition levels between male and female MS neurologists. Today, there is increasing awareness of gender disparities in academic medicine, which is also seen in neurology and multiple sclerosis (MS) research . NeverthFrom an academic and research point of view, women are less likely to participate in collaborations that lead to publication. Several studies across the world show that women have been historically underrepresented as first and last authors in publications and from phase 3 clinical trials in MS, sponsored by pharmaceutical companies . At the Neglecting the role of women in academic leadership positions hinders the visibility and recognition of research and leadership in MS. This phenomenon could exclude or delay important contributions to science. This can affect progress toward a better understanding of the pathogenesis, treatment, and prognosis of neurological diseases including MS . IncreasThis study aims to establish the gender distribution among researchers and clinical practitioners in multiple sclerosis in Colombia and raise awareness about gender disparities in this area.P ≤ 0.05 were considered statistically significant. Data were analyzed using IBM SPSS Statistics 26.We performed a cross-sectional survey study of Colombian neurologists and neurology residents currently members of the Colombian Neurology Association who agreed to participate in our research. Questions included demographics, the field of interest in neurology, mentoring during residency, publication authorship, income, and participation in pharmaceutical-industry events. Gender was categorized in a binary manner as male and female. Mean and standard deviation (SD) were used for quantitative variables and frequency for qualitative variables. To evaluate the influence of gender, linear or logarithmic regression was used as appropriate. n = 135, 67.2%) with men being 32.8% (n = 65) . All the Colombian regions were represented in the survey (n = 64) had an interest in demyelinating diseases and MS, of whom 46.8% (n = 30) were female. In subgroup analysis, we found that a subspecialty or master's degree in demyelinating diseases (n = 16) was completed by 62.5% (n = 10) of women and 37.5% of men (n = 6). Of the women with MS training, only 50% (n = 5) had more than three publications as the first author of a scientific article compared to men . After adjusting the number of publications by gender, there were no significant differences between men and women . However, only 16.6% (n = 5) of women had a visible academic, leadership, or teaching position compared with men 75.7% (n = 25). Regarding participation in industry activities as an advisory or focus group, female representation is evidently less than male . When we compared female and male participation as a speaker, we found a significant difference in this field   . At lease survey . Of thos= 0.000) .p = 0.006). Women in MS earned between USD 2,500 and 3,800 per month, while men earned between USD 3,800 to 5,070 , while female mentors accounted for only 2.5% of the cases. In the distribution of mentorship in educational programs in Colombia, it can be observed that only 2% of the mentorship is exclusively by women  and who were located in the main cities, Bogotá and Medellín. Recent data from 2020 (not yet published) calculates a total of 547 neurologists. Even with the higher number of men in the neurology field, the survey was predominantly completed by women, which may reflect the lack of visibility and awareness of the gender gap in our country , where it is observed that there is no woman as an authority, and women represent only 20% of the entire Latin American committee, which should be taken into account for future inclusions and adjustments .Despite the uniqueness of this study of female neurologists in Colombia, our study has some limitations. Even though there was a representation of all the territories in the country, we received information from only 201 of the 550 neurologists registered in Colombia, which suggests that there may have been underrepresented neurologists who do not have access to social media  or electronic platforms through which the survey was socialized. Another limitation is that variables–such as the number of hours worked by each gender and time spent at work–were not considered in this study and should be included in any future analysis.Quantification and recognition of the gender gap is the first step in taking action. Initiatives in the field of MS such as the one led by International Women in MS (IWIMS)  seek to Nonetheless, it is important to highlight the current actionable efforts to narrow the gap. Ten years ago, there were no women as opinion leaders in the MS field in Colombia. This initiative is, in fact, a step forward to achieving a more equal and just environment for the practice of neurology in our country.Our data highlight considerable differences between male and female physicians' opportunities in MS. Despite a higher number of female physicians trained in MS in Colombia, they tend to have lower incomes and only a minority have had a visible academic, leadership, or teaching position when compared to their male counterparts. We believe that it is time for the MS community to work tirelessly to achieve equal, equitable participation of women at all levels throughout the world and develop mechanisms to identify inequalities, and thus, encourage efforts to raise awareness of gender-gap disparities.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by the Ethics Committee of the CAYRE MS Center. Written informed consent from the patients/participants or patients/participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.AC-V and MZ: writing-review and editing. CR-A and AC-V: writing-original draft and formal analysis. CG-S: editing. CG-S and MR-M: investigation. AG-G, MR-M, CG-S, and AN-G: data curation. MZ: conceive and design the survey and collected data. 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Second-generation antipsychotics are associated with significant weight gain. The aim of this systematic review and meta-analysis was to determine the efficacy and safety of metformin for the treatment of weight gain in children and young adults treated with second-generation antipsychotics.We followed PRISMA guidelines to evaluated studies published before March 2020 in Medline, Google Scholar, PubMed, Cochrane library database, annual scientific sessions of the American Psychiatric Association, American Academy of Child and Adolescent, Psychiatry, and American Society of Clinical Psychopharmacology. Studies included compared metformin with the placebo for management of weight gain in children and adolescents taking atypical antipsychotics. Non-randomized studies, animal experiment studies, editorials, and review studies were excluded. Multiple parameters, including change in anthropometric-biochemical parameters, drug discontinuation rate, and side effects among the groups were assessed. The random-effects method was used for meta-analysis.p-value < 0.001)], and BMI z score  compared to control. Metformin was also associated with a significant reduction in insulin resistance . There were higher odds of nausea-vomiting  and diarrhea  in the metformin group. However, there was no difference in drug discontinuation rate .Four studies with were included in the final analysis . After pooled analysis, 12–16 weeks of metformin therapy was associated with a significant reduction in weight [(mean difference (MD): −4.53 lbs, confidence interval (CI): −6.19 to −2.87, Metformin may prove beneficial in the treatment of weight gain in children treated with second-generation antipsychotics. The pooled treatment effect showed a significant reduction in BMI Z-score and weight in just 12–16 weeks. The limitations include small sample size, variation in metformin dose, and duration of treatment. This meta-analysis should be interpreted as promising, and further larger studies are warranted before drawing a conclusion. Antipsychotics are used in the child and adolescent patient population to treat psychosis, treatment-resistant depression, bipolar disorder, ADHD, and anger/irritability associated with autism in children, as well as used off-label to treat ailments ranging from conduct disorder to hyperkinetic disorder, among others –4. AccorAntipsychotics are highly effective and well-tolerated in the treatment of psychosis . First-gMetformin is a biguanide drug that is widely used to treat type 2 diabetes and works by increasing insulin sensitivity, decreasing glucose production in the liver, and decreasing intestinal glucose absorption. Metformin is also known to increase peripheral utilization of glucose and suppress appetite . It may We perform a systematic review and meta-analysis of current literature to determine the efficacy and safety of metformin for the treatment of weight gain in children and young adults treated with second-generation antipsychotics.We evaluated all the relevant studies published before March 2020. We included all the studies performed in children and adolescents, where metformin was used and compared with the placebo for the weight gain management in patients taking atypical antipsychotics. The studies were searched using MeSH  term “metformin”, “overweight”, “child”, “adolescent”, “antipsychotic agents”, “Increased body weight” . StudiesAll non-randomized, animal experiment studies, editorial, and review studies were excluded. Selection of Studies and Data Extraction was conducted in two separate stages. In the first stage, two researchers  independently screened all non-duplicate references initially retrieved as potentially pertinent and excluded those not relevant based on title or abstract. A final list was agreed on, with discrepancies resolved by consensus between the two authors. In the second stage, full-text versions of the articles passing initial screening were downloaded and independently assessed for eligibility by the researchers. Data were collected from all the studies for baseline characteristics, change in anthropometric-biochemical parameters, drug discontinuation rate, and side effects of both the groups.2 test. The inconsistency was assessed with the I2 test that describes the percentage of the variability in effect estimates that is due to heterogeneity. Publication bias was assessed by visual inspection of the funnel plot of precision. The statistical level of significance for the summary treatment effect estimate was analyzed in a random effect model by inverse variance and Mantel- Haenszel method  conducted in children or young adults were included in the final analysis (26–29) .Klein et al. assessed metformin treatment of weight gain associated with the initiation of atypical antipsychotic therapy in a 16-week double-blind study performed in patients of 10–17 years of age. Only patients who gained >10% of their pre-drug weights in less than a year of treatment with atypical antipsychotic agents were included. All patients were on a stable dose of antipsychotics for at least 3 months. Patients were followed up at weeks 4, 8, 12, and 16 for anthropometric measurements and interviewed for side effects. At each visit, blood samples were obtained for lactic acid, sodium, potassium, BUN, creatinine, bicarbonate, liver enzymes, and pregnancy testing. Also, blood samples were obtained for insulin levels, insulin resistance, and fasting glucose blood level at weeks 8 and 16. All patients received nutritional counseling at weeks 4, 8, and 12.2) and almost half the weight on an average compared to other studies.Arman et al. evaluated the effect of metformin vs. placebo on treatment on the risperidone induced weight gain in patients with Schizophrenia or Schizoaffective disorder. It was a 12-week double-blind clinical trial where all patients were <20 years of age and were taking risperidone and were antipsychotic naïve. A total of 49 patients were recruited; however, 17 of 49 were excluded due to side effects or not able to complete the medication protocol. Patients were followed up weekly for side effects monitoring by phone follow up. In addition, data on anthropometric  and biochemical parameters  were collected at week four and week 12. Patients in this study had very low BMI  significantly in metformin group . There was no heterogeneity in weight change analysis [I2: 22%], however, in BMI-z score change analysis there was a moderate heterogeneity [I2: 60%]. In addition, metformin was associated with reduction in insulin resistance . Data on biochemical parameters were available for only two studies [28–29], and it showed beneficial effect for all parameters; however, it was non-significant change .A total of 213 patients were included in the final analysis; 106 patients in metformin and 107 patients in the control group. After pooled analysis, metformin group was associated with a significant reduction in weight from baseline compared to control  . Since, p-value: 0.14]; however, metformin was associated with higher number of nausea and vomiting  and diarrhea  (There was no difference in drug discontinuation rate  . There w: 0.002] , side ef: 0.002] , three pThis is the first meta-analysis focusing on the efficacy as well as the safety of metformin treatment for weight gain in children and adolescents undergoing treatment with second-generation antipsychotic medications. Second-generation antipsychotics are very effective medications, but the side effect of weight gain is a significant concern –13. TherAccording to the pooled analysis of randomized clinical trials, at 12–16 weeks after starting the treatment, metformin was associated with almost 5 lbs reduction in weight compared to the placebo. Moreover, it was associated with a significant reduction in BMI z-score and insulin resistance. There was more reduction in body weight and BMI z-score at 24 weeks of follow-up. Overall, patients in the metformin group had fewer problems with aggression/hostility; which imply that it also helped in symptom relief . There wRecent studies have shown that schizophrenia may itself contribute to metabolic syndrome. Lang et al. conducted a study on 430 first-episode drug-naïve schizophrenia patients. Authors reported that the metabolic syndrome co-existed in the early stages of schizophrenia in the absence of antipsychotic treatment . Also, tDespite promising results, our study has several limitations. First, the overall sample size was small despite four studies. Second, the dose and duration of metformin were different in each study. Third, inclusion criteria for weight gain before the study were different in each study and in the study by Arman et al. , where iMetformin was beneficial in treating weight gain in children and adolescents treated with second-generation antipsychotics in our meta-analysis of randomized controlled trials. Although the pooled treatment effect is significant with almost 5 lbs difference in just 12–16 weeks, a small number of studies and variation in metformin dose and duration of treatment in each study make our results promising but not conclusive and worthy of further investigation. The result should be interpreted as a positive hypothesis that can pave the way for a future clinical trial design that would address unanswered questions such as long-term outcome, change in psychiatric symptoms, metformin as a preventive strategy for weight gain, preferred dose, and length of therapy, and its specific use in the context of antipsychotic usage.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.ZM, CT, and AR contributed to the idea, writing, editing, and reviewing of the manuscript. RV and MA contributed to the writing, editing, and reviewing of the manuscript. RM, JR, and AL contributed to the reviewing of the manuscript. All authors contributed to the article and approved the submitted version.


Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease that has led to millions of confirmed cases and deaths worldwide. Traditional Chinese Medicine plays an irreplaceable role in the treatment and prevention of epidemics in China. Western medicine improves clinical symptoms as well as bringing many adverse reactions. The combination of Chinese and western medicine can significantly improve the clinical symptoms and efficacy of patients. Currently, there is a lack of systematic reviews on the comparison of the incidence of adverse reactions between the difference treatments. We conducted this study to evaluate the comparison of the incidence of adverse reactions between herbal decoction and Chinese patent medicine combined with western medicine in treatment of COVID-19.Randomized controlled trials in 9 databases from December 2019 to September 2022, will be included, without language restrictions. Two independent researchers will screen and select studies, extract data, and evaluate the study quality. The Cochrane risk-of-bias tool for randomized controlled trials will be used to assess the risk of bias in the included studies. Statistical analyses will be conducted using Review Manager.Our findings will compare the incidence of adverse reactions between herbal decoction and Chinese patent medicine combined with western medicine in treatment of COVID-19, which will be disseminated in a relevant conference and published in a peer-reviewed publication.This study will not include personal information. Ethical approval is not required for this study.CRD42022371001. The clinical manifestations of COVID-19 appear to be broad, ranging from fever, cough, tiredness, loss of taste or smell, sore throat, headache, pain and discomfort, and diarrhea, to severe symptoms such as loss of speech, mobility or confusion, severe pneumonia, and even death. Public health emergencies not only cause damage to the material life of society, but also affect the mental health of the public and patients.The world was surprised by the rapid spread of coronavirus disease 2019 (COVID-19), leading to a pandemic, death, and post-COVID syndrome. The first case of COVID-19 emerged in China in late 2019,9 The combination of Chinese and western medicine can greatly reduce the side effects caused by simply taking western medicine. Chinese patent medicine Lianhua Qingwei has the functions of anti-virus, anti-bacteria, inhibiting respiratory inflammation, reducing fever, relieving cough and resolving phlegm, etc.,11 It can also reduce the adverse reactions such as vomiting and diarrhea caused by chemical drugs, which to some extent makes up for the defects of Western medicine treatment, and has important clinical significance.According to the TCM theory, herbal decoction belongs to syndrome differentiation treatment. For patients with complex symptoms, decoction has the advantages of flexible compatibility, paying attention to prescribing a prescription for one person, and strong pertinence, which can well reduce all kinds of adverse reactions.Western medicine is mainly antiviral in the treatment of COVID-19. Oral western medicine alone will produce many adverse reactions, such as nausea, vomiting and anorexia, liver function damage, skin itching, abdominal pain and diarrhea. During the COVID-19 epidemic, Chinese medicine has been used as a complementary treatment in China and has played a huge role in the treatment of COVID-19. Studies have shown that Traditional Chinese Medicine (TCM) has unique advantages in enhancing immunity, improving clinical symptoms of COVID-19, reducing complications and improving quality of life.However, whether Chinese medicine can significantly reduce the incidence of adverse reactions needs further studied. In this paper, herbal decoction combined with western medicine and Chinese patent medicine combined with western medicine were statistically analyzed, aiming to find out the reasons for the inconsistent incidence of adverse reactions between the two treatment methods and provide reference for clinical medication of COVID-19. If amendments are required, we will update our protocol to include any changes in the entire research process.This study has been registered with PROSPERO , and the registration number is CRD42022371001. This protocol is reported based on the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols (PRISMA-P) 2015.The PICOS principles will be consulted to establish the inclusion and exclusion criteria for this systematic review.Randomized controlled trials on the combination of Chinese herbal and western medicine in the treatment of COVID-19 will be comprehensively searched without restrictions on language or publication date. Additionally, unpublished documents will be manually searched. The following will be excluded: reviews; experience summaries; retrospective trials; prescription statistics; case reports; animal research literature; literature without adverse reaction outcomes; trials in which the western medicine group and the combined Western and Chinese/Western medicine group combined other treatments; trials in which the combined Western and Chinese medicine group had patients taking both herbal decoction and Chinese patent medicine; trials that treat only one symptom of COVID-19; taking medicine before and after self-control trials; trials in which the literature indicated that the grouping was non-randomized.Participants who have been assessed as COVID-19 will be included. There are no restrictions on gender, education, race, age, or disease stage.Intervention: The Chinese and western medicine combination group was treated with decoction or Chinese patent medicine combined with western medicine.Control: The western medicine group alone was treated with the same western medicine as the combination group.The outcome index was the occurrence of adverse reactions.According to the PICO principles of the Cochrane Manual for the Systematic Evaluation of Interventions   and the treatment protocols recommended in the “New Coronavirus Pneumonia Protocols (First to Eighth Editions),” combined with the clinical practice for the use of drugs for new coronavirus pneumonia, to set the search terms.We will conduct our research in five English databases, including PubMed, Embase, Cochrane Library, Web of Science, Medline, and in four Chinese databases, including China National Knowledge Infrastructure, China Biology Medicine disc, Wanfang Database, and VIP Database. Using different databases, we will combine keywords and free words for a comprehensive search. Taking PubMed as an example, Table The search strategy and study selection will be performed independently by 2 researchers (Y.L.Z. and L.X.H.), and the final research choices will be agreed upon. Two researchers independently evaluate the same article to determine their eligibility for inclusion and resolved differences through consensus, which will be managed by a third reviewer (Y.W.Y.). The selection process will be summarized using a PRISMA flow diagram. Details of the selection procedure for the studies are shown in the PRISMA flow chart Fig. .According to the Cochrane Handbook for Systematic Reviews of Interventions, the two researchers (Y.L.Z. and L.X.H.) will extract data, including the first author, year of publication, sample size, age, intervention measures, and number of adverse reactions. All database retrieval, literature screening and information extraction were carried out by two researchers in accordance with pre-set rules and standards. In case of any disagreement, a joint decision was made after discussion with a third party.If the information is missing or unclear, we will try to contact the corresponding author for more detailed information. If it fails, we will analyze it based on the available data. The rating results will be cross-checked, and discrepancies will be resolved through discussions and arbitration with a third author (Y.W.Y.).Two researchers (Y.L.Z. and L.X.H.) will assess the quality of the included studies independently by utilizing the Cochrane Risk of Bias assessment tool. As specified by the Cochrane Handbook (version 6.0), the following sources of bias will be considered: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessments, incomplete outcome data, selective reporting, and other sources of bias. Studies will be rated as having a high, low, or unclear risk of bias as appropriate. In addition, the results will be divided into high, moderate, low, and very low quality.The Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the overall quality of the evidence derived from the included studies.Comparision of acupuncture efficacy will be performed by Review Manager software 5.4. For continuous results, the data are represented as the mean difference or standard mean difference with a 95% confidence interval. When dichotomous data were available, a hazard ratio with 95% confidence interval was used. When binary data exist, the RR format is changed for analysis.I2. If I2 ≤ 50% and P > .1, statistical homogeneity will be considered good. A fixed-effects model will be used for merging. If I2 > 50% or P ≤ .1, which indicates statistical heterogeneity, the source of heterogeneity will be further analyzed. A random-effects model will be used for meta-analysis after excluding obvious clinical heterogeneity. When there is obvious clinical heterogeneity, it should be treated by subgroup analysis, sensitivity analysis, or only descriptive analysis.Clinical and statistical heterogeneity between the studies will be assessed. Clinical heterogeneity will be assessed according to the similarity of research objects, intervention measures, control, and outcome indicators, while statistical heterogeneity will be evaluated by If more than 10 studies are included, we will use funnel plot and Egger’s test to assess the publication bias.P value and I2 were used to judge the heterogeneity. When P > .1 and I2 ≤ 50%, homogeneity among studies is considered, and the fixed-effects model will be used. When P ≤ .1 and I2 > 50%, it was considered that heterogeneity existed among the studies. Therefore, a random-effects model will be used for analysis, and sensitivity analysis method was used to speculate the source of heterogeneity. Subgroup or sensitivity analyses will be performed, if there is significant clinical heterogeneity. P < .05 was considered statistically significant. Funnel plots were drawn and analyzed for more than 10 literatures.We take advantage of Review Manager software 5.4 for data analysis and synthesis. The relative risk and 95% confidence interval were used to analyze the effect values, and the  The following subgroup analyses will be considered: gender, age, intervention time, intervention cycle, and course of the disease.If the heterogeneity is high, we will also perform subgroup analysis to calculate the combined statistics.Sensitivity analysis will be performed to investigate the robustness of the primary outcomes, which includes assessing the method quality, study quality, and impact of sample size and missing data.Since this study will be a secondary analysis of primary studies, no patients or public participants will be involved, and no primary data will be collected. Therefore, ethical approval is not required for this study. The results of this study will be shared and presented in conference reports and peer-reviewed journals.This article is the first to analyze the effects of decoction and Chinese patent medicine combined with western medicine on the incidence of adverse reactions in the treatment of COVID-19. As an external treatment method of TCM, Chinese medicine has the characteristics of simple and simple verification. It can not only assist the treatment but can also greatly reduce the adverse effects.This study provides explanations for the inconsistent results of numerous studies, as well as providing exploration directions for reducing the risk of COVID-19 treatment. We hope that this review will provide more convincing evidence for clinicians to treat these conditions and help them make appropriate decisions.All the authors had access to the data and played a role in writing the manuscript. All authors have read and approved the final manuscript.Data curation: Yunliang Zhang.Formal analysis: Xuhao Li.Methodology: Wenyan Yu, Xuhao Li, Yunliang Zhang.Project administration: Wenyan Yu.Resources: Yunliang Zhang.Software: Yunliang Zhang.Visualization: Xuhao Li.Writing – original draft: Yunliang Zhang.Writing – review & editing: Wenyan Yu.


Diet is one of the leading risk factors for non-communicable diseases and is related to sociodemographic and lifestyle factors, including sex. These associations vary across populations. We aimed to investigate which factors are associated with dietary patterns among adults living in Mexico City by sex.n = 1,142; 413 men and 729 women). Dietary information was collected using a semi-quantitative food frequency questionnaire. Foods and beverages were categorized into 23 food groups to identify dietary patterns by cluster analysis. Sociodemographic and lifestyle variables included were self-reported through standardized questionnaires. We assessed the association of sociodemographic and lifestyle factors with dietary patterns through a multinomial logistic model stratified by sex.We used data from the Mexico City Diabetes Representative Study, a cross-sectional, multistage, stratified, and cluster-sampled survey in Mexico City . Divorced or separated men  and those living with a partner  had a higher relative probability of consuming a fast food dietary pattern than the prudent one, compared to single men. Men living with a partner  or working long shifts  had a higher probability of consuming a basic pattern rather than a prudent one compared to peers. Among women, those with high SES had a lower probability of consuming the “basic” pattern rather than the “prudent” pattern compared to those with low SES. No lifestyle factors were associated to dietary patterns.Men living in Mexico City with lower education, age, non-single, and working long hours , and women with lower age, education, and socioeconomic level are prone to adhere to unhealthy diets. These associations are likely to be driven by gender roles. Unhealthy diets are one of the major lifestyle risk factors for non-communicable diseases (NCDs), which account for more than 75% of the deaths worldwide , 2. In MDifferences by sex in dietary patterns have been described previously in the Mexican population –10. It hThe aim of this study was to evaluate the association of sociodemographic and lifestyle factors with dietary patterns by sex of adults living in Mexico City in 2015, using the Mexico City Diabetes Representative Study.We conducted a secondary study using data come the Mexico City Diabetes Representative Study, a cross-sectional, multistage, stratified, and cluster-sampled survey, conducted between May and June 2015 in Mexico City. Census tracts, defined by National Institute of Geographics and Informatics, were the primary sampling units. Details of sampling procedures are described elsewhere . BrieflyTable 2). SES was constructed using principal components analysis (PCA). Household characteristics  were entered into the PCA. The main factor was extracted and divided into tertiles . The detailed methodology is described elsewhere  .Lifestyle variables included smoking status, sleep duration, alcohol use, sitting time, and physical activity volume. Smoking status was categorized as never, former, and current. Healthy sleep duration considers people reporting sleeping 7 h or more, while unhealthy consider people reporting <7 h .Alcohol use was classified into three categories: never, low (five drinks or less per week), and high (more than five drinks per week).Physical activity volume was measured using the short version of the International Physical Activity Questionnaire (IPAQ). The IPAQ consists of 7 questions that measure moderate to vigorous physical activity, walking, and sitting time. Data were processed following the IPAQ Analysis guidelines , and metSitting time was measured as an indicator of sedentary behavior. Hours and minutes of sitting time in 1 day of the last 7 days were asked. Daily sitting hours were estimated.Diet information was collected with a validated semi-quantitative food frequency questionnaire (SFFQ) . The SFFTo identify dietary patterns, we categorized foods and beverages from the SFFQ into 23 food groups . Food gr®.The resulting dietary patterns were described according to the mean energy contribution (%). We first descriptively examined the sociodemographic and lifestyle variables in the total sample and by sex. We then assessed the adjusted relative risk ratio (RRR) of belonging to a dietary pattern through a multinomial logistic model stratified by sex. We considered the dietary patterns as the outcome variable using the healthier pattern as the reference category, and sociodemographic , and lifestyle factors  as independent variables. The established significance level was at alpha 0.05. All the analyses were performed using expansion weights and adjusted by survey design with the SVY module of Stata 14Three main dietary patterns were identified. The first pattern had the highest contribution from foods commonly considered healthy ; therefore, we named this pattern “prudent.” Sweetened cereals, corn-based foods, sweetened beverages, sweets and desserts, and fast food contributed heavily to the second pattern; we named this pattern “fast food.” The third pattern was characterized by high consumption of corn-tortillas and legumes, which are basic elements of the Mexican diet; this pattern was named “basic” .In the total sample, the most consumed pattern was the “fast food” (41.5%), and the less consumed was the “prudent” pattern (24.9%); we observed similar distributions by sex. Participants were, on average, 40.1 years old and had 12.5 years of school attainment. More than half were from the low and middle socioeconomic status (58.0%) and lived with a partner (55.9%). In the total sample, 38.3% were unemployed, with a higher unemployment rate among females (51.3%) compared to males (22.5%) .Almost a third were current smokers (31.2%); the prevalence was higher in men (43.6%) than women (21.0%). In total, 30.2% of participants reported sleeping <7 h per day, and three in every four reported consuming five or fewer alcoholic drinks per week. On average, participants reported 3.9 h per day of sitting time and only 8.9% reported low physical activity levels .We identified three major dietary patterns in the surveyed population in Mexico City: prudent, fast food, and basic. These dietary patterns were similar to those found in other studies in Mexico , 18. WhiStudies exploring associations between dietary patterns and lifestyle variables are sparse. Previous reports showed associations between unhealthy lifestyles, such as current smokers , sedentaThe results showed associations between demographic factors and dietary patterns in men and women. School attainment and age were associated with dietary patterns among both men and women. These results are consistent with studies reporting positive associations between higher education , 33 and Associations between dietary patterns and marital status were observed only in men. Although explaining the findings stratified by sex may be challenging because our results are based on a sex variable, these associations may respond to gender role constructs. Mexican men have been traditionally considered as “providers.” On the other hand, women tend to be responsible for family care and wellbeing , 35, witcomida corrida” in Mexico. The “comida corrida” is a cheap home-cooked lunch (<3 USD) available in “fondas” or small restaurants that cater to Mexican working-class adults. Due to the high commuting times in Mexico City, most people have to eat out of the home, making this food option a very affordable and accessible one, especially for those that work long periods. However, working hours may not represent shifts or type of work and only paid jobs were considered for the analysis. This may exclude women working at home or self-employed adults.Similarly, working for more than 48 h was associated with a higher probability of having a basic pattern in men, but not women. The basic pattern identified in our study has characteristics of a “We observed that a high SES was associated with a healthier dietary pattern among women. In men, we did not find an association between SES and dietary pattern. These results are consistent with those reported in high-income countries , 38. TheOur study provides an overview of the dietary behavior of Mexico City residents in 2015, although this panorama may have changed in several ways in recent years. There is evidence that the COVID-19 lockdown in 2020  has reprThere are some limitations to the current study. First, even though dietary patterns offer a broader vision of the way populations eat, they are specific to the population studied, limiting the comparability of findings. Second, temporal associations cannot be inferred due to the inherent limitation of the cross-sectional design of this survey. Third, the gender roles discussed focus on the traditional male-female couple model. Future studies will be necessary to better understand the potential role of gender in same-sex couples in dietary patterns. Finally, all the information was self-reported, so we do not rule out the possibility of measurement error –46. SpecMen living in Mexico City with lower education, age, non-single, and working long hours , and women with lower age, education, and socioeconomic level are prone to adhere to unhealthy diets. These associations are likely to be driven by gender roles due to the differences observed in men and women. The design of nutrition programs should consider gender perspectives to accomplish positive results in men and women.alejandra.jauregui@insp.mx.The data analyzed in this study is subject to the following licenses/restrictions: Data could be accessed under permission of the principal investigator of the study. Requests to access these datasets should be directed to AJ, The studies involving human participants were reviewed and approved by the Ethics Committee of the National Institute of Public Health . The patients/participants provided their written informed consent to participate in this study.CO-S, CH-A, and NS-O developed research questions, analyzed, interpreted the data, and wrote the first draft of the manuscript. NL-O and AJ contributed data collection and supported to analyze the data. SB support to interpreted the data and assisted in the writing of the manuscript. All authors read and approved the final manuscript.This study was funded by the Robert Wood Johnson Foundation (RWJF) (Award number: 74155) and Bloomberg Philanthropies (Award number: 43003). The Mexican Ministry of Health provided additional funding through a collaboration agreement with Novo-Nordisk. The National Council for Science and Technology supported CIOS, CHA, and NASO's time writing the paper. The study sponsors had no role in the study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Emergency medical services (EMSs) are a critical component of health systems, often serving as the first point of contact for patients. Understanding EMS supply and demand is necessary to meet growing demand and improve service quality. Nevertheless, it remains unclear whether the EMS supply matches the demand after the 2016 healthcare reform in China. Our objective was to comprehensively investigate EMS supply–demand matching, particularly among urban vs. sub-urban vs. rural areas.Data were extracted from the Tianjin Medical Priority Dispatch System (2017–2021). From supply and demand perspectives, EMS resources and patient characteristics were analyzed. First, we performed a descriptive analysis of characteristics, used Moran's I to explore the spatial layout, and used the Gini coefficient to evaluate the equity of EMS supply and demand. Second, we analyzed urban–sub-urban–rural variation in the characteristics of EMS supply and demand by using the chi-square test. Finally, we examined the association between the EMS health resource density index and the number of patients by using the Spearman correlation and divided supply–demand matching types into four types.P = 0.000) in urban, sub-urban, and rural areas. There was no spatial autocorrelation among medical emergency stations, of which the G values by population, geographical distribution, and the health resource density index were 0.132, 0.649, and 0.473, respectively. EMS demand was the highest in urban areas, followed by sub-urban and rural areas . The EMS supply met the demand in most districts . The high supply–high demand types with stationary demand trends were distributed in urban areas; the low supply–high demand types with significant demand growth trends were distributed in sub-urban areas; and the low supply–low demand types with the highest speed of demand growth were distributed in rural areas.In 2021, the numbers of medical emergency stations and ambulances were 1.602 and 3.270 per 100,000 population in Tianjin, respectively. There were gradients in the health resource density index of the number of emergency stations (0.260 vs. 0.059 vs. 0.036; EMS supply quantity and quality were promoted, and the supply met the demand after the 2016 healthcare reform in Tianjin. There was urban–sub-urban–rural variation in EMS supply and demand patterns. Emergency medical services (EMSs) are integral to immediate critical care, stabilization of life-threatening diseases, timely triage, and transportation in prehospital settings –3. Most Most research has focused mainly on the spatial layout and accessibility of EMS facilities for optimal allocation –23. Liu The purpose of this study was to comprehensively determine urban–sub-urban–rural variation in the supply and demand patterns of EMS by examining the characteristics, spatial layout, and equity after healthcare reform in the megacity of Tianjin, China. The results will provide a reference for further advancing medical reform, implementing the Healthy China 2030 strategy, and proposing feasible proposals to improve EMS sustainable development in the megacities of developing countries.2. Tianjin has a single EMS provider, namely, the Tianjin Medical Emergency Center, operated by the Tianjin Health Commission; the Tianjin Medical Emergency Center is a publicly funded system and covers all emergency medical calls within the city. In 2017, focused healthcare reform was initiated in Tianjin to set up a pilot program for a purely prehospital care model, and the electronic medical records and intelligent dispatch were standardized based on the Medical Priority Dispatch System (MPDS). An electronic record was automatically created for each patient by using EMS with a unique registration number and was recorded in real-time on the operating system. The database contained a complete collection of every EMS dispatch record generated in all districts of Tianjin.Tianjin is a coastal megacity, administratively equivalent to a province, in the North China Plain, with a population of approximately 14 million people and an area of 11,947 kmWe designed a retrospective study to comprehensively evaluate the supply and demand patterns of EMS after the healthcare reform in the urban, sub-urban, and rural areas of Tianjin.Data related to EMS supply and demand during the calendar years 2017 through 2021 were extracted based on routinely collected ambulance dispatch data from the MPDS of Tianjin Emergency Medical Center. The data elements about both EMS supply and demand in this study were as follows: (i) the numbers of medical emergency stations, ambulances, prehospital emergency physicians (PEPs), and nurses; and (ii) the date of the emergency call, demographic characteristics and initial diagnosis of each patient, and EMS incident location. The inclusion criteria were as follows: patients transported by ambulance from the scene to the hospital or from one hospital to another hospital. Data related to the current situation were from the Tianjin Statistical Yearbook and Health Statistical Yearbook.We analyzed the variation in EMS demand in urban, sub-urban, and rural areas according to EMS incident location. Tianjin consists of 16 districts. Based on the geocoding system, the districts were divided into three regions: urban areas , sub-urban areas , and rural areas .Prehospital emergency physicians made initial diagnoses and recorded electronic records of each patient according to the MPDS . The sopMoran's I is a way to measure spatial autocorrelation. Global Moran's I was used for the spatial autocorrelation of EMS supply , 29. Evii and j are the region indices and Wij indicates the adjacency between area i and area j. Two districts were considered adjacent if they shared a border. Yi and Yj denote the numbers of medical emergency stations in areas i and j, respectively, and Y is the average of the number of medical emergency stations in the entire district. A value of 0 indicates that the data have no spatial autocorrelation. A positive Moran's I indicates the clustering of similar values, whereas a negative Moran's I indicates the clustering of dissimilar values.where The Gini coefficient is a tool used to assess the equity of health resource supply and demand in terms of demographic and geographical aspects. The Gini coefficients were derived from the Lorenz curves. With regard to the Lorenz curve, the x-axis represents the cumulative percentage of population or geography, and the y-axis represents the cumulative percentage of EMS supply and demand. A 45° line indicates absolute equity. A larger distance from the diagonal line indicates greater unfairness. Formula (3) was used to calculate the Gini coefficients.Xi is the cumulative percentage of health resources and demand in the ith district of Tianjin city after ranking according to the per capita or the regional average share of health resources and demand. Yi is the cumulative percentage of population and geography in the ith district of Tianjin after ranking according to the per capita and the regional average share of EMS supply and demand. K is the total number of districts. G is the value of the Gini coefficient.The health resource density index (HRDI) displays the influence of population and geographical factors on the agglomeration of EMS supply and demand while avoiding bias caused by a single population or geographical aspect. Formula (4) was used to calculate the HRDI.HRi is the health resource and demand quantity for the ith district. Ai is the geography of the ith district (km2). Pi is the population of the ith district. HRDI is the value of the HRDI.In the analysis of EMS supply, the following data were analyzed: the number of medical emergency stations, ambulances, PEPs, and nurses with consideration of demographic and geographical dimensions. In the analysis of EMS demand, the date of the emergency call, gender, initial diagnosis of each patient, and EMS incident location was analyzed.t-test and the Mann–Whitney test, respectively. Joinpoint regression was used to identify annual potential trends in the EMS demand in Tianjin from 2017 to 2021 by calculating the annual percentage change (APC). Counts from the Poisson regression model and grid search method were selected. A permutation test with the Bayesian information criterion was used to select the best model, applying a Bonferroni correction to the type I error to correct for multiple testing. The APC and 95% confidence intervals (CI) were estimated every year on a log scale. Associations between basic characteristics of the current situation and EMS demand and EMS resource supply and demand in different districts were examined by using the Spearman correlation.Descriptive analysis of the EMS supply and demand characteristics was expressed as the median and interquartile spacing [M ]. Categorical variables were analyzed by using the chi-square test, and continuous variables with a near-normal distribution and variables with skewed distributions were analyzed by using the We divided the districts into two groups (high EMS supply and low EMS supply) according to the median value of the HRDI and divided the districts into two groups (high EMS demand and low EMS demand) according to the average number of EMS patients per year. Relying on the aforementioned, we divided the supply and demand patterns of EMS into four types: high supply–high demand, high supply–low demand, low supply–low demand, and low supply–high demand.Data management was performed using Microsoft Excel 2019 , and statistical analyses were carried out using the Statistic Package for Social Sciences, version 26.0 . Geospatial visualizations and spatial analysis were obtained using ArcGIS 10 . The Joinpoint Regression Program, version 4.9.0.0 , was used to carry out joinpoint regression , 31. TheThe purely pre-hospital care model was set up with the three-level network system of “medical emergency center, medical emergency sub-centers, and medical emergency stations” in Tianjin in 2017. The number of EMS resources, such as medical emergency stations, PEPs, and nurses, greatly increased from 2017 to 2021, especially in 2019 .As of 2021, there was one medical emergency center, 11 medical emergency subcenters, and 220 medical emergency stations. The number of medical emergency stations was 1.602 per 100,000 population .The number of ambulances was 449 and was 3.270 per 100,000 population  in 2021. There were four types of ambulances as follows: type 1 ambulances (with oxygen delivery facility and for nonemergency patients), type 2 ambulances , type 3 ambulances , and type 4 ambulances .Upon each activation, each ambulance was equipped with a PEP, a nurse, two stretchers, and a driver. As of 2021, there were 1,092 PEPs and 673 nurses. The doctor–nurse ratio was 1.624:1. The number of PEPs was 0.795 per 10,000 population.P = 0.000). In terms of geographical distribution  and the HRDI , the number of emergency stations was the highest in urban areas, followed by sub-urban and rural areas . The high-low cluster area was in Binhai District; the low-high cluster area was in Jinghai District. The number of medical emergency stations per 100,000 population was the highest in Heping District and the lowest in Jinghai District. The number of medical emergency stations per 1 km2 was the highest in Heping District and the lowest in Ninghe District. The HRDI with medical emergency stations was the highest in Heping District and the lowest in Wuqing District.al areas . NotablyConsidering demographic and geographical dimensions, we analyzed three aspects of equity in the distribution of EMS resources. The G values of EMS supply by population were 0.132 in Tianjin, thus indicating that the EMS supply by population distribution in Tianjin was relatively fair. The G values of EMS supply by geographical distribution and HRDI in Tianjin were 0.649 and 0.473, respectively, thus indicating that the EMS supply by geographical distribution and HRDI distribution in Tianjin was relatively unfair.The process of EMS utilization in Tianjin was as follows : The calP = 0.000)  was 76% in 2017, while the percentage was maintained at 100% from 2019 to 2021 (= 0.000) . Steps 1P = 0.000).From 2017 to 2021, 1,010,771 patients using EMS were included in this study, and 202,154 patients per year were treated in Tianjin. The EMS demand increased with an annual growth rate of 33.6  . The EMSThe joinpoint analysis indicated that annually from 2017 to 2021, the numbers of EMS patients in sub-urban  and rural areas  increased significantly, while the number of EMS patients in urban areas was stationary . Overall trends for increased EMS patient numbers in most sub-urban and rural areas, including Beichen , Dongli , Xiqing , Jinnan , Wuqing , Ninghe , Baodi , and Jinghai  districts, were observed in detail. The number of EMS patients in other districts remained stable from 2017 to 2021 .P = 0.000). There was a greater demand for EMS among male patients (P = 0.000). An age difference was found among urban, sub-urban, and rural patients using EMS; urban EMS patients were older (P = 0.000)  .In urban areas, most diagnoses were non-specific diagnoses , followed by diagnoses of traumatic injury , cerebrovascular diseases , cardiovascular diseases , and respiratory diseases . In sub-urban areas, most diagnoses were non-specific diagnoses , followed by diagnoses of traumatic injury , cerebrovascular diseases , cardiovascular diseases , and respiratory diseases . Traumatic injury  was the most common diagnosis in rural areas; the next most common were non-specific diagnoses  and diagnoses of cardiovascular diseases , cerebrovascular diseases , and respiratory diseases . Note that 71.418% of patients with genitourinary system diseases in Tianjin were in urban areas; 52.735% of patients with infectious diseases in Tianjin were in sub-urban areas. Compared to patients with other diseases, traumatic injury and chemical–physical damage patients seemed to be more numerous in rural areas .P = 0.000). Spatially, the demand for EMS in Tianjin was high in the middle and low on the sides  and population aged over 60 . EMS demand was not associated with the gross domestic product per capita .Urban areas had the most demand for EMS ; sub-urban areas  and rural areas  had the next highest demand . The matching types of EMS supply and demand were mainly “high supply–high demand” in urban areas  and in sub-urban areas (Beichen and Dongli districts) and “low supply–low demand” in rural areas   . There wEmergency medical services in Tianjin are still developing. EMS resources, including the number of medical emergency stations, ambulances, and human resources, increased after years of reform and development. The number of medical emergency stations was approximately 1 per 60,000 population in Tianjin in 2021; this result agreed with the criterion of the plan that stipulates the standard of 1 per 80,000 population and more than 1 per 140,000 population in Shanghai , 33.Moreover, EMS quality was promoted after healthcare reform based on the data on prehospital emergency calls received within 10 s, the response time, and the fatality rate. The percentage of prehospital emergency calls received within 10 s has become an important quality control indicator for EMS. Since the healthcare reform in 2017, all emergency calls have been answered by the medical emergency center, and the number of call takers has increased. The percentage of prehospital emergency calls received within 10 s has been maintained at 100% since 2019. The response time continued to decrease to 7.863 min in Tianjin in 2021. It has been reported that Shanghai required the average EMS response time to be within 12 min , the medWe found that the EMS demand per 1,000 population was 14.580 each year in Tianjin, which, compared to other places, seems to have a lower demand for EMS. It has been reported that EMS demand per 1,000 population is 23.9 each year in Taiwan and China and 31–48 in America . Our resThe Tianjin Health Commission takes control of the overall planning and distribution of EMS resources at the city level in accordance with the population size of areas and the differences in district characteristics, such as the location, socioeconomic status, population density, age structure of the population, and health-seeking behaviors of patients. From urban areas to rural areas, population density and the level of economic development decrease gradually. The geographical area of the rural areas is larger and farther from the urban areas. To increase response rates, the emergency medical subcenter implemented regional ambulances dispatched in rural areas, which were different from urban and sub-urban areas in Tianjin.Spatially, the EMS supply in Tianjin was the highest in urban areas, followed by sub-urban areas, and the lowest in rural areas. In particular, there were fewer EMS resources in Jinghai, Baodi, and Ninghe Districts. We should focus on strengthening EMS resources in these rural areas. The distribution of EMS resources was relatively fair according to the population and relatively unfair according to the geographical area and HRDI in Tianjin. This finding is consistent with the results of other studies showing that the fairness of health resource supply distribution according to the population was higher than that according to the geographical area in China , 39 mainWe found that EMS demand was the highest in urban areas, followed by sub-urban areas, and the lowest in rural areas; this result is similar to other relevant research results , and EMSTo optimize regionalized plans of EMS resources precisely, we explored differences in EMS demand characteristics. The time trends in the numbers of patients using EMS differed among urban, sub-urban, and rural areas. The EMS demand in urban areas was the highest throughout the study period. The annual growth rate of EMS appears to be higher among rural residents. This result indicated that the gap in EMS demand among urban, sub-urban, and rural areas was gradually narrowing , 40. As Interestingly, we observed that the high supply–high demand types with stationary demand trends were distributed mainly in urban areas; the low supply–high demand types with significant demand growth trends were distributed mainly in sub-urban areas; and the low supply–low demand types with the highest speed of demand growth were distributed mainly in rural areas. Our study comprehensively analyses urban–sub-urban–rural variation in EMS from both the supply and demand sides according to standardized electronic medical records for five consecutive years and uses classic measures and indicators , 24. TheThis study also has several limitations. First, this study did not consider the spillover effects of adjacent units. Dispatching an ambulance follows the principle of proximity. For instance, if the patient with an EMS demand is on the border of one district, the station dispatching the ambulance may be dispatched from a station in another nearby district. Second, considering that doctors and nurses do not work at only one station and rotate at several stations in a subcenter, in turn, we analyzed only the spatial layout and equity of EMS supply according to the number of medical emergency stations. Third, we only described EMS demand from the perspective of utilization. Importantly, utilization is an objective measure of the throughput of a process relative to demand. Thus, we analyzed EMS demand using the data of EMS patients conservatively. Fourth, insights into urban–sub-urban–rural differences in EMS supply and demand from our study may be applicable to Tianjin, China only and might not be transferable to other regions with different population compositions and healthcare infrastructures.Emergency medical services supply quantity and quality were promoted, and the supply met the demand in most districts in Tianjin after years of healthcare reform. The high supply–high demand types with stationary demand trends were distributed mainly in urban areas. The low supply–high demand types with significant demand growth trends were distributed mainly in sub-urban areas. The low supply–low demand types with the highest speed of demand growth was distributed mainly in rural areas. Our results may be a reasonable solution for improved EMS in Tianjin and other megacities in upper-middle-income countries.caochunxia@tju.edu.cn.The datasets presented in this article are not readily available because data and analyses are not publicly available as they were used under license for the current study. Data is however available from the authors upon reasonable request. Requests to access the datasets should be directed to The study protocol was approved by the Ethics Committee of Tianjin University (Project-No. 2021-166). As agreed by the Ethics Committee, this study was performed on anonymized health-related data; therefore, there was no need for written informed consent from individual patients .YL: conceptualization, methodology, and writing—original draft. JL and TL: data curation and data analysis. JG: resources and data curation. XL: visualization and data curation. HF: funding acquisition and supervision. CC: project administration, methodology, and writing—reviewing and editing. All authors contributed to the article and approved the submitted version.