There is evidence suggesting racial disparities in diagnosis and treatment in bipolar disorder (BD) and schizophrenia (SZ). The purpose of this study is to compare psychiatric diagnoses and psychotropic use preceding a first episode of mania (FEM) or psychosis (FEP) in racially diverse patients.Using a comprehensive medical records linkage system , we retrospectively identified individuals diagnosed with BD or SZ and a documented first episode of mania or psychosis. Illness trajectory before FEP/FEM were characterized as the time from first visit for a mental health complaint to incident case. Pathways to care and clinical events preceding FEP/FEM were compared based on subsequent incident case diagnosis (BD or SZ) and self-reported race (White vs. non-White).p < 0.001) with an older age at time of first visit for a mental health complaint . There were no significant differences by race in FEM pathway to care or age of first seeking mental health. Overall non-White patients had lower rates of psychotropic use.A total of 205  incident cases were identified in the REP. Duration of psychiatric antecedents was significantly shorter in non-White patients, compared to White patients (2.2 ± 4.3 vs. 7.4 ± 6.6 years; These data are unable to ascertain reasons for shorter duration of psychiatric antecedents and later age of seeking care, and more broadly first age of initial symptom presentation. If symptoms are confirmed to be earlier than first time seeking care in both groups, it would be important to identify barriers that racial minorities face to access timely psychiatric care and optimize early intervention strategies. The hetIt has long been recognized that race-related factors, including but not limited to barriers to access health care, play a deleterious role in the timely diagnosis at the initial presentation of BD and SZ , 14. FurRecognizing the known racial disparities in access to care for BD and SZ, in this study we sought to retrospectively review pathways to care and longitudinal patterns of mental healthcare utilization, psychiatric diagnoses and psychotropic treatments in White and non-White individuals from 27 counties in Minnesota who progressed to meet diagnostic criteria for BD or SZ.2.2.1.Subjects were identified through the Rochester Epidemiology Project (REP) which is an integrated comprehensive medical record utilized thus far for more than 2000 observational studies of acute and chronic disease incidence and outcomes, including bipolar disorder, in a defined population of Olmsted County, Minnesota and 26 additional surrounding counties. Findings from studies using the REP have shown to be extrapolated to other populations in the United States and globally . This poInclusion criteria for the initial search were (a) patients born after 1985 who (b) diagnosed with bipolar disorder (types I or II) or schizophrenia spectrum disorders, including schizoaffective disorder, (c) between 2000 and 2019 and (d) resided in Olmsted County and surrounding counties on the date of the diagnostic code assignment. The initial search yielded 1,335 subjects who were selected for further manual screening by two psychiatrists (MG and JO-O) for diagnostic confirmation, based on DSM criteria, and for identification of individuals with a recorded first episode of mania or psychosis  in their medical charts. Disagreements in case ascertainment were solved by a panel of three senior psychiatrists . The latter search identified a total of 205  with a first episode recorded and were further analyzed for characterization of the illness trajectory and included for this study, while those without a clearly recorded first episode were excluded from the study. Detailed information about the specifics of the search strategy, including specific diagnostic codes used for BD and SZ, coding systems, case ascertainment, extracted data and study population has been previously published .This study received approval from the institutional review boards (IRBs) of Mayo Clinic and Olmsted Medical Center, who provided a Health Insurance Portability and Accountability Act (HIPAA) waiver, in line with state, federal, and international recommendations. Due to the latter, written informed consent was not required for passive medical record review in the REP .2.2.Within the REP, race and ethnicity are determined by patient self-report, and listed categories are based on the standardized classification of the National Institutes of Health (NIH) to promote uniformity of data on race and ethnicity, including an additional option for patients who refused to provide these data and one for those who self-identified with another or more than one race . CategorThe racial and ethnic composition of the population in the REP is predominantly White but known to be representative of Minnesota and the Upper Midwest and to be similar to the overall composition of the United States’ population . Hence, 2.3.2.3.1.We searched the REP and associated medical records to identify distinct types of early life traumatic experiences  and diagnostic codes of common child and adolescent psychiatric disorders. Assessment of substance use was defined as the utilization of any licit or illicit substance without necessarily constituting a substance use disorder . Exposure to psychotropic medications prior to an incident case was collected through review of clinical notes and prescription registry in the REP, and medications were classified by psychotropic class  and specific drug name.2.3.2.The pathway to care start point was defined as the first encounter with a health care provider on which an International Classification of Disease (ICD) code for a psychiatric diagnosis or complaint was added to the patient’s chart, while the first episode, or endpoint, was defined as the clinical encounter in which the patient was first observed to have symptoms of psychosis or mania and received an associated diagnosis, as determined by a clinician’s assessment. The first contact with REP was defined as the first interaction with a health provider in the Olmsted County area  for any health concern.2.4.χ2) for categorical measures and two-sample t-tests for continuous measures, respectively. We then tested for differences in prodrome duration , age at first medical visit and first visit for a mental health complaint, and age of first psychiatric hospitalization between the same groups using ANOVA (two-sample t-tests) or Kruskal–Wallis non-parametric ANOVA based on normality assumption. Statistical analyses were performed using Jamovi.We first compared sociodemographic and clinical variables, and rates of psychotropic prescriptions between White and non-White individuals with a known diagnosis of BD or SZ using chi-square tests  and 131 with a first episode of psychosis (FEP); both samples were comprised mainly of men . The self-reported racial composition of the FEM group was 75.7% White, 17.6% African/African American/Black, 1.4% of Asian/Asian American, 3% as Other and 1.4% did not specified their racial background, whereas in the FEP group, 61.1% of the participants self-identified as White, 23.7% were of African/African American/Black, 8.4% as Other race, 2.3% of Asian/Asian American, 0.8% Indigenous American and 3.8% that did not specify their race . Of noten = 26) were born outside of the United States . Based on further chart review, within the foreign-born patients, 50% voluntarily immigrated to the U.S. and 26.9% arrived as refugees (forced migration), while no information regarding immigration status was found for the remaining 23.1%. Only four participants with FEM (22.2% of the non-White group) were foreign-born , three of which arrived as refugees and one as voluntary immigrant. For both FEP and FEM, mean age (SD) at arrival to the United States of those with available data (n = 28) was 10.3 (6.5) years. In this line, childhood trauma associated with war and terrorism was significantly more common in non-White individuals with a FEP .Within the FEP group, 51% of the non-White participants (3.2.p < 0.001). This was not observed for FEM. The same trend was observed in autism spectrum disorder before a FEP . No large differences in conduct disorders and oppositional defiant disorder were observed in the two cohorts.p < 0.001; FEM: 38.9% vs. 71.4%; p = 0.01). A similar trend was seen in anxiety disorders in both cohorts .While depressive disorders were very frequent in both FEP and FEM, non-White patients were less frequently diagnosed with depression , hallucinogens , hypnotics  and opioid use . While limited by a lower sample size, In FEM, a similar trend was seen for alcohol use, while the opposite was seen for the rest of the assessed substances, where substance use was more common in non-White individuals; these findings, however, were not significant and limited by a lower sample size.With regards to substance use before a first episode, White FEP patients had a significantly higher prevalence of alcohol . After stratifying by psychotropic groups, differences between racial categories were still statistically significant, particularly in FEP. Antidepressant use before a FEM was significantly more common in White patients ; the same prescription trend was observed in FEP . Antipsychotic use before a FEP was also significantly more common in White individuals  and so were stimulant prescriptions ; no significant differences were observed in antipsychotic and stimulant use before a FEM. Mood stabilizer use before a first episode was uncommon in all groups.Overall, psychotropic prescriptions before a first episode were significantly more common in White patients who developed a FEM or a FEP than in non-White patients . Age at the time of a first episode did not vary between groups in both patients with psychosis and with mania and was consistent with the ages of onset reported in the literature (p < 0.001); no significant differences were observed in the prodrome duration for bipolar patients. Similarly, non-White patients who further developed a FEP had their first visit for a psychiatric complaint (prodrome onset) at a significantly older age than White patients . No significant differences were observed in the age of first psychiatric hospitalization for both cohorts (BD and SZ). However, hospitalization before first episode was uncommon in both cohorts .4.To our knowledge, this is the first study using representative data from a community sample to compare racial differences in pathways to care, conceptualized from clinical events and psychiatric care  preceding a first episode of mania or psychosis. In a U.S. patient database built upon a medical records-linkage system, non-White patients with a known diagnosis of schizophrenia, when compared to White patients, had a significantly shorter duration of the pathways to care, as defined by the time from the first visit for a mental health complaint to the incident case (FEP). This shortened duration appears to be driven, among other factors, by a first mental health-related clinical contact at a significantly older age than White patients. As a potential consequence of this delayed initiation in psychiatric care, particularly in SZ, prodromal phases in non-White patients were characterized by fewer psychiatric diagnoses and lower rates of psychotropic utilization in comparison to White patients. While these some of these differences were not statistically significant in patients with bipolar disorder, the trends were somewhat similar. Furthermore, White patients from both cohorts had their first contact with the health care system in Olmsted County at a significantly earlier age than non-White patients.The present study has several strengths. First, by focusing on the prodromal phases of bipolar disorder and schizophrenia in racially diverse groups specifically, we addressed an important gap in the literature, offering insights into the pathways to care and clinical experiences that precede an incident case of mania or psychosis in patients of racially diverse backgrounds, enabling a better of understanding of the lived experiences and barriers that minoritized individuals face when seeking mental health care. Second, all cases were individually assessed and had the diagnosis and date of first episode manually confirmed by psychiatrist chart review providing higher diagnostic validity and reliability. In this line, the use of REP resources enabled an extensive follow-up from first contact with the local healthcare providers until incident case of mania or psychosis, allowing for a retrospective assessment of a well-defined population-based cohort while addressing the risk of recall bias .Our finding of a significantly shorter duration of the pathways to care in non-White patients with a FEP, rather than corresponding to a race-specific variation of symptom presentation, may suggest that racially diverse patients experience an aversive pathway to care  that leads to a subsequent delay in the first contact with health services for psychiatric complaints. While, at first sight, the lack of variations at age of first episode in both BD or SZ might suggest that the illness onset was not impacted by the delayed initiation of mental health care, further assessment of the symptom severity of the first episode and the clinical setting  where it was diagnosed may provide a more comprehensive and accurate assessment of the impact of delayed care. Restricted access to care, which disproportionately impacts racial and ethnic minorities, inevitably prolongs the duration of untreated illness, which has been associated with worse symptomatic and functional outcomes and subsequent illness trajectories of bipolar disorder and schizophrenia , 32. BarPsychotropic medication use before a first episode was significantly lower in racially diverse patients from both of our study groups. This finding was consistent across all psychotropic categories except mood stabilizers. In particular, antidepressant prescriptions were significantly lower in non-White patients which is particularly relevant considering the high rates of depression preceding an index (hypo)manic episode and the frequency of a depressive index episode (over 50% of the cases) . HoweverWhile our study offers insights into potential health disparities in non-White patients before a first episode of mania or psychosis, this study has several limitations that need to be considered. In merging individuals of other than White racial backgrounds into one large group (non-White patients) there is a risk of overlooking the unique experiences of each racial group. This decision was made in order to address the relatively small sample size of certain racial groups, a consequence of the racial composition of Olmsted County. Because some patients in the different cohorts were not born in Olmsted County, Minnesota and moved in later, this might have altered the age of first contact with the regional health system. The retrospective design of this study entails several risks of bias including selection bias; however, the REP addresses limitations known to administrative registry-based databases, which are frequently passively fed with diagnoses and procedures, by including longitudinal comprehensive medical information from individual medical records . Third, gardearesendez.manuelandres@mayo.edu.The data analyzed in this study is subject to the following licenses/restrictions: datasets are not available in order to protect patient confidentiality. Requests to access these datasets should be directed to The studies involving humans were approved by Mayo Clinic Institutional Review Board, Olmstead Medical Center Institutional Review Board. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements.MG-R, AMi, MAF, and JO-O: writing and original draft preparation. MG-R, JO-O, AMi, MFS, ME, BC, PG, MB, IM, JV, AO, AMc, MAF, and MT-D: critical revision of the article contributing with ideas related to their area of expertise. MG-R, JO-O, and PG: data collection. AMi: statistical analysis. MG-R, AMi, BC, JV, JO-O, MAF, MB, MT-D: analysis and interpretation. MG-R, MAF, and BC: contribution to conceptualization. All authors contributed to the article and approved the submitted version.This study was supported, in part, by the Luther Automotive Foundation and Mayo Foundation; neither had a role in the design, conduct, analysis, or submission of the study. This study was also made possible using the resources of the Rochester Epidemiology Project, which is supported by the National Institute on Aging of the National Institutes of Health under Award Number R01AG034676. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.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 current study aimed to investigate the determinants of high double product (DP) by evaluating the association between resting DP, which is calculated as systolic blood pressure (SBP) multiplied by heart rate (HR), and blood test results and lifestyle factors.This research included 973 participants in the baseline survey of the KOBE study, which included a cohort of urban residents. The possible DP determinants were identified by examining the association between lifestyle factors and laboratory findings and DP by analyzing covariance adjusted for sex and age. Logistic regression analysis was performed with high DP (SBP × HR ≥ 9145 mmHg beats/min or quintile according to sex) as outcome and DP determinants as independent variables.Age, hematocrit, and gamma-glutamyl transferase (log) level were positively associated with a high DP in both men and women. In addition, a high DP was positively associated with Homeostatic Model Assessment for Insulin Resistance score in women alone. Meanwhile, the amount of exercise was negatively associated with a high DP in men alone.High DP values at rest were associated with insulin resistance, gamma-glutamyl transferase, and the amount of exercise in participants without underlying disease.https://doi.org/10.1265/ehpm.23-00002.The online version contains supplementary material available at   Double product (DP) is calculated by multiplying systolic blood pressure (SBP) and heart rate (HR) and is a surrogate marker of myocardial oxygen demand and cardiac work –3. In clSBP and HR are risk factors of CVD –18. And Since many cardiovascular diseases, including heart failure, have been found to be negatively correlated with their prognosis and heart rate , β-blockTherefore, this study examined the association between DP and lifestyle factors and blood test results in healthy individuals. We aimed to identify the determinants of high DP levels and provide useful insights for health guidance.We analyzed data collected from the baseline survey (2010/2011) of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study, an urban cohort research that used daily health as an index. The KOBE study aimed to identify the causes of daily health problems and to obtain lifestyle-related findings that can be used to maintain and prevent poor quality of life. A long-term observational study was conducted using these indicators as endpoints to elucidate factors associated with common diseases and worsening quality of life among the participants of the Kobe study. The baseline study was started in 2010, and follow-up surveys were conducted every 2 years. This study used data from a baseline survey conducted between July 2010 and December 2011. The details have been published in previous studies –27. The The eligibility criteria of the KOBE study were as follows: 1) participants aged 40–74 years during the start of the study, 2) those without a history of cancer or CVD, 3) those not receiving treatment for hypertension, diabetes, or dyslipidemia, and 4) those who were subjectively healthy. During the study, the participants were in a fasting state, and they underwent an interview, physical/physiological examination, and blood/urine tests. During the interview, the participants answered self-administered questionnaires about their lifestyle habits, including medication and medical history and smoking and drinking habits.Of 1117 participants who met the abovementioned criteria, 973 (289 men and 684 women) were included in the study.  after a 5-min rest, and the average was obtained. DP was calculated as the product of the mean SBP and HR.https://www.srl-group.co.jp/english). Fasting blood glucose level (mg/dL) was assessed using the glucose oxidase method, and glycated hemoglobin (HbA1c) levels were evaluated using the latex agglutination test. High-density lipoprotein cholesterol (HDL-C), triglyceride, and creatinine levels were calculated using the enzymatic method, and low-density lipoprotein cholesterol (LDL-C) levels were evaluated using the Friedewald’s equation ). In women, age , HOMA-IR (log) score , γ-GTP level (log) , and hematocrit  were positively associated with a high DP. Furthermore, the logistic regression analysis results with quintile as outcome were similar as in Model A, except that the effect of γ-GTP (log) in women was eliminated  level were positively associated with a high DP in both men and women. HOMA-IR score (log) was positively associated with a high DP in women, and the amount of exercise was negatively associated with a high DP in men.The findings of this study can be explained by previous studies. Hasegawa et al. conducted a cross-sectional study of 2736 Japanese men and women in their 40s and 60s living in central Tokyo. Results showed that sex, SBP, DBP, serum triglyceride and fasting blood glucose levels, and white blood cell count were significantly associated with HR . FurtherA significant positive association between hematocrit and a high DP has also been observed. The participants in this study did not include those with polycythemia vera, and their hematocrit value was within approximately normal limits. Stress polycythemia could have been present due to sympathetic tone , which cFurthermore, in this study, a high DP was associated with γ-GTP levels in both men and women. γ-GTP level is correlated with drinking , which iHOMA-IR score, similar to HR determinants, was mainly the determinant of DP proposed in our study, and factors in previous studies were extracted. Age and γ-GTP, which are the determinants of high DP values, similar to SBP determinants, were identified. DP is a product of SBP and HR, and the determinants could involve known factors from both. However, this study aimed to validate whether DP is similar to the determinant of SBP and HR, or which determinant is similar. A high DP includes cases of a normal SBP but a high HR. Currently, the predictive power of HR is not as strong as SBP. Hence, the use of DP in physical examination can detect the risk of SBP being overlooked because it is normal.Further data found no significant association between exercise habits and DP. In addition, there was no significant association between walking time and DP in both men and women. Therefore, it is difficult to assess physical activity by walking time alone. Several reports have shown that aerobic exercise above certain levels decreases SBP and HR –48. HoweThis study had several limitations. First, it was cross-sectional in nature. Thus, causal relationships cannot be evaluated. Initially, the association between each exposure coefficient and DP must be actively assessed. When interpreting the study results, it is always necessary to cautiously determine whether a causal relationship exists. Second, the participants were health conscious and had a high amount of regular exercise and low BMI. Hence, caution should be taken when examining the external validity of the study results. However, it is important to identify the determinants of DP among healthy participants in terms of early primary prevention in the community. In addition, the inclusion of a large number of women could have caused selection bias. Third, the KOBE study examined daily walking time and habitual physical activity only. Therefore, the overall amount of physical activity throughout daily life was not evaluated. In the future, it will be necessary to assess the total amount of physical activity in daily life in addition to exercise habits and to examine the association between DP and exercise intensity. Further, a longitudinal study should be performed to examine the association between DP and CVD outcomes.Calculating DP is very simple and requires no additional cost. From a hygienic and public health point of view, DP is expected to become a simple valuable evaluation item for the health status of the general population. Based on this study, glucose intolerance, alcohol consumption and low physical activity were considered to be valuable health determinants when we were focusing on DP and/or heart rate. Furthermore, recent studies indicated that forest bathing attenuated sympathetic nerve activity, and decrease blood pressure and heart rate –50; thusDP takes into account the predictive power of HR for CVD and mortality and has the potential to detect future risks that may be missed by SBP alone. In this study, in a healthy Japanese population, high DP was positively associated with age, hematocrit, and γ-GTP in both men and women. Furthermore, it was associated with higher HOMA-IR in women and a lower amount of exercise in men. This study suggests that DP may be improved by decreasing insulin resistance and γ-GTP levels, i.e., avoiding excessive alcohol drinking, and increasing the amount of exercise.


Stenotrophomonas maltophilia is a little-known environmental opportunistic bacterium that can cause broad-spectrum infections. Despite the importance of this bacterium as an emerging drug-resistant opportunistic pathogen, a comprehensive analysis of its prevalence and resistance to antibiotics has not yet been conducted.A systematic search was performed using four electronic databases  up to October 2019. Out of 6,770 records, 179 were documented in the current meta-analysis according to our inclusion and exclusion criteria, and 95 studies were enrolled in the meta-analysis.S. maltophilia was 5.3 % , with a higher prevalence in the Western Pacific Region  and a lower prevalence in the American regions . Based on our meta-analysis, the highest antibiotic resistance rate was against cefuroxime , while the lowest resistance was correlated with minocycline .Present analysis revealed that the global pooled prevalence of S. maltophilia infections has been increasing over time. A comparison of the antibiotic resistance of S. maltophilia before and after 2010 suggested there was an increasing trend in the resistance to some antibiotics, such as tigecycline and ticarcillin-clavulanic acid. However, trimethoprim-sulfamethoxazole is still considered an effective antibiotic for treating S. maltophilia infections.The results of this study indicated that the prevalence of  Stenotrophomonas maltophilia is an environmental Gram-negative bacillus that has been the subject of extensive research over the last two decades due to its status as the only known species of Stenotrophomonas to cause opportunistic infections in humans   , 4. The it (ICU) .S. maltophilia to several classes of antibiotics, there are restricted therapeutic choices for its infections. This bacterium can resist the β-lactam antibiotics (most notably carbapenems) by producing ß-lactamase enzymes, including L1 and L2. It also disrupts the action of aminoglycosides by hydrolyzing enzymes such as acetyl-transferases or modifying the structure of lipopolysaccharide. In addition, low membrane permeability and the overproduction of efflux pumps are other mechanisms that render S. maltophilia resistant to a broad range of antibiotics  has approved a guideline document with recommendations for treating fections . Trimethfections . Other dic areas , 12.S. maltophilia and its resistance to commonly used antibiotics. We conducted this systematic review of global human infections due to S. maltophilia over the last 31 years.The main objective of this study was to assess the global prevalence of Stenotrophomonas maltophilia” OR “Xanthomonas maltophilia” AND “antibiotic resistance” AND “minimum inhibitory concentration” AND “disk agar diffusion” AND “multilocus sequence typing” AND “E-test” AND “antimicrobial resistance gene”. The databases were searched up to 20 October 2019 without any start time limitation.Four electronic databases, including MEDLINE (via PubMed), Embase, Web of Science, and Scopus, were systematically searched using different combinations of the following keywords: “The study was carried out based on the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . Two disS. maltophilia isolation among diverse patients in combination with the antibiotic resistance rates of the isolates to various antibiotics, or reported only the antibiotic resistance rates of the isolates. Only articles about the clinical isolates of S. maltophilia were enrolled, and studies on the environmental isolates were not considered.Articles were included if they reported the prevalence of S. maltophilia or tested a total isolate <10 were not assessed. Articles that reported antibiotic resistance as MIC 90 or those that evaluated the combinatorial effects of antibiotics were not enrolled. Studies that considered S. maltophilia a Gram-negative bacterium and reported a total antibiotic resistance rate in Gram-negative bacteria were excluded. Articles were removed if they tested only the resistant isolates or reported only the prevalence of S. maltophilia infection.Conference papers were not evaluated as they did not provide sufficient information for quality assessment. Dissertations and theses were excluded. Articles with unrelated topics, duplicates or overlapping studies, reviews, meta-analyses or systematic reviews, case reports, brief reports, notes, editorials, correspondence, short communications, and letters to the editors were not included. Studies with languages other than English or with unavailable full text were dismissed. Studies that evaluated species other than Two independent researchers read the included articles in full text and extracted the following details: first author's name, year of study, year of publication, location of the study (country and region), sample size , type of samples, antibiotic susceptibility testing methods used , the antibiotic resistance rate of isolates against various antibiotics, frequency of resistance genes, and frequency of different sequence types. Any discrepancy between the two reviewers was settled by consensus.Two reviewers separately evaluated the quality of the included studies using the Joanna Briggs Institute (JBI) critical appraisal checklist for studies reporting prevalence data . This scI2 statistics. An I2 between 0 and 25% suggests low heterogeneity, 25–50% indicates moderate heterogeneity, 50–75% represents substantial heterogeneity, and 75–100% shows considerable heterogeneity. Subgroup meta-analysis was employed to compare the prevalence of S. maltophilia based on WHO-defined regions and 5-year time intervals. In addition, the antibiotic resistance rates of isolates were compared based on world regions and whether they were reported before or after 2010. To assess the potential risk of publication bias, Begg's rank correlation and Egger's weighted regression methods in combination with a funnel plot were used   software version 2.0 . A random-effect model was used for meta-analysis and to pool the estimations. The prevalence of the investigated phenomenon was presented as a forest plot diagram, which shows the estimated prevalence and its relevant 95% confidence interval (CI). Heterogeneity between studies was reported by on bias) .n = 1,245), repetitive articles (n = 470), reviews (n = 234), systematic reviews (n = 3), case reports (n = 64), letters to the editors (n = 60), conference abstracts (n = 111), editorials (n = 9), short surveys (n = 10), correspondence (n = 2), notes (n = 12), reports (n = 3), a book (n = 1), articles with a total sample of <10 strains (n = 17), non-English studies (n = 47), and articles that studied environmental samples (n = 21). In addition, 30 articles were removed because their full texts were not available. The eligibility of 817 full-text articles was assessed and, ultimately, 179 studies met the inclusion criteria and were enrolled in the qualitative analysis. Of these, 95 studies reporting the prevalence of S. maltophilia infection were selected for quantitative analysis . The characteristics of the 179 included studies are summarized in A total of 6,770 records were identified through searches of the four aforementioned electronic databases . After rn = 57, 32%), followed by the West-Pacific Region , the Region of the Americas , the Eastern Mediterranean Region , and the South-East Asian Region . There was no independent study from the African Region. Twenty-four studies (13%) were conducted across different continents and were, therefore, classified as multiple region studies and did not conform to the WHO categories  regions, most studies were from the European Region . The most frequent sources of S. maltophilia isolation were respiratory samples  and blood   . The qua23, 24%) .S. maltophilia infection was estimated to be 5.3 %  (P > 0.05). However, Begg's test showed evidence of publication bias in the 95 analyzed studies (P = 0.017). Additionally, the corresponding funnel plot indicated publication bias  among the selected studies  revealed that the prevalence rate of 2015 See   showed an overall increasing trend. In the Western Pacific Region, the prevalence rate of S. maltophilia decreased from 2006 to 2010; however, the prevalence rates in the European Region and the Regions of America increased after this time interval , E-test, and automated methods . Broth micro-dilution was the most frequently used assay. The standards used for interpreting the results of susceptibility assays varied, with different breakpoints used, such as those of the Clinical and Laboratory Standards Institute (CLSI), National Committee for Clinical Laboratory Standards (NCCLS), European Committee on Antimicrobial Susceptibility Testing (EUCAST), U.S. Food and Drug Administration (FDA), British Society for Antimicrobial Chemotherapy (BSAC), TRUST, and Comité de l'Antibiogramme de la Société Française de Microbiologie (CA-SFM) (The susceptibility of (CA-SFM) .S. maltophilia isolates were to cefuroxime , cefoxitin , ampicillin , imipenem , and meropenem , while the lowest resistance rates were to doxycycline  and minocycline .As shown in S. maltophilia before and after 2010 , while in a similar investigation . The differences between the inclusion and exclusion criteria applied in these two studies may explain the differing results. In the current study, the global prevalence rate of S. maltophilia isolation from clinical samples was 5.3%, and according to the WHO classification, the highest prevalence rate of S. maltophilia isolation was observed in the Western Pacific Region (10.5%), followed by the European Region (7.9%), which may be due to their long-shared land border. Among the reasons for the discrepancies in the prevalence of Stenotrophomonas maltophilia infection in different world regions, we can mention the following: disparate health policies in each country affect the importance of pathogens, so, in some countries, Stenotrophomonas maltophilia is still considered an unimportant opportunistic pathogen, so few studies have been reported. For example, most of the cases were documented in European , followed by blood samples (24%). This finding is consistent with other studies, in which fections , 197. Hosolation . In a lacreasing , 198. Thcreasing , 200. Fopathogen , 201. Mopathogen .S. maltophilia infections is challenging due to the difficulty of differentiating colonization from infection and the intrinsic resistance of this bacterium to multiple classes of antibiotics. The WHO has classified S. maltophilia as one of the leading multidrug-resistant organisms in hospital settings  evaluated a specific number of ples see  is relatates see , so we cS. maltophilia, compared with other Gram-negative species, this bacterium is remarkably understudied. Thus, collecting and analyzing data related to different aspects of S. maltophilia may assist in improving the clinical management of challenges caused by this bacterium. This meta-analysis presents the global antibiotic resistance of S. maltophilia over the last 31 years and demonstrates different rates of resistance in world geographical regions, as well as the growing trend of resistance to most antibiotics. The variations in antibiotic resistance of S. maltophilia isolates in different regions may be the result of the use of different protocols for patient treatment. Additionally, the improper and experimental use of antibiotics plays an important role in increasing resistance, leading to an increased risk of treatment failure. To address this issue, it is necessary to carry out antibiotic sensitivity tests before prescribing antibiotics and implementing an antimicrobial stewardship program for every hospital, as well as provide continuous training for clinicians about their performance in the hospital environment. Finally, collecting and preparing local sensitivity patterns will be effective in allowing the selection of the optimal empiric treatment for S. maltophilia infections.In conclusion, despite the undeniable clinical impact of MB contributed to the study design, data extraction, data analysis, design and production of figures, and wrote and revised the final manuscript. AS-M contributed to the study design, data extraction, data analysis, and writing of the manuscript. GB contributed to the data analysis and statistical analysis, designed and produced figures, and writing of the manuscript. EE contributed to the study design, data extraction, and writing of the manuscript. LJ contributed to the study design and the writing and revision of the final manuscript. RB contributed to the study design, data analysis and interpretation, and the writing of the manuscript. ME designed the study, oversaw the analysis, and wrote and revised the final manuscript. FJ designed the study, was the arbiter for the study searches and data extraction, and wrote and revised the final manuscript. All authors contributed to the article and approved the submitted version.


Amblyomma sculptum is a relevant tick species from a One Health perspective, playing an important role as a vector of Rickettsia rickettsii, the main agent of spotted fever rickettsiosis in Brazil. In this study, we evaluated the susceptibility of two A. sculptum populations from Goiás state (midwestern Brazil) to different acaricides. The first tick population (GYN strain) originated from an experimental farm, where the ticks are annually exposed to acaricides. The second (PNE strain) was collected in a national park , where the ticks had not been exposed to acaricides. Immersion tests were conducted with 21-day-old laboratory-reared larvae and nymphs originating from adult ticks collected in the areas mentioned above. The chosen acaricides were two synthetic pyrethroids (cypermethrin and deltamethrin), one organophosphate (chlorfenvinphos), one formamidine (amitraz), and two combinations of pyrethroids and organophosphates . Mortality data were used to determine the lethal concentration (LC) values at which 50%, 90%, and 99% of the ticks died , and resistance ratios (RR) were calculated based on the LC values. The RR revealed differences between the acaricide-exposed (GYN) and unexposed (PNE) tick strains. The PNE strain larvae and nymphs were susceptible to all the tested acaricides. The GYN strain larvae were tolerant to cypermethrin, whereas the nymphs were tolerant to deltamethrin, chlorfenvinphos, and the combination of cypermethrin, chlorpyrifos, and citronellal (2 < RR ≤ 10). The GYN strain nymphs were resistant to amitraz (RR > 10). This is the first report of A. sculptum nymphs with resistance to amitraz and tolerance to deltamethrin, chlorfenvinphos, and the combination of cypermethrin, chlorpyrifos, and citronellal. Amblyomma sculptum is a three-host ixodid tick, whose preferred hosts are horses , capybaras (Hydrochoerus hydrochaeris), and tapirs (Tapirus terrestris) [A. sculptum ticks are generalists, parasitizing wild and domestic animals, as well as humans. Amblyomma sculptum is present in different South American countries, such as Argentina, Bolivia, Brazil, and Paraguay [Amblyomma sculptum, which is a member of the Amblyomma cajennense complex, is the principal vector of Rickettsia rickettsii, the main agent of spotted fever rickettsiosis in Brazil [restris) ,2,3,4. HParaguay ,6. Thesen Brazil ,8, and cn Brazil . TherefoA. sculptum are more susceptible to acaracides than adults are [A. sculptum in Brazil is the application of synthetic acaricides among horses between April and October [Studies have shown that larvae and nymphs of ults are ,11. Thus October ,11, when October . The mos October .Rhipicephalus microplus (cattle ticks) and Rhipicephalus sanguineus sensu lato (brown dog ticks) [A. sculptum, are limited. A recent study reported resistance to amidines and cypermethrin (synthetic pyrethroid) in the different life stages of Amblyomma mixtum, which also belongs to the A. cajennense complex [A. sculptum adults [A. sculptum populations from Goiás. We were interested in comparing the susceptibility of two strains, one from a national park (with no previous exposure to acaricides) and another from an experimental farm (with previous exposure to acaricides).The indiscriminate use of acaricides is a long-standing problem in tick control worldwide, with several reports of acaricide resistance in important tick species, such as g ticks) ,14,15. U complex . In 2011m adults . In thisThe Ethics Committee on Animal Use of the Federal University of Goiás (CEUA/UFG) approved this study (protocol number 071/22), which was conducted in accordance with the ethical principles of animal experimentation. The Chico Mendes Institute for Biodiversity (ICMBio Permit No. 70143-2) authorized the collection of ticks in Emas National Park.A. sculptum ticks are known to be present: Emas National Park (PNE) and the experimental farm of the School of Veterinary and Animal Science of the Federal University of Goiás (EVZ/UFG).The study was carried out in Goiás state, whose climate is tropical, with two well-defined seasons; i.e., dry (May–September) and rainy seasons (October–April). Most of the state’s territory is situated within the Cerrado biome, the most diverse tropical savanna on Earth. The ticks were collected between October 2021 and October 2022 in two areas  where A.R. microplus, A. sculptum is commonly found on dairy cattle due to their close contact with capybaras. Dairy cattle and capybaras share a pasture during the night, and a high level of environmental infestation by Amblyomma ticks has been previously detected in this area using the dragging method [The PNE  is a national park and an environmentally preserved area of the Cerrado biome. The park covers an area of approximately 132,000 ha, distributed across the municipalities of Mineiros, Chapadão do Céu, and part of Costa Rica (Mato Grosso do Sul), but the ticks were collected in Mineiros. Domestic animals are absent, and there is no history of acaricide treatment in this area. For this study, the ticks collected in the PNE (namely PNE strain) were considered to be the susceptible strain in the immersion tests for a statistical comparison with the ticks collected in the experimental farm . This experimental farm  is in the municipality of Goiânia  (421.36 km from PNE) and consists of an area where chemical acaricides are often used on dairy cattle ,19. In ag method .A. sculptum adults were collected in PNE and the experimental farm, respectively.Tick collections were conducted using the dragging method . DragginOryctolagus cuniculus), one for each tick strain used in this study. The rabbits were kept in suitable cages under controlled environmental conditions (temperature of 20 °C) with water and food ad libitum. All tick infestations were conducted inside cotton sleeves glued to the rabbits’ shaved dorsum, as previously described [Cavia porcellus), following the same procedures as for rabbits.The adult ticks fed on rabbits  and amitraz were also included. Although they are not specifically indicated for horses, their inclusion was justified by the direct coexistence between capybaras and cattle in the experimental farm, where exposure to these acaricides occurs [R. microplus on dairy cattle in the experimental farm [Synthetic pyrethroids (deltamethrin and cypermethrin) and organophosphates (chlorfenvinphos) were chosen because they are commonly used for controlling s occurs ,18,19. Ital farm ,26. The tal farm .Commercial products  were dirThe lethal concentration (LC) values for commercial products containing a single active ingredient were calculated based on the concentrations in parts per million (ppm). However, for acaricide combinations, the LC values were calculated using percentages of commercial acaricide. An initial concentration of 100% as indicated on the package leaflet was considered the reference point for these calculations .2 stimulus (by blowing on them) were considered dead. Mortality was calculated according to the formula: mortality (%) = dead larvae × 100/total larvae.LITs were performed according to the methodology described by Sabatini et al. . Two indNITs were conducted as LITs were , with so50, LC90, and LC99, respectively) were determined using Probit analysis based on the mortality data obtained from LITs and NITs. Ninety-five confidence intervals (95% CI), chi-square (X2) and slope values were also calculated using RStudio software, version 4.3.1. For comparison between the GYN and PNE strains, resistance ratios (RR) were calculated using the LC values of the susceptible strain . The ticks were categorized as susceptible (RR ≤ 2), tolerant (2 < RR ≤ 10), or resistant (RR > 10) based on the classification system established by Kaplan et al. [50, RR90, and RR99). Additionally, overlapping confidence intervals between the strains were considered as statistically non-significant [The LC values at which 50%, 90% and 99% of the ticks died  were lower than those for the GYN strain (previously exposed to acaricides), with a few exceptions see . The PNEA. sculptum GYN strain was collected [R. microplus on cattle may have resulted in the selection of a tolerant A. sculptum population. This is certainly a hypothesis that deserves further investigation.The nymphs showed a tolerance to the combination of chlorpyrifos + cypermethrin + citronellal (RR > 2), which could possibly be explained by their tolerance to the individual classes of pyrethroids and organophosphates. Although these combinations are not licensed for use on horses according to the package insert, they have been used on dairy cattle in the experimental farm where the ollected ,19,25,26R. microplus is a one-host tick, and therefore, it remains in contact with the treated animals for longer as compared to A. sculptum, which is a three-host tick [R. microplus completes up to five or six generations per year [In this regard, the higher frequency of acaricide resistance in cattle ticks as compared to that of horse ticks could be related to different factors, including the much higher frequency of acaricide application on cattle than that on horses . Moreoveost tick . Finallyper year , which mOverall, higher acaricide concentrations were necessary to kill the nymphs as compared to the larvae in the present study. For example, a six times lower concentration of deltamethrin was sufficient to achieve 99% mortality in the larvae as compared to that of the nymphs. This natural resistance mechanism across different tick stages has been reported in a previous study, in which fed and unfed ticks were also compared . The stuA. sculptum nymphs. The LC50 and LC90 of amitraz for the GYN strain (resistant) were 56.2 and 20 times greater, respectively, than those of the PNE strain (susceptible). In the only previous study assessing the susceptibility of A. sculptum to amitraz [Amitraz is not recommended for horses due to its toxicity, which can lead to colic and even death . The exp amitraz , the autA. sculptum, which are predominantly maintained by wildlife, but can also infest domestic animals and humans, are of great significance from a One Health perspective. Wild animals such as capybaras are coming into closer contact with humans due to the impact of anthropic actions on natural environments, and scenarios like the one described in this study, where capybaras and cattle share pastures, are becoming increasingly common [R. microplus) in areas where other relevant tick species  are present.Ticks, such as y common . This coy common . In a siA. sculptum, further research is advocated to investigate whether other A. sculptum populations in Brazil are resistant to these acaricides and to ascertain the possible mechanisms underlying acaricide resistance in this tick species. In this perspective, it would be important to develop molecular methods for large-scale acaricide resistance surveillance in this tick species. This could include, for instance, PCR assays to detect single-nucleotide polymorphisms (SNPs) at target sites, such as the voltage-gated sodium channel for pyrethroids.Considering the medico-veterinary significance of A. sculptum nymphs from the experimental farm  were resistant to amitraz and tolerant to deltamethrin, chlorfenvinphos, and to a combination of chlorpyrifos + cypermethrin + citronellal. The larvae were tolerant to cypermethrin. On the other hand, the larvae and nymphs originating from a preservation area (no previous contact with acaricides) were susceptible to all the acaricides tested.We conclude that


Capsule endoscopy (CE) is a minimally invasive examination for evaluating the gastrointestinal tract. However, its diagnostic yield for detecting gastric lesions is suboptimal. Convolutional neural networks (CNNs) are artificial intelligence models with great performance for image analysis. Nonetheless, their role in gastric evaluation by wireless CE (WCE) has not been explored.Our group developed a CNN-based algorithm for the automatic classification of pleomorphic gastric lesions, including vascular lesions , protruding lesions, ulcers, and erosions. A total of 12,918 gastric images from 3 different CE devices  were used from the construction of the CNN: 1,407 from protruding lesions; 994 from ulcers and erosions; 822 from vascular lesions; and 2,851 from hematic residues and the remaining images from normal mucosa. The images were divided into a training  and validation data set. The model's output was compared with a consensus classification by 2 WCE-experienced gastroenterologists. The network's performance was evaluated by its sensitivity, specificity, accuracy, positive predictive value and negative predictive value, and area under the precision-recall curve.The trained CNN had a 97.4% sensitivity; 95.9% specificity; and positive predictive value and negative predictive value of 95.0% and 97.8%, respectively, for gastric lesions, with 96.6% overall accuracy. The CNN had an image processing time of 115 images per second.Our group developed, for the first time, a CNN capable of automatically detecting pleomorphic gastric lesions in both small bowel and colon CE devices. The detection and treatment of multiple gastric lesions is of uttermost importance. Conventional esophagogastroduodenoscopy (EGD) is the current standard of care for gastric evaluation, either in a screening setting or in patients with upper gastrointestinal (GI) symptoms, given its ease in identifying and treating gastric lesions. However, upper endoscopy is an invasive examination, with a non-neglectable risk of perforation, bleeding, infection, or even cardiopulmonary adverse events . FurtherCapsule endoscopy (CE) is a minimally invasive examination that allows the entire visualization of the GI tract , with eaThe large number of image frames presented by CE devices favors the development of artificial intelligence (AI) tools for image analysis. Convolutional neural networks (CNNs) are a multilayer AI architecture with high performance levels for image analysis, inspired in the neural architecture of the human visual cortex, making it suitable for detection of imaging patterns . RecentlThis multicentric multidevice study was based on gastric images obtained from 3 different types of CE devices  in 2 different centers , comprising 5,846 CE examinations in 4,372 patients.This project was developed in a noninterventional fashion . This study was performed following the Declaration of Helsinki and with approval from the ethics committee of São João University Hospital/Faculty of Medicine of the University of Porto (No. CE 407/2020). Information potentially associated with the identification of the patients was omitted, and effective data anonymization for researchers involved in CNN development was assured by random number assignment for each patient. A legal team with Data Protection Officer Certification (Maastricht University) ensured the nontraceability of data and conformity with the general data protection regulation.CE procedures were conducted using 3 different CE devices: the PillCam SB3 system , the PillCam Crohn's (Medtronic), and the OMOM HD . Images from PillCam SB3 and PillCam Crohn's CE were reviewed using PillCam software version 9 (Medtronic), whereas images from the OMOM HD device were reviewed using the Vue Smart software (Jinshan Science & Technology). Possible patient-identifying information  was removed by image processing. After that, each extracted frame was stored and labeled with a consecutive number.Each patient was asked to undergo bowel preparation in line with previous recommendations by the European Society of Gastrointestinal Endoscopy . In summThe gastric segment video was reviewed for identification of multiple gastric lesions. This included the first gastric image distal to the esophagogastric junction until the last image before the appearance of the duodenal mucosa. The whole group of gastric lesions included vascular lesions , protruding lesions, ulcers, and erosions. The definitions of the different lesions were adapted from classification scores used in small bowel CE (SBCE) . RegardiClassification of the extracted images was performed by 3 gastroenterologists with CE expertise , each having read over 1,000 CE examinations before this study. The inclusion of a specific image implied the concordance of classification between at least 2 experts.After evaluating all the examinations, 12,918 selected gastric images from 107 CE examinations were inserted into a CNN model with transfer learning. The full image data set had 1,407 images of protruding lesions; 994 from ulcers and erosions; 822 from vascular lesions; and 2,851 from hematic residues, with the remaining images being from normal mucosa.The selected images were divided into 2 different data sets, one training data set , which was divided into 3 independent subsets, and an independent validation data set . On division, all images from a given patient were allocated to the same data set (patient-split design). The validation data set was used to evaluate the performance of the CNN model. The study design is summarized with a flowchart presented in Figure When creating the CNN, the Xception model with its weights trained on ImageNet was used. To transfer this learning to our data, the convolutional layers of the model were kept. We removed the last fully connected layers and attached fully connected layers based on the number of classes used to classify our endoscopic images.Our group used 2 blocks, each having a fully connected layer, followed by a dropout layer of 0.25 drop rate. After these 2 blocks, a dense layer with a size defined as the number of categories to classify was added. A learning rate of 0.0001, batch size of 128, and 20 epochs were set by trial and error. We used TensorFlow 2.3 and Keras libraries to prepare the data and run the model. The analyses were performed with a computer equipped with an Intel Xeon Gold 6130 processor  and a NVIDIA Quadro RTX 4000 graphic processing unit .For each image, the CNN model calculated the probability for each category , with a given probability Figure . A higheAt the first experiment, a 3-fold cross-validation was performed, with the division of the development data set into 3 even-sized image subsets. The primary performance measures included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. These measures were represented with their means and 95% confidence intervals. The precision-recall (PR) curve and area under the precision-recall curve were used to measure the performance of the model.The performance results from the 3-fold subsets were used to identify the better parameters of the CNN. These parameters were then applied in the validation data set, which was evaluated afterward.Statistical analysis was performed using Sci-Kit learn version 0.22.2 .From a total of 5,846 CE examinations, our group developed a CNN-based model with 12,918 gastric images. Each image was evaluated by the CNN, which predicted a classification, subsequently compared with the experts' labelling. The repeated data inputs in the subset folds of the training data set allowed the adjustment of the CNN parameters. Subsequently, the fine-tuned CNN performance was evaluated in the validation data set.For the first analysis, a 3-fold cross-validation of the training data set was performed. The performance results of the 3-folds of the training model are presented in Table In the second analysis, the remaining 10% of the retrieved images were used as a validation data set for evaluation of the CNN's performance. The confusion matrix between the trained CNN and experts' classification is presented in Table The CNN's image processing time of the validation data set was 115 images per second (8.7 milliseconds per frame), with a total viewing time of 14.2 seconds.In this proof-of-concept study, our group developed a WCE-based CNN capable of detecting multiple gastric lesions in both SBCE and CCE devices. This model demonstrated high performance levels in all the evaluated parameters, with 97.4% sensitivity, 95.9% specificity, and 96.6% global accuracy for pleomorphic gastric lesions. These results were achieved with an image processing time of 115 images per second. Furthermore, the diagnostic yield of the model was verified not only in SBCE devices but also in CCE, with 3 different types of CE devices. Thereby, our group reckons that the development of AI-powered WCE might change the landscape regarding the classification of pleomorphic gastric lesions .Furthermore, it is important to consider some methodology points about this study. The division between training and validation data sets was based on a patient-split design. Thus, all the given images from a single patient were included in the same data set. In the development of a CNN model, the inclusion of similar images in both data sets could imply an overfitting of the model (because the model would recognize a very similar image present in the training data set). Therefore, we believe that the risk of the model's overfitting was reduced. Moreover, a 3-fold cross-validation was performed. The data set was divided into 3 equal-sized, nonoverlapping folds, with images from a single examination allocated exclusively to one-fold. The average of these metrics across all iterations was used as an aggregate measure of the model's performance. This aggregated performance measure provides a more reliable assessment of the model's ability to classify new, unseen images, increasing confidence in the model's generalizability. In addition, our group used PR curves instead of receiver-operating characteristic (ROC) curves for the model evaluation. In cases of data imbalance in a certain variable, ROC curves are known for being excessively optimistic in the evaluation of a model/biomarker performance , with PRThe interoperability challenge is one of the main points of interest in the implementation of AI-based technologies in medicine , with thRecently, the concept of WCE-based panendoscopy has been the focus of numerous studies . HoweverNonetheless, there are intrinsic limitations of the WCE to be considered. WCE is performed without air insufflation and stomach cavity distention, and the devices' movement depends only on abdominal peristalsis. This results in a significant reduction in stomach surface visualization, mainly the more proximal part and the fundus. The evaluation of gastric lesions by CE has regained a renewed interest with the development of magnetic controlled CE (MCE), a subtype of CE with good performance in evaluating gastric lesions, even in asymptomatic individuals ,28. Xia Our group developed the first CNN model for gastric lesion evaluation by SBCE and CCE with high sensitivity, specificity, accuracy, and image processing capacity. However, despite the promising results of our model, this is only a proof-of-concept study and the first step to the application of this model to a real clinical scenario.Nonetheless, our study has several limitations. First, this study was conducted in a retrospective manner. Therefore, in the future, larger prospective multicentric studies are needed for assessment of the clinical utility of this tool. Furthermore, our results were based on still images, requiring studies with real-time WCE videos in the future.In conclusion, the use of CNN models in clinical practice can become the standard of care in only a few years. In the gastroenterology field, optimization of WCE examinations with CNN-based technologies has been evolving recently, but the role of these systems for detection of gastric lesions in conventional WCE has not been explored yet.Our CNN system was the first, to our knowledge, to detect gastric lesions with high accuracy and sensitivity, with excellent imaging processing times in SBCE and CCE devices. The application of these systems in clinical practice will favor the cost-effectiveness of WCE in a panendoscopy evaluation, with an associated standardization of the classification and reduction of the reading time of the examination. Larger multicentric prospective real-time studies are needed to confirm this proof-of-concept study.Guarantor of the article: Miguel Mascarenhas Saraiva, MD, PhD.Specific author contributions: M.M. and F.M.: equal contribution in study design, image extraction, drafting of the manuscript, and critical revision of the manuscript. T.R. and J.A.: bibliographic review, image extraction, and critical revision of the manuscript. P.C. and M.M.: bibliographic review, drafting of the manuscript, and critical revision of the manuscript. J.F.: construction and development of the CNN, statistical analysis, and critical revision of the manuscript. P.A., H.C., M.M.S., and G.M.: study design and critical revision of the manuscript. All authors approved the final version of the manuscript.Financial support: The authors recognize NVIDIA support for the graphic unit acquisition.Potential competing interests: None to report.✓ Capsule endoscopy (CE) is a minimally invasive examination for evaluating the entire gastrointestinal tract.✓ The diagnostic yield of CE for gastric lesions is suboptimal.✓ Our group developed a convolutional neural network-based model for the classification of pleomorphic gastric lesions.✓ The model’s diagnostic yield was verified in both small bowel and colon CE devices.✓ Artificial intelligence algorithms could increase the diagnostic yield of capsule panendoscopy.


Globally, 1.3 billion people were considered food insecure as of 2022. In the Caribbean region, the prevalence of moderate or severe food insecurity was 71.3% as of 2020, the highest of all subregions in Latin America. Experienced based measurement scales, like the Latin American and Caribbean Food Security Scale, are efficient measurement tools of food insecurity used globally. The Eastern Caribbean Health Outcomes Research Network (ECHORN) Cohort Study is a population-based longitudinal cohort study in the two Caribbean U.S. territories of Puerto Rico and the U.S. Virgin Islands, as well as in Barbados and Trinidad & Tobago. The purpose of this research was to examine the demographic, psychosocial, behavioral, and environmental risk factors associated with household food insecurity (HFI) among adults ≥40 years of age in the ECHORN cohort.A cross-sectional analysis of baseline ECHORN cohort study data was conducted. The primary outcome was household food insecurity . A total of 16 known and potential risk factors were examined for their association with HFI. The ANOVA and chi-square statistics were used in bivariate analysis. Ordinal logistic regression was used for the multivariable and sex stratified analyses.More than one-quarter of the sample (27.3%) experienced HFI. In bivariate analyses, all risk factors examined except for sex, were significantly associated with HFI status. In the multivariable analysis, all variables except sex, education, marital status, smoking status, and residing in Puerto Rico were significant predictors of HFI in the adjusted model. In sex stratified analysis, depression, food availability, self-rated physical health, and island site were significantly associated with increased odds of worsening HFI for women, but not for men. Source of potable water was an important risk factor for both men and women.The prevalence of HFI in the ECHORN cohort study is comparable to other studies conducted in the region. While women did not have an increased risk of HFI compared to men, a different set of risk factors affected their vulnerability to HFI. More research is needed to understand how water and food security are interrelated in the ECHORN cohort. GloballIn the Caribbean region, the prevalence of moderate or severe food insecurity was 71.3 percent in 2020, the highest of all subregions in Latin America when measured using the Food Insecurity Experience Scale . In thisHousehold food insecurity must be considered in the context of water security . There iExisting cross-sectional and prospective epidemiologic studies that have examined risk factors for food insecurity are primarily focused on the United States or other high resource settings. In the U.S. these risk factors include having a lower level of education, never being married or being divorced/separated, being young, renting, or being African American or Hispanic , 34. Few2The ECHORN study protocol was reviewed and approved by the Institutional Review Boards at Yale University, the University of Puerto Rico Medical Sciences Campus, the University of the Virgin Islands, the University of the West Indies – Cave Hill, and St. Augustine (Trinidad) campuses, and the Ministry of Health of Trinidad and Tobago. All participants provided their fully informed consent prior to initiating study procedures. The current analysis was approved by the Data Access and Scientific Review committee of the ECHORN Cohort Study.2.1Eligible participants at baseline were 40 years of age and older, English or Spanish speaking, able to provide informed consent, non-institutionalized at the time of data collection, had reliable contact/residential information, were semi-permanent or permanent residents of the island for 10 or more years, and had no plans to permanently relocate in the next 5 years.n = 2,961) has been described in detail elsewhere .The sampling methodology for the baseline ECHORN cohort  . The 9-i2.3® question: “Please look at this figure, with steps numbered from 1 at the bottom to 10 at the top. Suppose the top of the ladder represents the richest people of this island and the bottom represents the poorest people of this island. Taking into consideration your current personal situation, what is the number of the step on which you would place yourself?” Responses ranged from 1 poor to 10 high and were categorized into bottom, middle, and top quantiles. Marital status was measured by asking “What is your current relationship status” and responses categorized into married, single, separated/divorced, or widowed.Sixteen risk factors were chosen and examined based on existing literature and potential risk factors specific to this population, based on experience working in the region. Demographic factors included age at baseline interview (continuous), sex, level of education, perceived economic status, marital status, island site , home ownership status (Yes/No), and whether the participant had moved in the past year (Yes/No). Sex was measured on the baseline survey using the following question, “What sex were you at birth?” Educational attainment was measured using the question, “What is the highest year of school that you completed?” Responses were categorized into less than high school (or secondary school), high school graduate, some college, and college and higher. Perceived economic status was measured using an adapted version of the World Gallup PollPsychosocial factors included were emotional support, and depression. Emotional support was measured using the PROMIS Emotional Support short form . ResponsBehavioral factors included current smoking and self-reported physical health scores. Current smoking status (Yes/No) was measured using two variables: “Have you EVER smoked any tobacco product, such as cigarettes, cigars, or tobacco pipe? Yes/No. Those that answered Yes were asked “Do you still smoke cigarettes, cigars, or tobacco pipe regularly? By regularly we mean at least 20 cigarettes or 1 cigar or half an ounce sachet of loose tobacco per month.” The PROMIS Global Physical Health score was used to assess participant reported physical health , 40. Theor usually/always. Mode of transportation to the grocery store was measured with a single item: “What is the most typical way you travel to the store for your groceries?” and responses were dichotomized: drive own car/ride with friend/family or take the bus/taxi/bike/walk. Water insecurity was measured by a single item asking about source of potable water: “What is the main source of water supply for members of your household? This item was used as a proxy for water insecurity. Responses were dichotomized as water secure (water piped into dwelling) and water insecure (water not piped into dwelling).Environmental factors included fruit and vegetable availability and quality, mode of transportation to the grocery store, and water source as a proxy for water security. Fruit and vegetable availability and quality were measured as follows: “Thinking about food resources in your neighborhood, how often are a large selection of fresh fruits and vegetables, excluding provisions, available in my neighborhood?” and “Thinking about food resources in your neighborhood, how often are the fresh fruits and vegetables in your neighborhood of high quality?” Responses were dichotomized into never/rarely/sometimes 2.4n = 2,961). The model was run in the following ways: (1) On the full sample using all 9 ELCSA items; (2) on the full sample using 8 of 9 ELCSA items (removing number 9—begging); (3) on the sample from each island ; (4) removing individual participants identified as outliers—both on the full sample using all 9 items and for each island site using the 9-item scale. Unidimensionality of the scale by island was further assessed using Differential Item Functioning (DIF). DIF analysis was performed to compare scale performance for each island to the full sample. Measure, Infit values, and differences in item performance were assessed by island site. A detailed description of the RASCH results can be found in Rasch modeling was used to assess the ELCSA scale’s psychometric properties since this was the first time the scale was being used in the ECHORN Cohort. The Rasch model is a 1-parameter item response model, a modeling technique that is consistently applied in studies using the ELCSA and other food insecurity scales , 41–43. Next, univariate and bivariate analyses were conducted to determine the prevalence of household food insecurity, describe the overall sample by each risk factor, and to examine the association between household food insecurity and each risk factor. Study variables were summarized using means and standard deviations or frequency distributions for the total sample and by level of household food insecurity. The analysis of variance and the chi-square test were used to examine the association between potential risk factor variables and household food insecurity. Tetrachoric and polychoric correlation coefficients were also examined to determine whether collinearity existed between specific study variables: education, perceived economic status, water supply (which may be a marker for economic status in the Caribbean region), and home ownership. Finally, multivariable ordinal logistic regression was then used to determine the association between household food insecurity (mild to moderate/severe) and each risk factor holding all other variables constant. The analysis was first conducted for the full sample, then stratified by sex as women are more likely to experience HFI than men .33.1Rasch modeling of the ELCSA scale in the ECHORN sample indicated that the full 9-item scale for adults used with the full cohort (rather than by island site) was the best fit. The Cronbach’s Alpha for the scale was 0.90. 3.2The final sample size consisted of 1,939 individuals with a baseline household food insecurity score and non-missing data for the examined risk factors. More than one-quarter of the sample (27.3%) experienced some level of household food insecurity . Respondents were on average 57 years of age (S.D. 10.5) and nearly two-thirds were female. Nearly one-third had no high school education, 41% were married, nearly two-thirds owned their own home and 50% rated themselves in the middle economic quartile of their respective island. Nearly 15% of respondents did not have water piped directly into their homes  compared to those without depressive symptoms. This is compared to 59% increased odds among men; however, this effect estimate was not statistically significant .4This study aimed to examine demographic, psychosocial, behavioral, and environmental factors associated with HFI in a four-island Caribbean cohort. Identified demographic risk factors included younger age, lack of home ownership, and lack of stable housing. Psychosocial and behavioral risk factors included were depression, low emotional support, and poor self-rated physical health. Environmental risk factors included lack of food availability, lack of high-quality foods, and lack of water piped directly into the home. Our findings demonstrate that the prevalence of household food insecurity in the ECHORN Cohort is comparable to other studies that have been conducted in the region. A study of adults in Trinidad, showed a 25.0% prevalence of HFI and found that lower household income and physical disability were each independently associated with HFI . AnotherThe findings presented above differ from the existing literature in important ways. First, women are more likely to experience HFI than men, globally ; howeverFurthermore, this study adds to the growing body of literature examining the association between water and food insecurity. Source of potable water-a proxy for water insecurity-was a significant predictor of HFI for both men and women, such that those without water piped directly into their home had an increased odds of experiencing HFI. We did not find evidence of multicollinearity between water source and other indicators of socioeconomic status such as education, perceived economic status, and home ownership, suggesting that source of potable water is an independent risk factor for HFI in this sample. To our knowledge, this is the first multi-country study in the Caribbean region to examine the association between water security and HFI. Recent scholarship on water and food security suggests collecting more and better data on water insecurity, including prevalence data . We will4.1We used a validated and well-tested measure of household food insecurity for this research and confirmed its robust psychometric properties in the ECHORN cohort. We also examined known and potential risk factors for HFI (based on our knowledge of the region), which allowed us to identify important risk factors specific to the populations under study. This research fills a gap in the literature with respect to identifying and understanding risk factors for household food insecurity in the Caribbean region, and strongly calls for applying the lessons learned in these settings to the design of similar policy relevant studies in other regions of the world. Importantly, we present evidence of a link between source of potable water, a proxy for water security, and household food insecurity in the ECHORN cohort. These findings have important implications for understanding how to improve the governance of food and water security systems and the coordination needed between them.With respect to study limitations, the cross-sectional nature of this analysis only allows us to draw conclusions about the association between the studied risk factors and household food insecurity in the region, without comment on causality. In addition, these findings pertain to the ECHORN cohort study sites only and cannot be extrapolated to other nations or territories in region.5This cross-sectional, multi-country study was designed to identify risk factors for household food insecurity in the Eastern Caribbean. The findings fill a gap in the literature with respect to understanding risk factors for HFI and have important implications for future research and policy in this area. Future research should examine these risk factors longitudinally, with a focus on understanding the transition from a food secure to a food insecure state over time in the ECHORN cohort. Additional work will examine whether household food insecurity is associated with specific cardiometabolic conditions in the cohort and what role water security also plays in these relationships.https://www.echorn.org/request-echorn-data).The datasets generated and analyzed for this study are available upon request to the ECHORN Data Access and Scientific Review committee  campuses, and the Ministry of Health of Trinidad and Tobago. This study were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.JM-B: Conceptualization, Formal analysis, Methodology, Project administration, Supervision, Visualization, Writing – original draft, Writing – review & editing. AH-F: Formal analysis, Methodology, Software, Supervision, Writing – review & editing. DG: Data curation, Formal analysis, Methodology, Writing – review & editing. CO: Writing – review & editing. LA: Writing – original draft, Writing – review & editing. OA: Data curation, Funding acquisition, Resources, Writing – review & editing. RM: Data curation, Funding acquisition, Resources, Writing – review & editing. CN: Data curation, Funding acquisition, Resources, Writing – review & editing. MN: Data curation, Funding acquisition, Resources, Writing – review & editing. MN-S: Data curation, Funding acquisition, Resources, Writing – review & editing. RP-E: Conceptualization, Methodology, Supervision, Writing – review & editing.


A generalised estimating equation (GEE) was used to assess the association of Na intake, K intake and their ratio on BP, WC, and waist-to-height ratio (WHtR). Results: Our results indicate a significant positive association between K intake and WHtR, and even though the model was adjusted for age and sex, there was still an association with WHtR. The Na/K ratio was associated with both BP measurements and abdominal obesity, respectively. Furthermore, Na/K was shown to be associated with an increased risk of developing HT and abdominal obesity. Conclusions: In our study, we observed that an increase in the Na/K ratio is a predictor of HT and abdominal obesity over time compared to Na and K alone. However, more studies are required to further prove this.Background: Hypertension (HT) and obesity have both been on the rise in children. Each is associated with an increase in cardiovascular disease risk, and both track into adulthood. Objectives: This study aimed to identify the association of sodium intake (Na), potassium (K) intake, and sodium-to-potassium (Na/K) ratio with the development of HT and abdominal obesity amongst the Ellisras rural population over time. Methods: In this longitudinal study, data on dietary intake of Na and K were collected using a 24 h recall questionnaire from a total of 325 participants tracked from 1999 (5–12 years), 2001 (7–14 years), and 2015 (18–30 years). The averages of Na and K intake were analysed using local food tables and the South African Food Composition Database System (SAFOODS). In addition, blood pressure (BP) and anthropometric measurements (waist circumference (WC) and height) were also examined. Parametric (independent  Hypertension and obesity have both been on the rise in children. Both track into adulthood and are linked to an increased risk of cardiovascular disease, which increases the prevalence of heart disease and its associated morbidity and mortality . South APotassium is an essential mineral for human health ,6. It isEvidence reveals a link between sodium consumption and blood pressure (BP) levels . Excess Obesity has lately attracted attention as another potential health-related result despite the distinct detrimental effects of increased sodium intake on hypertension . Adult oThis study is a component of the Ellisras Longitudinal Study (ELS), the regional specifics of which have been covered elsewhere . At firsAs described by Whelton et al. (2018) , blood pA 24 h recall questionnaire was used to gather dietary data . Particip-value of ≤0.05 was chosen as the statistical significance for all tests.In order to conduct the statistical analysis, the IBM SPSS Statistics software package (version 27.0) was employed. Descriptive statistics were produced for all the variables to provide frequencies (expressed as percentages), means, and standard deviations in order to describe and characterise the samples. The normality of the variables was evaluated by the Shapiro–Wilk test. To ascertain the variation in males and females throughout the years and between the years, parametric (one-way ANOVA), Chi-square, and Fisher’s exact tests were used. To evaluate the relationship between sodium and potassium consumption, as well as their ratio with BP, WC, and WHtR, and further analyse the relationship with hypertension and abdominal obesity, generalised estimating equations (linear and binary logistics) were used. A p > 0.05) or females (p > 0.05). The dietary mean of K intake significantly decreased from the first year of assessment to the last year of assessment in both males (p < 0.001) and females (p < 0.001). Meanwhile, the dietary mean of the Na/K ratio significantly increased over the years in both males (p < 0.001) and females (p < 0.001). Furthermore, the mean of both SBP and DBP significantly increased from the first year of assessment to the last year of assessment, respectively, in both males (p < 0.001) and females (p < 0.001). The mean of abdominal indices (WC and WHtR) significantly increased over the years in both males (p < 0.001) and females (p < 0.001). p < 0.05), K intake (p < 0.001), and Na/K ratio (p < 0.001)) significantly increased over the years for the total population. In addition, the mean of BP measurements of the total population significantly increased from the first point of measurement, with SBP (p < 0.001) increasing to 120.75 mmHg and DBP (p < 0.001) increasing to 70.67 mmHg in the last year of measurement, respectively. The mean of abdominal indices significantly increased from the first measurement (54.44 cm-WC and 0.41-WHtR), with WC increasing to 79.0 cm and WHtR increasing to 0.48 in the last year.p < 0.001). The prevalence of abdominal obesity according to WC significantly decreased in males, whereas in females, it increased from the first point of measurement to the third year (p < 0.001). In addition to this, both males’ and females’ prevalence of abdominal obesity according to WHtR significantly increased over the measured years (p < 0.001). The results in p < 0.001). In addition, the prevalence of abdominal obesity according to WC significantly decreased by 5% from the first point of measurement to the last year of assessment (p < 0.001). Meanwhile, the prevalence of abdominal obesity significantly increased from 0.3% at the first measurement to 35.7% in the last year of measurement (p < 0.001).p-value = 0.012), and even after age and gender were considered in the model, there was still an association with WHtR  p-value = 0.024). The sodium-to-potassium ratio was significantly associated with SBP  p-value < 0.001), DBP  p-value = 0.003), WC  p-value < 0.001) and WHtR  p-value = 0.015), respectively. However, when the model was adjusted for age and sex, an association was not found between the sodium-to-potassium ratio and blood pressure measurements and abdominal indices, respectively. p-value = 0.004) and abdominal obesity  p-value = 0.004) compared to Na and K intake alone. However, when age and sex were taken into account, the sodium-to-potassium ratio was not found to increase the risk of developing hypertension and abdominal obesity, as shown in The results in The purpose of this study was to investigate the association of sodium and potassium intake and their ratio on hypertension and abdominal obesity in the same participants over time in Ellisras. The results of our study indicated that K was significantly associated with WHtR. The outcome of these results could be due to a lack of intake of fruits and vegetables in 2015 compared to 2001 , resulting in a decline in the mean intake of K over the years. Most studies in this field that have been conducted over the past five years indicate that the K effect on obesity is a new topic, and more robust studies with better design are warranted , especiaOur results, on the one hand, showed no relationship between Na and BP measurements and abdominal indices. Although Na mean intake significantly increased over time, the increase was not significant enough to be associated with BP measurement and abdominal indices in this sample population of Ellisras.Our study results revealed that the Na/K ratio is the predictor of HT and abdominal obesity compared to Na and K alone. This means that an increase in the Na/K ratio increases the risk of developing hypertension by 1.603-fold and abdominal pain by 1.797-fold over time. Due to the lack of sufficient studies, we could not compare this study with relevant studies. However, Ge et al. (2016) also discovered that the urine Na/K ratio was independently related to obesity and that a high Na/K ratio could increase the risk of obesity . HoweverOn the other hand, BP measurements showed a significant mean difference in males and females over the years. Significant differences in the prevalence of hypertension, WC, and WHtR were observed in both genders over the years. Over time, there were significant variations in potassium, the sodium-to-potassium ratio, hypertension, WC, and WHtR prevalence. It must be noted that many of the participants were classified as underweight, as stated by van Den Ende et al. (2014) . TherefoThe change in political, social, and economic factors in South Africa has resulted in increased urbanisation and progress . The incThere are a few limitations regarding this study. The first is the use of the 24 h recall questionnaire compared to the 24 h urinary excretion, as 24 h excretion is considered the golden standard method of obtaining data on sodium and potassium intake in population surveys and is more accurate than the 24 h recall questionnaire . The secIn conclusion, this current study showed a significant positive association between K and WHtR. In addition, there is a significant positive relationship between the Na/K ratio, BP measurements (SBP and DBP), and abdominal indices (WC and WHtR). An increase in the Na/K ratio was further found to increase the risk of developing HT and abdominal obesity over time. However, more data are crucial in establishing the effectiveness of Na reduction and the increase in K intake, and with the use of more valuable methods, we can better understand their effect on blood pressure and abdominal weight, especially in Africa. Longitudinal studies in children provide a tremendous global resource to direct prevention strategies for HT and abdominal obesity.