The models with these compounds explained 72% of the glycemia variability . Ni showed a significantly influence on IL-6 variability (β = 0.85: R2 = 0.36). Changes in glycemia could be related to exposure to low levels of Asi and Ni, representing risk factors for metabolic diseases. Body mass index would confuse the relation between IL-6 and Ni levels, probably due to known chronic inflammation present in obese people.Chile is a mining country, where waste mining is frequently found in the vicinity of inhabited areas. To explore the association between metal exposure and alterations in glucose metabolism, inflammatory status, and oxidative stress in individuals with chronic exposure to metals, a cross-sectional study was performed with 25 volunteers, between 45–65 years old. Inductive coupled plasma mass spectrometry (ICP-MS) was used to measure urinary levels of total arsenic (As) and its metabolites, cooper, nickel, chromium, and lead. Lipid profile, glucose, and insulin were measured in blood, as well as inflammation  and oxidative stress  markers. Increased levels of Low-density lipoprotein, high-density lipoproteins, cholesterol and 8-OHdG, and the index for homeostasis model assessment—insulin resistance (HOMA-IR) were observed in 72%, 60%, and 56% of the volunteers, respectively. Blood-glucose levels were correlated with dimethylarsinic acid (DMA) (R Mining waste contains high concentrations of chemical products, often being stored in dams or reservoirs, causing an important source of contamination by inorganic chemical elements ,2. AmongIn Chile, a country whose gross domestic product (GDP) strongly depends on mining activity, a total of 726 mining waste deposits have been identified . AdditioThe lifestyle, diet, and aging of the population have led to an increase in chronic diseases worldwide. Particularly in Chile, there is an increase in the prevalence of metabolic diseases according our national health surveys , and it To the best of our knowledge, no studies have been conducted in Chile on the association between heavy metal exposure and the above health markers. The objective of this article was to explore the association between chronic exposure to metals and alterations in biochemical parameters associated with glucose metabolism, inflammatory status, and oxidative stress, in residents from the urban area of Chañaral Bay, Chile, chronically exposed to metals.The results shown in this report were obtained from a larger study carried out in the city of Chañaral, whose objective was to establish the exposure to metals after a large flood that occurred in March 2015. In that case, the main study was carried out under the approval of the committee of ethics of the School of Medicine . An exploratory cross-sectional study was performed. Adult volunteers, ages 45 to 65, and with uninterrupted residence in the city of Chañaral for the past 5 years were invited to participate [Among the participants from the bigger study, a subsample was identified. Volunteers with a medical diagnosis of autoimmune pathologies and allergies, thyroid abnormalities, diabetes, hypercholesterolemia, and insulin resistance were excluded to avoid confusion bias. Each participant was asked to sign an informed consent and was interviewed at their home by trained personnel. Each volunteer answered a questionnaire regarding demographic characteristics , lifestyles , metal exposure (eating fish and shellfish), and health status (chronic diseases self-reported), and donated a 50 mL urine sample at the time of the interview. All the procedures were previously used in the National Health Surveys ,21. The i), As species including As(III), As(V), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), arsenobetaine (AsBet), Cu, Ni, Cr, and Pb were established in laboratories of the Chilean Nuclear Energy Commission (CCHEN), using the validated technique of ICP-MS. Limits of detection (LOD) for each metal were 0.35 µg/L. All samples exceeded LOD for total As and Asi. On the other hand, 0% of samples did not exceed its LOD for MMA, copper, and lead.Urinary levels of total arsenic (As), inorganic arsenic  were used to measure inflammation and oxidative stress markers (IL-6 and 8-OHdG). For this, 1 mL plasma samples were quantified using human IL-6 ELISA kit, EH21IL6; INVITROGEN,  and oxidative DNA damage ELISA kit, STA-320 . For both kits, 50 μL of the original sample was used. A calibration curve was carried out and the absorbance measurement was at 450 nm in the multifunctional microplate reader, NOVOstar 0700 . These results were obtained in the Environmental Neurotoxicology laboratory of the Universidad Católica del Norte in Coquimbo, Chile.t-Student test; on the contrary, non-parametric variables were expressed as median (interquartile range) and comparisons were performed using U Mann–Whitney test. For the biochemical parameters, normal values were then established according to the National Health Survey [Univariate and bivariate descriptive statistical analyses were performed to determine the distribution of the damage and exposure parameters. Parametric variables were expressed as mean ± SD and comparisons were performed using h Survey : insulinh Survey .According to the manufacturers, the cut-off points were for IL-6 (median and range) 2.59 (0.89–7.28) (pg/mL), and for 8-OHdG (mean ± SD) 6.61 ± 0.18 ng/mL, respectively.In those metals with values lower than the LOD, these were analyzed considering values given by the square root of the LOD divided by 2 for statistical analysis .p-value < 0.05). The statistical programs SPSS version 17.0  and R  were used [Correlations and multivariate linear regression models were also performed to establish the role of other variables. Hypothesis tests were proven with a significance level of 5% , Asi , and Ni .Significant correlations between biochemical and clinical parameters with levels of metals are presented in Additionally, the dichotomization by each biochemical/metabolic parameter by individual between normal or abnormal values resulted in the distribution showed in p = 0.022). It was possible to observe a tendency to altered glycemia in those individuals with highest levels of DMA and Asi, however these differences were not significant . A significant increase of AsBet level (3.06-fold) in subjects with altered total cholesterol was found (p = 0.016), and there is a clear tendency towards lower levels of AsBet in subjects with insulin resistance with respect to those with normal HOMA-IR index (p = 0.059). Individuals presenting higher levels of 8-OHdG also showed low levels of Aso.A similar pattern was observed for IL-6, where individuals with lower levels of inflammation did not show detectable levels of nickel (i (β = 6.68), and Ni (β = 6.87), were jointly able to explain 72% of the glycemia variability (p = 0.002). Nickel showed a significantly influence on IL-6 variability . The remaining biochemical and clinical parameters were not significantly associated with any metals.Finally, in order to determine whether age, sex, and BMI influenced the biochemical/metabolic parameters, irrespective of metal concentration, multivariate regression models were performed . Female The objective of this article was to evaluate the association between exposure to mining waste metals and alterations in biochemical parameters associated with glucose metabolism, inflammatory status, and oxidative stress, in residents of the urban area of Chañaral Bay, Chile; an area with historical exposure to metals.i with no differences by sex. These results obtained in this small sample are below other values from national studies [This preliminary study shows that the metal levels in urinary samples were low. Especially, Cu and Pb were below their detection limits. The most relevant results were obtained for total and As studies ,26.Regarding biochemical parameters, those related to cholesterol were the most prevalently altered, especially LDL and HDL  exceeding other values measured in similar Chilean studies .i and Ni, differences were observed between high levels and altered glycemia ; AsBet levels showed significant differences with total cholesterol. In relation to the early biomarkers of inflammation and oxidative stress, it was only possible to establish a significant difference for high levels of IL-6 in people exposed to Ni. In adjusted models, the differences continued being significant for Asi and Ni when glycemia levels increased. However, this tendency vanished for total cholesterol and AsBet when adjusting by sex, age, and BMI. An interesting result was observed by introducing BMI as a variable in the models, considering that an important proportion of the studied individuals showed increased BMI. It turned out that obesity would be confusing the relation between IL-6 and nickel, by increasing the influence of nickel in the inflammatory status of individuals in over 40% (from 25% to 36%) when including BMI in the model. This is not rare, since obese people are proven to have a permanent increased inflammatory status [For Asy status . On the p = 0.059). In other words, it could be considered that AsBet ingested through the seafood diet would be a protective factor for insulin resistance [i and glycemia. In this case, individuals who presented with altered glycemia also had a higher concentration of DMA and Asi in the urine. This association was not statistically significant individually , probably because of the small sample studied. Nevertheless, the influence of metals in increasing the glycemia was significant when performing the regression model.Among the toxicological implications of our findings, it is noteworthy that AsBet is a low toxicity organic arsenic compound, whose source of exposure is through diet. AsBet is abundant in fish, shellfish, and seaweed. Therefore, a possible explanation for the association between high levels of AsBet and high cholesterol could be a diet based on shellfish consumption. On the other hand, individuals who presented with HOMA-IR index in normal ranges had higher levels of AsBet in urine compared to individuals with altered HOMA index, these differences being close to statistical significance (sistance ,30. Simisistance . It is ksistance ,33. Specsistance  transducFinally, detectable levels of Ni were found in individuals with high glycemia and elevated levels of IL-6, a marker of inflammation . SeveralGiven the exploratory nature of the study carried out, several limitations should be reported. Among them, its low sample size, with small number of men and a unique sample from the study area, does not allow for stratified analyses by sex or other variables such as smoking habits. Moreover, only two biological markers related to cellular damage were analyzed. Since these analyses were preliminary and due to the small sample size, we also do not correct for multiple comparisons.Despite the limitations of an exploratory study, this report provides promising indicators of early damage in people with heavy metal exposure and advocates for the exploration of biomarkers related to metabolic alterations—including a broad spectrum of other early damage markers—in population-based studies. This kind of evidence will be critical for protecting populations chronically exposed to metals and other compounds, such as As, even those with currently low levels.The results obtained in this pilot study will allow us to strengthen and expand our study of chronic diseases, especially those of a metabolic type, associated with environmental conditions, beyond lifestyles, diet, or genetic conditions. In developing countries, as is the case in Latin America, it is necessary to broaden the scope as there are high rates of chronic alterations together with exposure to a mix of pollutants. The results presented have generated an alert in our communities linked to mining activities. At the level of health public policies, we need to not only to measure their levels of metals by biomonitoring but also to establish associations with metabolic alterations at the population level and reduce the current exposures.This exploratory analysis shows a positive association between urinary Ni levels and glycemia and the inflammation marker IL-6.Despite the current low levels of metals and As, and their compounds, there is a positive association between urinary AsBet levels and total cholesterol, and between urinary inorganic arsenic levels and glycemia. There is a negative association between urinary AsBet and 8-OHdG.i and Ni. Both contaminants will be present in people from communities similar to Chañaral with respect to waste mining.The results from this small sample evidence a possible mechanism related to the occurrence of chronic diseases, especially among those related to alterations of glucose metabolism and chronic inflammation in people exposed to low levels of AsInterestingly, the exposure to AsBet, a compound considered safe in health risk assessment and associated with high total cholesterol, should be evaluated in future studies.Finally, considering the importance of mining, and the exposure to metals and As in the general population of those residing close to mining facilities, exposure to metals and As is a risk factor that must be explored together with health effects related to metabolic diseases.


Importance: While the literature documenting health disparities has advanced in recent decades, less is known about the pattern of racial/ethnic disparities in emergency care in the United States.Objective: To describe the trends and differences of health outcomes and resource utilization among racial/ethnic groups in US emergency care for adult patients over a 12-year period.Design, Setting, and Participants: This cross-sectional study of emergency department (ED) data from the nationally representative National Hospital Ambulatory Medical Survey (NHAMCS) examined multiple dimensions of ED care and treatment from 2005 to 2016 among adults in the US.Main Outcomes and Measures: The main outcomes include ED care outcomes , resource utilization outcomes , and patients' waiting time in the ED. The main exposure variable is race/ethnicity including white patients (non-Hispanic), black patients (non-Hispanic), Hispanic patients, Asian patients, and Other.Results: During the 12-year study period, NHAMCS collected data on 247,989 adult (> 18 years old) ED encounters, providing a weighted sample of 1,065,936,835 ED visits for analysis. Asian patients were 1.21 times more likely than white patients to be admitted to the hospital following an ED visit . Hispanic patients presented no significant difference in hospital admission following an ED visit  with white patients. Black patients were 7% less likely to receive an urgent ESI score than white patients less likely to receive immediate or emergent scores, as opposed to semi- or non-urgent scores. Black patients were also 10% less likely than white patients to be admitted to the hospital and were 1.26 times more likely than white patients to die in the ED or hospital.Conclusions and Relevance: Race is associated with significant differences in ED treatment and admission rates, which may represent disparities in emergency care. Hispanic and Asian Americans were equal or more likely to be admitted to the hospital compared to white patients. Black patients received lower triage scores and higher mortality rates. Further research is needed to understand the underlying causes and long-term health consequences of these disparities. Nearly two decades ago, the Institute of Medicine (IOM) released a historic report documenting significant racial and ethnic disparities in the US healthcare delivery system, along with policy recommendations to address their findings . The IOMConsistent with these findings, the ED is more likely to serve as the entry point into the healthcare system for racial and ethnic minorities than it is for white populations in the US , 6. UponIn seeking to explore and document racial and ethnic disparities in ED care and outcomes, we and prior researchers recognize the nature of race and ethnicity as socially-constructed categories that have real consequences for the experiences and life chances of people of color within US society writ large , and alsThis is a cross-sectional study of ED data obtained from a multiyear, nationally representative survey carried out in the US. This study used preexisting, de-identified data and thus was categorized as exempt by the University of Michigan's Institutional Review Board.N = 1,560,846,342) visits from 3,764 hospital-based EDs were included in the survey datasets from 2005 to 2016. To restrict our sample to adult patients with one documented race/ethnicity, we excluded all pediatric visits  and patients with unknown or multiple races , resulting in a total of 247,989  patients visits for analysis.The study population was derived from the National Hospital Ambulatory Medical Survey (NHAMCS) Emergency Department Subfile (NHAMCS-ED) between 2005 and 2016 . NHAMCS-The primary study outcome variables include the triage level [emergency severity index [ESI], a five-level ED triage algorithm providing clinically relevant stratification of patients into five groups from 1 [most urgent] to 5 [least urgent] on the basis of visit acuity level and resource needs], hospital admission, intensive care unit (ICU) admission, death in the ED/hospital, medical resources utilization  and variables indicative of socioeconomic status, including residence type , insurance type , arrival mode, arrival day of the week, and time category. We also included clinical variables such as triage vital signs . Additional patient-level covariates included whether or not the patient had visited the ED within the past 72 h. We also included information on the US census region of the ED and the primary reason for the ED visit based on system-based symptom clusters . We used these symptom clusters as they were present in the dataset for the entire patient population.Population characteristics were described and compared among different racial/ethnic groups. The proportion of each outcome variable among different racial/ethnic groups and covariate groups were compared using chi-square tests. Multivariable logistic regression models were used to estimate the association between each binary outcome  and racial/ethnic groups. Multinomial logistic regression models were used to estimate the association between the ESI scores  and racial/ethnic groups. Models were sequentially adjusted for demographic, socioeconomic, and visit/clinical variables; specifically, we adjusted for ESI scores to test for changes in the associations between racial/ethnic group and binary outcomes. Multivariable linear regression was used to test the association between the waiting time and length of visit (continuous variables) and racial/ethnic groups after adjusting for other confounding variables. Because these two variables are not normally distributed, a log transformation was performed prior the regression model. Poisson regression was used to model trends in the outcome rates among racial/ethnic groups, adjusting for age, gender, and insurance type, with time modeled linearly as years since 2005. An interaction between the racial/ethnic group and time was included in each model to test whether the trend in each outcome differed by racial/ethnic group.The NHAMCS-ED dataset used in this analysis relies on imputation for missing data. Specifically, the survey uses a hot deck-based single, sequential regression methodology to impute 3-digit ICD-9-CM codes for items such as age, sex, primary diagnosis, ED volume, and geographic region. The other variables were imputed with the median of the corresponding variables prior to generating the logistic regression models and multivariable linear regression models. SAS (version 9.4) was used for analyses, and alpha = 0.05 was set as the statistical significance threshold.During the 12-year study period between 2005 and 2016, NHAMCS collected data on 247,989 adult (> 18 years old) ED encounters with a discrete race categorization, providing a weighted sample of 1,065,936,835 for analysis . The anaAfter adjusting for other covariates (including ESI level), black patients and Hispanic patients were also 10% less likely than white patients to be admitted to the hospital following their ED visit . Asian patients were 1.21 times more likely than white patients to be admitted to the hospital following an ED visit . Black patients were 1.14 times more likely to receive ICU admission in the fully adjusted models . Odds of dying in the hospital/ED differed among the groups. Relative to white patients, Black patients were 1.26 times more likely to die in hospital ; Hispanic patients, 1.12 times more likely ; Asian patients, 1.64 .p < 0.001) as compared to white patients (After adjusting for other covariates (including ESI level), black patients were 16%  less likely to receive any imaging and 4%  less likely to have a blood test during ED visit than white patients. In contrast, Asian patients were 1.22  times more likely than white patients to receive a blood test. Hispanic and Asian patients were 1.10 times and 1.15 times  more likely to receive a procedure in the ED than white patients. After adjusting for other covariates, waiting times in the ED were significantly longer for all minorities (patients .p < 0.01). Of particular note, hospital and ICU admission for white patients decreased by 30.01 and 30.57%, respectively, compared to 42.48 and 57.79% for black patients. Death rates in the ED for black and white patients decreased over the 12 years by 37.84 and 33.33%, respectively, whereas the Asian and Hispanic patients' death rates increased by 250.00 and 10.53%, respectively . Blood test rates and medical imaging utilization rates in the ED increased (though with different 2006–2016 percent changes) while the procedure utilization rates dropped across all racial/ethnic groups.We observed significant racial/ethnic differences in the evaluation and management of adult patients in the ED based on the nationally representative NHAMCS, between 2005 and 2016. In the ED, black patients and those in the other racial/ethnic group were less likely than white patients to receive immediate or urgent ESI scores as opposed to semi- or non-urgent care needs. Our study indicates that this racial/ethnic disparity could not be explained by demographic, socioeconomic, or factors related to the patients' clinical presentation or the context of their visit. While we cannot infer the cause of these ESI disparities based on the current study, we point to two potential explanations. First, as past research has found, racial/ethnic minorities are less likely than white patients to have a primary care provider and are more likely to rely on ED services for routine care needs . This diUnlike the other racial/ethnic minority groups, Asian patients were more likely than white patients to present to the ED with immediate or urgent care needs. While the higher socioeconomic indicators ascribed to the Asian patients in our sample  may contribute, it is worth noting that the pattern remained in the fully adjusted models accounting for these factors. Unfortunately, due to a lack of granularity in the NHAMCS-ED, we were unable to further stratify the Asian sample by region or country of origin, nor could we test for the effects of patient-level factors such as income, education, primary language, or duration of US residence on the outcomes analyzed in this study. Such information would be valuable in attempting to explain the divergent patterns observed between Asian patients and other racial/ethnic minorities included in our sample .N = 54).Black groups were also less likely than white patients to be admitted to the hospital following an ED encounter after controlling for model covariates. Compared to white patients, Asian patients were either more or equally likely to be admitted to the hospital following an ED visit, which again diverges from the pattern of the other racial/ethnic groups and cannot be fully explained by the factors available in the NHAMCS-ED dataset. Although mortality rates were <1% for all groups, Asian and black patients were more likely than white patients to experience in-hospital death following an ED visit, after we adjusted for the patients' ESI scores. While the data indicate that Asian patients have remarkably high odds (1.93), compared to white patients, of dying in the ED/hospital, we suspect that this result may owe in part to the small sample size of Asian patients relative to the other racial/ethnic groups and the infrequency of deaths in the ED/hospital  may involve abstraction errors, missing responses, and inaccurate responses. However, we do not suspect that such systematic biases would moderate the associations with race/ethnicity noted herein in any consistent way. Additionally, 6% of the total NHAMCS-ED sample was removed for not having a documented race/ethnicity; however, this figure is below the acceptable non-response threshold for this type of data source and thus does not invalidate the primary exposure variable for this analysis . AnotherThe emergency care of black patients was characterized by disparities in multiple dimensions of care. Namely, black patients received lower ESI scores, were less likely to receive tests in the ED, were less likely to be admitted to the hospital and/or ICU, and had a higher death rate in the ED and hospital. Some of these findings were in contrast to Hispanic and Asian patients, who, in general, received equivalent or greater ED resources compared to white patients. Further research is needed to understand the underlying causes and long-term health consequences of these racial/ethnic disparities in ED care in order to inform clinical guidelines and policies for eliminating racial differences in this critical area of US healthcare.https://www.cdc.gov/nchs/ahcd/index.htm.Publicly available datasets were analyzed in this study. The data can be accessed from the CDC website: XZ: full access to all the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis. XZ and PM: concept and design. MC, XZ, and TH: drafting of the manuscript. RS, SB, and PM: critical revision of the manuscript for important intellectual content. XZ: statistical analysis. XZ and PM: obtained funding. XZ, MC, and TH: administrative, technical, or material support. XZ and PM: supervision. All authors: acquisition, analysis, or interpretation of data.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.


The ESAS and PSQI questionnaires confirmed these positive results . Conclusions: This prospective investigation by an Italian expert group, has confirmed that careful management of BTcP induces a paramount improvement on the HRQoL. Because in cancer patients there is a high prevalence of BTcP and this severe acute pain has deleterious consequences, this information can have an important clinical significance.Objectives: To explore the effect of breakthrough cancer pain (BTcP) treatment on quality of sleep and other aspects of the health-related quality of life (HRQoL) in patients with cancer pain. Methods: In an observational, multicenter, cohort study, cancer patients from palliative care units, oncology departments, and pain clinics and affected by BTcP were included. Enrolled patients were assessed at the four visits: T0 (baseline), T7, T14, and T28. Stable chronic background pain  during the whole study period was mandatory. BTcP was treated through transmucosal fentanyl. Three questionnaires were used to measure the HRQoL: EORTC QLQ-C15-PAL, Pittsburgh Sleep Quality Index (PSQI), and the Edmonton Symptom Assessment System (ESAS). RESULTS: In 154 patients, the HRQoL showed a significant improvement for all physical and emotional characteristics in the EORTC QLQ-C15-PAL, except for nausea and vomiting (linear  Pain is one of the most frequent symptoms in cancer patients as it occurs in 20–30% of cases during the initial stages and in up to 75% of patients in advanced disease. The prevalence of cancer pain at any stage of the disease is over 50%. Concerning pain intensity, moderate to severe pain can affect up to 40% of all patients. Furthermore, this symptom strongly affects the patient’s health-related quality of life (HRQoL) and daily activities throughout the cancer disease . As a con = 4016), dissected the features of this painful phenomenon and demonstrated that in 86% of patients the occurrence of BTcP induced a marked interference with their daily activities [Assessment and management of cancer pain become particularly critical when the patient faces temporary exacerbations of pain despite adequate control with opioids. This phenomenon, termed as breakthrough cancer pain (BTcP), is a very frequent condition as approximately 70% of patients suffering from chronic pain of oncological nature report episodes of BTcP . TypicalThe present observational study—indicated as breakthrough cancer pain evaluation study (BEST-Study)—aimed at assessing the impact of BTcP management on HRQoL, sleep and daily activities in patients from different clinical settings and with adequately controlled background pain through strong opioids. This clinical study was conducting by following the Declaration of Helsinki’s ethical principles. Individuals with a diagnosis of any type of solid cancer and affected by chronic pain effectively controlled—numeric rating scale (NRS) ≤4—by around-the-clock (ATC) opioid maintenance therapy through ≥ 60 mg of oral morphine equivalent daily doses (OMEDD) on the day of enrollment, were included in this national multicenter prospective cohort study, from March 2015 to August 2017. Approval from the Institutional Medical Ethical Committee (protocol 32/14 OSS) of the Istituto Nazionale Tumori-Fondazione Pascale, Naples was obtained, and patients signed informed consent before enrolling in the study. The Strengthening Reporting of Observational Studies in Epidemiology (STROBE) guidelines were followed .Patients’ eligibilities were evaluated by an oncologist or pain specialist or palliative care specialist and in-hospital patients, outpatients, and those in home-care settings, were included. Each participating patient was observed for a maximum of 28 days. During the study, patients underwent to four consultations starting from baseline examination (T0) for enrolment and data collection. In particular, in this initial step demographic characteristics, settings, tumor type, background pain characterization (the type of pain and pain intensity), and performance status through the Eastern Cooperative Oncology Group (ECOG) 0–5 scale, were collected. Each participating patient was then evaluated after 7 days (T7), 14 days (T14), and 28 days from baseline (T28), .Data were collected from the patient’s medical records and summarized in e-CRF (electronic Case Report Form). The definition of BTcP was: a transitory pain exacerbation of moderate to severe intensity that occurs spontaneously or predictably , well diThe impact on BTcP treatment through transmucosal fentanyl on HRQoL, sleep quality and daily activities in patients with background pain adequately controlled by ATC opioids as maintenance therapy.The primary objective of the study was to define:The HR quality of life (QoL) was measured by the European Organization of Research and Treatment Quality of Life Questionnaire-Cancer 15 (EORTC QLQ-C15-PAL)  and the Baseline background pain characteristics;BTcP features including type , and the number of episodes. Differences according to visits  on number of BTcP episodes were evaluated;BTcP management in terms of median time to pain relief.The secondary objective was to evaluate the:Any serious adverse event related to background pain therapy and for BTcP management was reported.p-value indicates the statistical trend for the four measures, while the square p-value shows the statistical change from the last visit to the baseline (T28 vs. T0). Categorical variables were presented by frequencies and percentages. The general linear model (GLM) for repeated measures analysis was used. This statistical approach is mathematically identical to multiple regression analysis and it is particularly useful for the correlation of multiple qualitative and quantitative variables. According to this strategy, the mean-scores for HRQoL parameters in T0, T7, T14, and T28 were evaluated: the linear Results were only based on non-missing data , unless specified otherwise; in particular, the number of patients that completed each visit was taken into account: T0 = 154 pts; T7 = 136 pts; T14 = 124 pts and T28 = 100 pts. The Bonferroni’s method can be used to compare different groups at the baseline. It provides a pairwise comparison of the means, investigates on the relationship between variables, or examines one or more endpoints in clinical trials. To obtain effect size, partial eta-squared (η2p) was calculated. Estimates of effect size give a partial eta squared (η2p) value for each effect and each parameter considered. The partial eta-squared statistic describes the proportion of the total variability attributable to a factor . ® SPSS® Statistics, version 25 . All statistical tests were two-sided, and p values of less than 0.05 were considered significant.Statistical analyses were performed using IBMWe used a mathematical approach that could allow us to obtain the greatest amount of information despite the reduced sample size. In particular, since each score represented a continuous quantity, to make the variable discrete, we applied a statistical approach proposed by Osaba et al.  which alAn adjusted logistic regression analysis was performed to assess the association between the best response of HRQoL questionnaires  and some covariates. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated. p-value = 0.1), and dyspnea . Moreover, there was a significant improvement in the global health status at the end of the study (p = 0.002)  .p = 0.002, and p < 0.0001 respectively) , and in all domains of the HRQoL including psychological outcomes (ESAS), after 28 days of observation (ctively) . ConcernConsistent results were found when QoL best response was calculated A. The imp= 0.01). Finally, data from the PSQI questionnaire indicated that the older age (>70) is significantly associated with worse sleep quality (OR = 8.46 95% CI 2.46–29.11). Subsequently, the improved were compared with worse response to assess variables that contributed to explain this difference for the three questionnaires adopted . Some covariates were also studied. p = 0.2) (p < 0.001). The reduction was also significant for the clusters 8-14 and 15-21 events. In particular, 15-21 episodes at baseline were reported for about 15% of patient to decrease to 7% at T28 (p < 0.001) (p < 0.0001 ). Furthermore, the number of patients who responded to treatment in 20–30 minutes also dropped significantly from about 29.2% to 15% (p < 0.0001). On the contrary, the response increased in ultra-short (<5 min) and short  times. In addition, in these ranges, the variations were significant (p < 0.0001) (p = 0.2) A. At T0,< 0.001) B. Concer 0.0001) C.The major limitation of the study seems to be the poor consistency of the sample size. For instance, the small size simple and the lack of a complete multivariate analysis, associated with the rapid-onset opioids (ROO) pharmacokinetics features  made it difficult to establish how the therapeutic variable was related—in a cause-effect relationship—with the type of response. However, thanks to the statistical approach adopted which combined the multivariate analysis with the careful interpretation of the changes in the HRQoL scores, we were able to measure the change in the four observation times for each patient enrolled, estimating, in turn, the trend. In other words, an ’outcome’ variable was established making the analysis independent from the sample size. In addition, adjusted multivariate analysis was also applied to the three questionnaires. Another limitation is the lack of data on the type of treatment of background pain . As a characterization of therapy was not the aim of the study, we considered all patients with OMEDD of ≥ 60 mg and well-controlled pain to be enrolled. Finally, the lack of the control group due to the study design did not allow for a precise analysis of different dose response patterns. We hope that the data from this observational investigation can be used to design controlled studies.This study explored the effect of BTcP treatment on several aspects of the HRQoL in patients with cancer pain. The HRQoL was investigated through a battery of tools capable of evaluating the largest number of domains. General data were investigated by the EORTC QLQ-C15-PAL, the PSQI questionnaire served to evaluate sleep quality, and the ESAS one helped to explore general domains and psychological aspects of cancer pain including anxiety and depression.In regards to BTcP management, we have chosen to treat BTcP through rapid-onset opioids (ROOs), drugs specifically indicated for this purpose. ROOs, indeed, have a pharmacodynamics that mirror the sudden start and brief duration of the pain event . HoweverAlthough the HRQoL investigated through the EORTC QLQ-C15-PAL instrument showed a significant amelioration in the global health status at the end of the study and a significant improvement for all physical and emotional descriptors of the questionnaire, except for nausea and vomiting, and dyspnea. Concerning dyspnea, it is a symptom of advanced disease, whereas nausea and vomiting are mainly related to opioid therapy but can be also related to the cancer disease itself, and anticancer therapies. Having observed an improvement for constipation and not for nausea and vomiting, perhaps may indicate that during opioid therapy more attention is paid to constipation than to other adverse effects that only apparently have a lower impact on HRQoL. p < 0.0001) at the end of the study. Nevertheless, the adjusted logistic regression analysis demonstrated that the elderly patients (>70 years) had a risk 8.5 fold higher than those observed in patients less than 60 years of age. These findings are not surprising as a recent cross-sectional multicenter study has highlighted that around 80% of cancer patients experienced poor sleep quality, and this issue mainly concerns older patients [Concerning quality of sleep, compared to the baseline we observed a significant improvement (patients . The clip < 0.0001). However, the regression analysis failed to find a correlation between these positive results and age-related factors, gender, and type of underlying pain. Whatever the underlying correlation, we can assume that the treatment of cancer pain induces an important improvement of multiple patient’s psychological aspects [The ESAS questionnaire also showed a significant improvement between the end and the beginning of the study ( aspects . p < 0.01). Several pieces of evidence suggested that different pain thresholds may exist between men and women. Physiologic factors such as ovarian hormone and increased serotonergic activity, and psychological dynamics  have been called into question to explain this phenomenon which, in turn, must be better explained [Further significant data came from the regression analysis. Female gender, for example, was associated with an improvement in global health status (xplained . Howeverxplained . Again, xplained . ProbablOf note, the main finding that is found in all questionnaires is the paramount role of pain therapists as there was significant improvement in the setting of patients treated by these clinicians. Pain therapists are perhaps more likely to perform pain management through tailored therapies and by coordinating multidisciplinary strategies . The impWith regards to background pain, the best results have been achieved in patients with mixed pain, although only in the EORTC questionnaire. The data can be explained with probable greater attention towards forms of pain that represent a challenge for those who must treat chronic pain.The analysis of BTcP and its trend during the investigation period showed interesting data. Our study suggested that adequate BTcP management can probably reverberate on the characteristics of BTcP by reducing the number of episodes. Of note, there was also an improved response to therapy. The phenomenon, however, requires further investigation as multiple factors such as type and course of cancer disease, clinical setting, and background pain therapy can influence the incidence and characteristics of BTcP. Furthermore, this unpredictable severe acute pain represents a heterogeneous condition and includes spontaneous forms and those induced by voluntary, or involuntary movements. Therefore, especially incident pain benefits from better therapy. In a longitudinal study, carried out on in-hospital patients, the incidence changed over time, falling from 87% to 32% after six months from the first detection. The greatest decrease in BTcP occurrence concerned the incident subtype . MoreoveBTcP treatment remains a great challenge in medicine. It requires, indeed, individualized treatment through the involvement of a multidisciplinary team. Despite the limitations, results from this multicenter, observational cohort study conducted by an Italian expert group, has confirmed that accurate management of BTcP from the baseline may improve several aspects of the HRQoL. Because of in cancer patients there is a high prevalence of BTcP and this severe acute pain has deleterious clinical consequences, this information can have an important clinical significance. In this population, more attention should be given to the treatment of sleep disturbances and the management of nausea and vomiting. Further studies are needed to verify the fascinating hypothesis that adequate BTcP treatment can probably reduce the number of episodes, also improving its response to therapy, and in turn, the HRQoL of these fragile individuals.


Substance use disorders (SUDs) have been described as a dysfunctional way to compensate for deficiencies in that person’s underlying attachment system. Furthermore, the neuropeptide oxytocin (OT), which is a critical component of the neurobiology of the attachment system, has been shown to effectively reduce addictive behavior and therefore has been discussed as a potential medication in SUD treatment. This study investigates variation in peripheral OT plasma levels as a function of exposure to an attachment-related stimulus in SUD patients compared to healthy controls (HCs).A total sample of 48 men, 24 inpatients in maintenance treatment who were diagnosed with poly-drug use disorder (PUD) and 24 HC, was investigated. A 15-min exposure to the Adult Attachment Projective Picture System (AAP) was used as an attachment-related stimulus and coded for attachment status. Blood samples before and after the AAP-assessment were taken and assayed for OT levels. Variation in baselines level of OT was examined in relation to the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), the Adult Attachment-Scale (AAS), and the Brief Symptom Inventory (BSI).Following the AAP stimulus controls showed no significant difference in OT levels elevation from baseline compared to the PUD group’s OT levels. Furthermore, in the PUD group only OT-baseline-levels may be negatively associated with the AAS subscale “Comfort with Closeness” and “Anxiety” and lifetime substance use.Our results suggest that peripheral OT levels in poly-drug users undergoing maintenance treatment are not significantly different in responsiveness to an attachment related stimulus compared to HC. With regard to non-significant tendencies observed in this study which hint toward decreased OT-reactivity in the PUD group, further research is needed to explore this hypothesis with increased statistical power. Substance use disorders (SUDs) have been characterized as a compulsive substance use without consideration of the negative consequences  and are From a psychodynamic perspective, SUD has been understood in relation to attachment disorder  and as aAttachment research across mammalian species has suggested that the neuropeptide oxytocin (OT) plays a central role in the neurobiological processes involved in the formation and maintenance of social bonds , interpeIn the context of addiction, beneficial effects of administered OT on drug tolerance, withdrawal and seeking have been proposed across various substance classes , 34. IndPrevious research indicated a relationship between the administration of stimuli designed to activate the attachment system of participants and the OT-system. One such measure, the Adult Attachment Projective Picture System (AAP) was shown to significantly increase OT levels . This stWhat is more, in recent years, several reviews have been published which critically asses methodical flaws frequently observed within the research of the human OT system e.g., –45]. The. The45)]With this in mind, this study aimed to enhance the understanding the relationship between attachment and the OT-system in patients with SUD. We sought to address two primary aims. First, using baseline levels of peripheral OT, we examined their associations with substance use (using the ASSIST), attachment , and current symptoms (using the Brief Symptom Inventory). In relation to the first aim, we expected to find OT levels negatively associated with insecure attachment patterns and psychopathological symptom burden in the PUD group. Our second aim follows the experimental study by Krause et al. , which fM = 27.42, SD = 4.82), consisting of one clinical  and one non-clinical group . Participants in the clinical group met diagnostic criteria for PUD (F19.2), diagnosed according to the International Classification of Diseases version 10 (ICD 10)   by a licSD = 13.8) and received either Levo-Methasan (n = 21), Bupensan (n = 1), Substitol Retard (n = 1), or Compensan Retard (n = 1) as a substitution agent, with daily doses ranging from 2 to 320 mg, depending on patient and medication. Furthermore, 21 PUD patients received additional psychopharmacological medication: 16 (66.67%) received antipsychotics and 19 (79.17%) received antidepressants. Participants of the non-clinical group, exclusively non-smoking men, reported either none or just a few previous experiences with illegal substances. With the exception of occasional consumption of alcohol, no use of psychoactive substances was reported by HC in the last 30 days prior to the investigation and no use of psychopharmacological medication. HCs were included if they reported no past or present psychiatric disorder or chronic disease.Before participating in the study PUD patients had been in maintenance therapy for a mean time of 15 weeks . The AAP interviews were administered by a trained psychologist in a standardized manner according to the published administration requirements. Following the AAP, and 25 min after the first blood sample a second blood sample was collected, again via venipuncture. The psychometric assessment (described below) took place online via Lime-Survey® before the experiment.In order to eliminate any effects due to circadian rhythms the timing of the experiment was standardized. Participants were asked to fast for at least 3 hours before arriving in the laboratory (between 12.00 am and 3.30 pm), avoid caffeinated drinks and to refrain from smoking on the day of participation, before and during the experiment. After written informed consent was obtained and the subjects were notified about the course of the experiment, the first venipuncture and blood collection was performed. Immediately after, the AAP  was applAlcohol, Smoking and Substance Involvement Screening Test  assesseAdult Attachment Scale . Follow = 3.97; p = 0.05) and Comfort with Depending on others  = 3.61; p = 0.06) and higher depressive symptom burden  = 8.27; p < 0.05). With regard to the Bonferroni corrected alpha level, no group differences remained significant Furthermore, the between group tests for differences in the measures of mental health and attachment the PUD group showed a tendency toward less Comfort with closeness  and lifetime substance use over all substance classes . Furthermore, OT-reactivity showed non-significant tendencies with Comfort with closeness  and Lifetime substance use . Moreover, as shown in r = −.51–.49; all p < 0.05). No correlation remained significant if corrected for multiple comparisons .Correlations over PUD showed that baseline OT-levels were related to less Comfort with closeness (In order to enhance the understanding of the relationship of OT to SUD, we investigated the differences in psychopathology, attachment, and the OT-system between PUD patients undergoing maintenance treatment compared to HC, as well as differences in peripheral OT response to an attachment-related stimulus. Our results suggest that PUD patients were higher OT at baseline compared to a HC group. In response to the attachment stimulus containing the AAP procedure, differences between the PUD and HC groups regarding OT-reactivity remained non-significant. Furthermore, baseline OT-levels showed a significant relationship with decreased Comfort with closeness in PUD patients.However, these results should be interpreted with caution. In the first instance, the sample size of the study was small and there were numerous significance tests run. Following Nave et al.  and McCuThe finding of increased OT-baseline in the PUD group is in contrast to many other studies . The intOT-reactivity in PUD patients did not significantly differ from variability of HC participants. Based on previous research it might be speculated , 42, thaContradicting recent literature , 67, no In general, the main results in this study may be influenced by several effects brought about by a combination of psychopharmacology, maintenance, and long-term psychotherapeutic treatment.In addition, our findings designate a negative relationship between baseline OT-level and Comfort with Closeness in PUD patients. Corresponding to recent findings by Torres et al. , which sMoreover, we observed tentative hints toward a link between OT-reactivity and increased Comfort with closeness which, however, did not achieve statistical significance. Similarly, Krause et al.  did not Findings of the present study are mainly limited by the sample size, the exclusion of the female gender and the use of self-report measures. Furthermore, the measurement of OT is controversially discussed in literature , 71.Furthermore, nicotine abstinence was not given in PUD patients prior to the investigation in this study, which might be seen as a characteristic of PUD patients in maintenance treatment. However, in line with previous research, nicotine abuse was not related to OT , 73. Morvia the Adult Attachment projective task compared to HCs. The meaning of this finding is complicated by a number of confound in the PUD group related to both the pharmacological and psycho-social treatments they are receiving. The current findings which indicate non-significant tendencies however are an important preliminary finding which we hope will motivate more research using an experimental paradigm to further explore this hypothesis.This study suggests that peripheral OT levels in poly-drug users undergoing maintenance treatment do not show significant differences regarding responsive to an attachment related stimulus delivered This article contains previously unpublished data. Datasets are available on request.This study was carried out in accordance with the recommendations of the ethics guidelines of the Karl Franzens University of Graz, Austria. The protocol was approved by the ethics committee of the Karl Franzens University of Graz, Austria. Written informed consent in accordance with the Declaration of Helsinki was given by all subjects.JT, EW, and HU conceptualized the study. JT, AK, FT, AR, and collected the data. JT, AB, SS, BR, TP, and KL analyzed the data. JT and AB interpreted the AAP data. JT, MH-R, HU, and AL drafted and revised the manuscript. EW, H-PK, AB, MH-R, HU, JF, and AL critically reviewed the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Identifying cognitive impairment early enough could support timely intervention that may hinder or delay the trajectory of cognitive impairment, thus increasing the chances for successful cognitive aging.We aimed to build a prediction model based on machine learning for cognitive impairment among Chinese community-dwelling elderly people with normal cognition.A prospective cohort of 6718 older people from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) register, followed between 2008 and 2011, was used to develop and validate the prediction model. Participants were included if they were aged 60 years or above, were community-dwelling elderly people, and had a cognitive Mini-Mental State Examination (MMSE) score ≥18. They were excluded if they were diagnosed with a severe disease  or were living in institutions. Cognitive impairment was identified using the Chinese version of the MMSE. Several machine learning algorithms  were used to assess the 3-year risk of developing cognitive impairment. Optimal cutoffs and adjusted parameters were explored in validation data, and the model was further evaluated in test data. A nomogram was established to vividly present the prediction model.The mean age of the participants was 80.4 years (SD 10.3 years), and 50.85% (3416/6718) were female. During a 3-year follow-up, 991 (14.8%) participants were identified with cognitive impairment. Among 45 features, the following four features were finally selected to develop the model: age, instrumental activities of daily living, marital status, and baseline cognitive function. The concordance index of the model constructed by logistic regression was 0.814 (95% CI 0.781-0.846). Older people with normal cognitive functioning having a nomogram score of less than 170 were considered to have a low 3-year risk of cognitive impairment, and those with a score of 170 or greater were considered to have a high 3-year risk of cognitive impairment.This simple and feasible cognitive impairment prediction model could identify community-dwelling elderly people at the greatest 3-year risk for cognitive impairment, which could help community nurses in the early identification of dementia. Dementia constitutes a major health care burden nationally and worldwide . ApproxiGood evidence already exists that specific risk factors can contribute to increased dementia risk at different life stages. The risk factors are education in early life, hypertension and obesity in midlife, and smoking and depression in later life . PredictMachine learning has recently been used to produce a prediction model for practice. Machine learning can help in modeling information based on causal and/or statistical data, potentially revealing hidden dependencies between factors and diseases in a big data environment . PublishWe systematically searched PubMed  and found four studies in which machine learning was used to identify risk factors for dementia among people with normal cognition at baseline. One study  used unsHowever, a variety of difficulties have been identified in implementing the results of machine learning in clinical practice, as the data have been collected at one time point only, meaning that the causality of the data can be questioned . Some prThis study strictly followed the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD): The TRIPOD Statement . In thisP<.001) and had lower physical function scores (P<.001) and lower baseline cognition scores (P<.001). The two groups were not significantly different in terms of sex (P=.45).We included 11,788 participants from the 2008-09 wave, and 6718 participants were eligible for model development and internal validation. Participants were included if they were (1) aged 60 years or above; (2) community-dwelling elderly people; and (3) normally cognitive (MMSE score ≥18). They were excluded if they (1) were diagnosed with a severe disease  or (2) lived in an institution. A detailed flow chart of participant selection is shown in Cognitive impairment was defined by the Chinese version of the Mini-Mental State Examination (CMMSE) , which wPredictors related to cognitive impairment were assessed a priori based on clinical importance, scientific knowledge, and predictors identified in previously published studies . We therCategorical variables have been reported as numbers and proportions, and compared using a chi-square test or Fisher exact test. Continuous variables have been expressed as medians with IQRs and compared using the Wilcoxon test when data were not normally distributed. Detailed information is presented in We divided the original data into a 2/3 training set, 1/6 validation set, and 1/6 test set . The traP value <0.05 was considered to indicate statistical significance.In addition, if logistic regression performs well compared with the other three methods, we will formulate a nomogram based on the result of logistic regression for practical use. The nomogram works by proportionally converting each regression coefficient into a 0 to 100-point scale, with 100 points being the highest β coefficient. The points across each independent variable are added to derive total points, which are translated to predicted probabilities . All anaP<.001). Detailed information is presented in A total of 6718 participants were involved. Forty-five explanatory variables were selected, and these variables included nine items of demographic characteristics, five items of lifestyle, 10 items of mental health, five items of leisure activities, two items of sleep, seven items of chronic diseases, two items of physical function, four items of the anthropometric index, and one item of baseline cognitive function. Six variables of demographic characteristics , four variables of lifestyle , eight variables of mental health , five variables of leisure activity , two variables of sleep , five variables of chronic diseases , two variables of physical function , one variable of anthropometric measurement (BMI), and baseline MMSE were significantly associated with a 3-year risk of cognitive impairment (NB combined with RFE showed that accuracy (0.8342) was the highest with four features included in the model . RF combined with RFE showed that the model involving 45 variables had the highest accuracy (0.8502), while the model including four variables had an accuracy of 0.8304 . ConsideThe training, validation, and test sets involved 4514, 1100, and 1104 points of data, respectively. We tried to use several widely applied machine learning algorithms  for the construction of the prediction models in the training set.We used a receiver operating characteristic (ROC) curve, specificity, sensitivity, accuracy, and specificity/sensitivity to evaluate the prediction model in both validation and test data. Before the evaluation, optimal cutoffs were determined by maximizing the Youden index  by the ROC curve in the validation set. In the test set, ROC curves revealed that logistic regression and NB had better predictive performances, with an area under the curve of 0.814. The area under the curve of XGBoost (0.811) was less than that of logistic regression and NB. RF underperformed, with an area under the curve of 0.780 .The model of NB performed well in terms of specificity, with a value of 0.776. The specificities of the models of logistic regression (0.770), RF (0.645), and XGBoost (0.738) were lower than that of NB. The model of RF performed well in terms of sensitivity, with a value of 0.793. The sensitivities of the models of logistic regression (0.701), NB (0.672), and XGBoost (0.724) were lower than that of RF. The accuracy of the NB model (0.760) was higher than the accuracies of the other three models. All details about the parameters of the models developed with different algorithms are shown in As the prediction developed by logistic regression performed well, a nomogram  was usedIn this study, we developed a prediction model for forecasting the 3-year risk of cognitive impairment among 6718 community-dwelling elderly individuals aged 60 years or older with normal cognitive function via machine learning algorithms. The model performed comparably to the best available biomarkers, such as apolipoprotein genotype ,17, but Feature or variable selection is central in the development of a prediction model . Out of In this study, age was one of the predictors for the risk of cognitive impairment. It has already been estimated that, in 2020, 83% of people aged 75 years or above live with dementia in the US . Those aWe found that marital status was a strong predictor for the risk of cognitive impairment. A recent meta-analysis involving 812,047 participants evaluated the association between marriage and dementia. The results showed that life-long single and widowed older people were respectively 1.42 and 1.20 times more likely to be diagnosed with dementia compared with married older people . AnotherAn association between physical function and cognitive capacity among older people has been found in previous studies ,40. Our Baseline cognitive function affected the degree to which cognitive scores changed over time and had a profound effect on further cognitive impairment. In one study using UK biobank data to assess the effect of baseline cognitive performance on a prediction model for 3 to 8-year risk of dementia, the results showed that cognitive performance added up to 5% (from 0.78 to 0.83) to the discriminative accuracy of the ROC model developed with the variables of age, sex, education, family history, and depression . The MMSOur study has limitations, which should be considered in the interpretation of the study results. First, retained cohort members were younger and had on average better cognitive and physical functioning than those who dropped out, which can lead to studies being severely underpowered and biased toward the healthier part of the aging population. As we used a nationally representative database, the ascertainment bias could, to an extent, be limited. Second, we utilized a cross-validation approach to model development and assessment. The results still need to be validated in an independent cohort. Third, we used cohort studies with insufficient details on the duration of marriage, widowhood, and divorce to allow the exploration of a dose-response effect. A future study could take the dose-response effect of marital status on cognitive function into consideration. Fourth, the baseline MMSE was used as one of the predictors. However, other specific cognitive domains, such as memory and executive function, could also be used as features, and they might perform better than whole cognitive function. Fifth, our models were based on a prospective cohort that may have some level of bias. A prospective external validation cohort is needed for further confirmation in future research. Lastly, some predictors used in our study were measured by self-reporting, resulting in information bias. Nevertheless, self-reported data are more feasibly collected in primary health care settings, and the results can be generalized to wider communities. Despite these limitations, we believe that the results are usable in terms of cognitive impairment prevention and further intervention globally.This is one of the first studies where a machine learning approach has been used in a nursing context. The study showed that machine learning can be used more widely in nursing science in different contexts and various functions. The prediction models exert implications in the three-grade prevention system of diseases . In the This study provides guidance for future research as well. First, the use of several algorithms to construct prediction models in specific diseases offers more opportunity to find a more suitable model with a high area under the curve and accuracy. Second, selecting the most suitable predictors is important for developing a prediction model to use in clinical practice. Easy-to-acquire, noninvasive, and low-cost variables are welcome in clinical nursing, and invasive biomarkers could improve the prediction. The former is more suitable for community health care and any clinical environment because of large populations and insufficient staff and funds, while the latter is more applicable in more specific clinical environments for people with high risk of diseases. Lastly, we included Chinese elderly people aged 60 years or above and developed a cognitive impairment prediction model. Further studies could develop cognitive impairment prediction models for middle-aged people as the World Health Organization has suggested to increase the cognitive reserve in mid-life and early aging (45-70 years) .In the future, the results of this study could be used in countries and areas with less human resources, such as low- and middle-income countries, to identify elderly people with a high risk of developing cognitive deficiency in the next 3 years . Simple, relevant, and easy-to-detect risk factors would save time and resources in health care and would especially help nursing staff identify those people who are at high risk of developing cognitive impairment. As family members living with elderly people do not always recognize the early signs of dementia , the kno


Posttraumatic stress disorder (PTSD) is one of the psychopathological consequences of sexual and/or physical abuse. The economic burden is assumed to be high, whereas health-related quality of life and education is negatively affected. This study aims to determine health care costs, health-related quality of life, and educational interruption in adolescents and young adults with PTSD after sexual and/or physical abuse in Germany.This analysis used data of 87 participants aged 14–21 years of a randomized controlled trial. Health care utilization, health-related quality of life (EQ-5D-5L), sick leave days, productivity, and delay or failure to achieve educational aims were assessed. Health care costs from a payer perspective were calculated using unit costs for the year 2014.Mean health care costs for a six-month period were 5,243€ (SE 868€). In particular, costs of inpatient stays in psychiatric hospitals, general hospitals and rehabilitation as well as child welfare institutions were high. In addition, health-related quality of life was lower due to anxiety/depression, resulting in a mean EQ-5D index and EQ-VAS score of 0.70 and 61.0, respectively. Furthermore, participants reported on average 27 sick leave days, a productivity loss of 61%, and a delay in education attainment as well as having been unable to achieve educational aims.PTSD in adolescents and young adults is associated with a high economic burden. Health-related quality of life was substantially reduced. Furthermore, delay and productivity losses in education were observed.th March 2013; https://www.drks.de.German Clinical Trials Register identifier: DRKS00004787; date of registration: 18 Posttraumatic stress disorder (PTSD) is characterised by distress symptoms lasting more than one month following a traumatic event, such as sexual and/or physical abuse, accidents or war experiences. According to DSM-IV, PTSD is characterised by intrusive reliving of the traumatic events, avoidance of reminders of the trauma, and hyperarousal symptoms. Furthermore, patients have to suffer from clinical distress, or experience difficulties in social or occupational functioning to be diagnosed with PTSD .The high lifetime prevalence of PTSD has been estimated by numerous studies , 3. As iPatients often suffer from long-term consequences such as mental and somatic comorbidities, unemployment and reduced productivity as well as reduced quality of life –8. MoreoInternational treatment guidelines as the one by the National Institute for Health and Care Excellence (NICE) recommend trauma-focused cognitive behavioural therapy or eye movement desensitization and reprocessing therapy . Based oEven though the consequences of PTSD are significant, only a limited number of health economic studies addressing PTSD after sexual abuse exist , 12–16. To our knowledge, only one empirical health economics study that focusses on cost of illness of adolescents and young adults with PTSD after sexual and/or physical childhood abuse in the UK has been published . This stTherefore, this study estimated the economic consequences of PTSD with respect to health care utilisation, costs and health-related quality of life for adolescents and young adults with PTSD in Germany. In addition, it determined the impact of PTSD on educational interruption, which could be considered as an indicator of future indirect costs.This study used baseline data on health care utilisation and health-related quality of life of participants enrolled in a multicentre randomized controlled trial (RCT) for adolescents and young adults with PTSD , 19. StuParticipants with a primary diagnosis of PTSD related to childhood sexual and/or physical abuse were eligible to participate, provided they were also between the ages of 14 and 21, had no or a stable psychopharmacological medication (for ≥ 3 weeks) and lived in stable conditions. Furthermore, sufficient knowledge of German language was required. Participants with current severe or life-threatening suicidality or self-harming behaviour within the last 6 month, IQ ≤ 75, current substance dependence (abstinence < 6 months), or a substance-induced disorder, any documented pervasive developmental disorder, lifetime psychotic or bipolar disorder (unclear cases were included) according to the DSM-IV-TR , 19.Socio-demographics included individual characteristics  as well as family background , living situation, education and educational level of the parents. Clinical parameters included information on previous treatment and the severity of PTSD as measured by the Clinician Administered PTSD Scale for Children and Adolescents (CAPS-CA) , 21. TheHealth care utilisation during the six months prior to baseline was assessed using an adapted version of the Client Socio-demographic and Service Receipt Inventory (CSSRI) questionnaire . Utilisa5) different health states, which could be transferred to the EQ-5D index. The EQ-5D index is a score between -0.661 (extreme problems) and 1   . In addi health) .Educational interruptions were assessed by questions concerning school education and professional training, including the number of days absent from school/professional training due to PTSD over the previous six months. Even if patients had participated at school/professional training, productivity loss might have occurred. Therefore, productivity loss at school/professional training due to PTSD was considered using a visual analogue scale ranging from 0 (“no productivity loss”) to 10 (“complete productivity loss”). In addition, educational delays due to PTSD were assessed by asking for repeated years at school. Furthermore, participants reported failed school graduation or professional training graduation due to PTSD. Finally, problems in finding a professional training position or job were evaluated by a visual analogue scale between 0 (“no problems”) and 10 (“severe problems”). As most participants did not complete school yet, educational interruptions and productivity loss at school were not monetarily valued.The maximum missing rate per variable in the evaluated data set was 23% for sick leave days at school. Of all participants, 10% did not report their achieved educational level or their health care utilisation for inpatient stays in general hospitals and rehabilitation. In 5% to 10% of all cases information on child welfare institutions, outpatient physician visits, counselling, and inpatient stays in psychiatric hospitals was missing. The proportions of missing values for all other variables were 5% or less. Even though no common threshold for an inconsequential proportion of missing data is reported in the literature, the use of imputation methods for missing rates above 5% is recommended . As the We analyzed costs, health-related quality of life and variables on education/professional training using descriptive statistics, and determined the influence of age, gender, CAPS-CA total score, and psychiatric comorbidities on costs and health-related quality of life to identify subgroups of patients with increased and decreased costs or health-related quality of life. For total cost data generalized linear models (GLMs) with a Gamma distribution and a log-link function were used, whereas health-related quality of life was analyzed using linear regression. For all analyses, a significance level of 5% was applied.Subgroup analyses determined costs by study centres and treatment options. Differences between subgroups were tested using regression analyses adjusted for age, gender, CAPS-CA total score, and psychiatric comorbidities.All computations were conducted with R (3.5.1). In particular, the R-package “mice” was used for multiple imputation .Participants had a mean age of 18.1 (SD 2.3) years, and 15% were male  for the 6-month prior to baseline  and 10 (“severe problems”).Our analyses revealed a high burden of direct costs, reduced health-related quality of life and educational interruption among adolescents and young adults with PTSD.Costs were mainly due to psychiatric hospitals, general hospitals and rehabilitation. As most of the participants had at least one psychiatric comorbidity, inpatient costs may be due to these. In addition, high costs were due to the utilisation of child welfare institutions. Of all participants, 15% were living neither at home nor with relatives/friends. The trigger of the disease may be the reason, as it is often located in the family environment. Almost every participant used outpatient physician treatment. Yet, compared to inpatient treatment costs, only moderate outpatient treatment costs were observed. More than half of the outpatient treatment costs were due to psychological treatment.To our knowledge, one study has estimated cost of PTSD in children and adolescents  and onlyUnfortunately, no cost data for young patients with PTSD or a representative sample of adolescents and young adults of the general population in Germany have been published. One study reported costs for the German health care system for adult with PTSD . In lineHealth-related quality of life in adolescents and young adults with PTSD was markedly reduced. Participants indicated a mean EQ-5D Index and EQ-VAS score of 0.70 and 61.0, respectively. Our results showed considerable impairments for participants with PTSD, when compared with a representative German population sample aged between 8 and 18 years . PersonsOn the EQ-5D-5L dimension anxiety/depression, 13% and 22% of the participants reported extreme and severe problems, whereas only 2% in the general populations were impaired extremely or severely. Furthermore, 90% of the participants with PTSD reported to have any problems due to anxiety/depression, which was much more frequent compared with only 22% of the general population. In addition to problems due to anxiety/depression, our results indicated problems of adolescents and young adults with PTSD in the EQ-5D-5L dimension of pain/discomfort. Whilst only 2% and 26% of the general population reported to have extreme/severe and slight/moderate problems respectively, 13% and 61% of the adolescents and young adults with PTSD reported such problems. Furthermore, participants with PTSD reported more problems in the dimensions of mobility and usual activities, although less frequently than in the dimensions of anxiety/depression and pain/discomfort. Problems with usual activities were rated to be extreme/severe or slight/moderate by 13% and 44% of the participants, whereas only 1% and 12% of the persons of the general population reported such problems. Furthermore, 28% of the participants with PTSD experienced slight/moderate problems in the dimension of mobility compared to 4% in the general population. Both problems due to mobility, as well as usual activities may be due to the desire among those diagnosed with PTSD to avoid the re-experience of the traumatic event and/or the hyperarousal caused by the traumatic event. For both, persons with PTSD and the general population, only few problems were reported on the dimensions self-care, where more than 94% experienced no problems. In conclusion, health-related quality of life was decreased among adolescents and young adults with PTSD. In particular, anxiety/depression seems to have a substantial influence.To our knowledge only one other studies reported health-related quality of life for children with PTSD aged between 9 and 11 years . ParticiDuring a six-month period, adolescents and young adults with PTSD had on average 27 sick leave days in school/professional training. Productivity was reduced by 61%.In line with our results, a recently published systematic review considering the impact of traumatic experiences on school performances revealed a reduced school performance of participants with PTSD . FurtherFurthermore, adolescents and young adults with PTSD had achieved a lower educational level compared with the German population . SpecifiEven though PTSD is highly prevalent and has significant consequences, only a small number of studies have examined its effects on costs, health-related quality of life and education in adolescents and young adults. Although the estimated number of unreported cases of abuse-related PTSD is high, we were able to provide empirical data of 87 adolescents and young adults with PTSD to close this gap in the literature. The evaluation of resource utilisation was adapted to the study population, and the costs associated with the utilisation of the established CSSRI youth welfare services, social counselling and child welfare institutions were also assessed. Costs due to transport and long-term nursing care were not assessed. Instead of indirect costs due to absenteeism from work and productivity loss, performance of adolescents and young adults with PTSD at school/professional training were evaluated. Finally, we used advanced statistical methods. Missing values were handled by multiple imputation using MICE. MICE is widely used to impute values missing (completely) at random, thus a loss of statistical power was avoided. In addition, the skewness in cost data was taken into account using GLMs assuming a Gamma distribution and log-link function.Even though the study was carried out carefully, it does include some limitations. First, the sample size of the study (n=87) was rather small. As the distribution of cost data was skewed, the small sample size may have led to a bias in cost calculations. Nevertheless, results showed a reduced quality of life and high costs for adolescents and young adults with PTSD. Second, multiple imputation using MICE requires missing at random (MAR). Unfortunately, no statistical test exists to distinguish between MAR and missing not at random (MNAR), thus MNAR could not be ruled out. However, sociodemographic statistics for persons, who did not report health care utilization in major cost drivers , did not differ compared with those of the complete sample. Finally, almost half of the participants had not completed school yet. Therefore, results on educational interruption cannot be interpreted as long-term consequences of PTSD. In addition, further problems may arise in later working life . Therefore, future research should consider long-term economic consequences of PTSD in adults after sexual and/or physical abuse.Finally, costs were collected independent of seasons for 6 months prior to baseline, so that the influence of seasons on health care utilization could not be determined. However, a seasonal influence on the results was not expected, because no seasonal clinical events are known for PTSD.PTSD in adolescent and young adults has a high economic burden. High costs due to inpatient stays in psychiatric hospitals, general hospitals and rehabilitation as well as child welfare institutions occurred. Health-related quality of life was substantially reduced. Furthermore, considerable delays and productivity losses in education were observed.The datasets presented in this article are not readily available because of ethical and confidentiality concerns.The studies involving human participants were reviewed and approved by Ethics Committee of Catholic University Eichstätt-Ingolstadt, Eichstätt, Germany; the Freie Universitaet of Berlin,Berlin, Germany; and the Goethe University Frankfurt, Frankfurt am Main, Germany. Written informed consent was obtained from all participants and in the case of minors from the participants' legal guardian.ER, RS, BR, RR, and H-HK conceived the study and developed the design. JD was responsible for the analysis and wrote the first draft. All authors contributed to the article and approved the submitted version.This study was supported by grants from the German Ministry of Education and Research . The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.RR reported being paid fees for workshops and presentations on posttraumatic stress disorder (PTSD) treatment and coauthoring a book on cognitive processing therapy. RS reported being paid fees for workshops and presentations on PTSD treatment.The remaining 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.


Surgical Site Infections (SSIs) are among the leading causes of the postoperative complications. This study aimed at investigating the epidemiologic characteristics of orthopedic SSIs and estimating the under-reporting of registries using the capture-recapture method.N = 503). Second, 202 samples were randomly selected to assess patients` characteristics.This study, which was a registry-based, cross-sectional one, was conducted in six educational hospitals in Tehran during a one-year period, from March, 2017 to March, 2018. The data were collected from two hospital registries  and Health Information Management database (HIM)). First, all orthopedic SSIs registered in these sources were used to perform capture-recapture (Staphylococcus aureus (11.38%) was the most frequently detected bacterium in orthopedic SSIs. The median time between the detection of a SSI and the discharge was 17 days. The results of a study done on 503 SSIs showed that the coverage of NNIS and HIM was 59.95 and 65.17%, respectively. After capture-recapture estimation, it was found that about 221 of orthopedic SSIs were not detected by two sources among six hospitals and the real number of SSIs were estimated to be 623 ± 36.58  and under-reporting percentage was 63.32%.Totally, 76.24% of SSIs were detected post-discharge. To recognize the trends of SSIs mortality and morbidity in national level, it is significant to have access to a registry with minimum underestimated data. Therefore, according to the weak coverage of NNIS and HIM among Iranian hospitals, a plan for promoting the national Infection Prevention and Control (IPC) programs and providing updated protocols is recommended. Escherichia-coli, accounting for 6.7–50% of incidence, and the second one is gram-positive Staphylococcus aureus, causing SSI in procedures [Surgical Site Infection (SSI) is one of the most common surgical-related problems in the world, especially in developing countries . SSI is ocedures . In Eastocedures . The oveocedures .Due to the nature of orthopedic surgeries and special patients under this procedure with variety of conditions and disorders  the risk of surgical site infection is higher compared to other procedures. The incidence of orthopedic SSIs in Iran was 8.8% in 2018; This type of infection has been responsible for long hospitalization period and bad prognosis , 11.In Iran, there are two hospital information sources for registering HAIs. One of these information sources is Health Information Management (HIM) that plays a role in maintaining and collecting the medical records. In this unit, all medical and health information of patients is registered based on ICD-10 and ICD-9-CM coding system . The secThus, to realize the real distribution and trends of diseases in order for controlling and preventing its outcomes in the country, complete data with minimum underestimation is required. This study was conducted aiming at the estimation of the number of orthopedic SSIs from 2017 to 2018 using the capture-recapture method. At the second stage, the existing problems in NNIS among hospitals under study in Iran were reported.N = 503, after the exclusion of duplicates) Fig. This registry-based, cross-sectional study was conducted in six educational hospitals in Tehran from March, 2017 to March, 2018. First, six hospitals (over 250 beds) were randomly selected. After that, data were collected from two sources in hospitals. One of them is the information of patients infected in orthopedic surgeries from 21 March, 2017 to 21 March, 2018 - orthopedic SSIs were based on the health information management (HIM) reporting. The second one was the orthopedic SSIs which were based on National Nosocomial Infections Surveillance system (NNIS) registries in each six mentioned hospitals. Overall, we collected 262 and 241 identical codes of SSIs from HIM and NNIS, respectively from 2017 to 2018 . Furthermore, the completeness percentages of HIM and NNIS based on the capture-recapture method were 42.05 and 38.68%, respectively and under-reporting was 63.32%. This indicates the completeness of SSI registries was low, and about half of the cases were missed among the respective six hospitals in Tehran from 2017 to 2018.Staphylococcus aureus (11.38%) and Klebsiella (10.89%) were the most frequent bacteria in orthopedic SSIs. Furthermore, 5 (2.47%) cases died due to orthopedic SSIs. A statistically significant association was observed between the type of microorganism (P = 0.001) and time between surgery to infection (P < 0.001) with occurrence of SSIs (post or pre discharge).In Table P < 0.001)  days. After operation, SSIs led to longer hospitalization with median of 17 8-29) days. Also, the median length of surgery to infection occurrence was 27.5 days, which has been longer among post discharge SSIs (36.5 days) . About 2.47% of cases died due to orthopedic surgical site infection. These results are in line with other literatures in which SSI was more among males and middle-aged patients with fatality rate of 2–3%. However, Al-Mulhim, et al. found that SSI was more common in younger patients with an average age of 38 in Saudi Arabia , 18.Surgical site infection may lead to many complications, among which one is prolonged hospitalization due to infection. In this study, the median days of hospitalization due to orthopedic surgery was 17 days while the median length of hospitalization due to SSI was 11 days. This finding is similar to other prior studies that reported the mean of hospitalization days due to SSI; it varied from 4 to 32 days and the average length of increased hospitalization due to orthopedic SSIs was 19.8 days while the average length of stay for patients with no post-surgical infection was lower at 9.1 days . Thus, SAfter study on post- discharge and pre-discharge SSIs, it was observed that 76.24% of SSIs occurred after discharge, among which 45.54% occurred within 31 days after orthopedic procedure and, totally, 17.82% of SSIs were detected within 90 days to one year after orthopedic surgery. This varies by the type of orthopedic procedures. So that, 19.57% of SSIs due to ORIF procedures occurred post-discharge within 90 days to one year after surgery. These results were in line with other studies in which it was reported that the length of time between discharges to the detection of orthopedic SSIs varied between 8 days to 8 months. In another study, it was reported that most SSIs were detected after the 21st postoperative day , 24. As As it was mentioned, In Iran, there are two independent registries in each hospital. One of them is HIM that generally recognizes and registers all disease cases using ICD-10 and ICD-9 criteria from medical reports of each patient. The other is NNIS that registers HAIs in each hospital. After collecting all reported HAIs from hospitals in the country, based on the NNIS report, all of them are reported to Iranian Center for Communicable Disease Control (ICCDC) in the Ministry of Health and Medical Education . Thus, tLack of data linkage between emergency units of hospitals and private clinics with NNIS:In Iran, only in-patients with severe HAIs, are registered as infected cases. Therefore, probable HAIS that are referred to private clinics or hospital emergency rooms are not being recorded as nosocomial infections and it leads to possibly of missing patients with subclinical infections;Lack of data linkage between HIM unit and NNIS;Lack of active surveillance system: NNIS in Iran is currently a passive surveillance, it means that health care workers report notifiable nosocomial cases on a case-by-case basis and it is impossible to ensure compliance by health care providers. so, it leads to under-reporting , 28;Lack of post-discharge surveillance;Non-reliable laboratory investigation methods : prescription of antibiotics, as a routine implementation before surgeries, can affect the results of laboratory tests  and can Limited human and technical resources to register and quality control of NNIS.Furthermore, after capture-recapture was observed, the completeness of NNIS was 38.68%. In other words, under-reporting of orthopedic SSIs among six educational hospitals was about 63.32%. This finding was in line with another study in which under-reporting of SSIs in ICU was 82.2% in 2019 . Under-rWith regard to the existing problems, it is recommended to plan for updating the existing prevention and controlling NNIS protocols in Iran. Some actions that can be taken are antibiotic prescription monitoring, assigning and retraining health care workers with experience of registry management and infection prevention and control, planning to provide the infrastructure for linkage of data among hospitals, clinics, and emergency units using electronic medical records, taking advantage of Standardized Infection Ratio (SIR) as a summary measure recommended by the National Healthcare Safety Network (NHSN) to track Health care-associated Infections (HAIs) , assigniSome limitations of the current study should be noted. First, because of the lack of time and the large number of hospitals, we could not conduct a study on all educational hospitals in Tehran province. Second, since private hospitals did not cooperate, we conducted this study in six educational hospitals in Tehran.In order for knowing the trends of mortality and morbidity in hospitals and in country also for aiding health care services for planning prevention strategy, it is important to have access to a registry with minimum underestimated data. Hence, according to the moderate coverage of NNIS and HIM data sources among Iranian hospitals, it is highly necessary to promote the national Infection Prevention and Control (IPC) programs and to provide updated protocols.