Project description:The aim of this study was to evaluate the influence of sex on serum paraoxonase-1 (PON1) activities and on its relationship with cardiovascular disease risk factors such as overall and central obesity. Arylesterase and lactonase activities of PON1 were assessed in 374 women and 92 men. Both arylesterase and lactonase activities were significantly higher in women compared to men (p<0.001), irrespectively of confounders such as high density lipoprotein-cholesterol, age, smoking and body mass index or waist circumference. Sex also strongly influenced the interplay between PON1 and both fat measures, with only the arylesterase showing a significant and independent inverse correlation with the former parameter (r = -0.248, p<0.001) and the risk of overall obesity (odds ratio: 0.559, 95% confidence interval: 0.340-0.919) in women, but not in men; conversely, neither of the two activities remained associated with waist circumference in men or women after full adjustment. Noteworthy, the association between arylesterase and BMI in the female subsample was significant among women younger than forty-five years (r = -0.453, p<0.001, R 2 = 0.207). In conclusion, our study suggests that sex might chiefly influence PON1 activity and its contribution to cardiovascular disease risk. Further studies are needed to confirm and clarify our preliminary findings.
Project description:Chronic urticaria (CU) is one of the most common dermatological diseases and has a significant impact on the quality of life of patients. However, the pathogenesis of this disease remains unclear. Autoimmunity in chronic spontaneous urticaria (CSU) has received considerable attention and has been studied previously. Atopy is an important characteristic of CU; however, it has not been fully recognized. Atopy predisposes individuals to immune responses to allergens, leading to type 2 inflammation and immunoglobulin E (IgE) overproduction. Compared with healthy individuals, patients with CU have a higher proportion of atopy, and an atopic background is correlated with the clinical characteristics of CU. The total IgE levels in patients with CU is significantly higher than those in healthy individuals. Although its level is not higher than that in classic allergic diseases, it is closely related to CU. Exogenous allergens, auto-allergens, and specific IgEs, which are closely related to atopy, have been reported, and their roles in CU pathogenesis are also being studied. Local and systemic atopic inflammation is present in patients with CU. This review summarizes the current knowledge regarding atopy and CU, speculating that there are CU subtypes, such as atopic CSU or atopic chronic inducible urticaria (CIndU) and that atopy may be involved in the pathogenesis of CU. These findings provide a new perspective for a comprehensive understanding of the clinical features of CU and further research regarding its pathogenesis.
Project description:ObjectivesTo investigate the impact of gender on multimorbidity in northern Iran.DesignA cross-sectional analysis of the Golestan cohort data.SettingGolestan Province, Iran.Study population49 946 residents (age 40-75 years) of Golestan Province, Iran.Main outcome measuresResearchers collected data related to multimorbidity, defined as co-existence of two or more chronic diseases in an individual, at the beginning of a representative cohort study which recruited its participants from 2004 to 2008. The researchers utilised simple and multiple Poisson regression models with robust variances to examine the simultaneous effects of multiple factors.ResultsWomen had a 25.0% prevalence of multimorbidity, whereas men had a 13.4% prevalence (p<0.001). Women of all age-groups had a higher prevalence of multimorbidity. Of note, multimorbidity began at a lower age (40-49 years) in women (17.3%) compared with men (8.6%) of the same age (p<0.001). This study identified significant interactions between gender as well as socioeconomic status, ethnicity, physical activity, marital status, education level and smoking (p<0.01).ConclusionPrevention and control of multimorbidity requires health promotion programmes to increase public awareness about the modifiable risk factors, particularly among women.
Project description:ObjectiveTo establish a score threshold that constitutes a clinically relevant change for each domain of the Expanded Prostate Cancer Index Composite (EPIC) Short Form (EPIC-26). Although its use in clinical practice and clinical trials has increased worldwide, the clinical interpretation of this 26-item disease-specific patient-reported quality of life questionnaire for men with localized prostate cancer would be facilitated by characterization of score thresholds for clinically relevant change (the minimally important differences [MIDs]).MethodsWe used distribution- and anchor-based approaches to establish the MID range for each EPIC-26 domain (urinary, sexual, bowel, and vitality/hormonal) based on a prospective multi-institutional cohort of 1201 men treated for prostate cancer between 2003 and 2006 and followed up for 3 years after treatment. For the anchor-based approach, we compared within-subject and between-subject score changes for each domain to an external "anchor" measure of overall cancer treatment satisfaction.ResultsWe found the bowel and vitality/hormonal domains to have the lowest MID range (a 4-6 point change should be considered clinically relevant), whereas the sexual domain had the greatest MID values (10-12). Urinary incontinence appeared to have a greater MID range (6-9) than the urinary irritation/obstruction domain (5-7).ConclusionUsing 2 independent approaches, we established the MIDs for each EPIC-26 domain. A definition of these MID values is essential for the researcher or clinician to understand when changes in symptom burden among prostate cancer survivors are clinically relevant.
Project description:To observe the impact of acute renal morbidities with obstetrical emergencies on maternal health.In this study pregnant women between 28-40 weeks gestational period and delivered women in their puerperal period up to 42 days after delivery having acute renal problems associated with obstetrical emergencies were included. Pregnant and delivered women with obstetrical emergencies and associated other morbidities were excluded. These women were registered on the predesigned proforma after taking written informed consent and taking approval from institutional ethic research committee. The data was collected and analyzed on SPSS version 21.Out of these 196 total registered women, majority of these women 81(41.32%) were between 21-30 years of age and multiparous women with parity four and above were 83(42.34%). Commonest presenting symptoms were generalized oedema 123(62.75%) and oligouria 92(46.93%). Frequent obstetrical emergencies observed were pre-eclampsia 53(27.04%), post partum haemorrhage 48(24.48%) and ante partum haemorrhage 36(18.36%) women. The complete recovery was observed in 86(43.87%) women, while mortality was seen in 56(28.57%) women.Renal morbidities were more frequently observed in obstetrical emergencies leading to high morbidity and mortality rate.
Project description:BackgroundThe minimum clinical important differences (MCIDs) of resilience instruments in patients with cancer have not been comprehensively described. This study was designed to evaluate MCIDs of 10-item and 25-item resilience scales specific to cancer (RS-SC-10 and RS-SC-25).MethodsFrom June 2015 to December 2018, RS-SCs were longitudinally measured in 765 patients with different cancer diagnoses at baseline (T0) and 3 months later (T1). The EORTC QLQ-C30, Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Allostatic Load Index were measured concurrently as anchors. Anchor-based methods (linear regression, within-group), distribution-based methods(within-group), and receiver operating characteristic curves (ROCs, within-subject) were performed to evaluate the MCIDs.Results623 of 765 (84.1%) patients had paired RS-SCs scores. Moderate correlations were identified between the change in RS-SCs and change in anchors (r = 0.38-0.44, all p < 0.001). Linear regression estimated + 8.9 and - 6.7 as the MCIDs of RS-SC-25, and + 3.4 and - 2.5 for RS-SC-10. Distribution-based methods estimated + 9.9 and - 9.9 as the MCIDs of RS-SC-25, and + 4.0 and - 4.0 for RS-SC-10. ROC estimated + 5.5 and - 4.5 as the MCIDs of RS-SC-25, and + 2.0 and - 1.5 for RS-SC-10.ConclusionsThe most reliable MCID is around 5 points for RS-SC-25 and 2 points for RS-SC-10. RS-SCs are more responsive to the worsening status of resilience in patients with cancer and these estimates could be useful in future resilience-based intervention trials.
Project description:BackgroundThe rationale for ethnic differences in bladder cancer (BCa) susceptibility is an important open question. In this study, we raised the hypothesis that the APOBEC3-rs1014971 variant associated with BCa risk and APOBEC-mutagenesis probably contribute to ethnic differences.MethodsWe calculated the ethnicity-stratified 5-year age-adjusted incidence rates of BCa using the US SEER database. We performed somatic mutational-signature analyses and compared the APOBEC-related mutational contribution across BCa tumors in patients of different ethnicities. We analyzed the allele frequency distribution of APOBEC3-related rs1014971 in contemporary populations of different ethnicities and in ancient human genomes. We also analyzed the natural selection profiles and ages of the investigated SNPs.ResultsWe validated the ethnic difference in BCa risk using US SEER data, revealing Caucasians to be at >2-fold greater risk than Asians / Pacific islanders. In contemporary populations, we observed a coherent ethnic distribution in terms not only of the allele frequency of APOBEC3-related rs1014971, but also the mutational contribution of APOBEC-mediated mutagenesis in BCa tumors. Population genetics and ancient genome analyses further suggested that the diverse ethnic distribution of rs1014971 could be rooted in human evolution.ConclusionsIt is possible that APOBEC3-related rs1014971 is involved in the different BCa incidence across ethnic groups, and this difference is potentially derived from human evolution. Our findings suggested an evolutionary link between contemporary population-level variations in malignancy susceptibility and pathogen-driven selection in the past, not unlike previously reported cases of certain autoimmune and metabolic disorders.
Project description:Clinical research has become increasingly globalized, but the extent of globalization has not been assessed. To describe the globalization of clinical research, we used all (n = 13,208) multinational trials registered at ClinicalTrials.gov to analyzed geographic connections among individual countries. Our findings indicate that 95% (n = 185) of all countries worldwide have participated in multinational clinical research. Growth in the globalization of clinical research peaked in 2009, suggesting that the global infrastructure that supports clinical research might have reached its maximum capacity. Growth in the globalization of clinical research is attributable to increased involvement of non-traditional markets, particularly in South America and Asia. Nevertheless, Europe is the most highly interconnected geographic region (60.64% of global connections), and collectively, Europe, North America, and Asia comprise more than 85% of all global connections. Therefore, while the expansion of clinical trials into non-traditional markets has increased over the last 20 years and connects countries across the globe, traditional markets still dominate multinational clinical research, which appears to have reached a maximum global capacity.
Project description:RationaleThe University of California, San Diego Shortness of Breath Questionnaire (UCSDSOBQ) is a frequently used domain-specific dyspnea questionnaire; however, there is little information available regarding its use and minimum important difference (MID) in fibrotic interstitial lung disease (ILD). We aimed to describe the key performance characteristics of the UCSDSOBQ in this population.MethodsUCSDSOBQ scores and selected anchors were measured in 1933 patients from the prospective multi-center Canadian Registry for Pulmonary Fibrosis. Anchors included the St. George's Respiratory Questionnaire (SGRQ), European Quality of Life 5 Dimensions 5 Levels questionnaire (EQ-5D-5L) and EQ visual analogue scale (EQ-VAS), percent-predicted forced vital capacity (FVC%), diffusing capacity of the lung for carbon monoxide (DLCO%), and 6-min walk distance (6MWD). Concurrent validity, internal consistency, ceiling and floor effects, and responsiveness were assessed, followed by estimation of the MID by anchor-based (linear regression) and distribution-based methods (standard error of measurement).ResultsThe UCSDSOBQ had a high level of internal consistency (Cronbach's alpha = 0.97), no obvious floor or ceiling effect, strong correlations with SGRQ, EQ-5D-5L, and EQ-VAS (|r| > 0.5), and moderate correlations with FVC%, DLCO%, and 6MWD (0.3 < |r| < 0.5). The MID estimate for UCSDSOBQ was 5 points (1-8) for the anchor-based method, and 4.5 points for the distribution-based method.ConclusionThis study demonstrates the validity of UCSDSOBQ in a large and heterogeneous population of patients with fibrotic ILD, and provides a robust MID estimate of 5-8 points.
Project description:ObjectivesPrimary objective is to determine if transfusion of short storage RBCs compared with standard issue RBCs reduced risk of delirium/coma in critically ill children. Secondary objective is to assess if RBC transfusion was independently associated with delirium/coma.DesignThis study was performed in two stages. First, we compared patients receiving either short storage or standard RBCs in a multi-institutional prospective randomized controlled trial. Then, we compared all transfused patients in the randomized controlled trial with a single-center cohort of nontransfused patients matched for confounders of delirium/coma.SettingTwenty academic PICUs who participated in the Age of Transfused Blood in Critically Ill Children trial.PatientsChildren 3 days to 16 years old who were transfused RBCs within the first 7 days of admission.InterventionsSubjects were randomized to either short storage RBC study arm (defined as RBCs stored for up to seven days) or standard issue RBC study arm. In addition, subjects were screened for delirium prior to transfusion and every 12 hours after transfusion for up to 3 days.Measurements and main resultsPrimary outcome measure was development of delirium/coma within 3 days of initial transfusion. Additional outcome measures were dose-response relationship between volume of RBCs transfused and delirium/coma, and comparison of delirium/coma rates between transfused patients and individually matched nontransfused patients. We included 146 subjects in the stage I analysis; 69 were randomized to short storage RBCs and 77 to standard issue. There was no significant difference in delirium/coma development between study arms (79.5% vs 70.1%; p = 0.184). In the stage II analysis, adjusted odds for delirium in the transfused cohort was more than eight-fold higher than in the nontransfused matched cohort, even after controlling for hemoglobin (adjusted odds ratio, 8.9; CI, 2.8-28.4; p < 0.001).ConclusionsRBC transfusions (and not anemia) are independently associated with increased odds of subsequent delirium/coma. However, storage age of RBCs does not affect delirium risk.