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Results | PMC10318767 |
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Determination of the optimal cut-off value | ALRI | The optimal cut-off values for lactate dehydrogenase, alkaline phosphatase, De Ritis ratio, APRI, ALRI, ANRI, and APPRI were 191.00, 102.00, 1.52, 0.12, 7.50, 3.18, and 0.46, respectively (Supplementary Fig. The associations between preoperative serum liver enzyme markers and clinicopathological features were presented in Supplementary Tables | PMC10318767 |
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Development and validation of prognostic nomograms for predicting OS and DFS in patients with stage II/III CRC | tumor, CRC | TUMOR, COLORECTAL CANCER | Next, nomograms that incorporated De Ritis ratio and significant clinicopathological features (age, gender, CEA, CA19-9, tumor location, pathological classification, differentiation degree, histological classification, TNM stage, tumor diameter, preoperative chemotherapy, and radiotherapy) were developed, which aimed to quantitatively predict the 1-, 3- and 5-year OS and DFS for the individual patient with stage II/III CRC (Fig. Nomograms to predict 1-, 3-, and 5-year overall survival for patients with colorectal cancer. Nomograms were performed by using significant clinicopathological features and De Ritis ratio to predict 1-, 3-, and 5-year overall survival Nomograms to predict 1-, 3-, and 5-year disease-free survival for patients with colorectal cancer. Nomograms were performed by using significant clinicopathological features and De Ritis ratio to predict 1-, 3-, and 5-year disease-free survival The calibration curves of the nomograms for predicting the probabilities of postoperative 3-year OS (Fig. In the training cohort, nomograms for predicting both OS and DFS had a stable prognostic performance at various follow-up times (Supplementary Table The clinical utility of the nomograms, TNM and AJCC system for predicting 5-year overall survival. AUC, area under the ROC curve. Comparisons of the time-dependent AUCs of the nomograms, TNM system, and AJCC system for 5-year overall survival prediction in the training set The clinical utility of the nomograms, TNM and AJCC system for predicting 5-year disease-free survival. AUC, area under the ROC curve. Comparisons of the time-dependent AUCs of the nomograms, TNM system, and AJCC system for 5-year disease-free survival prediction in the training set | PMC10318767 |
Clinical utility of the prognostic nomograms | CRC | The decision curve analyses were conducted to determine the clinical utility of the nomograms by quantifying the net benefits at different threshold probabilities. The decision curves for the nomogram in the training set indicated that when the threshold probabilities of the OS and DFS prediction were in the range of 10%-70% (Fig. Collectively, the decision curve showed that the prediction ability of the nomograms was superior to the TNM and AJCC staging for patients with stage II/III CRC, which supported their favorable clinical utility in predicting OS and DFS. | PMC10318767 |
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Discussion | gallstones, tumor, cancers, death, CRC, fatty liver, ALRI, cirrhosis, human malignancies, hepatobiliary disorders, heart, skeletal muscle, mitochondrial dysfunction | GALLSTONES, TUMOR, CHOLECYSTITIS, CANCERS, RECURRENCE, FATTY LIVER, CIRRHOSIS, HEPATOBILIARY DISORDERS, MICROSATELLITE INSTABILITY, ACUTE VIRAL HEPATITIS, GALLBLADDER POLYPS, MITOCHONDRIAL DYSFUNCTION | Serum liver enzyme markers, as readily-available and non-invasive clinical parameters, have great potential for predicting the prognosis of human malignancies. Our study, for the first time, comprehensively evaluated the prognostic values of lactate dehydrogenase, alkaline phosphatase, De Ritis ratio, APRI, ALRI, ANRI, and APPRI in a large retrospective CRC cohort. Among these serum liver enzyme markers, only De Ritis ratio was identified as an independent prognostic factor for predicting the OS and DFS of patients with stage II/III CRC, which was also verified in the testing set. Based on the results of C-index, time-dependent ROC, and decision curve analyses, the nomograms combining De Ritis ratio and significant clinicopathological features had higher accuracy, improved discrimination, and greater clinical benefits in predicting the overall survival, recurrence/metastasis compared with TNM and AJCC staging.Aspartate aminotransferase and alanine aminotransferase are enzymes produced by cancerous and non-cancerous cells, and then released into peripheral blood. Alanine aminotransferase is mainly distributed in the liver, while aspartate aminotransferase is widely expressed in different tissues including the liver, heart, skeletal muscle, and kidney [The De Ritis ratio, initially described as a characteristic of acute viral hepatitis [Warburg effect may explain the mechanisms of the prognostic ability of De Ritis ratio. In the view of Warburg, there was mitochondrial dysfunction in tumor cells [Previous studies also indicated that lactate dehydrogenase, alkaline phosphatase, APRI, and ALRI were significant prognostic factors for metastatic CRC patients [Considering that individuals with hepatobiliary disorders may have abnormal levels of serum liver enzymes, which may influence the assessment of prognostic values of markers. Our study excluded CRC patients with fatty liver, cirrhosis, cholecystitis, gallstones, and gallbladder polyps. Although our study included patients with positive HBs-Ag and/or positive HCV-Ab, the prognostic values of markers were not affected due to the small proportion. Because postoperative treatment also has an important effect on prognosis, the prognostic effects of markers were adjusted by postoperative chemotherapy and radiotherapy in the multivariate Cox models.Nomograms are widely used in oncology and have been validated to compare favorably to the conventional TNM staging systems in many cancers [Compared with previous studies, our study systematically investigated and validated the prognostic role of lactate dehydrogenase, alkaline phosphatase, De Ritis ratio, APRI, ALRI, ANRI, and APPRI based on a cohort containing quite a large number of patients with stage II/III CRC. In addition, new prognosis prediction models incorporating De Ritis ratio and significant clinicopathological features, also have been successfully developed. The advantages of this study include not only exploring the serum biomarkers associated with the prognosis of stage II/III CRC patients but also performing personalized survival prediction, which could help clinicians to identify patients at high risk of recurrence and death. Our study also has several limitations. First, all the patients in the training and testing sets came from a single-center cohort, which may bring selection bias. Multi-center cohorts should be conducted to further validate the prognostic ability of De Ritis ratio and the universal application of the optimal cut-off values of De Ritis ratio. Second, this study was a retrospective cohort and it comes with a limitation that some data on clinicopathological features are lacking, such as lymphovascular invasion, tumor budding, tumor-infiltrating lymphocyte, and microsatellite instability. | PMC10318767 |
Conclusions | CRC | Our study demonstrates that De Ritis ratio has the ability to independently predict the prognosis of patients with stage II/III CRC. The nomograms incorporating De Ritis ratio and clinicopathological features show higher accuracy, improved discrimination, and greater clinical utility in terms of personalized survival prediction. | PMC10318767 |
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Acknowledgements | Not applicable. | PMC10318767 |
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Authors’ contributions | Yanlong Liu and Yashuang Zhao designed the study. Jinming Fu, Fenqi Du, Tian Tian, Yupeng Liu, Ding Zhang, Lijing Gao, and Ting Zheng contributed to the generation, collection, assembly, analysis and/or interpretation of data. Jinming Fu, Hao Huang, Dapeng Li, and Lei Zhang performed the statistical analysis. Jinming Fu wrote the manuscript. Yashuang Zhao, and Yanlong Liu revised the manuscript. All the authors have read and approved the final manuscript. All authors contributed to the article and approved the submitted version. | PMC10318767 |
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Funding | Cancer | ONCOLOGY, CANCER | This study was supported by grants from the Beijing Xisike Clinical Oncology Research Foundation (Y321MX2016-045), the Heilongjiang Sunshine Health Foundation (H21L0802), the Post-doctoral Scientific Research Developmental Fund of Heilongjiang (LBH-Q18085), and the Harbin Medical University Cancer Hospital Preeminence Youth Fund (JCQN2019-04). | PMC10318767 |
Availability of data and materials | The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. | PMC10318767 |
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Declarations | PMC10318767 |
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Ethics approval and consent to participate | Cancer | CANCER | This study complied with the standards of the Helsinki Declaration. The study involving human participants was conducted under the supervision of the Ethics Committee of the Harbin Medical University Cancer Hospital. The data for analysis were obtained from retrospective medical records. We have processed the data and concealed the patient’s personal information. Therefore, according to the national legislation and the relevant clauses of the China Association for Ethical Studies ( | PMC10318767 |
Consent for publication | Not applicable. | PMC10318767 |
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Competing interests | The authors declare no competing interests. | PMC10318767 |
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References | PMC10318767 |
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Introduction | obesity | OBESITY | Quality of life (QoL) is a comprehensive and multidimensional construct including several domains of subjective experiences such as physical ability, psychological well-being, social interactions, and school performance [Emotional eating defined as eating as a response from negative or overwhelming feelings is highly prevalent in adults with obesity [Therefore, the aim of the present study was to investigate whether there is an association between QoL and emotional overeating in a Danish sample of 7–14 years old children with overweight and obesity. | PMC10746571 |
Methods | The present cross-sectional study is based on baseline questionnaire data from the COPE-study, which is a nonrandomized controlled trial (Briefly, participating children were recruited in collaboration with two well-established multicomponent lifestyle camps in Denmark. Children from 7-14 years of age, who struggle with overweight/obesity, low self-esteem, and/or unhappiness, could be referred to attend camp for 10 weeks. The lifestyle camps focus on a healthy lifestyle and aim to improve QoL in children. All children attending camp from October 2020 to March 2022 were invited to participate and parents/guardians provided written consent for their child to participate in this study. | PMC10746571 |
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Measurements | obesity, overweight | OBESITY | Background characteristics, e.g., sex and household income per year, were assessed by a self-developed parent-reported questionnaire. Camp staff measured body weight (kg) and height within the first week of camp. Body weight (kg) was measured according to standard procedures using a bioelectric impedance (InBody model 270, Hopkins Medical Products, Grand Rapids, MI, USA) and height (meters) was measured using a fixed wall measuring tape. An age-and-sex-adjusted Body Mass Index Standard Deviation Score (BMI-SDS) was calculated using WHO AnthroPlus software, and children with a BMI-SDS > 1SD were defined as having overweight and children with a BMI-SDS > 2SD were defined as having obesity [ | PMC10746571 |
The pediatric quality of life inventory questionnaire (PedsQL 4.0) | QoL was measured using the validated Danish translation of the Pediatric Quality of Life Inventory 4.0 questionnaire (PedsQL 4.0.), and permission to use the PedsQL questionnaire was granted by the original author [ | PMC10746571 |
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Child eating behavior questionnaire (CEBQ) | eating behaviors, satiety, slowness | The original Child Eating Behavior Questionnaire (CEBQ) [CEBQ contains 35 questions subdivided into eight different eating behaviors: food responsiveness, enjoyment of food, desire to drink, satiety responsiveness, slowness in eating, food fussiness, emotional undereating, and emotional overeating [ | PMC10746571 |
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Statistical analysis | REGRESSIONS | Children were excluded from the present study if they did not answer the PedsQL questionnaire and the CEBQ at baseline. Data from the CEBQ did not fulfill the assumption of linearity, and therefore, the EOE-score and the FR-score were categorized into three categories: “Low” (score ≤ 2), “Medium” (score > 2–3), and “High” (score > 3). Descriptive analysis was stratified by EOE-categories. Differences within groups were tested using the chi-squared test for all included categorical variables. Categorical variables are displayed as absolute numbers and percentages [Multiple linear regressions were applied to determine the association between children’s QoL and EOE. Potential associated factors were considered in the statistical analysis including gender, BMI-SDS, and socioeconomic status measured as household income per year.Based on previous evidence suggesting an association between food addiction and EOE [ | PMC10746571 |
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Results | In total, 322 children were invited to participate and 236 children accepted the invitation. Seven children withdrew from the study before or during camp, 93 children were non-participants, while 45 children were excluded due to missing data (Fig. Flowchart of the study participantsIncluded children (Participant characteristics (Participants characteristics divided by low EOE-score, medium EOE-score, and high EOE-score (Low EOE-score ≤ 2, medium EOE-score > 2–3, high EOE-score > 3 | PMC10746571 |
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Discussion | QoL impairment, overeating with loss of control), disordered eating, binge eating | Based on the results of the present study, QoL is associated with EOE in 7-14-year old children. Children with a high tendency of EOE had a lower QoL compared to children with a lower tendency of EOE. However, due to the study design, it was not possible to determine causality.The present findings are essential in line with current sparse evidence, suggesting that binge eating (overeating with loss of control) is a marker of QoL impairment [The rationale behind the present study was a lack of studies within this field in general and, in addition, a lack of studies investigating Danish children and adolescents, while the hypothesis was based on the existing literature in conjecturing a negative association between QoL and disordered eating [Current evidence investigating QoL and EOE in children and adolescents is scarce, and most evidence investigating this issue included adolescents and adults. Identified previous studies primarily examined the relationship between binge eating and QoL in adolescents and children [ | PMC10746571 |
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Strengths and limitations | Despite the novelty of the findings in the present study, some limitations are obvious. The representativeness of the target population is to some degree questionable as children attending camp has a slightly different social background (e.g., more children live with a single parent) and higher morbidity compared to children with overweight and obesity not attending camp [ | PMC10746571 |
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Acknowledgements | The authors thank Julemærkefonden and the multicomponent lifestyle camps in Hobro and Fjordmark for collaborating on this study. | PMC10746571 |
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Authors’ contributions | IA, DJ, and JB designed this study; DJ collected the data; IA performed the statistical analysis and wrote the initial manuscript. DJ and JB critically revised the manuscript. IA and DJ had the primary responsibility for the final content. All authors have read and agreed to the published version of the manuscript. | PMC10746571 |
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Funding | Diabetes | DIABETES | Open access funding provided by Aarhus University Hospital This research was funded by Steno Diabetes Center Aarhus (SDCA) which is partially funded by an unrestricted donation from the Novo Nordisk Foundation, Sygeforsikringen “danmark,” and Arla Foods Amba (unrestricted grant). | PMC10746571 |
Availability of data and materials | The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. | PMC10746571 |
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Declarations | PMC10746571 |
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Ethics approval statement | -20 | The local Committee of Ethics have approved all parts of the COPE-study (journal number: 1–10-72–73-20). The COPE-study was performed in accordance with good clinical practice and conformed to the Declaration of Helsinki. | PMC10746571 |
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Consent to participate | Parents/guardians provided written consent for their child to participate in the study. | PMC10746571 |
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Consent for publication | Not applicable. | PMC10746571 |
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Competing interests | The authors declare no competing interests. | PMC10746571 |
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References | PMC10746571 |
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Background | overweight, ® | OBESE | Obex® may be helpful in reducing body weight and fat. The current study was carried out to evaluate the efficacy and safety of Obex® in the treatment of overweight and obese subjects. | PMC9940432 |
Methods | overweight | OBESE | A double-blind, randomised, controlled phase III clinical trial was conducted involving 160 overweight and obese subjects (BMI ≥ 25.0 and < 40 kg/m | PMC9940432 |
Results | After 3 months of Obex®, 48.3% of the participants (28/58) achieved complete success in reducing both weight and waist circumference by greater than or equal to 5% from baseline, as opposed to 26.0% (13/50) of individuals receiving placebo ( | PMC9940432 |
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Conclusions | obesity, ® | OBESITY | The consumption of Obex® together with lifestyle changes increased HDL-c, contributed to a rapid reduction of weight and waist circumference, as well as improved insulin homeostasis, which did not occur in the placebo group, and appears to be safe as an adjunct at conventional obesity treatment. | PMC9940432 |
Trial registration | Clinical trial protocol was registered in the Cuban public registry of clinical trials under code RPCEC00000267 on 17/04/2018 and also registered in the international registry of clinical trials, ClinicalTrials.gov, under code: NCT03541005 on 30/05/2018. | PMC9940432 |
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Keywords | PMC9940432 |
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Introduction | Obesity, obesity, T2D, obese, ®, medicantions, impaired fasting glucose, prediabetes, overweight, metabolic syndrome | OBESITY, OBESITY, OBESE, ADVERSE EVENTS, PREDIABETES, INSULIN RESISTANCE, METABOLIC SYNDROME, INSULIN SENSITIVITY | The incidence of overweight and obesity has reached epidemic levels and represents a major serious threat to public health on a global scale [Obesity is a major risk factor for T2D and prediabetes [In the United States of America, the age-adjusted prevalence of overall obesity increased from 35.4% in 2011–2012 to 43.4% in 2017–2018 [Obesity has increased globally and at least 2.8 million people die each year from obesity or being overweight. In 2015, a total of 107.7 million children and 603.7 million adults were obese. In more than 70 countries, the prevalence of obesity has doubled since 1980, and it has increased continuously in the majority of other countries [The current explosion in T2D and obesity prevalence rates is a result of significant secular changes in lifestyle and environment which may have a tendency to cluster within families (obvious examples include foetal environment, socioeconomic status, dietary preferences, food availability, a more sedentary way of life, stress, pharmaceutical or endocrine disruptors, and a lower microbial diversity of the gut microbiota composition in obesity) [Over the next twenty years, overweight and obesity in all Latin American countries are estimated to increase [For the treatment of obesity and prediabetes, a number of medicantions have been used, including sibutramine, rimonabant, orlistat, lorcaserin, phentermine/topiramate, exenatide, liraglutide, thiazolidinediones, acarbose, and metformin, among others [The nutritional supplement Obex®, produced by Laboratorios Catalysis, has recently entered the market. It is specifically produced with natural antioxidants and helps to lose weight, with no adverse events having been reported so far. Several articles [In 2015, Medialdea et al. found that taking the Obex® supplement was beneficial for the treatment of central obesity and prevention of metabolic syndrome in climacteric women. [In an earlier exploratory study in overweight or obese subjects with impaired fasting glucose levels, consumption of Obex® achieved a reduction in several anthropometric measurements (body weight, BMI, waist circumference, waist-to-hip ratio, and conicity index) and improved fasting glucose levels and high-density lipoprotein cholesterol (HDL-c) concentrations, as well as insulin sensitivity and insulin resistance indexes [The aim of this study was to examine the efficacy and safety of Obex® treatment in combination with lifestyle changes on anthropometric, clinical, and biochemical characteristics in overweight and obese individuals. | PMC9940432 |
Material and methods | PMC9940432 |
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Participants | sepsis, eating disorders, prediabetes, thyroid dysfunction, overweight, hypo-, acromegaly, type 2 diabetes, hypersensitivity | SEPSIS, OBESE, DISEASE, TYPE 1 DIABETES, CHRONIC DISEASES, DISORDERS, PREDIABETES, THYROID DYSFUNCTION, HYPERTHYROIDISM, HYPERCORTISOLISM, INSULIN RESISTANCE, ASYMPTOMATIC HYPOGLYCAEMIA, HYPERSENSITIVITY, ACROMEGALY, TYPE 2 DIABETES, DISEASES | Subjects were recruited through written advertisements contained in brochures produced for the study. The clinical trial was also promoted through direct communication and via opportunistic population screening in overweight and obese subjects.Participants were included if they were aged 20–60 years, had a BMI ≥ 25.0 kg/mParticipants with any of the most significant systemic, inflammatory or chronic diseases were excluded that were likely to affect study endpoints, as well as a history of or current condition of neurological or psychological disease, including eating disorders or substance use disorders. Participants who took oral or injectable contraceptives and women who were pregnant or breastfeeding were also excluded. Likewise, those who were shown to have thyroid dysfunction (hypo- or hyperthyroidism), type 1 diabetes, type 2 diabetes or prediabetes treated with oral hypoglycaemic agents, as well as those with any of the following characteristics: diseases manifesting insulin resistance (IR) (e.g. acromegaly and endogenous hypercortisolism), sepsis, use of medications that affect weight in the last 3 months, inability to follow instructions, symptomatic hypoglycaemia in the last month, known hypersensitivity to any of the formulation components, use of immunosuppressive drugs in the previous 5 years or having abused alcohol/drugs, were also excluded from the study. Individuals who used steroids, anti-inflammatory medications, multivitamins and/or antioxidants were not allowed.Patients who did not complete the minimum treatment time (three months) were also excluded. In the case of subjects who completed treatment for at least three months but subsequently discontinued treatment, only the three-month period in which the clinical trial groups were compared was taken into account for analysis. | PMC9940432 |
Sample size estimation | The estimation of the sample size was based on the rate of weight reduction with non-pharmacological treatment (diet and physical activity) is approximately 15% (p1) and it is assumed that we want to achieve a success rate of 35% (p2) in the experimental group (patients with Obex® treatment), i.e. we aim to detect a difference of 20% between the two treatments, with a Type I error = 0.05 and a Type II error = 0.2. Under the above assumptions, a total of 146 patients would need to be included, 73 in each treatment group. Assuming a probable subject loss of 10.0% during the trial, a total of 160 patients (80 in each treatment group) would then need to be recruited to ensure adequate power. | PMC9940432 |
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Ethical considerations | ® | The study protocol was approved by the Research and Ethics Committee of the Cuban Endocrinology Institute and was conducted following the Declaration of Helsinki. Obex® is registered as a nutritional supplement with the National Institute of Nutrition and Food Hygiene in Havana, Cuba. Written consent was obtained from all patients before the study enrolment. This clinical trial was registered in the Cuban public registry of clinical trials under the code | PMC9940432 |
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Study design and dietary supplementation regimen | obese, overweight, Diabetes | OBESE, DIABETES | The present study was a randomised double-blind parallel-group placebo-controlled phase III trial performed at the Institute of Endocrinology, Havana, Cuba, in overweight and obese adults who met the selection criteria.After an initial evaluation, all subjects who met the eligibility criteria and wanted to participate in the study were enrolled consecutively. The study included 160 subjects who were administered Obex® or placebo (4 g sachets) twice daily for 6 months (24 weeks). In addition, non-pharmacological treatment consisting of lifestyle changes (physical activity and hygiene, and dietary measures) was prescribed.All subjects received advice and information regarding diet and nutrition at the Dietetic Department of the Diabetes Care Centre of the Institute of Endocrinology, where their diets were drawn up based on their daily calorie intake requirement per kilogram body weight and their level of physical activity. Individuals were provided with diets with the following proportion of nutrients: 55–60% carbohydrates, 15–20% protein, and 20% fat. Diets ranged from 1200 to 1500 cal [Several interim assessments were performed at 1.5, 3.0, and 4.5 months, including physical examination, anthropometric measurements (weight, height, waist, and hip circumference), physical activity through the IPAQ questionnaire [Randomisation within the study was designed using a computerised random number generator. All personnel involved in the study remained unaware of the correspondence between the codes and the content of the sachets. The treatments used for the study (Obex® and placebo) were provided by Laboratorios Catalysis, labeled with the randomisation code only. Code-to-sachet content associations were kept in a sealed envelope under the custody of the Head of the Research Methodology Department of the Institute of Endocrinology. Seal and envelope integrity was checked every three months. At the end of the study, the envelope was opened.Individual assessment of response was performed after three and six months of treatment. The complete success of weight and waist circumference reduction was considered to be when participants achieved a ≥ 5% reduction in both weight and waist circumference relative to the baseline value; partial success was when subjects achieved a ≥ 5% reduction in either of the two main anthropometric measurements (weight or waist circumference), and failure was considered to be when subjects did not achieve a ≥ 5% reduction in either weight or waist circumference or when an increase in both parameters was observed.At 12 weeks, subjects in both groups who had a reduction ≥ 5% of their body weight and waist circumference were categorised as early responders and continued participating in the study for up to 24 weeks. Once the optimal early response criterion was identified, subjects were classified as early responders (ERs) or early non-responders (ENRs) [The study was monitored by the National Coordinating Centre for Clinical Trials (Centro Nacional Coordinador de Ensayos Clínicos, CENCEC). The clinical trial began in November 2018 (first person in) and lasted until June 2019 (last person completed). | PMC9940432 |
Study product | The dietary supplement Obex® used in this study was supplied by Laboratorios Catalysis. This product is marketed as a food supplement by Laboratorios Catalysis (Macarena, no. 14 28,016 Madrid, Spain). The sachets of Obex® (4 g) contained the ingredients specified in Table Qualitative-quantitative composition of Obex®Nutritional analysis of 100 g of Obex® showed that it contained 377 kcal (1,602 kJ) as the energy value, 77.3 g of carbohydrates, 12.6 g of proteins and 2.0 g of total fatsAfter the initial assessment, all subjects who met the eligibility criteria and wished to participate in the study were subsequently enrolled. Subjects were randomly assigned to receive either Obex® (80) or placebo (The effects of Obex® were assessed three and six months after the start of treatment and compared with the placebo group | PMC9940432 |
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Adverse events | diarrhoea, nausea, bloating, dyspepsia, headache, rashes | ADVERSE EVENTS, ADVERSE EVENT | Every one and a half months, a clinical examination of the participants was performed to determine whether they experienced any adverse events. Adverse events such as rashes, headache, diarrhoea, nausea, dyspepsia, and bloating were recorded. | PMC9940432 |
Physical examination | BLOOD, CREST | The physical examination included assessments of height, weight, waist and hip circumference, and blood pressure. The physical assessments were performed at baseline, 3 and 6 months after starting Obex® or placebo.Height and weight were measured, and body mass index (BMI) was calculated as weight (kg) divided by height squared (mWaist circumference (WC) was measured with the person standing, with an inelastic tape at the midpoint between the lower margin of the rib cage and the superior iliac crest, during mild expiration. Waist-to-hip ratio (WHR) was defined as the ratio of waist girth to the circumference of the hips measured at the greater trochanter. Measurements were obtained in duplicate, and their averages were used for the analysis. The waist/height ratio (WHTR) was calculated as WC (cm) divided by height (cm). The conicity index was calculated according to the formula proposed by Valdez [Blood pressure was measured three times after a 5-min rest in the sitting position using standard mercury sphygmomanometers [ | PMC9940432 |
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Laboratory tests | BEN | INSULIN SENSITIVITY, INSULIN RESISTANCE, INSULIN SENSITIVITY | At the start of the study (baseline) and six months, venous blood samples were collected after an overnight fast for biochemical assessments: fasting plasma glucose, lipid profile (total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol), creatinine, uric acid and hepatic enzymes, as well as a second blood sample taken 2 h after the oral glucose tolerance test (OGTT), and the values were recorded. In addition, fasting insulin concentrations were also measured.The fasting glucose and insulin concentrations were calculated for each subject on two separate occasions: at baseline and 5 min. To calculate the insulin resistance index (HOMA-IR), insulin secretion index (HOMA-β) and insulin sensitivity indexes (IS), the averages of the fasting glucose and insulin values were obtained at baseline and after 5 min.The insulin resistance index was calculated using the Matthews homeostasis model assessment (HOMA-IR) (fasting insulin μU/ml x fasting glucose mmol/l / 22.5) [Three indirect indices were used to calculate the insulin sensitivity (IS). They were calculated according to the following formulae:Quantitative Insulin Sensitivity Check Index (QUICKI) = 1 / [log fasting insulinBennett index (BEN) = 1 / (log fasting insulinRaynaud index (RAY) = [40 / fasting insulinFasting and 2-h plasma glucose and lipid profile, including total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol, in addition to creatinine and uric acid (UA), as well as hepatic enzymes and haemoglobin, were measured enzymatically using a biochemistry analyser (Mindray BS-200E, China) using commercial kits from C.P.M. Diagnostic Research (Italy) (The fasting plasma insulin concentration was measured by immunoradiometric assay (IRMA, Izotop, Hungary) ( | PMC9940432 |
Outcomes | INSULIN RESISTANCE, INSULIN SENSITIVITY | The primary outcome was a change in anthropometric measurements and glucose, insulin and lipid concentrations, as well as variations in insulin release, insulin resistance, and insulin sensitivity. Secondary outcomes were variation in serum creatinine, uric acid, hepatic enzymes and change in blood pressure. The change (variation) was the difference obtained between baseline and the end of treatment (6 months).Another primary outcome was variation in the biochemical measurements, as well as differences in insulin release, insulin resistance and insulin sensitivity between the ERs and ENRs for each treatment group (Obex® and placebo), in addition to the change obtained between baseline and 6 months of treatment in the ERs and ENRs in each treatment group among subjects who completed the trial. | PMC9940432 |
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Statistical analysis | Data were expressed as mean ± standard deviation and as percentages for categorical variables (before and after). Differences between groups (Obex® and placebo) were analysed by Mann–Whitney nonparametric independent sample test.Wilcoxon signed-rank tests were used to compare changes between baseline and the end of treatment (6 months) and the Friedman test was used for several related samples. In addition, both Pearson's Chi-square test and Fisher's exact test were used for categorical variables.Mann–Whitney tests were also used to compare baseline values between ERs and ENRs within each treatment group (Obex® and placebo). Wilcoxon-rank sum tests were utilised to compare changes at baseline and after six months of treatment between ERs and ENRs within each group.All significance tests and resulting | PMC9940432 |
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Acknowledgements | The authors would like to thank the staff at the Biochemistry Laboratory, Institute of Endocrinology, for their excellent collaboration. Special thanks to Eduardo Sanz (Catalysis, S.L.) for his helpful comments. And finally, we are grateful to the patients for participating in this trial. | PMC9940432 |
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Authors’ contributions | REV, JRA, ADRR | JRA | Conceptualisation, methodology, investigation, writing – preparation and writing of the original draft – review & editing, ECR, ICD, JRA, JCH, AICG, YAD, JHR and SMJ; software, ECR; data curation, JRA and TMGC; JVR, AAA, ADRR and REV, formal analysis; visualisation, LJE and YAR; supervision, JRA, ZBB and ESE; project administration, ICD. All the authors have read and agreed to the published version of the manuscript. | PMC9940432 |
Funding | This research was partly funded by Catalysis, S.L. (Madrid, Spain), which provided both products (Obex® and placebo) used for the trial. | PMC9940432 |
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Availability of data and materials | The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. | PMC9940432 |
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Declarations | PMC9940432 |
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Ethics approval and consent to participate | ® | The study protocol was approved by the Research and Ethics Committee of the Cuban Endocrinology Institute and was conducted following the Declaration of Helsinki. Obex® is registered as a nutritional supplement with the National Institute of Nutrition and Food Hygiene in Havana, Cuba. Written consent was obtained from all patients before the study enrolment. | PMC9940432 |
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Consent for publication | Not applicable. | PMC9940432 |
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Competing interests | The authors declare no conflicts of interest. The authors are responsible for the content and writing of the article. The funders had no role in the study design, data collection and analysis, decision to publish or manuscript preparation. | PMC9940432 |
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References | PMC9940432 |
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Aim | GESTATIONAL DIABETES | To determine the effectiveness of despatching an electronic reminder of participation in screening for gestational diabetes. The reminder was sent to the women 1–8 years after delivery. | PMC9872380 |
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Methods | GESTATIONAL DIABETES | A registry-based, randomized controlled trial in the North Denmark Region among women with gestational diabetes. Randomization was made, which included seven groups stratified by the child’s birth year (2012–2018). The intervention group received standard care supplemented by an electronic reminder through a secure nationwide email system ( | PMC9872380 |
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Results | multiparity | TYPE 2 DIABETES | A total of 471 (32.1%) women participated in screening. The primary outcome was experienced by 257 women (35.1%) in the intervention group and 214 women (29.2%) in the control group. The effect of the reminder seemed to increase with recipient’s age, non-western origin, urban dwelling, and multiparity. Of those who participated in follow-up screening, 56 (3.8%) were diagnosed with type 2 diabetes. | PMC9872380 |
Conclusion | Electronic reminders, based on the principles of informed choice and patient-centred care, to women have been shown to support life-long participation in follow-up screening. Attempts to further stimulation of coverage could however be considered. | PMC9872380 |
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Trail registration | ISRCTN registry (22/04/2022, ISRCTN23558707). | PMC9872380 |
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Keywords | PMC9872380 |
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Introduction | GDM, gestational diabetes | GDM, GESTATIONAL DIABETES | The prevalence of gestational diabetes (GDM) varies regionally, thus affecting approximately 7–8% of pregnancies in Europe [Although reminder interventions have been found effective in targeting some of the many documented barriers to follow-up screening after birth, the effect varies strongly across settings [As previous studies of the effect of reminder interventions have followed women for only 12 months after birth, the available data concern the short-term effects of screening [The aim of this study was to determine the effectiveness of an electronic reminder intervention targeting women whose pregnancy was complicated by GDM with regard to increasing participation in follow-up screening in general practice clinics. All women in the cohort who had delivered between 2012 and 2018 were eligible. | PMC9872380 |
Materials and methods | PMC9872380 |
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Study design and participants | PMC9872380 |
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Design and setting | This study was designed as a two-armed, single-blinded randomized controlled trial. The setting was the North Denmark Region, with approximately 0.6 million inhabitants [ | PMC9872380 |
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Participants | PMC9872380 |
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Inclusion and exclusion criteria | GDM | GDM | Women who had given birth between 2012 and 2018 and were diagnosed with GDM were eligible for inclusion. Diagnostic test during pregnancy consists of an oral glucose tolerance test (OGTT) with diagnostic criteria of a 2-h blood glucose (≥ 9.0 mmol/l) [ | PMC9872380 |
Identification and data sources | death | Women were identified via the National Patient Register, which is based on all hospital admissions in Denmark, contains personal information on patients, including CPR number, home municipality, age, parity (primipara or multipara), BMI and death [ | PMC9872380 |
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Sample size | The sample size was determined on the basis of a risk difference calculation. Based on participation rates in the region and a reminder intervention achieving an effect above 10% points [ | PMC9872380 |
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Study intervention | noninsulin-treated GDM, GDM, type 2 diabetes mellitus, insulin-treated GDM | GDM, TYPE 2 DIABETES MELLITUS | In the setting of the North Denmark region, women with a pregnancy complicated by GDM are routinely informed by a nurse or midwife about the increased risk of type 2 diabetes mellitus and the recommendation of follow-up screening after birth. If the woman has insulin-treated GDM, an appointment for the first screening is scheduled at two to three months after birth, while it is left to women with noninsulin-treated GDM to book a screening appointment with their GP. In all cases, the woman is responsible for booking further screening appointments in the years following birth in general practice. Overall, the region has high participation rates for the first screening, while a significant decline is observed in the following years [Women who had participated in screening in the previous 12 months were asked to disregard the reminder, which was sent through a secure nation-wide email system accessed by almost all citizens in Denmark for information from public authorities (e.g., the healthcare system, tax authorities, etc.). Women can access the Danish secured email systems by use of a mobile application. The system was thus easily accessible [To support adoption [ | PMC9872380 |
Randomization | GDM | GDM | The study population was stratified on the calendar year for the GDM pregnancy, based on the birth year of the child. An independent statistician was tasked with randomization into either intervention group or control group within each stratum using R Core Team software (2020) [ | PMC9872380 |
Outcome assessment | GDM, diabetes | GDM, DIABETES | The primary outcome was any participation in follow-up screening after receiving a reminder, defined as the performance of the recommended blood test for diabetes. In general practice, HbA1c are the recommended diagnostic test used for women with previous GDM [ | PMC9872380 |
Data analysis | ®, diabetes | DIABETES | The baseline characteristics of all randomized women were compared descriptively, showing frequency and percentages in total and between the control and intervention groups. Categorizations of baseline characteristics included Age (≤ 25 Years, 26–35 Years, 36–50 Years), Ethnicity (Danish/western, non-western), Employment status in percentages (defined as number of weeks as self-supporting, including women on maternity leave and state education support 0–2 years before despatch of reminders) (≥ 80%, 20–80%, ≤ 20%) [We estimated the effect of the intervention by reporting risk ratios (RR), risk differences (RD) and 95% confidence intervals (CI) for primary outcomes. To calculate the number of women diagnosed with diabetes and a A forest plot graphically displayed the estimated results according to stratified groups representing years after birth. To estimate the effect of the intervention for different subgroups, we also stratified for age, ethnicity, employment status, municipality, parity, and BMI. All statistical analyses were performed using Stata 16.1 software for Windows® (StataCorp., College Station, TX, USA). | PMC9872380 |
Results | PMC9872380 |
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Recruitment and participant flow | diabetes | DIABETES | Of the 1708 women assessed for eligibility, 188 had a diabetes diagnosis prior to birth (Fig. Flowchart | PMC9872380 |
Postpartum follow-up and early detection of diabetes | type 2 diabetes mellitus | EVENT, TYPE 2 DIABETES, TYPE 2 DIABETES MELLITUS, SECONDARY | Screening involved 471 (32.1%) women. The primary outcome event was experienced by 257 women (35.1%) in the intervention group and 214 women (29.2%) in the control group. We demonstrated a 20% increased chance of participation in screening in the intervention group (RR: 1.20; 95% CI 1.03–1.39) and a 5% increase in absolute risk (RD: 0.05; 95% CI 0.01–0.10] (Table Outcome: participation in screeningScreening was performed using a HbA1c test in 415 women (NPU27412), a OGTT in 34 women (NPU21530), by P-glucose testing (NPU02192) of 14 women, while 8 women were tested according to the performance code for GPs (Code:7136).The effect was highest immediately after the reminder was sent out in August/September and October (Fig. Histogram illustrating the distribution of participation in screening in time after despatching the reminderFigure Forest plot illustrating the effect of the reminder according to stratified groups representing years after birthAmong the women who participated in follow-up screening, 56 (3.8%) were diagnosed with type 2 diabetes mellitus after the reminder was despatched.The secondary outcome (type 2 diabetes diagnosis) was detected in 32 women within the intervention group and in 24 women in the control group. No significant difference was found ( | PMC9872380 |
Identified harms | No significant harms were identified as a result of the study. | PMC9872380 |
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Discussion | PMC9872380 |
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Key results | GDM | GDM, RECRUITMENT | This study demonstrates a significant increase in participation in screening among women with prior GDM who receive an email reminder in comparison with women who receive only standard care. Our results thereby corroborate the growing body of evidence that reminding women to be screened after birth are effective [Contextual factors may explain the variations in effect found between this study and previous studies [Our study also found a stronger effect of the reminder among urban women. However, it is important to notice that women from rural areas in general seems to participate in screening more than women from urban areas but might not be especially responsive to a reminder.The reminder nevertheless seems to support continuity of care for women with previous GDM, a group that has expressed discontent about fragmented care and little opportunity to receive elaboration on health risks and recommendations [Drawing on the unique possibility offered by Denmark’s civil registration number system to link individual data across multiple nationwide registers, our simple intervention design enabled us to identify and recruit participants, despatch the reminders, and assess outcomes without causing any significant disturbances for current practices. This ensured sufficient recruitment and retention rates with no loss to follow-up, a frequent challenge to the feasibility of executing interventions studies [Reflection on coverage of an intervention in a specific service setting gives indications of its integration [However, as poor communication across sectors and GP clinics’ insufficient information on risks and recommendations may challenge participation in follow-up screening [ | PMC9872380 |
Strengths and limitations | GDM | MINOR, EVENT, GDM, SECONDARY, TYPE 2 DIABETES MELLITUS | The simple study design, with its adaptation to existing system resources, ensured the inclusion of practically all cases and high follow-up rates. The validity of the Danish National Patient Register database enabled the identification of women with a GDM diagnosis, lending strong support to our expectation that women receiving this diagnosis through ICD-10 coding during pregnancy/childbirth are correct [To ensure the long-term sustainability of the reminder intervention, we included women who had been screened in the previous 12 months. Any negative consequences of receiving an irrelevant reminder were limited by encouraging the women to disregard it, but more knowledge of women’s perspectives on receiving the reminder is, however, needed to ensure that no significant harms were associated with this study. The results of a qualitative study of this are forthcoming.In the assessment of the primary outcome, several data sources were used to secure identification of an event which according to recommendations could include three different blood tests. However, in relation to the secondary outcome, ICD-10 coding fails to securely identify those who are merely diagnosed and treated for type 2 diabetes mellitus in general practice [Our subgroup analysis contributes to the discussion of the design of future electronic reminder systems, but its results should be interpreted with caution as the numbers were small and randomization may not have been maintained in the subgroups. Moreover, knowledge of insulin therapy rates during pregnancy with GDM should be classified, as it can affect women's motivation to participate in screening. Nevertheless, the RCT design is expected to have distributed the number of women who have received insulin therapy during pregnancy equally between the control and the intervention group.Informing GPs about the study before despatching the reminder may have increased uptake of screening in the control group, which may have resulted in an underestimation of the effect of the reminder. However, we believe this would have had a minor effect as GPs properly are inundated by information, and that the reminder was addressed to women. | PMC9872380 |
Implications for practice and research | GDM, diabetes | GDM, IMPAIRED GLUCOSE TOLERANCE, DIABETES | We urge general practice clinics to continue to strengthen attempts to engage in the decision-making process with women and support knowledge transfer between healthcare sectors. Such challenges appear to have diminished the effect of the reminder, creating a barrier to follow-up screening. Even if the reminder were routinely despatched, women should be offered support for their decision-making, especially if their GDM pregnancy occurred several years earlier. Nevertheless, routine use of reminders should be considered, in order to strengthen women's opportunity to be tested and, in dialogue with general practitioners, gain information on how diabetes conversion can be prevented. It is especially important in a Danish setting where evidence-based lifestyle interventions are not systematically available to women with impaired glucose tolerance (IGT). Our work has implications for all research concerning the coverage of reminder interventions. An adjunct process evaluation to our study, which is currently being analysed, can help generate more knowledge about women's experiences of receiving the reminder and participating in screening. Also, no previous cost-effectiveness studies on the use of reminder systems to increase uptake in screening after birth for this specific group of women have been identified. Finally, should potentials of yearly reminders and more knowledge about the specific subgroups be analysed. | PMC9872380 |
Conclusion | Electronic reminders to women can support the recommendation of participation in follow-up screening, as this study test found that a reminder beyond the first 12 months after birth are effective in increasing women’s participation in screening. The reminder is based on the principles of informed choice and patient-centred care, which are believed to be a strength. The advantage of the intervention stems from its simplicity and the use of a nationwide secure email system linked to women’s CPR number, for which policy makers should analyse contextual conditions for implementation. Attempts to further stimulation of coverage could however be considered, possibly focusing on strengthen engagement of women in the decision-making process and support of knowledge transfer between healthcare sectors. | PMC9872380 |
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Acknowledgements | The research was funded by the Department of Midwifery and the Sustainable Science research programme at University College of Northern Denmark, the Department of Health Science and Technology, Aalborg University, and the Clinical Nursing Research Unit, Aalborg University Hospital. The academic work was also supported by the Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPH’er), a UKCRC Public Health Research Centre of Excellence. | PMC9872380 |
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Authors’ contributions | JHN, KF, JKK and CO all contributed to development of the study protocol. KF retrieved the register data. Supported by KF, JHN was responsible for organizing the despatch of the reminder and conducted the data analysis. JHN wrote the first draft of the paper while KF, JKK and CO contributed to interpretation of data. The final version of this article was discussed, revised and approved by all authors. | PMC9872380 |
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Funding | This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. | PMC9872380 |
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Availability of data and materials | All data generated or analysed during this study are included in this published article. | PMC9872380 |
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Declarations | PMC9872380 |
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Ethics approval and consent to participate | The Danish science ethics committee of the North Denmark Region, Denmark was approached and it waived the need for ethics approval as well as informed consent. The study thereby adheres to Danish legislation [ | PMC9872380 |
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Consent for publication | Not applicable. | PMC9872380 |
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Competing interests | The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. | PMC9872380 |
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References | PMC9872380 |
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Introduction | peripheral nerve block | VASODILATION, COLD, VASODILATATION, COMPLICATION | The results of the pinprick and cold tests performed on the arm, forearm, and wrist-wrist areas of patients scheduled for upper extremity procedures are subjective and dependent on patient’s compliance. The purpose of this study was to determine whether the perfusion index (PI) could be used as an objective indicator to demonstrate block efficacy. Fifty patients between the ages of 18 and 65 years who were scheduled for upper extremity procedures and had an American Society of Anesthesiologists risk assessment class of I–II were included in this study. Infraclavicular block was performed on the patients using the peripheral nerve stimulation and ultrasonography. Preoperative and postoperative PI values were measured and recorded. The pinprick test took an average of 7.98 ± 1.49 minutes to turn positive, whereas the grade 3 of Modified Bromage Scale took an average of 11.08 ± 1.71 minutes. Differences between baseline values and perioperative values were found to be significantly different in the paired comparisons of the PI values. With 80% sensitivity and 80% specificity, increases in the PI value by or above 3.8 units were indicative for sensory block. With 84% sensitivity and 84% specificity, increases in the PI value by or above 3.9 units were indicative for grade 3 of Modified Bromage Scale in patients. It was determined that the PI is a faster, more reliable, and simpler technique than conventional methods for determining the efficacy of a block because of the vasodilatation that occurs before sensory and motor block.A common anesthetic technique for procedures on the upper extremities is brachial plexus (BP) block. The infraclavicular technique has increased in popularity with the use of ultrasonography (USG) in the clinical settings, as it has a lower complication rate and is both practical and simple to use [Assessment of sensory and motor functions helps determine whether peripheral nerve block is successful. The traditional methods, such as pinprick test and Modified Bromage Scale (MBS), often utilized in this examination are subjective and dependent on the patient’s cooperation [An increase in PI readings when peripheral nerve block is performed is due to vasodilation and an increase in blood flow in the extremity. Therefore, an increase in PI values can assess the indirect success of peripheral nerve block administered without requiring the patient’s cooperation [In this study, the applicability of PI as an objective metric demonstrating the success and efficacy of infraclavicular block was evaluated. | PMC10171442 |
Materials and methods | nerve injury, thumb abduction, infections, pain, diabetes, peripheral vascular disease, allergies | INFILTRATION, INFECTIONS, ALLERGIES | The study was conducted at the Adıyaman University Research and Training Hospital between 01 August 2021 and 15 April 2022.The study included 50 patients between the ages of 18 and 65 years who were in the American Society of Anesthesiologists (ASA) I–II group and were scheduled for upper extremity surgery (hand, wrist, and forearm). Patients with diabetes, peripheral vascular disease, allergies to the local anesthetics (LAs), alpha- or beta-blocker use, local infections at the site of the operation, suspicion of nerve injury found during a neurologic examination prior to surgery, and refusal to participate in the study were excluded from the study.The time of block induction was defined as the infiltration of LA into the perineural area with a needle under ultrasound guidance. Peripheral oxygen saturation, heart rate, non-invasive arterial blood pressure values, and the PI values measured at both upper extremities were recorded in patients before block induction (0 min) and 5, 10, and 20 min after block completion.Asepsis in the infraclavicular region was achieved when the patient was laid in the supine position with their head turned to the opposite side. The median, lateral, and posterior cords of the BP were visualized using a high-frequency linear ultrasound probe around the artery in the infraclavicular area. To perform the USG guided in-plane technique, a 22G 50-mm needle was used. A second confirmation was performed using a nerve stimulator (NS) by applying 0.2–0.8 mA electrical stimulation. After observing the motor response of each chord, perineural LA infiltration was administered to each cord. For this treatment, each patient received 20 mL of 0.5% bupivacaine (Buvicaine 0.5%, 5 mg/mL Polifarma) and 2% lidocaine (Jetmonal 2%, 20 mg/mL, Adeka, Turkey).The sensory onset times of the block in all upper extremity areas, including the axillary nerve (lateral side of the upper arm), musculocutaneous nerve (lateral side of the forearm), radial nerve (dorsal part of hand at the 2nd metacarpophalangeal joint), median nerve (thenar eminence), ulnar nerve (little finger), and cutaneous nerves, were measured every 5 min until 30 min after the last injection (medial side of the upper arm and the medial side of the forearm). Three minutes after the block was induced, the pinprick test was used to assess and record the degree of sensory blockage in the affected arm (0: no sensory block; 1: sensation of touch present, no pain; 2: no sensation of touch, no pain). The PI readings were recorded at this exact time, along with the minute the pinprick test was positive.Every 5 min, until the 30 min, 5 motor nerves were evaluated for the motor block: the musculocutaneous (elbow flexion), radial (thumb abduction), median (third digit flexion), ulnar (fifth digit flexion), and the axillary nerve (arm abduction). The results were then compared with those of the other arm. Three minutes after the block was induced, the degree of motor blockade in the affected arm was measured and recorded every minute using the MBS (0: no block, the patient can lift the arm; 1: motor strength reduced, but the arm can move; 2: the arm is immobile, but the digits can move; 3: complete block, no movement in the arm or hand). The minute the grade reached 3 on the MBS was noted, as well as the PI values at that exact moment.The application of peripheral nerve blocks, the inspection of sensory-motor blocks, and the assessment of PI values were performed by several researchers. Both the patients and researchers were blinded to the examination findings and measured values. | PMC10171442 |
Ethical statement | This study was conducted in accordance with the principles of the Helsinki Declaration and all applicable national regulations and institutional policies (as revised in 2013). This study was reviewed and approved by Adıyaman University Clinical Studies Ethics Committee (decision date: 23/06/2020, decision number: 2020/6-18) and registered on clinicaltrials.gov (NCT05234541). Written informed consent was obtained from all participants included in this study. | PMC10171442 |