ABSTRACT
Despite current polysaccharide and conjugate vaccine use, pneumococcal diseases remain prevalent in older adults. VAX-24 is a 24-valent pneumococcal conjugate vaccine (PCV) containing eCRM, a proprietary carrier protein with non-native amino acids (para-azidomethyl-L-phenylalanine) that undergo site-specific conjugation to pneumococcal polysaccharides that have been activated with a small-molecule linker (dibenzocyclooctyne). Site-specific conjugation utilizing click chemistry enables consistent exposure of T-cell epitopes, reduction in carrier protein to pneumococcal polysaccharide ratio, and enhances manufacturing process consistency to improve PCVs by increasing serotype coverage while minimizing carrier suppression. Healthy adults aged 65 or older were randomized in a 1:1:1:1 ratio to receive a single injection of VAX-24 at 1 of 3 dose levels (1.1, 2.2, or a mixed dose of 2.2 or 4.4 mcg) or Prevnar 20® (PCV20) in a phase 2, blinded study. Primary outcome measures were solicited local and systemic events within 7 days post-vaccination, unsolicited adverse events (AEs) within 1 month, and serious AEs, medically attended AEs, or new onset of chronic disease within 6 months of vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) were measured pre-vaccination and at 1 month post-vaccination. Of 207 participants enrolled, 200 completed the trial. Safety profiles were comparable across the three VAX-24 doses and PCV20. Robust OPA and IgG immune responses were seen for all 24 serotypes. On average, immune responses to VAX-24 2.2 mcg dose were similar or higher compared to PCV20. In adults ≥ 65 years, VAX-24 had a safety profile similar to PCV20 through six months post-vaccination and induced robust OPA and IgG responses to all 24 serotypes, supporting prior data showing that site-specific conjugation allows for increased serotype coverage with similar or higher immune response vs other PCVs. The outcome of this phase 2 study further supports use of VAX-24 2.2 mcg dose in phase 3 trials. Clinicaltrials.gov: NCT05297578.
ABSTRACT
PURPOSE: Validation metrics are a key prerequisite for the reliable tracking of scientific progress and for deciding on the potential clinical translation of methods. While recent initiatives aim to develop comprehensive theoretical frameworks for understanding metric-related pitfalls in image analysis problems, there is a lack of experimental evidence on the concrete effects of common and rare pitfalls on specific applications. We address this gap in the literature in the context of colon cancer screening. METHODS: Our contribution is twofold. Firstly, we present the winning solution of the Endoscopy Computer Vision Challenge on colon cancer detection, conducted in conjunction with the IEEE International Symposium on Biomedical Imaging 2022. Secondly, we demonstrate the sensitivity of commonly used metrics to a range of hyperparameters as well as the consequences of poor metric choices. RESULTS: Based on comprehensive validation studies performed with patient data from six clinical centers, we found all commonly applied object detection metrics to be subject to high inter-center variability. Furthermore, our results clearly demonstrate that the adaptation of standard hyperparameters used in the computer vision community does not generally lead to the clinically most plausible results. Finally, we present localization criteria that correspond well to clinical relevance. CONCLUSION: We conclude from our study that (1) performance results in polyp detection are highly sensitive to various design choices, (2) common metric configurations do not reflect the clinical need and rely on suboptimal hyperparameters and (3) comparison of performance across datasets can be largely misleading. Our work could be a first step towards reconsidering common validation strategies in deep learning-based colonoscopy and beyond.
Subject(s)
Colonic Neoplasms , Deep Learning , Humans , Colonoscopy , Colonic Neoplasms/diagnosis , Image Processing, Computer-Assisted/methodsABSTRACT
INTRODUCTION: The increase in measles cases in early 2019 led to the implementation of several preventive measures focused mainly on health care providers. The study aimed to evaluate the seroprevalence of measles antibodies among employees of a large hospital and, a year apart, the rate of seroconversion in a pilot sample of the revaccinated subjects. METHODS: In 3027 employees of the University Hospital Olomouc, specific immunoglobulin G levels were tested on a voluntary basis. Those with insufficient levels were offered a booster dose. About approximately one year after the booster dose, the same test was performed in a sample of 52 employees. RESULTS: Of the tested subjects with a mean age of 41.8 ± 9.2 years, 54.0% were seropositive. A higher proportion of seropositivity as well as higher absolute values of antibody titers were noted in those born before routine vaccination was introduced in 1969. A total of 80.9% of the seronegative subjects opted for a booster dose. Seroconversion occurred in 73.2% of retested subjects. The relative increase of post-booster antibody titers was moderately correlated with age (r = 0.47, p < 0.05). CONCLUSION: The proportion of seronegative employees of a large hospital reached 46.0%, being higher in younger individuals. Seroconversion occurred in 73.2% of booster dose recipients included in a pilot sample for reanalysis. A statistically significant correlation was noted between the relative increase of antibody titers and age.
Subject(s)
Antibodies, Viral , Measles , Adult , Hospitals, University , Humans , Measles/epidemiology , Measles/prevention & control , Middle Aged , Pilot Projects , Seroepidemiologic StudiesABSTRACT
BACKGROUND: Risk factors other than supplemental oxygen might play a role in the development of retinopathy of prematurity (ROP). In Indonesia ROP occurs in infants up to 34 weeks and 2000âg. Risk factors for the development of ROP in Indonesian NICUs have not been evaluated. Our aim was to identify other risk factors than the use of oxygen in the development and progression of ROP in preterm infants in Indonesia. METHODOLOGY: Data on 98 preterm infants with ROP and 77 controls were collected from four NICUs and two eye centers in Jakarta, Indonesia, between 2009 and 2014. We used multivariate logistic regression analysis to determine the relationship between infants and environmental variables and the development and progression of ROP. We obtained variables for ROP severity by using Cox regression analysis. RESULTS: Factors associated with the development of ROP were birthweight (BWt), intrauterine growth retardation (IUGR), exchange transfusion, duration of oxygen supplementation, minimum saturation monitor setting, and socioeconomic factors. Regarding the progression, gestational age (GA), out-born, duration of supplemental oxygen, minimum saturation monitor setting, and socioeconomic factors were identified as risk factors. CONCLUSION: The use and control of supplemental oxygen are the main risk factors for the development and progression of ROP in preterms in Indonesia. Additionally, we confirm that GA, BWt, and IUGR are risk factors. Moreover, we found exchange transfusion to be a risk factor, and we found a lower rate of ROP in infants from a lower socioeconomic background. These risk factors apply to infants with a GA up to 34 weeks and a BWt up to 2000âg.
Subject(s)
Birth Weight , Fetal Growth Retardation/epidemiology , Gestational Age , Oxygen Inhalation Therapy/statistics & numerical data , Retinopathy of Prematurity/epidemiology , Social Class , Case-Control Studies , Disease Progression , Exchange Transfusion, Whole Blood/statistics & numerical data , Female , Humans , Indonesia/epidemiology , Infant, Extremely Low Birth Weight , Infant, Extremely Premature , Infant, Low Birth Weight , Infant, Newborn , Infant, Premature , Infant, Small for Gestational Age , Infant, Very Low Birth Weight , Male , Proportional Hazards Models , Retinopathy of Prematurity/physiopathology , Risk FactorsABSTRACT
BACKGROUND: Anastomotic leakage is still the most frequent cause of postoperative mortality following esophageal and cardial surgery. The German Advanced Surgical Study Group recommended that endoscopy should be the first diagnostic method if leakage is suspected. The German Surgical Endoscopy Association developed and validated a definition and severity classification of anastomotic leakage following esophageal and cardial resection. MATERIAL AND METHODS: In 2010 the international study group on insufficiency published a definition and severity grading of anastomotic leakage following anterior resection of the rectum, which was validated in 2013. The severity of anastomotic leakage should be graded according to the impact on clinical management: type I requires only conservative management, type II requires interventional radiological or endoscopic treatment and type III requires surgical revision. In contrast to the rectal classification type III is divided into a category without (type IIIa) or with (type IIIb) conduit resection and diversion. The validation was carried out on a 10-year collective from the university hospitals in Heidelberg and Tübingen. RESULTS: From 2006-2015 all 92 patients who developed an anastomotic leakage following esophageal and cardial resection were enrolled in the study. We found a significant increase in the length of stay in the intensive care unit (ICU) with increasing classification type (pâ¯< 0.0143). Furthermore, there was a significant correlation with the general classification of postoperative complications according to Clavien-Dindo as well as with mortality (pâ¯< 0.001). DISCUSSION: Standardized parameters are the prerequisite to be able to compare the results between hospitals and studies. The validation of the suggested classification shows that the differentiation between the groups is substantiated by the correlation to the length of ICU stay, Clavien-Dindo and mortality and will therefore contribute to a better comparability of data on leakage following esophageal resection in the future.
Subject(s)
Anastomotic Leak , Esophagus/surgery , Cardiac Surgical Procedures/adverse effects , Conservative Treatment , Humans , Postoperative ComplicationsABSTRACT
OBJECTIVE: The aim of this study was to compare results of two commercially available kits used for routine detection of Rotavirus A in human stool samples with results of commercial quantitative reverse-transcription PCR (RT-qPCR) test and in-house RT-qPCR. MATERIAL AND METHODS: In total, 749 stool samples were screen-ed with the use of four different methods. The samples were collected from four diagnostic laboratories from March 2016 to June 2017. Diagnose of gastrointestinal disorders was stated in one third of tested patients, the rest of samples was collected from patients with other primary diagnose. The samples were tested with the enzymatic immunoassay (EIA) (RIDASCREEN® Rotavirus) and with rapid diagnostic immunochromatographic test (RDT) (IMMUNOQUICK® No-Rot-Adeno). As a reference method a commercial RT-qPCR test was used (Primerdesign Genesig® Kit) and it was compared with in-house RT-qPCR test prepared in our laboratory. The samples which in the reference RT-qPCR gave positive signal of reaction in cycle 28 or higher (Ct 28) were assessed as negatives in order to include only samples with some clinical relevance into sensitivity determination. RESULTS: Diagnostic sensitivity was assessed as 84.2% for EIA and 82.5% for RDT. The specificity of those tests was calculated as 97.8% for EIA and 96.4% for RDT. The performance of both diagnostic tests describing their positive predictive value was determined to be 87.3% for EIA and 80.3% for RDT. Negative predictive value was calculated to be 97.2% for EIA and 96.8% for RDT. Proportion of RVA-positive samples determined with the reference RT-qPCR test with our own cut-off level was 15.2% (n=114). Comparisons of the in-house and reference RT-qPCR tests showed very good agreement of results. The sensitivity of the in-house test was 100% and its specificity 99.7%. CONCLUSIONS: RT-qPCR is more sensitive for surveillance of rotavirus gastroenteritis than routinely used EIA or RDT methods. The specificity of both evaluated tests was very high. However, EIA was in all performance parameters assessed better than RDT.
Subject(s)
Chromatography , Immunoenzyme Techniques , Reverse Transcriptase Polymerase Chain Reaction , Rotavirus Infections , Rotavirus , Chromatography/standards , Feces/virology , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/virology , Humans , Immunoassay/standards , Immunoenzyme Techniques/standards , Reverse Transcriptase Polymerase Chain Reaction/standards , Rotavirus/isolation & purification , Sensitivity and SpecificityABSTRACT
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown origin. Previous bile proteomic analyses in patients with PSC have revealed changes in disease activity specific to malignant transformation. In this study, we established a reference bile duct-derived bile proteome for PSC that can be used to evaluate biliary pathophysiology. Samples were collected from patients with PSC or with choledocholithiasis (control) (n=6 each). Furthermore, patients with PSC-associated cholangiocarcinoma (CC) and with CC without concomitant PSC were analyzed. None of the patients showed signs of inflammation or infection based on clinical and laboratory examinations. Proteins overexpressed in patients with PSC relative to control patients were detected by two-dimensional difference gel electrophoresis and identified by liquid chromatography-tandem mass spectrometry. Functional proteomic analysis was performed using STRING software. A total of 101 proteins were overexpressed in the bile fluid of patients with PSC but not in those of controls; the majority of these were predicted to be intracellular and related to the ribosomal and proteasomal pathways. On the other hand, 91 proteins were found only in the bile fluid of controls; most were derived from the extracellular space and were linked to cell adhesion, the complement system, and the coagulation cascade. In addition, proteins associated with inflammation and the innate immune response-e.g., cluster of differentiation 14, annexin-2, and components of the complement system-were upregulated in PSC. The most prominent pathways in PSC/CC-patients were inflammation associated cytokine and chemokine pathways, whereas in CC-patients the Wnt signaling pathway was upregulated. In PSC/CC-patients DIGE-analysis revealed biliary CD14 and Annexin-4 expression, among others, as the most prominent protein that discriminates between both cohorts. Thus, the bile-duct bile proteome of patients with PSC shows disease-specific changes associated with inflammation and the innate immune response even in the absence of obvious clinical signs of cholangitis, malignancy, or inflammation. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni and Peter Jansen.
Subject(s)
Bile Duct Neoplasms/metabolism , Bile Ducts/metabolism , Bile/chemistry , Cholangiocarcinoma/metabolism , Cholangitis, Sclerosing/metabolism , Adult , Aged , Aged, 80 and over , Bile/immunology , Bile Duct Neoplasms/immunology , Bile Duct Neoplasms/pathology , Bile Ducts/pathology , Case-Control Studies , Cholangiocarcinoma/immunology , Cholangiocarcinoma/pathology , Cholangitis, Sclerosing/immunology , Cholangitis, Sclerosing/pathology , Choledocholithiasis/metabolism , Choledocholithiasis/pathology , Cohort Studies , Cytokines/analysis , Cytokines/immunology , Cytokines/metabolism , Female , Humans , Immunity, Innate , Lipopolysaccharide Receptors , Male , Middle Aged , Proteomics , Up-Regulation , Wnt Signaling Pathway/immunologyABSTRACT
Human milk provides optimal nutrition for the term new-born infant. This milk might give the infant certain advantages over formula milk, and the potential advantages are reviewed in this commentary. It is concluded that there are advantages to breastfeeding, but that these are limited for an infant in an industrialised country receiving adequate formula milk. Breastfeeding should be encouraged, but there is insufficient reason for a mother who either is not able or not willing to breastfeed to feel guilty about not doing so.
Subject(s)
Bottle Feeding/psychology , Breast Feeding , Guilt , Mothers/psychology , Animals , Female , Humans , Infant , Milk, Human , NetherlandsABSTRACT
The interdisciplinary management of postoperative complications in liver transplantation is of extreme importance. Due to organ shortage and prioritization of the most severely ill recipients in the model for end-stage liver disease (MELD)-based allocation, both donor and recipient associated morbidity are increasing. An interdisciplinary, structured monitoring concept is essential for the timely identification and specific treatment of postoperative complications. Interdisciplinary clinical rounds, laboratory testing and Doppler ultrasound monitoring of the graft perfusion are as important as comprehensive anti-infection prophylaxis and immunosuppression. Arterial perfusion disorders of any kind, biliary complications and postoperative fluid accumulation demand individualized therapeutic concepts. In summary, the success of liver transplantation depends on the communication and coordinated interdisciplinary cooperation of all disciplines involved.
Subject(s)
Cooperative Behavior , Interdisciplinary Communication , Liver Transplantation , Patient Safety/standards , Postoperative Complications/therapy , Graft Survival , Humans , Postoperative Complications/diagnosis , Postoperative Complications/etiology , ReoperationABSTRACT
BACKGROUND: Alkaline phosphatase (ALP) is an important serum marker in primary sclerosing cholangitis (PSC). Patients with obstruction of the large bile ducts due to dominant strictures (DS) are a special, clinically important phenotype. AIM: To determine the impact of ALP reduction on liver transplantation-free survival in PSC patients with DS. METHODS: Prospective cohort study in 215 PSC patients. We performed subgroup analysis for patients without DS (no DS, n = 84), DS at first presentation (DS early, n = 72) and development of DS during the course of the study (DS late, n = 59). We evaluated two scores of ALP reduction. ALP reduction 1 was defined as ALP normalisation, 50% reduction compared with baseline values, or reduction below 1.5 times of upper limit of normal (ULN) within 6 months. ALP reduction 2 was defined as ALP reduction below 1.5 times of ULN within 12 months. RESULTS: Of the patients, 59.5% reached an ALP reduction 1 and 56.7% according to ALP reduction 2. Achievement of each score was associated with longer transplantation-free survival in all three groups (ALP reduction 1: no DS P = 0.001; DS early P < 0.001; DS late P = 0.022; ALP reduction 2: no DS P = 0.014; DS early P = 0.001; DS late P = 0.002). Cox-regression analysis revealed each score as an independent predictor for improved transplantation-free survival (ALP reduction 1 and 2 P < 0.001 each). We further analysed previously published scores of ALP improvement in PSC showing also improved survival in patients with ALP normalisation or a reduction below 1.5 times of ULN (P = 0.003, P = 0.001, respectively), whereas the score determined by 40% reduction did not show significant differences in survival (P = 0.55). CONCLUSIONS: Reduction in alkaline phosphatase values within the first year is associated with improved transplantation-free survival in patients with primary sclerosing cholangitis independent of the presence of dominant strictures. Alkaline phosphatase might be an adequate surrogate marker for outcome assessment in clinical studies both for patients with and without dominant strictures.
Subject(s)
Alkaline Phosphatase/blood , Cholangitis, Sclerosing/complications , Cholangitis, Sclerosing/enzymology , Constriction, Pathologic/complications , Adult , Biomarkers/blood , Cholangitis, Sclerosing/blood , Constriction, Pathologic/blood , Constriction, Pathologic/enzymology , Female , Humans , Kaplan-Meier Estimate , Liver Transplantation , Male , Prospective StudiesABSTRACT
BACKGROUND: Innovative surgical techniques in colorectal surgery aim to provide diminished surgical injury and at least equivalent or even improved quality of treatment and oncological results. High level clinical studies are mandatory to examine the feasibility and advantages (or disadvantages) of new operative techniques. OBJECTIVES: Laparoscopic colonic resection for cancer has been investigated with respect to safety and oncological quality in various prospective randomized studies (COST study, COLOR-I and CLASICC). The minimally invasive procedure is feasible and safe which was demonstrated in many studies but can these results be extrapolated to laparoscopic rectal cancer surgery? RESULTS: The short term outcomes of the COLOR-II trial were published recently and laparoscopic resection for rectal cancer was not found to be inferior compared to open resection. Recovery after laparoscopic surgery was better than after open surgery. Laparoscopic surgery was found to have significant advantages with respect to blood loss, operating time, use of pain medication, early restoration of bowel function and reduction of hospital stay as well as the lateral safety margins in the distal third of the rectum. The long-term results focussing on local recurrence showed a positive trend in favor of laparoscopic rectal surgery and will be published shortly. CONCLUSION: Laparoscopic total mesorectal excision (TME) appears to have clinically measurable short-term advantages in patients with primary rectal cancer based on the evidence of randomized studies. Laparoscopic rectal cancer resection may become the gold standard in the future.
Subject(s)
Evidence-Based Medicine , Laparoscopy , Rectal Neoplasms/surgery , Disease-Free Survival , Humans , Randomized Controlled Trials as Topic , Rectal Neoplasms/mortality , Rectal Neoplasms/pathologyABSTRACT
AIM: Up to 18.1% of Dutch children aged 3-5 are overweight and up to 3.3% are obese, with higher levels in girls. This study assessed the effect of a multidisciplinary intervention programme on health-related quality of life (HRQoL) in this patient group. METHODS: We randomised 75 children to a multidisciplinary intervention, comprising dietary advice, exercise sessions and psychological counselling for parents or the standard care programme, providing healthy lifestyle advice. The parents completed quality of life and child health questionnaires at baseline and after 16 weeks and 12 months. RESULTS: At 16 weeks, children in the intervention group experienced more bodily pain and less mental health than the standard care group, but at 12 months, this difference disappeared and they showed a more positive change in HRQoL than the standard care group, especially for the physical domain. When we combined both groups, a decreased BMIz-score over 12 months was associated with increased global health and reduced visceral fat correlated with increased general health. CONCLUSION: At 12 months, a multidisciplinary intervention programme for overweight and obese children aged 3-5 years had beneficial effects on HRQoL, especially for the physical domain. Reduced obesity parameters correlated with several increased HRQoL parameters.
Subject(s)
Overweight/therapy , Pediatric Obesity/therapy , Quality of Life , Child, Preschool , Female , Humans , Male , Patient Care TeamABSTRACT
BACKGROUND: A recent genome-wide association study identified the FUT2 secretor status and genotype defined by the single-nucleotide polymorphism rs601338 as potential genetic risk factor in primary sclerosing cholangitis (PSC), which significantly influences biliary bacterial composition. AIM: To determine the impact of the rs601338-FUT2 genotype on frequency of biliary infections, development of dominant stenosis and liver-transplantation-free survival in patients with PSC. METHODS: Cohort study of 215 patients with PSC treated at our tertiary care centre with respect to their rs601338-FUT2 genotype. Results of endoscopic retrograde cholangiography and bile culture were analysed; 639 biliary samples were obtained, cultured and subjected to microbial analysis. Clinical and laboratory data were analysed using chart reviews. RESULTS: For the rs601338-FUT2 genotype, 69 patients (32.1%) were found to be wildtype (GG), 97 (45.1%) patients were heterozygous (AG) and 49 patients (22.8%) were homozygous-mutated (AA). In addition to alterations in the bacterial pattern, especially in heterozygous carriers, patients with mutated alleles had a marked increase in the frequency of biliary Candida infections (P = 0.025). Further, patients with mutated alleles showed an increased frequency of episodes of cholangitis (P = 0.0025), development of dominant stenosis (P < 0.002) and a reduced actuarial transplantation-free survival (P = 0.044). Levels of biliary Ca19-9 were significantly elevated in the homozygous-mutated patients. CONCLUSIONS: The rs601338-FUT2 genotype is strongly associated with episodes of cholangitis, fungobilia and the incidence of dominant stenosis, which are three clinical hallmarks of PSC; FUT2 is thus an important genetic risk factor for host-microbial diversity and disease progression in PSC.
Subject(s)
Candida/isolation & purification , Candidiasis/epidemiology , Cholangitis, Sclerosing/complications , Constriction, Pathologic/epidemiology , Fucosyltransferases/genetics , Adult , Alleles , Bile/microbiology , Candidiasis/etiology , Cholangiography/methods , Cholangitis, Sclerosing/genetics , Cholangitis, Sclerosing/microbiology , Cohort Studies , Constriction, Pathologic/etiology , Constriction, Pathologic/genetics , Disease Progression , Female , Genotype , Heterozygote , Humans , Incidence , Male , Polymorphism, Single Nucleotide , Prospective Studies , Risk Factors , Galactoside 2-alpha-L-fucosyltransferaseABSTRACT
STUDY QUESTION: Do paternal and maternal lifestyle factors influence the risk of hypertensive pregnancy complications, gestational diabetes mellitus (GDM), spontaneous preterm birth and small-for-gestational-age (SGA)? SUMMARY ANSWER: Paternal lifestyle factors do not exert an independent effect on the investigated outcomes while maternal prepregnancy BMI and maternal smoking during pregnancy influence the risk of hypertensive pregnancy complications, GDM and SGA. WHAT IS KNOWN ALREADY: Maternal lifestyle factors are associated with perinatal complications, but the impact of paternal lifestyle factors is unclear. STUDY DESIGN, SIZE, DURATION: Data from the GECKO (Groningen Expert Center for Kids with Obesity) Drenthe cohort, a prospective population-based birth-cohort of children born between April 2006 and April 2007 in a northern province of The Netherlands, were analysed. The parents of 2958 children (62% of those approached) gave their consent to participate in the study and the data of 2264 (77%) couples were available for analysis. PARTICIPANTS/MATERIALS, SETTINGS, METHOD: All pregnant women in the Dutch province of Drenthe with an expected date of delivery between April 2006 and April 2007 were invited to participate and included during the third trimester of their pregnancy or within 6 months after delivery. All consenting couples received extensive questionnaires including lifestyle, biological and socio-demographic-related questions covering the period of 6 months prior to conception. Outcome data were obtained from midwives and hospital registries. Univariable and multivariable logistic regression analyses were used to determine the impact of the lifestyle factors on the primary outcome measures. MAIN RESULTS AND THE ROLE OF CHANCE: Of all 2264 women, 241 women (10.6%) developed a hypertensive pregnancy complication, 50 women (2.2%) developed GDM, 79 (3.5%) children were spontaneously delivered preterm and 155 children (6.8%) were SGA. All paternal and maternal lifestyle factors were positively correlated. Multivariable analysis showed that paternal lifestyle factors did not have an independent influence on the investigated outcomes. Of the maternal factors, prepregnancy BMI was independently associated with an increased risk of a hypertensive disorder during pregnancy (odds ratio (OR): 1.12, 95% CI 1.09-1.16), a higher risk of GDM (OR BMI >23 kg/m(2), per BMI unit: 1.13, 95% CI 1.08-1.18) and with a decreased risk of SGA (OR per BMI point 0.94, 95% CI 0.90-0.99). Maternal smoking during pregnancy was significantly associated with SGA (OR 3.00, 95% CI 1.80-4.99) in multivariable analysis. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the questionnaire may have induced recall bias. Selection bias might have occurred, as ethnic minorities were less willing to co-operate in the GECKO Drenthe study. The possibility of misclassification bias regarding the primary outcome measures cannot be ruled out. Inclusion bias might have occurred as not all questionnaires of the parents of the children participating in the GECKO Drenthe cohort were completed. WIDER IMPLICATIONS OF THE FINDINGS: Paternal lifestyle factors do not have an independent effect on the investigated adverse pregnancy outcomes. However, as paternal and maternal lifestyles are positively correlated, both partners should be involved in preconception counselling regarding the investigated outcome measures.
Subject(s)
Life Style , Maternal Behavior , Paternal Behavior , Pregnancy Complications/epidemiology , Female , Gestational Age , Humans , Infant, Small for Gestational Age , Logistic Models , Multivariate Analysis , Odds Ratio , Pregnancy , Pregnancy Outcome , Retrospective Studies , SmokingABSTRACT
The paper presents an application of a special case of an Active Disturbance Rejection Controller (ADRC) in governing a proper realization of basic limb rehabilitation trainings. The experimental study is performed on a model of a flexible joint manipulator, whose behavior resembles a real robotic rehabilitation device. The multidimensional character of the considered assisting mechanism makes it a nontrivial modeling and control problem. However, by the use of the ADRC approach, the modeling uncertainty in the plant is partially decoupled from the system, which increases the robustness of the whole control framework against both internal and external disturbances.
Subject(s)
Exercise Therapy/instrumentation , Man-Machine Systems , Models, Theoretical , Rehabilitation/instrumentation , Robotics/instrumentation , Therapy, Computer-Assisted/instrumentation , Algorithms , Computer Simulation , Equipment Design , Equipment Failure Analysis , Extremities , Feedback , HumansABSTRACT
Skipping breakfast is associated with higher BMI in children aged 5 years and older. However, not much is known about this association in younger children. In the Dutch GECKO Drenthe birth cohort we examined the association between breakfast skipping and objectively measured overweight at the age of 2 (n=1488) and 5 (n=1366) years. At 2 years, 124 (8.3%) children were overweight and 44 (3.0%) did not eat breakfast daily. At 5 years, 180 (13.2%) children were overweight and 73 (5.3%) did not eat breakfast daily. Children belonging to families of non-Dutch origin, those with lower educated parents and those with single parents skipped breakfast more often. Breakfast skipping in 2- and 5-year-olds is rare in the Netherlands. We found no association between skipping breakfast and overweight, neither at age 2 (odds ratio (OR): 1.85 (95% confidence interval (CI): 0.61-5.64)) nor at age 5 (OR: 0.46 (95% CI: 0.19-1.11)). Also the type of breakfast was not related to overweight at 5 years. An explanation for this finding might be that skipping breakfast is not (yet) an issue in these children.
Subject(s)
Breakfast , Child Behavior , Feeding Behavior , Overweight/epidemiology , Parenting , Body Mass Index , Child Nutritional Physiological Phenomena , Child, Preschool , Cohort Studies , Female , Health Promotion , Humans , Male , Netherlands , Odds Ratio , Overweight/etiology , Socioeconomic Factors , Surveys and QuestionnairesABSTRACT
BACKGROUND: Cytokines might be helpful to diagnose late onset sepsis (LOS) in newborn infants. Many studies on cytokines did not discriminate culture-proven from clinically-suspected sepsis; however, such differentiation is clinically useful. OBJECTIVES: To evaluate the feasibility to differentiate among culture-proven LOS, clinical LOS and controls using a battery of cytokines. STUDY DESIGN: This prospective study was conducted at the NICU of Harapan-Kita Women and Children's Hospital, Jakarta-Indonesia. Three groups of infants with postnatal age >72 hours of age were enrolled in the study: culture-proven sepsis group (PS) (n = 18), clinical sepsis group (CS) (n = 25) and control group (n = 34). A battery of 25 cytokines was measured in each infant five times: at enrollment, after 4 hrs, 12 hrs, 24 hrs, and 48 hrs using Invitrogen-immunoassays-Luminex™100. RESULTS: There were no significant differences in gestational age or mode of delivery among the three groups. IL-1ß, IL-2r, IL-6, IL-8, IL-10 and MIP-1a were significantly higher at all measurement points in group PS compared to controls. IL-13 was lower at all measurement moments in group CS compared to controls, IL-12 was lower and IP-10 higher between 0 and 24 hrs. IL-1Ra, IL-6, IL-8, IL-13, IL-15, TNFα, MIP-1a and MIP-1b were higher at all the measurement moments in group PS compared to group CS. The ROC curves show that IL-6, IL-8, IL-15, MIP-1a, MIP-1b and TNFα have a sensitivity and specificity between 80 and 85% during the first 24-48 hours after the onset of infection. IL-6, IL-15, MIP-1a, MIP-1b and TNFα showed the best likelihood ratios. CONCLUSIONS: IL-6, IL8, IL 15, MIP-1a, MIP-1b and TNFα are potentially good markers for detecting a proven LOS. In case these cytokines are not elevated in sick infants, other causes than an infection have to be identified.
Subject(s)
Cytokines/metabolism , Sepsis/diagnosis , Case-Control Studies , Feasibility Studies , Female , Humans , Infant, Newborn , Male , Prospective Studies , ROC Curve , Sensitivity and SpecificityABSTRACT
Cytomegalovirus (CMV) can cause severe infections with serious consequences in renal transplant recipients. Disseminated CMV infections can affect almost every organ, but obstructive cholestasis and cholangitis, as a consequence of a CMV-induced papillitis, is extremely rare. We are reporting a rare case of obstructive cholestasis and cholecystitis due to CMV-related inflammation of the major duodenal papilla in a 60-year-old woman 3 months after renal transplantation. In addition, the patient suffered from a disseminated CMV infection with ulcerative esophagitis and gastritis. Because of the severe CMV infection, failure of the renal graft occurred. Obstructive cholestasis was resolved through internal stenting, and the progressive cholecystitis necessitated an emergency cholecystectomy. Following antiviral therapy with ganciclovir, the gastrointestinal ulcerations regressed and renal function was restored. Diagnosis of the CMV-related disease was established only in tissue samples, whereas standard serologic tests had failed.
Subject(s)
Acalculous Cholecystitis , Ampulla of Vater/virology , Cholangitis , Cholestasis, Intrahepatic , Common Bile Duct Diseases , Cytomegalovirus Infections , Kidney Transplantation/adverse effects , Acalculous Cholecystitis/complications , Acalculous Cholecystitis/virology , Allografts , Cholangitis/complications , Cholangitis/virology , Cholestasis, Intrahepatic/complications , Cholestasis, Intrahepatic/virology , Common Bile Duct Diseases/complications , Common Bile Duct Diseases/virology , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/virology , Female , Humans , Middle AgedABSTRACT
The first measurement of the three-body photodisintegration of longitudinally polarized (3)He with a circularly polarized γ-ray beam was carried out at the High Intensity γ-ray Source facility located at Triangle Universities Nuclear Laboratory. The spin-dependent double-differential cross sections and the contributions from the three-body photodisintegration to the (3)He Gerasimov-Drell-Hearn integrand are presented and compared with state-of-the-art three-body calculations at the incident photon energies of 12.8 and 14.7 MeV. The data reveal the importance of including the Coulomb interaction between protons in three-body calculations.
ABSTRACT
AIM: To comparing attitudes towards end-of-life (EOL) decisions in newborn infants between seven European countries. METHODS: One paediatrician and one lawyer from seven European countries were invited to attend a conference to discuss the practice of EOL decisions in newborn infants and the legal aspects involved. RESULTS: All paediatricians/neonatologists indicated that the best interest of the child should be the leading principle in all decisions. However, especially when discussing cases, important differences in attitude became apparent, although there are no significant differences between the involved countries with regard to national legal frameworks. CONCLUSION: Important differences in attitude towards neonatal EOL decisions between European countries exist, but they cannot be explained solely by medical or legal reasons.