Vitamin D intake in Australian adults and the modeled effects of milk and breakfast cereal fortification

Objective: Vitamin D intake from foods or supplements is a safe and attractive means to improve vitamin D status of populations. The aim of this study was to help identify population subgroups that would benefit most from efforts to increase intake. To do so, we investigated which personal characteristics are associated with vitamin D intake in an Australian population and modeled possible effects of expanded food fortification practices. Methods: We investigated vitamin D intake in a population-based random sample of 785 adults, using a validated food frequency questionnaire, and assessed associations with personal and behavioral characteristics. We identified vitamin D food sources and modeled the hypothetical effects of blanket fortification of milk and breakfast cereals. Results: Average total vitamin D intake was 4.4 (±4.0) μg/g and below adequate intake for most participants in all age and sex subgroups. Higher intake was associated with being female, having a serious medical condition, energy intake below the median, and vitamin D supplement use (all P < 0.05). The "meat, fish, and eggs" food group contributed most to total vitamin D intake (51%), followed by dairy products and related foods (43%). If all milk and breakfast cereals were to be fortified with vitamin D, the average intake of vitamin D from foods would increase from 3.6 (±2.4) μg/d to 6.3 (±3.2) μg/d, with similar increases in all age and sex subgroups. Conclusions: Vitamin D intake in Australia is generally below recommended levels, and few personal characteristics help to identify subgroups with low intake. Blanket vitamin D fortification of milk and breakfast cereals would substantially increase average vitamin D intake in Australian adults of all ages

Trends of cutaneous melanoma in the Netherlands: increasing incidence rates among all Breslow thickness categories and rising mortality rates since 1989

Abstract: Background: It has been debated that the epidemic of melanoma is largely due to overdiagnosis, since increases in incidence were mainly among thin melanomas and mortality rates remained stable. Our objective was to examine this controversy in the Netherlands. Patients and Methods: Information on newly diagnosed melanoma patients was obtained from the Netherlands Cancer Registry (NCR). European Standardised Rates (ESR) and Estimated Annual Percentage Change (EAPC) were calculated for the period 1989-2008.Cohort-based, period-based and multivariate survival analyses were performed. Results: The incidence rate of melanoma increased with 4.1% (95% CI: 3.6-4.5) annually. Incidence rates of both thin melanomas (. 1mm) and thick melanomas (> 4 mm) increased since 1989. Mortality rates increased mainly in older patients (>65 years). Ten-year relative survival of males improved significantly from 70% in 1989-1993 to 77% in 2004-2008 (p < 0.001) and for females the 10-year relative survival increased from 85% to 88% (p < 0.01). Recently diagnosed patients had a better prognosis even after adjusting for all known prognostic factors. Conclusion: Since incidence of melanomas among all Breslow thickness categories increased as well as the mortality rates, the melanoma epidemic in the Netherlands seems to be real and not only due to overdiagnosis

Nationwide Evaluation of Congenital Hypothyroidism Screening during Neonatal Extracorporeal Membrane Oxygenation

Background: Thyroid hormone concentrations may deviate from normal values during critical illness. This condition is known as nonthyroidal illness syndrome (NTIS), and it can influence the results of screening for congenital hypothyroidism (CH) during neonatal extracorporeal membrane oxygenation (ECMO). Objectives: To determine the incidence of aberrant CH screening results in ECMO-treated neonates, to identify possible determinants, and to follow up patients with abnormal thyroid hormone concentrations. Methods: In this retrospective cohort study, we included 168 ECMO-treated neonates admitted from 2004 to 2014 and screened by protocol and divided them into the following 3 groups: group 1 (screened during ECMO, n = 107), group 2 (screened shortly before ECMO, n = 26), and group 3 (screened shortly after ECMO, n = 35). Results: CH screening results were aberrant in 67.3% (72/107) of the neonates screened during ECMO, in 73.1% (19/26) of the neonates screened before ECMO, and in 31.4% (11/35) of the neonates screened after ECMO (p < 0.001). Of the neonates with an aberrant screening result, all but 2 (i.e. 98%) had a low thyroxine concentration with a normal thyrotropin concentration at screening, as is seen in NTIS. None was diagnosed with CH. Mortality did not significantly differ between neonates with an aberrant screening result (32.4%) and neonates with a normal screening result (22.7%; p = 0.18). Screening before ECMO (OR 5.92; 95% CI 1.93-18.20), screening during ECMO (OR 4.49; 95% CI 1.98-10.19), and a higher Pediatric Logistic Organ Dysfunction-2 score (OR 1.31; 95% CI 1.04-1.66) were associated with an aberrant screening result. Conclusions: Aberrant CH screening results were found in most ECMO-treated neonates screened before or during ECMO, which is likely due to NTIS. Follow-up of thyroid hormone concentrations is best started after recovery from critical illness. Our results suggest that thyroxine therapy is not required during ECMO

Adaptation of the WHO maternal near miss tool for use in sub-Saharan Africa:An International Delphi study

Background: Assessments of maternal near miss (MNM) are increasingly used in addition to those of maternal mortality measures. The World Health Organization (WHO) has introduced an MNM tool in 2009, but this tool was previously found to be of limited applicability in several low-resource settings. The aim of this study was to identify adaptations to enhance applicability of the WHO MNM tool in sub-Saharan Africa. Methods: Using a Delphi consensus methodology, existing MNM tools were rated for applicability in sub-Saharan Africa over a series of three rounds. Maternal health experts from sub-Saharan Africa or with considerable knowledge of the context first rated importance of WHO MNM parameters using Likert scales, and were asked to suggest additional parameters. This was followed by two confirmation rounds. Parameters accepted by at least 70% of the panel members were accepted for use in the region. Results: Of 58 experts who participated from study onset, 47 (81%) completed all three rounds. Out of the 25 WHO MNM parameters, all 11 clinical, four out of eight laboratory, and four out of six management-based parameters were accepted, while six parameters (PaO2/FiO2 <200 mmHg, bilirubin > 100 mu mol/l or > 6.0 mg/dl, pH <7.1, lactate > 5 mu mol/l, dialysis for acute renal failure and use of continuous vasoactive drugs) were deemed to not be applicable. An additional eight parameters (uterine rupture, sepsis/severe systemic infection, eclampsia, laparotomy other than caesarean section, pulmonary edema, severe malaria, severe complications of abortions and severe pre-eclampsia with ICU admission) were suggested for inclusion into an adapted sub-Saharan African MNM tool. Conclusions: All WHO clinical criteria were accepted for use in the region. Only few of the laboratory-and management based were rated applicable. This study brought forward important suggestions for adaptations in the WHO MNM criteria to enhance its applicability in sub-Saharan Africa and possibly other low-resource settings

The interplay between tamoxifen and endoxifen plasma concentrations and coagulation parameters in patients with primary breast cancer

Background: Tamoxifen is an effective treatment for primary breast cancer but increases the risk for venous thromboembolism. Tamoxifen decreases anticoagulant proteins, including antithrombin (AT), protein C (PC) and tissue factor (TF) pathway inhibitor, and enhances thrombin generation (TG). However, the relation between plasma concentrations of both tamoxifen and its active metabolite endoxifen and coagulation remains unknown. Methods: Tamoxifen and endoxifen were measured in 141 patients from the prospective open-label intervention TOTAM-study after 3 months (m) and 6 m of tamoxifen treatment. Levels of AT and PC, the procoagulant TF, and TG parameters were determined at both timepoints if samples were available (n = 53–135 per analysis). Levels of coagulation proteins and TG parameters were correlated and compared between: 1) quartiles of tamoxifen and endoxifen levels, and 2) 3 m and 6 m of treatment. Results: At 3 m, levels of AT, PC, TF and TG parameters were not associated with tamoxifen nor endoxifen levels. At 6 m, median TF levels were lower in patients in the 3rd (56.6 [33] pg/mL), and 4th (50.1 [19] pg/mL) endoxifen quartiles compared to the 1st (lowest) quartile (76 [69] pg/mL) (P=0.027 and P=0.018, respectively), but no differences in anticoagulant proteins or TG parameters were observed. An increase in circulating TF levels (3 m: 46.0 [15] versus 6 m: 54.4 [39] pg/mL, P &lt; 0.001) and TG parameters was observed at the 6 m treatment timepoint, while AT and PC levels remained stable.Conclusions: Our results indicate that higher tamoxifen and endoxifen levels are not correlated with an increased procoagulant state, suggesting tamoxifen dose escalation does not further promote hypercoagulability.</p

Challenges in body composition assessment using air-displacement plethysmography by BOD POD in pediatric and young adult patients

Background &amp; aims: Air-Displacement-Plethysmography (ADP) by BOD POD is widely used for body fat assessment in children. Although validated in healthy subjects, studies about use in pediatric patients are lacking. We evaluated user experience and usability of ADP measurements with the BOD POD system in healthy children and pediatric and young adult patients. Methods: Using the experiences of seven cohort studies, which included healthy children and patients aged 2–22 years, we retrospectively evaluated the user experience with the User Experience Questionnaire (UEQ) (n = 13) and interviews (n = 7). Technical performance was studied using the quality control data collected by the ADP-system. Results: From 2016 to 2022, 1606 measurements were scheduled. BOD POD was mostly rated ‘user-friendly’, with a generally neutral evaluation on all scales of the UEQ. However, questionable reliability and validity of the results were frequently (86%) reported. We found a high technical failure-rate of the device, predominantly in stability (17%) and accuracy of the measurement (12%), especially in the ‘pediatric option’ for children aged &lt;6 years. Measurement failure-rate was 38%, mostly due to subject's fear or device failure, especially in young and lean children, and in children with physical and/or intellectual disabilities. Conclusion: We conclude that ADP by BOD POD in children and young adults is non-invasive and user-friendly. However, in specific pediatric populations, BOD POD has several limitations and high (technical) failure-rates, especially in young children with aberrant body composition. We recommend caution when interpreting body composition results of pediatric patients as assessed with BOD POD using the current default settings.</p

Challenges in body composition assessment using air-displacement plethysmography by BOD POD in pediatric and young adult patients

Background &amp; aims: Air-Displacement-Plethysmography (ADP) by BOD POD is widely used for body fat assessment in children. Although validated in healthy subjects, studies about use in pediatric patients are lacking. We evaluated user experience and usability of ADP measurements with the BOD POD system in healthy children and pediatric and young adult patients. Methods: Using the experiences of seven cohort studies, which included healthy children and patients aged 2–22 years, we retrospectively evaluated the user experience with the User Experience Questionnaire (UEQ) (n = 13) and interviews (n = 7). Technical performance was studied using the quality control data collected by the ADP-system. Results: From 2016 to 2022, 1606 measurements were scheduled. BOD POD was mostly rated ‘user-friendly’, with a generally neutral evaluation on all scales of the UEQ. However, questionable reliability and validity of the results were frequently (86%) reported. We found a high technical failure-rate of the device, predominantly in stability (17%) and accuracy of the measurement (12%), especially in the ‘pediatric option’ for children aged &lt;6 years. Measurement failure-rate was 38%, mostly due to subject's fear or device failure, especially in young and lean children, and in children with physical and/or intellectual disabilities. Conclusion: We conclude that ADP by BOD POD in children and young adults is non-invasive and user-friendly. However, in specific pediatric populations, BOD POD has several limitations and high (technical) failure-rates, especially in young children with aberrant body composition. We recommend caution when interpreting body composition results of pediatric patients as assessed with BOD POD using the current default settings.</p

Serum proteomics reveals hemophagocytic lymphohistiocytosis-like phenotype in a subset of patients with multisystem inflammatory syndrome in children

Children with Multisystem Inflammatory Syndrome in Children (MIS-C) can present with thrombocytopenia, which is a key feature of hemophagocytic lymphohistiocytosis (HLH). We hypothesized that thrombocytopenic MIS-C patients have more features of HLH. Clinical characteristics and routine laboratory parameters were collected from 228 MIS-C patients, of whom 85 (37%) were thrombocytopenic. Thrombocytopenic patients had increased ferritin levels; reduced leukocyte subsets; and elevated levels of ASAT and ALAT. Soluble IL-2RA was higher in thrombocytopenic children than in non-thrombocytopenic children. T-cell activation, TNF-alpha and IFN-gamma signaling markers were inversely correlated with thrombocyte levels, consistent with a more pronounced cytokine storm syndrome. Thrombocytopenia was not associated with severity of MIS-C and no pathogenic variants were identified in HLH-related genes. This suggests that thrombocytopenia in MIS-C is not a feature of a more severe disease phenotype, but the consequence of a distinct hyperinflammatory immunopathological process in a subset of children.</p

Serum proteomics reveals hemophagocytic lymphohistiocytosis-like phenotype in a subset of patients with multisystem inflammatory syndrome in children

Children with Multisystem Inflammatory Syndrome in Children (MIS-C) can present with thrombocytopenia, which is a key feature of hemophagocytic lymphohistiocytosis (HLH). We hypothesized that thrombocytopenic MIS-C patients have more features of HLH. Clinical characteristics and routine laboratory parameters were collected from 228 MIS-C patients, of whom 85 (37%) were thrombocytopenic. Thrombocytopenic patients had increased ferritin levels; reduced leukocyte subsets; and elevated levels of ASAT and ALAT. Soluble IL-2RA was higher in thrombocytopenic children than in non-thrombocytopenic children. T-cell activation, TNF-alpha and IFN-gamma signaling markers were inversely correlated with thrombocyte levels, consistent with a more pronounced cytokine storm syndrome. Thrombocytopenia was not associated with severity of MIS-C and no pathogenic variants were identified in HLH-related genes. This suggests that thrombocytopenia in MIS-C is not a feature of a more severe disease phenotype, but the consequence of a distinct hyperinflammatory immunopathological process in a subset of children.</p

Cervical pessary versus vaginal progesterone in women with a singleton pregnancy, a short cervix, and no history of spontaneous preterm birth at less than 34 weeks’ gestation: open label, multicentre, randomised, controlled trial

OBJECTIVE To compare the effectiveness of cervical pessary and vaginal progesterone in the prevention of adverse perinatal outcomes and preterm birth in pregnant women of singletons with no prior spontaneous preterm birth at less than 34 weeks’ gestation and who have a short cervix of 35 mm or less. DESIGN Open label, multicentre, randomised, controlled trial. SETTING 20 hospitals and five obstetric ultrasound practices in the Netherlands. PARTICIPANTS Women with a healthy singleton pregnancy and an asymptomatic short cervix of 35 mm or less between 18 and 22 weeks’ gestation were eligible. Exclusion criteria were prior spontaneous preterm birth at less than 34 weeks, a cerclage in situ, maternal age of younger than 18 years, major congenital abnormalities, prior participation in this trial, vaginal blood loss, contractions, cervical length of less than 2 mm or cervical dilatation of 3 cm or more. Sample size was set at 628 participants. INTERVENTIONS 1:1 randomisation to an Arabin cervical pessary or vaginal progesterone 200 mg daily up to 36 weeks’ of gestation or earlier in case of ruptured membranes, signs of infection, or preterm labour besides routine obstetric care. MAIN OUTCOME MEASURES Primary outcome was a composite adverse perinatal outcome. Secondary outcomes were rates of (spontaneous) preterm birth at less than 28, 32, 34, and 37 weeks. A predefined subgroup analysis was planned for cervical length of 25 mm or less. RESULTS From 1 July 2014 to 31 March 2022, 635 participants were randomly assigned to pessary (n=315) or to progesterone (n=320). 612 were included in the intention to treat analysis. The composite adverse perinatal outcome occurred in 19 (6%) of 303 participants with a pessary versus 17 (6%) of 309 in the progesterone group (crude relative risk 1.1 (95% confidence interval (CI) 0.60 to 2.2)). The rates of spontaneous preterm birth were not significantly different between groups. In the subgroup of cervical length of 25 mm or less, spontaneous preterm birth at less than 28 weeks occurred more often after pessary than after progesterone (10/62 (16%) v 3/69 (4%), relative risk 3.7 (95% CI 1.1 to 12.9)) and adverse perinatal outcomes seemed more frequent in the pessary group (15/62 (24%) v 8/69 (12%), relative risk 2.1 (0.95 to 4.6)). CONCLUSIONS In women with a singleton pregnancy with no prior spontaneous preterm birth at less than 34 weeks’ gestation and with a midtrimester short cervix of 35 mm or less, pessary is not better than vaginal progesterone. In the subgroup of a cervical length of 25 mm or less, a pessary seemed less effective in preventing adverse outcomes. Overall, for women with single baby pregnancies, a short cervix, and no prior spontaneous preterm birth less than 34 weeks’ gestation, superiority of a cervical pessary compared with vaginal progesterone to prevent preterm birth and consecutive adverse outcomes could not be proven