A validated Screening instrument for Child Abuse and Neglect (SCAN) at the emergency department.

The objective of this study is to develop and validate a screening instrument for the recognition of child maltreatment in the emergency department (ED). Existing data on screening questions and outcomes (diagnosis of child maltreatment) from three large observational screening studies at eight different EDs in the Netherlands were harmonized. A multivariate logistic regression was performed to develop the Screening instrument for Child Abuse and Neglect (SCAN). The SCAN was validated by performing a cross-validation and calculating the discriminative ability. A total of 24,963 patients were included. Out of the potential screening questions the following questions were included in the final instrument: is the injury compatible with the history, and does it correspond to the child's developmental level? (aOR 10.40, 95% CI 5.69-19.02), was there an unnecessary delay in seeking medical help? (aOR 3.45, 95% CI 1.73-6.88) and is the behaviour/interaction of the child and parents (carers) appropriate? (aOR 14.67, 95% CI 7.93-27.13). The SCAN had a pooled AUC of 0.75 (95% CI 0.63-0.87) in the cross-validation. The question "Are there other signals that make you doubt the safety of the child and/or family?" (available in only one of the original datasets, OR 182.9; 95% CI 102.3-327.4) was by consensus added to the final SCAN. CONCLUSION: This validated and brief Screening instrument for Child Abuse and Neglect (SCAN) is designed to improve early recognition of child maltreatment in the ED. A positive screening result of the SCAN warrants a thorough work-up for child maltreatment, including a top-toe examination, if necessary additional diagnostics and adequate safety measures. WHAT IS KNOWN: • Screening instruments increase the detection of possible cases of child maltreatment in the emergency department and support health care professionals to identify these cases. • The application of different screening instruments led to the need for one brief validated instrument. WHAT IS NEW: • This study presents a validated and brief Screening instrument for Child Abuse and Neglect (SCAN), consisting of four questions. • The SCAN supports professionals in detecting signals of child maltreatment, and a positive screening result should lead to a thorough work-up, including a top-toe examination, complete history, additional diagnostic tests and consultation of a child abuse expert.

The electrical heart axis in fetuses with congenital heart disease, measured with non-invasive fetal electrocardiography.

OBJECTIVES: To determine if the electrical heart axis in different types of congenital heart defects (CHD) differs from that of a healthy cohort at mid-gestation. METHODS: Non-invasive fetal electrocardiography (NI-fECG) was performed in singleton pregnancies with suspected CHD between 16 and 30 weeks of gestation. The mean electrical heart axis (MEHA) was determined from the fetal vectorcardiogram after correction for fetal orientation. Descriptive statistics were used to determine the MEHA with corresponding 95% confidence intervals (CI) in the frontal plane of all fetuses with CHD and the following subgroups: conotruncal anomalies (CTA), atrioventricular septal defects (AVSD) and hypoplastic right heart syndrome (HRHS). The MEHA of the CHD fetuses as well as the subgroups was compared to the healthy control group using a spherically projected multivariate linear regression analysis. Discriminant analysis was applied to calculate the sensitivity and specificity of the electrical heart axis for CHD detection. RESULTS: The MEHA was determined in 127 fetuses. The MEHA was 83.0° (95% CI: 6.7°; 159.3°) in the total CHD group, and not significantly different from the control group (122.7° (95% CI: 101.7°; 143.6°). The MEHA was 105.6° (95% CI: 46.8°; 164.4°) in the CTA group (n = 54), -27.4° (95% CI: -118.6°; 63.9°) in the AVSD group (n = 9) and 26.0° (95% CI: -34.1°; 86.1°) in the HRHS group (n = 5). The MEHA of the AVSD and the HRHS subgroups were significantly different from the control group (resp. p = 0.04 and p = 0.02). The sensitivity and specificity of the MEHA for the diagnosis of CHD was 50.6% (95% CI 47.5% - 53.7%) and 60.1% (95% CI 57.1% - 63.1%) respectively. CONCLUSION: The MEHA alone does not discriminate between healthy fetuses and fetuses with CHD. However, the left-oriented electrical heart axis in fetuses with AVSD and HRHS was significantly different from the control group suggesting altered cardiac conduction along with the structural defect. TRIAL REGISTRATION: Clinical trial registration number: NL48535.015.14.

Fetal myocardial deformation measured with two-dimensional speckle-tracking echocardiography: longitudinal prospective cohort study of 124 healthy fetuses.

OBJECTIVES: Two-dimensional speckle-tracking echocardiography (2D-STE) is a promising technique which allows assessment of fetal cardiac function, and can be used in the evaluation of cardiac and non-cardiac diseases in pregnancy. However, reliable fetal reference values for deformation parameters measured using 2D-STE are needed before it can be introduced into clinical practice. This study aimed to obtain reference values for fetal global longitudinal strain (GLS) and GLS rate (GLSR) measured using 2D-STE and compare right and left ventricular values. METHODS: This was a prospective longitudinal cohort study of uncomplicated pregnancies that underwent echocardiography every 4 weeks from inclusion at 18-21 weeks until delivery to obtain four-chamber loops of the fetal heart. Left and right ventricular GLS and GLSR were measured using 2D-STE at each examination. Using Bayesian mixed-effects models, reference values with lower and upper 5% prediction limits were calculated according to gestational age. Right and left ventricular GLS values according to gestational age were compared using the Wilcoxon signed-rank test. RESULTS: A total of 592 left ventricular and 566 right ventricular GLS and GLSR measurements were obtained from 124 women with uncomplicated pregnancy and non-anomalous, appropriately grown fetuses. Reference values were obtained for both fetal ventricles according to gestational week. GLS and GLSR values of both ventricles increased (i.e. became less negative) significantly during pregnancy. Right ventricular GLS values were significantly higher (i.e. less negative) than the respective left ventricular values at every gestational week. CONCLUSIONS: Reference values were obtained for fetal GLS and GLSR measured using 2D-STE. GLS and GLSR values increased significantly for both ventricles from the second trimester until delivery. GLS values were significantly higher for the right ventricle compared with the left ventricle. Future studies are needed to assess whether the obtained reference values are helpful in clinical practice in the assessment of pregnancy complications, such as fetal growth restriction or cardiac anomaly. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The provision of recipes and single-use herb/spice packets to increase egg and protein intake in community-dwelling older adults: a randomised controlled trial.

OBJECTIVE: This study investigated the impact of recipe and single-use herb/spice packet provision on egg intake and protein intake in community-dwelling individuals aged over 55 years. DESIGN: Using a randomised-controlled intervention design, 100 older adults were randomised to receive (n 53) or not receive (n 47) high-protein egg-based recipes and herb/spice packets through the post for 12 weeks, from June to December 2016. Egg intake, protein intake, adverse events, lean body mass and functional measures of lean body mass were measured at baseline, after the 12 weeks and after a further 12 weeks. SETTING: Bournemouth, UK. PARTICIPANTS: Community-dwelling older adults. RESULTS: Intention-to-treat data were analysed using regression, controlling for various demographic and lifestyle characteristics. Ninety-three individuals (intervention, n 50; control, n 43) completed assessments at all three time points. Egg intakes increased by end of intervention in both groups (mean: 4-5 eggs/month). After a further 12 weeks, higher egg intakes were sustained in the intervention group, while egg intakes in the control group returned to baseline levels (between-group difference: ß = -0·124, P = 0·047). No differences were found in other measures (largest ß = -0·106, P = 0·12). CONCLUSIONS: The provision of high-protein egg-based recipes and single-use herb/spice packets over 12 weeks increased egg intakes up to 12 weeks after end of intervention. Other factors may explain increased egg intakes during the intervention, but the sustained effects most plausibly result directly from recipe provision. Limited effects in other measures suggest that the recipes may have replaced as opposed to added to existing protein intakes.

A randomized controlled trial studying the effect of maternal hyperoxygenation on fetal heart rate in suspected fetal distress.

OBJECTIVE: To investigate the effect of maternal hyperoxygenation on fetal heart rate (FHR) when applied for suspected fetal distress during the second stage of term labor. APPROACH: A single-center randomized controlled trial was conducted in a tertiary care hospital in The Netherlands. Participants were included during the second stage of labor in case of an intermediary or abnormal FHR pattern. Patients were randomized to receive either 100% oxygen at 10 l/min until delivery, or conventional care without additional oxygen. The primary outcome was the change in FHR pattern before and after the onset of the study, measured as the change in depth and duration of FHR decelerations. Secondary outcome measures were features based on phase-rectified signal averaging (PRSA), baseline assignability, and deceleration characteristics of the FHR pattern. MAIN RESULTS: Between March 2016 and April 2018, 117 women were included. The FHR pattern could be analyzed for 71 participants, the other 46 women delivered before the end of the post time-frame. A 2.3% reduction in depth and duration of FHR decelerations was found after maternal hyperoxygenation, compared to a 10% increase in the control group (p = 0.24). Maternal hyperoxygenation had a significantly positive effect on PRSA metrics, with a decrease in PRSA-acceleration capacity (p = 0.03) and PRSA-deceleration capacity (p = 0.02) in the intervention group compared to the control group. SIGNIFICANCE: The difference in depth and duration of decelerations after the start of the study was not significantly different between both study groups. A statistically significant positive effect on PRSA-deceleration capacity and PRSA-acceleration capacity was found after maternal hyperoxygenation, which might be associated with a positive effect on neonatal outcome.

Diagnostic accuracy of saline contrast sonohysterography in detecting endometrial polyps in women with postmenopausal bleeding: systematic review and meta-analysis.

OBJECTIVE: In women with postmenopausal bleeding, endometrial polyps are a frequent finding and the risk of a focal (pre)malignancy in a polyp is up to 6%. Because of this reported risk, the detection of polyps in these women, preferably by a minimally invasive method, is important. The aim of this systematic review was to assess the accuracy of saline contrast sonohysterography (SCSH) for diagnosis of endometrial polyps in women with postmenopausal bleeding. METHODS: In August 2018, an electronic search was performed of MEDLINE, EMBASE and Web of Science databases to identify all diagnostic studies in which SCSH was used to detect endometrial polyps in postmenopausal women. Studies were included if SCSH was performed to detect endometrial polyps in women with postmenopausal bleeding and if detection of a polyp on hysteroscopy or diagnosis on histopathology was used as a reference standard. Two reviewers assessed methodological quality using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. Two separate analyses were performed for each reference standard. Pooled sensitivity and specificity were calculated using the hierarchical summary receiver-operating characteristics (HSROC) model and HSROC curves were plotted. RESULTS: After selection and quality assessment, five studies were included. Using 'polyps diagnosed with histopathology' as the reference standard, the pooled sensitivity of SCSH was 86.5% (95% CI, 63.6-100%) and the pooled specificity was 91.1% (95% CI, 63.2-100%). Using 'polyps seen on hysteroscopy' as the reference standard, the pooled sensitivity of SCSH was 85.1% (95% CI, 66.9-100%) and the pooled specificity was 84.5% (95% CI, 68.1-100%). Excluding the one study that included women in whom the SCSH examination was reported to be suboptimal, the pooled sensitivity increased to 90.7% (95% CI, 72.8-100%) using hysteroscopy as the reference standard. The sensitivity of hysteroscopy to detect polyps, as reported in two studies, was 81-98%. CONCLUSIONS: Provided that the SCSH examination is of optimal quality, it can be considered as a method to stratify women with postmenopausal bleeding for further diagnostic workup and treatment with hysteroscopy. In women without suspicion of a polypoid lesion on SCSH, and with a benign endometrial sample, expectant management should be considered. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Precisión del diagnóstico de la sonohisterografía con contraste salino en la detección de pólipos endometriales en mujeres con hemorragia postmenopáusica: revisión sistemática y metaanálisis OBJETIVO: En las mujeres con hemorragia postmenopáusica, los pólipos endometriales son frecuentes y el riesgo de una (pre)malignidad focal en un pólipo es de hasta el 6%. Debido a este riesgo reportado, es importante la detección de pólipos en estas mujeres, preferiblemente por un método mínimamente invasivo. El objetivo de esta revisión sistemática fue evaluar la precisión de la sonohisterografía con contraste salino (SCSH, por sus siglas en inglés) para el diagnóstico de pólipos endometriales en mujeres con hemorragia postmenopáusica. MÉTODOS: En agosto de 2018 se realizó una búsqueda electrónica en las bases de datos MEDLINE, EMBASE y Web of Science para identificar todos los estudios diagnósticos en los que se utilizó la SCSH para detectar pólipos endometriales en mujeres postmenopáusicas. Los estudios se incluyeron cuando la SCSH se realizó para detectar pólipos endometriales en mujeres con hemorragia postmenopáusica o cuando la detección de un pólipo en la histeroscopia o el diagnóstico sobre la histopatología se utilizó como estándar de referencia. Dos revisores evaluaron la calidad metodológica mediante la evaluación de calidad de la herramienta de estudios de precisión diagnóstica (QUADAS-2). Se realizaron dos análisis separados para cada estándar de referencia. La sensibilidad y especificidad combinadas se calcularon utilizando el modelo jerárquico de resumen de las características operativas del receptor (HSROC, por sus siglas en inglés) y se trazaron las curvas HSROC. RESULTADOS: Después de la selección y la evaluación de calidad, se incluyeron cinco estudios. Utilizando los 'pólipos diagnosticados con histopatología' como estándar de referencia, la sensibilidad combinada de la SCSH fue del 86,5% (IC 95%, 63,6-100%) y la especificidad combinada fue del 91,1% (IC 95%, 63,2-100%). Utilizando como estándar de referencia los 'pólipos observados en la histeroscopia', la sensibilidad combinada de la SCSH fue del 85,1% (IC 95%: 66,9-100%) y la especificidad combinada fue del 84,5% (IC 95%: 68,1-100%). Excluyendo el único estudio que incluyó mujeres en las que se reportó que el examen por SCSH no fue adecuado, la sensibilidad combinada aumentó al 90,7% (IC 95%: 72,8-100%), usando la histeroscopia como estándar de referencia. La sensibilidad de la histeroscopia para detectar pólipos, tal y como se informó en dos estudios, fue del 81-98%. CONCLUSIONES: Siempre que el examen por SCSH sea de calidad óptima, puede considerarse como un método para estratificar a las mujeres con hemorragia postmenopáusica para su posterior diagnóstico y tratamiento con histeroscopia. En mujeres sin sospecha de una lesión polipoide mediante SCSH y con una muestra endometrial benigna, se debe considerar el tratamiento expectante. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Determinants of perceived sleep quality in normal sleepers.

Objective: This study aimed to establish the determinants of perceived sleep quality over a longer period of time, taking into account the separate contributions of actigraphy-based sleep measures and self-reported sleep indices. Methods: Fifty participants (52 ± 6.6 years; 27 females) completed two consecutive weeks of home monitoring, during which they kept a sleep-wake diary while their sleep was monitored using a wrist-worn actigraph. The diary included questions on perceived sleep quality, sleep-wake information, and additional factors such as well-being and stress. The data were analyzed using multilevel models to compare a model that included only actigraphy-based sleep measures (model Acti) to a model that included only self-reported sleep measures to explain perceived sleep quality (model Self). In addition, a model based on the self-reported sleep measures and extended with nonsleep-related factors was analyzed to find the most significant determinants of perceived sleep quality (model Extended). Results: Self-reported sleep measures (model Self) explained 61% of the total variance, while actigraphy-based sleep measures (model Acti) only accounted for 41% of the perceived sleep quality. The main predictors in the self-reported model were number of awakenings during the night, sleep onset latency, and wake time after sleep onset. In the extended model, the number of awakenings during the night and total sleep time of the previous night were the strongest determinants of perceived sleep quality, with 64% of the variance explained. Conclusion: In our cohort, perceived sleep quality was mainly determined by self-reported sleep measures and less by actigraphy-based sleep indices. These data further stress the importance of taking multiple nights into account when trying to understand perceived sleep quality.

Long-term cognitive trajectories and heterogeneity in patients with schizophrenia and their unaffected siblings.

OBJECTIVE: This study aimed to assess the heterogeneity and stability of cognition in patients with a non-affective psychotic disorder and their unaffected siblings. In addition, we aimed to predict the cognitive subtypes of siblings by their probands. METHOD: Assessments were conducted at baseline, 3 and 6 years in 1119 patients, 1059 siblings and 586 controls from the Genetic Risk and Outcome of Psychosis (GROUP) study. Group-based trajectory modeling was applied to identify trajectories and clustered multinomial logistic regression analysis was used for prediction modeling. A composite score of eight neurocognitive tests was used to measure cognitive performance. RESULTS: Five stable cognitive trajectories ranging from severely altered to high cognitive performance were identified in patients. Likewise, four stable trajectories ranging from moderately altered to high performance were found in siblings. Siblings had a higher risk of cognitive alteration when patients' alteration was mild (OR = 2.21), moderate (OR = 5.70), and severe (OR = 10.07) compared with patients with intact cognitive function. The familial correlation coefficient between pairs of index patients and their siblings was 0.27 (P = 0.003). CONCLUSIONS: The cognitive profiles identified in the current study might be suitable as endophenotypes and could be used in future genetic studies and predicting functional and clinical outcomes.

Adult periodontitis treated with a new device for subgingival lavage-a randomized controlled clinical trial using a split-mouth design.

OBJECTIVES: To evaluate in patients with untreated adult periodontitis, the effect of treatment with a novel pocket irrigator/evacuator device (IED) compared to conventional subgingival debridement (CPT), both provided during the initial phase of active periodontal therapy. METHODS: This study was an examiner-blind, randomized controlled clinical trial using a split-mouth design. Systemically healthy patients with adult periodontitis were selected. Full-mouth probing pocket depth (PPD), gingival bleeding on pocket probing scores (BOPP), gingival recession (REC) and dental plaque (PI) were assessed at baseline. All participants received oral hygiene instructions and supragingival prophylaxis including polishing. In 2 randomly assigned contra-lateral quadrants, approximal sites were irrigated with the IED, whereas in the other quadrants, CPT was provided. The CPT consisted of subgingival debridement using ultrasonic devices followed by the use of hand instruments. At 3 months post-treatment, the clinical parameters were re-assessed. RESULTS: Twenty-five patients met the inclusion criteria and were willing to participate. At 3 months post-treatment, the PPD and BOPP had significantly improved for both treatment modalities. Pockets of ≥5 mm reduced by 0.64 mm in the IED group (P < .001), compared to a reduction of 0.82 mm for the CPT group (P < .001). With respect to the primary outcome parameter (PPD) and BI, the results with the IED were less pronounced. Between the test and control groups, no significant differences were observed for REC and PI. CONCLUSIONS: Oral hygiene instructions, supragingival prophylaxis and subgingival lavage with the IED resulted in a significant reduction in PPD and BOPP. However, the effect does not reach the results of CPT which included the subgingival use of ultrasonic and hand instruments.

Familial liability to psychosis is a risk factor for multimorbidity in people with psychotic disorders and their unaffected siblings.

BACKGROUND: Multimorbidity may impose an overwhelming burden on patients with psychosis and is affected by gender and age. Our aim is to study the independent role of familial liability to psychosis as a risk factor for multimorbidity. METHODS: We performed the study within the framework of the Genetic Risk and Outcome of Psychosis (GROUP) project. Overall, we compared 1024 psychotic patients, 994 unaffected siblings and 566 controls on the prevalence of 125 lifetime diseases, and 19 self-reported somatic complaints. Multimorbidity was defined as the presence of two or more complaints/diseases in the same individual. Generalized linear mixed model (GLMM) were used to investigate the effects of gender, age (adolescent, young, older) and familial liability (patients, siblings, controls) and their interactions on multimorbidity. RESULTS: Familial liability had a significant effect on multimorbidity of either complaints or diseases. Patients had a higher prevalence of multimorbidity of complaints compared to siblings (OR 2.20, 95% CI 1.79-2.69, P<0.001) and to controls (3.05, 2.35-3.96, P<0.001). In physical health multimorbidity, patients (OR 1.36, 95% CI 1.05-1.75, P=0.018), but not siblings, had significantly higher prevalence than controls. Similar finding were observed for multimorbidity of lifetime diseases, including psychiatric diseases. Significant results were observed for complaints and disease multimorbidity across gender and age groups. CONCLUSION: Multimorbidity is a common burden, significantly more prevalent in patients and their unaffected siblings. Familial liability to psychosis showed an independent effect on multimorbidity; gender and age are also important factors determining multimorbidity.

Survival analysis of the CEAwatch multicentre clustered randomized trial.

BACKGROUND: The CEAwatch randomized trial showed that follow-up with intensive carcinoembryonic antigen (CEA) monitoring (CEAwatch protocol) was better than care as usual (CAU) for early postoperative detection of colorectal cancer recurrence. The aim of this study was to calculate overall survival (OS) and disease-specific survival (DSS). METHODS: For all patients with recurrence, OS and DSS were compared between patients detected by the CEAwatch protocol versus CAU, and by the method of detection of recurrence, using Cox regression models. RESULTS: Some 238 patients with recurrence were analysed (7·5 per cent); a total of 108 recurrences were detected by CEA blood test, 64 (55·2 per cent) within the CEAwatch protocol and 44 (41·9 per cent) in the CAU group (P = 0·007). Only 16 recurrences (13·8 per cent) were detected by patient self-report in the CEAwatch group, compared with 33 (31·4 per cent) in the CAU group. There was no significant improvement in either OS or DSS with the CEAwatch protocol compared with CAU: hazard ratio 0·73 (95 per cent 0·46 to 1·17) and 0·78 (0·48 to 1·28) respectively. There were no differences in survival when recurrence was detected by CT versus CEA measurement, but both of these methods yielded better survival outcomes than detection by patient self-report. CONCLUSION: There was no direct survival benefit in favour of the intensive programme, but the CEAwatch protocol led to a higher proportion of recurrences being detected by CEA-based blood test and reduced the number detected by patient self-report. This is important because detection of recurrence by blood test was associated with significantly better survival than patient self-report, indirectly supporting use of the CEAwatch protocol.

Developmental trajectories of structural and pragmatic language skills in school-aged children with Williams syndrome.

BACKGROUND: This study aimed to compare developmental courses of structural and pragmatic language skills in school-aged children with Williams syndrome (WS) and children with idiopathic intellectual disability (IID). Comparison of these language trajectories could highlight syndrome-specific developmental features. METHOD: Twelve monolingual Dutch-speaking children with WS aged 5.10 to 13.3 years were assessed by means of standardised structural language tests measuring receptive and expressive vocabulary and sentence comprehension and production. Pragmatic language was evaluated by means of an expressive referential communication task and a retelling test. All of these language abilities were re-evaluated with the same measures after a period of 18 to 24 months. Performance was compared to 12 children with IID pairwise matched for chronological age (CA) and non-verbal fluid reasoning (Gf) at Time 1. Non-verbal mental age (NVMA) was taken into account when delineating developmental trajectories. RESULTS: Children with WS outperformed children with IID on expressive vocabulary development. In contrast, sentence comprehension was significantly poorer than in children with IID at the second time point. Increased variability and rather poor performance on pragmatic language tasks were demonstrated in the WS group. Irrelevant and off-topic extraneous information transfer continued to be a syndrome-specific characteristic of children with WS. CONCLUSION: The data provide new insights into diverging developmental trajectories across language domains. Expressive structural language skills tend to progress more rapidly than receptive language skills in children with WS causing more distinctive language profiles over time. Some children with WS seem to benefit from the growth in expressive structural language abilities to enhance their expressive pragmatic language skills, while in some others these abilities remain challenging. This study highlights the need for continued follow-up of language challenges in WS and for a dynamic and individualised interventional approach.

Steady-state vitamin K2 (menaquinone-7) plasma concentrations after intake of dairy products and soft gel capsules.

BACKGROUND: In a previous human intervention study, we observed an improved vitamin K status after 8 weeks of intake of a yogurt that was fortified with vitamin K2 (as menaquinone-7, MK-7) and enriched with vitamins C and D3, magnesium and polyunsaturated fatty acids. It was hypothesized that the added nutrients contributed to this improvement. Here we report on a study in which we compared the fasting plasma concentrations of MK-7 from (a) yogurt enriched with MK-7, vitamins D3 and C, magnesium, n-3 poly unsaturated fatty acids (n-3 PUFA) and fish oil (yogurt Kplus), (b) yogurt fortified with MK-7 only (yogurt K) and (c) soft gel capsules containing only MK-7. SUBJECTS/METHODS: For 42 days, healthy men and postmenopausal women between 45 and 65 years of age daily consumed either yogurt K, yogurt Kplus or capsules. Circulating MK-7, 25-hydroxy vitamin D (25(OH)D) and markers for vitamin K status (uncarboxylated osteocalcin (ucOC) and desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP)) were assessed. Plasma MK-7 was also measured during the washout period of 2 weeks. MK-7 and dp-ucMGP were measured in citrated plasma, and 25(OH)D3 and ucOC were measured in the serum. RESULTS: The increase in plasma MK-7 with the yogurt Kplus product was more pronounced than the increase in MK-7 with the capsules. Circulating dp-ucMGP and ucOC were significantly lowered after consumption of the yogurt products and the MK-7 capsules, reflecting vitamin K status improvement. No significant differences in fasting plasma concentrations of various biomarkers between the yogurts were found. CONCLUSIONS: Dairy matrix and nutrient composition may affect MK-7 delivery and improvement of vitamin K status. Yogurt fortified with MK-7 is a suitable matrix to improve the nutritional status of the fat-soluble vitamins.

Longitudinal Analysis of the Effect of Inflammation on Voriconazole Trough Concentrations.

Voriconazole (VCZ) exhibits great inter- and intrapatient variability. The latter variation cannot exclusively be explained by concomitant medications, liver disease or dysfunction, and genetic polymorphisms in cytochrome P450 2C19 (CYP2C19). We hypothesized that inflammatory response in patients under VCZ medication might also influence this fluctuation in concentrations. In this study, we explored the association between inflammation, reflected by the C-reactive protein (CRP) concentration, and VCZ trough concentrations over time. A retrospective analysis of data was performed for patients with more than one steady-state VCZ trough concentration and a CRP concentration measured on the same day. A longitudinal analysis was used for series of observations obtained from many study participants over time. The approach involved inclusion of random effects and autocorrelation in linear models to reflect within-person cross-time correlation. A total of 50 patients were eligible for the study, resulting in 139 observations (paired VCZ and CRP concentrations) for the analysis, ranging from 2 to 6 observations per study participant. Inflammation, marked by the CRP concentration, had a significant association with VCZ trough concentrations (P < 0.001). Covariates such as age and interacting comedication ([es]omeprazole), also showed a significant correlation between VCZ and CRP concentrations (P < 0.05). The intrapatient variation of trough concentrations of VCZ was 1.401 (confidence interval [CI], 0.881 to 2.567), and the interpatient variation was 1.756 (CI, 0.934 to 4.440). The autocorrelation between VCZ trough concentrations at two sequential time points was calculated at 0.71 (CI, 0.51 to 0.92). The inflammatory response appears to play a significant role in the largely unpredictable pharmacokinetics of VCZ, especially in patients with high inflammatory response, as reflected by high CRP concentrations.

Age of onset of recurrent respiratory papillomatosis: a distribution analysis.

OBJECTIVE: Distribution of age of onset of recurrent respiratory papillomatosis (RRP) is generally described to be bimodal, with peaks at approximately 5 years and 30 years. This assumption has never been scientifically confirmed, and authors tend to refer to an article that does not describe distribution. Knowledge of the distribution of age of onset is important for virological and epidemiological comprehension. The objective of this study was to determine the distribution of age of onset of RRP in a large international sample. DESIGN: Cross-sectional distribution analysis. PARTICIPANTS: Laryngologists from 12 European hospitals provided information on date of birth and date of onset of all their RRP patients treated between 1998 and 2012. Centers that exclusively treated either patients with juvenile onset RRP or patients with adult onset RRP, or were less accessible for one of these groups, were excluded to prevent skewness. MAIN OUTCOME MEASURES: A mixture model was implemented to describe distribution of age of onset. The best fitting model was selected using the Bayesian information criterion. RESULTS: Six hundred and thirty-nine patients were included in the analysis. Age of onset was described by a three component mixture distribution with lognormally distributed components. Recurrent respiratory papillomatosis starts at three median ages 7, 35 and 64 years. CONCLUSIONS: Distribution of age of onset of RRP shows three peaks. In addition to the already adopted idea of age peaks at paediatric and adult age, there is an additional peak around the age of 64.

Vitamin K Status Is not Associated with Cognitive Decline in Middle Aged Adults.

OBJECTIVES: The aim of this study was to examine the association between dephospho-uncarboxylated matrix Gla protein (dp-ucMGP), an indicator of vitamin K status, and cognitive decline, and the modifying role of 25(OH)D. DESIGN: Longitudinal study with six years follow-up. SETTING: Community based. PARTICIPANTS: 599 participants of the Longitudinal Aging Study Amsterdam (aged 55-65 years). MEASUREMENTS: Information processing speed and a composite Z-score by combining three domains of cognition reflecting general cognitive functioning. RESULTS: Generalized estimating equations (GEE) showed no significant associations between dp-ucMGP and decline in general cognitive functioning. Vitamin D modified the association between dp-ucMGP and speed of information processing (p<0.05). In the group with a 25(OH)D concentration > 50 nmol/l, the highest tertile of dp-ucMGP (>406 pmol/l), which corresponds to lower vitamin K levels, was associated with 1.5 higher score on information processing speed (p=0.023) as compared to the lowest tertile of dp-ucMGP. CONCLUSION: In contrast to our hypothesis, a suboptimal vitamin K was not associated with cognitive decline in middle-aged adults.

Intensified follow-up in colorectal cancer patients using frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging: Results of the randomized "CEAwatch" trial.

AIM: The value of frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging for detecting recurrent disease in colorectal cancer (CRC) patients was investigated in search for an evidence-based follow-up protocol. METHODS: This is a randomized-controlled multicenter prospective study using a stepped-wedge cluster design. From October 2010 to October 2012, surgically treated non-metastasized CRC patients in follow-up were followed in eleven hospitals. Clusters of hospitals sequentially changed their usual follow-up care into an intensified follow-up schedule consisting of CEA measurements every two months, with imaging in case of two CEA rises. The primary outcome measures were the proportion of recurrences that could be treated with curative intent, recurrences with definitive curative treatment outcome, and the time to detection of recurrent disease. RESULTS: 3223 patients were included; 243 recurrences were detected (7.5%). A higher proportion of recurrences was detected in the intervention protocol compared to the control protocol (OR = 1.80; 95%-CI: 1.33-2.50; p = 0.0004). The proportion of recurrences that could be treated with curative intent was higher in the intervention protocol (OR = 2.84; 95%-CI: 1.38-5.86; p = 0.0048) and the proportion of recurrences with definitive curative treatment outcome was also higher (OR = 3.12, 95%-CI: 1.25-6.02, p-value: 0.0145). The time to detection of recurrent disease was significantly shorter in the intensified follow-up protocol (HR = 1.45; 95%-CI: 1.08-1.95; p = 0.013). CONCLUSION: The CEAwatch protocol detects recurrent disease after colorectal cancer earlier, in a phase that a significantly higher proportion of recurrences can be treated with curative intent.