The relationship between anti-mullerian hormone in women receiving fertility assessments and age at menopause in subfertile women: evidence from large population studies

<p>Context: Anti-Müllerian hormone (AMH) concentration reflects ovarian aging and is argued to be a useful predictor of age at menopause (AMP). It is hypothesized that AMH falling below a critical threshold corresponds to follicle depletion, which results in menopause. With this threshold, theoretical predictions of AMP can be made. Comparisons of such predictions with observed AMP from population studies support the role for AMH as a forecaster of menopause.</p> <p>Objective: The objective of the study was to investigate whether previous relationships between AMH and AMP are valid using a much larger data set.</p> <p>Setting: AMH was measured in 27 563 women attending fertility clinics.</p> <p>Study Design: From these data a model of age-related AMH change was constructed using a robust regression analysis. Data on AMP from subfertile women were obtained from the population-based Prospect-European Prospective Investigation into Cancer and Nutrition (Prospect-EPIC) cohort (n = 2249). By constructing a probability distribution of age at which AMH falls below a critical threshold and fitting this to Prospect-EPIC menopausal age data using maximum likelihood, such a threshold was estimated.</p> <p>Main Outcome: The main outcome was conformity between observed and predicted AMP.</p> <p>Results: To get a distribution of AMH-predicted AMP that fit the Prospect-EPIC data, we found the critical AMH threshold should vary among women in such a way that women with low age-specific AMH would have lower thresholds, whereas women with high age-specific AMH would have higher thresholds (mean 0.075 ng/mL; interquartile range 0.038–0.15 ng/mL). Such a varying AMH threshold for menopause is a novel and biologically plausible finding. AMH became undetectable (<0.2 ng/mL) approximately 5 years before the occurrence of menopause, in line with a previous report.</p> <p>Conclusions: The conformity of the observed and predicted distributions of AMP supports the hypothesis that declining population averages of AMH are associated with menopause, making AMH an excellent candidate biomarker for AMP prediction. Further research will help establish the accuracy of AMH levels to predict AMP within individuals.</p&gt

Measuring vincristine-induced peripheral neuropathy in children with cancer: validation of the Dutch pediatric–modified Total Neuropathy Score

Purpose: The aims were to evaluate the construct validity and reliability of the Dutch version of the pediatric-modified Total Neuropathy Score (ped-mTNS) for assessing vincristine-induced peripheral neuropathy (VIPN) in Dutch pediatric oncology patients aged 5–18 years. Methods: Construct validity (primary aim) of the ped-mTNS was determined by testing hypotheses about expected correlation between scores of the ped-mTNS (range: 0–32) and the Common Terminology Criteria for Adverse Events (CTCAE) (range: 0–18) for patients and healthy controls and by comparing patients and controls regarding their total ped-mTNS scores and the proportion of children identified with VIPN. Inter-rater and intra-rater reliability and measurement error (secondary aims) were assessed in a subgroup of study participants. Results: Among the 112 children (56 patients and 56 age- and gender-matched healthy controls) evaluated, correlation between CTCAE and ped-mTNS scores was as expected (moderate (r = 0.60)). Moreover, as expected, patients had significantly higher ped-mTNS scores and more frequent symptoms of VIPN compared with controls (both p <.001). Reliability as measured within the intra-rater group (n = 10) (intra-class correlation coefficient (ICCagreement) = 0.64, standard error of measurement (SEMagreement) = 2.92, and smallest detectable change (SDCagreement) = 8.1) and within the inter-rater subgroup (n = 10) (ICCagreement = 0.63, SEMagreement = 3.7, and SDCagreement = 10.26) indicates insuffi

Factors associated with failed epidural blood patch after accidental dural puncture in obstetrics: a prospective, multicentre, international cohort study

BackgroundEpidural blood patch is commonly used for management of post-dural puncture headache after accidental dural puncture. The primary aim was to determine factors associated with failed epidural blood patch.MethodsIn this prospective, multicentre, international cohort study, parturients ≥18 yr receiving an epidural blood patch for treatment of post-dural puncture headache were included. Failed epidural blood patch was defined as headache intensity numeric rating scale (NRS) score ≥7 in the upright position at 4, 24, or 48 h, or the need for a second epidural blood patch, and complete success by NRS=0 at 0–48 h after epidural blood patch. All others were considered partial success. Multinominal logistic regression was used for statistical analyses with PResultsIn all, 643 women received an epidural blood patch. Complete data to classify failure were available in 591 (91.9%) women. Failed epidural blood patch occurred in 167 (28.3%) patients; 195 (33.0%) were completely successful and 229 (38.7%) partially successful. A total of 126 women (19.8%) received a second epidural blood patch. A statistically significant association with failure was observed in patients with a history of migraine, when the accidental dural puncture occurred between lumbar levels L1/L3 compared with L3/L5 and when epidural blood patch was performed bleeds were diagnosed.ConclusionsFailed epidural blood patch occurred in 28.3% of women. Independent modifiable factors associated with failure were higher lumbar level of accidental dural puncture and short interval between accidental dural puncture and epidural blood patch. A history of migraine was associated with a higher risk of second epidural blood patch.</div

Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients:A Post-Hoc Analysis of the MECANO Trial

The PRO-C6 assay, a reflection of collagen type VI synthesis, has been proposed as a non-invasive early biomarker of kidney fibrosis. We aimed to investigate cross-sectional and longitudinal associations between plasma and urine PRO-C6 and proven histological changes after kidney transplantation. The current study is a post-hoc analysis of 94 participants of the MECANO trial, a 24-month prospective, multicenter, open-label, randomized, controlled trial aimed at comparing everolimus-based vs. cyclosporine-based immunosuppression. PRO-C6 was measured in plasma and urine samples collected 6 and 24 months post-transplantation. Fibrosis was evaluated in biopsies collected at the same time points by Banff interstitial fibrosis/tubular atrophy (IF/TA) scoring and collagen staining (Picro Sirius Red; PSR); inflammation was evaluated by the tubulo-interstitial inflammation score (ti-score). Linear regression analyses were performed. Six-month plasma PRO-C6 was cross-sectionally associated with IF/TA score (Std. beta = 0.34), and prospectively with 24-month IF/TA score and ti-score (Std. beta = 0.24 and 0.23, respectively) (p <0.05 for all). No significant associations were found between urine PRO-C6 and any of the biopsy findings. Fibrotic changes and urine PRO-C6 behaved differentially over time according to immunosuppressive therapy. These results are a first step towards non-invasive fibrosis detection after kidney transplantation by means of collagen VI synthesis measurement, and further research is required

Implementing Individually Tailored Prescription of Physical Activity in Routine Clinical Care:Protocol of the Physicians Implement Exercise = Medicine (PIE=M) Development and Implementation Project

BACKGROUND: The prescription of physical activity (PA) in clinical care has been advocated worldwide. This "exercise is medicine" (E=M) concept can be used to prevent, manage, and cure various lifestyle-related chronic diseases. Due to several challenges, E=M is not yet routinely implemented in clinical care. OBJECTIVE: This paper describes the rationale and design of the Physicians Implement Exercise = Medicine (PIE=M) study, which aims to facilitate the implementation of E=M in hospital care. METHODS: PIE=M consists of 3 interrelated work packages. First, levels and determinants of PA in different patient and healthy populations will be investigated using existing cohort data. The current implementation status, facilitators, and barriers of E=M will also be investigated using a mixed-methods approach among clinicians of participating departments from 2 diverse university medical centers (both located in a city, but one serving an urban population and one serving a more rural population). Implementation strategies will be connected to these barriers and facilitators using a systematic implementation mapping approach. Second, a generic E=M tool will be developed that will provide tailored PA prescription and referral. Requirements for this tool will be investigated among clinicians and department managers. The tool will be developed using an iterative design process in which all stakeholders reflect on the design of the E=M tool. Third, we will pilot-implement the set of implementation strategies, including the E=M tool, to test its feasibility in routine care of clinicians in these 2 university medical centers. An extensive learning process evaluation will be performed among clinicians, department managers, lifestyle coaches, and patients using a mixed-methods design based on the RE-AIM framework. RESULTS: This project was approved and funded by the Dutch grant provider ZonMW in April 2018. The project started in September 2018 and continues until December 2020 (depending on the course of the COVID-19 crisis). All data from the first work package have been collected and analyzed and are expected to be published in 2021. Results of the second work package are described. The manuscript is expected to be published in 2021. The third work package is currently being conducted in clinical practice in 4 departments of 2 university medical hospitals among clinicians, lifestyle coaches, hospital managers, and patients. Results are expected to be published in 2021. CONCLUSIONS: The PIE=M project addresses the potential of providing patients with PA advice to prevent and manage chronic disease, improve recovery, and enable healthy ageing by developing E=M implementation strategies, including an E=M tool, in routine clinical care. The PIE=M project will result in a blueprint of implementation strategies, including an E=M screening and referral tool, which aims to improve E=M referral by clinicians to improve patients' health, while minimizing the burden on clinicians

The common ABCA4 variant p.Asn1868ile shows nonpenetrance and variable expression of stargardt disease when present in trans with severe variants

PURPOSE. To assess the occurrence and the disease expression of the common p.Asn1868Ile variant in patients with Stargardt disease (STGD1) harboring known, monoallelic causal ABCA4 variants. METHODS. The coding and noncoding regions of ABCA4 were sequenced in 67 and 63 STGD1 probands respectively, harboring monoallelic ABCA4 variants. In case p.Asn1868Ile was detected, segregation analysis was performed whenever possible. Probands and affected siblings harboring p.Asn1868Ile without additional variants in cis were clinically evaluated retrospe

Afrikaans as Standaard Gemiddelde Europees:Wanneer ‘n lid uit sy taalarea beweeg

A recent trend in the study of Standard Average European is the extraterritorial perspective of examining the extent to which non-European languages have converged with this Sprachbund as a result of contact with one or more of its members. The present article complements this line of research in that it investigates the extent to which a European language has diverged from Standard Average European after leaving the linguistic area. The focus is on Dutch, a nuclear member of the Sprachbund, and Afrikaans, its colonial offshoot. The two languages are compared with respect to twelve of the most distinctive linguistic features of Standard Average European. Afrikaans is found to share ten of them with Dutch, including anticausative prominence and formally distinguished intensifiers and reflexives, and could therefore still be considered a core member of the Sprachbund, despite deviations in the expression of negative pronouns and the grammaticality of external possessor constructions. This relatively low degree of divergence may be attributed to the continuity from Settler Dutch to at least the variety of Afrikaans on which the standard language is based and to the important role that Dutch continued to play in the history of Afrikaans