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Reliability and Agreement of Radiological and Pathological Tumor Size in Patients with Multiple Endocrine Neoplasia Type 1-Related Pancreatic Neuroendocrine Tumors
No full textBackground: Pancreatic neuroendocrine tumors (pNETs) have a high prevalence in patients with multiple endocrine neoplasia type 1 (MEN1) and are the leading cause of death. Tumor size is still regarded as the main prognostic factor and therefore used for surgical decision-making. We assessed reliability and agreement of radiological and pathological tumor size in a population-based cohort of patients with MEN1-related pNETs. Methods: Patients were selected from the Dutch MEN1 database if they had undergone a resection for a pNET between 2003 and 2018. Radiological (MRI, CT, and endoscopic ultrasonography [EUS]) and pathological tumor size were collected from patient records. Measures of agreement (Bland-Altman plots with limits of agreement [LoA] and absolute agreement) and reliability (intraclass correlation coefficients [ICC] and unweighted kappa) were calculated for continuous and categorized (< or ≥2 cm) pNET size. Results: In 73 included patients, the median radiological and pathological tumor sizes measured were 22 (3-160) and 21 (4-200) mm, respectively. Mean bias between radiological and pathological tumor size was -0.2 mm and LoA ranged from -12.9 to 12.6 mm. For the subgroups of MRI, CT, and EUS, LoA of radiological and pathological tumor size ranged from -9.6 to 10.9, -15.9 to 15.8, and -13.9 to 11.0, respectively. ICCs for the overall cohort, MRI, CT, and EUS were 0.80, 0.86, 0.75, and 0.76, respectively. Based on the 2 cm criterion, agreement was 81.5%; hence, 12 patients (18.5%) were classified differently between imaging and pathology. Absolute agreement and kappa values of MRI, CT, and EUS were 88.6, 85.7, and 75.0%, and 0.77, 0.71, and 0.50, respectively. Conclusion: Within a population-based cohort, MEN1-related pNET size was not systematically over- or underestimated on preoperative imaging. Based on agreement and reliability measures, MRI is the preferred imaging modality. </p
Systematic review
No full textBackground: Knowledge of the cost of illness of inflammatory bowel disease (IBD) is essential for health policy makers worldwide. Aim: To assess the cost of illness of IBD from the societal perspective taking into account time trends and geographical differences. Methods: A systematic review of all population-based studies on cost of illness of IBD published in Embase, Medline, Web of Science and Google Scholar. Methodology of included studies was assessed and costs were adjusted to 2018 US dollars. Results: Study methodologies differed considerably, with large differences in perspective, valuation method and population. For prevalent Crohn's disease (CD) cases in the last ten years annual healthcare costs were in Asia 1230-12 439 (15 807) and North America 14 454-1606 (14 572), 3228-13 559 (13 559). The main cost driver was medication, the cost of which increased considerably between 1985 and 2018, while outpatient and inpatient costs remained stable. IBD had a negative impact on work productivity. Annual costs of absenteeism for CD and UC were in Asia (with presenteeism) 5638-4828 (4828); Europe 641-2394 (5992); North America 307-1443 (2350). Conclusion: IBD societal cost of illness is increasing, driven by growing costs of medication, and varies considerably between continents. While biologic therapy was expected to decrease inpatient costs by reducing hospitalisations and surgery, these costs have not declined.</p
Anti-infectious decontamination strategies in Dutch intensive care units
No full textPurpose: Despite increasing evidence and updated national guidelines, practice of anti-infectious strategies appears to vary in the Netherlands. This study aimed to determine the variation of current practices of anti-infectious strategies in Dutch ICUs. Materials and methods: In 2018 and 2019 an online survey of all Dutch ICUs was conducted with detailed questions on their anti-infectious strategies. Results: 89% (63 of 71) of the Dutch ICUs responded to the online survey. The remaining ICUs were contacted by telephone. 47 (66%) of the Dutch ICUs used SDD, 14 (20%) used SOD and 10 (14%) used neither SDD nor SOD. Within these strategies considerable heterogeneity was observed in the start criteria of SDD/SOD, the regimen adjustments based on microbiological surveillance and the monitoring of the interventions. Conclusions: The proportion of Dutch ICUs applying SDD or SOD increased over time. Considerable heterogeneity in the regimens was reported. The impact of the observed differences within SDD and SOD practices on clinical outcome remains to be explored.</p
Metabolic syndrome following hypertensive disorders in pregnancy in a low-resource setting
No full textObjectives: Hypertensive disorders in pregnancy (HDPs) are associated with risk of future metabolic syndrome. Despite the huge burden of HDPs in sub-Saharan Africa, this association has not been adequately studied in this population. Study design: This was a prospective cohort study on pregnant women recruited between August 2017 - April 2018 and followed up to one year after their deliveries and evaluated for presence of metabolic syndrome at delivery, nine weeks, six months and one year. Main outcome measures: Prevalence of metabolic syndrome Results: A total of 488 pregnant women were included: 410 and 78 with HDPs and normotensive, respectively. None of the normotensive had metabolic syndrome until one year (1.7% = 1 out of 59 observations), while among those with HDPs were 17.4% (71 of 407), 8.7% (23 of 263), 4.7% (11 of 232) and 6.1% (17 of 278), at delivery, nine weeks, six months and one year postpartum, respectively. High BMI and blood pressure were the drivers of metabolic syndrome in this population. The incidence rate in HDPs versus normotensive at one year were, respectively, 57.5/1000 persons’ year (95%CI; 35.8 – 92.6) and 16.9/1000 persons’ years (95%CI; 2.4-118.3), with incidence rate ratio of 3.4/1000 person's years. Only parity significantly predicted the presence of metabolic syndrome at one year [(aOR= 3.26/delivery (95%CI; 1.21-8.79)]. Conclusion: HDPs were associated with a higher incidence of metabolic syndrome up to one year postpartum. Women with HDPs should be routinely screened for metabolic syndrome within the first year postpartum to reduce cardiometabolic risks.</p
Responses in knee joint muscle activation patterns to different perturbations during gait in healthy subjects
No full textPurpose: To compare the responses in knee joint muscle activation patterns to different perturbations during gait in healthy subjects. Scope: Nine healthy participants were subjected to perturbed walking on a split-belt treadmill. Four perturbation types were applied, each at five intensities. The activations of seven muscles surrounding the knee were measured using surface EMG. The responses in muscle activation were expressed by calculating mean, peak, co-contraction (CCI) and perturbation responses (PR) values. PR captures the responses relative to unperturbed gait. Statistical parametric mapping analysis was used to compare the muscle activation patterns between conditions. Results: Perturbations evoked only small responses in muscle activation, though higher perturbation intensities yielded a higher mean activation in five muscles, as well as higher PR. Different types of perturbation led to different responses in the rectus femoris, medial gastrocnemius and lateral gastrocnemius. The participants had lower CCI just before perturbation compared to the same phase of unperturbed gait. Conclusions: Healthy participants respond to different perturbations during gait with small adaptations in their knee joint muscle activation patterns. This study provides insights in how the muscles are activated to stabilize the knee when challenged. Furthermore it could guide future studies in determining aberrant muscle activation in patients with knee disorders.</p
International study to develop the WOUND-Q patient-reported outcome measure for all types of chronic wounds
No full textPatient-reported outcome measures (PROMs) for chronic wounds mainly focus on specific types of wounds. Our team developed the WOUND-Q for use with all types of wounds in any anatomic location. We conducted 60 concept elicitation interviews with patients in Canada, Denmark, the Netherlands, and the United States. Analysis identified concepts of interest to patients and scales were formed and refined through cognitive interviews with 20 patients and input from 26 wound care experts. Scales were translated into Danish and Dutch. An international field-test study collected data from 881 patients (1020 assessments) with chronic wounds. Rasch measurement theory (RMT) analysis was used to refine the scales and examine psychometric properties. RMT analysis supported the reliability and validity of 13 WOUND-Q scales that measure wound characteristics (assessment, discharge, and smell), health-related quality of life (life impact, psychological, sleep impact, and social), experience of care (information, home care nurses, medical team, and office staff), and wound treatment (dressing and suction device). The WOUND-Q can be used to measure outcomes in research and clinical practice from the perspective of patients with any type of wound.</p
FLT3-ITD mutations in acute myeloid leukaemia – molecular characteristics, distribution and numerical variation
No full textRecurrent somatic internal tandem duplications (ITD) in the FMS-like tyrosine kinase 3 (FLT3) gene characterise approximately one third of patients with acute myeloid leukaemia (AML), and FLT3-ITD mutation status guides risk-adapted treatment strategies. The aim of this work was to characterise FLT3-ITD variant distribution in relation to molecular and clinical features, and overall survival in adult AML patients. We performed two parallel retrospective cohort studies investigating FLT3-ITD length and expression by cDNA fragment analysis, followed by Sanger sequencing in a subset of samples. In the two cohorts, a total of 139 and 172 mutant alleles were identified in 111 and 123 patients, respectively, with 22% and 28% of patients presenting with more than one mutated allele. Further, 15% and 32% of samples had a FLT3-ITD total variant allele frequency (VAF) < 0.3, while 24% and 16% had a total VAF ≥ 0.7. Most of the assessed clinical features did not significantly correlate to FLT3-ITD numerical variation nor VAF. Low VAF was, however, associated with lower white blood cell count, while increasing VAF correlated with inferior overall survival in one of the cohorts. In the other cohort, ITD length above 50 bp was identified to correlate with inferior overall survival. Our report corroborates the poor prognostic association with high FLT3-ITD disease burden, as well as extensive inter- and intrapatient heterogeneity in the molecular features of FLT3-ITD. We suggest that future use of FLT3-targeted therapy could be accompanied with thorough molecular diagnostics and follow-up to better predict optimal therapy responders.</p
Hyperprolactinemia in adults with prader-willi syndrome
No full textPrader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder typically characterized by body composition abnormalities, hyperphagia, behavioural challenges, cognitive dysfunction, and hypogonadism. Psychotic illness is common, particularly in patients with maternal uniparental disomy (mUPD), and antipsychotic medications can result in hyperprolactinemia. Information about hyperprolactinemia and its potential clinical consequences in PWS is sparse. Here, we present data from an international, observational study of 45 adults with PWS and hyperprolactinemia. Estimated prevalence of hyperprolactinemia in a subset of centres with available data was 22%, with 66% of those related to medication and 55% due to antipsychotics. Thirty-three patients were men, 12 women. Median age was 29 years, median BMI 29.8 kg/m2, 13 had mUPD. Median prolactin was 680 mIU/L (range 329–5702). Prolactin levels were higher in women and patients with mUPD, with only 3 patients having severe hyperprolactinemia. Thyroid function tests were normal, 24 were treated with growth hormone, 29 with sex steroids, and 20 with antipsychotic medications. One patient had kidney insufficiency, and one a microprolactinoma. In conclusion, severe hyperprolactinemia was rare, and the most common aetiology of hyperprolactinemia was treatment with antipsychotic medications. Although significant clinical consequences could not be determined, potential negative long-term effects of moderate or severe hyperprolactinemia cannot be excluded. Our results suggest including measurements of prolactin in the follow-up of adults with PWS, especially in those on treatment with antipsychotics.</p
Predicting COVID-19 Cases and Deaths in the USA from Tests and State Populations?
No full textSchool of Mathematics and Statistics, University of Sydney, Department of Finance, Asia University, Taiwan,The paper presents a novel analysis of the US spread of the SARS-CoV-2 causes the COVID-19 disease across 50 States and 2 Territories. Simple cross-sectional regressions are able to predict quite accurately both the total number of cases and deaths, which cast doubt on measures aimed at controlling the disease via lockdowns. Population density appears to play a significant role in transmission. This throws in sharp relief the relative e_ectiveness of the at-tempts to risk manage the spread of the virus by flattening the curve' (aka planking the curve) of the speed of transmission, and the effcacy of lockdowns in terms of the spread of the disease and death rates. The algorithmic tech-niques, results and analysis presented in the paper should prove useful to the medical and health professions, science advisers, and risk management and deficision making of healthcare by state, regional and national governments in all countries.</p
Differences in P-glycoprotein activity in human and rodent blood–brain barrier assessed by mechanistic modelling
No full textVariation in the efficacy and safety of central nervous system drugs between humans and rodents can be explained by physiological differences between species. An important factor could be P-glycoprotein (Pgp) activity in the blood–brain barrier (BBB), as BBB expression of this drug efflux transporter is reportedly lower in humans compared to mouse and rat and subject to an age-dependent increase. This might complicate animal to human extrapolation of brain drug disposition and toxicity, especially in children. In this study, the potential species-specific effect of BBB Pgp activity on brain drug exposure was investigated. An age-dependent brain PBPK model was used to predict cerebrospinal fluid and brain mass concentrations of Pgp substrate drugs. For digoxin, verapamil and quinidine, in vitro kinetic data on their transport by Pgp were derived from literature and used to scale to in vivo parameters. In addition, age-specific digoxin transport was simulated for children with a postnatal age between 25 and 81 days. BBB Pgp activity in the model was optimized using measured CSF data for the Pgp substrates ivermectin, indinavir, vincristine, docetaxel, paclitaxel, olanzapine and citalopram, as no useful in vitro data were available. Inclusion of Pgp activity in the model resulted in optimized predictions of their brain concentration. Total brain-to-plasma AUC values (Kp,brain) in the simulations without Pgp were divided by the Kp,brain values with Pgp. Kp ratios ranged from 1 to 45 for the substrates investigated. Comparison of human with rodent Kp,brain ratios indicated ≥ twofold lower values in human for digoxin, verapamil, indinavir, paclitaxel and citalopram and ≥ twofold higher values for vincristine. In conclusion, BBB Pgp activity appears species-specific. An age-dependent PBPK model-based approach could be useful to extrapolate animal data to human adult and paediatric predictions by taking into account species-specific and developmental BBB Pgp expression.</p