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Whole genome sequencing of human metapneumoviruses from clinical specimens using MinION nanopore technology
No full textHuman metapneumovirus (HMPV), a member of the Pneumoviridae family, is a causative agent of respiratory illness in young children, the elderly, and immunocompromised individuals. Globally, viruses belonging to two main genetic lineages circulate, A and B, which are further divided into four genetic sublineages (A1, A2, B1, B2). Classical genotyping of HMPV is based on the sequence of the fusion (F) and attachment (G) glycoprotein genes, which are under direct antibody-mediated immune pressure. Whole genome sequencing provides more information than sequencing of subgenomic fragments and is therefore a powerful tool for studying virus evolution and disease epidemiology and for identifying transmission events and nosocomial outbreaks. Here, we report a robust method to obtain whole genome sequences for HMPV using MinION Nanopore technology. This assay is able to generate HMPV whole genome sequences from clinical specimens with good coverage of the highly variable G gene and is equally sensitive for strains of all four genetic HMPV sublineages. This method can be used for studying HMPV genetics, epidemiology, and evolutionary dynamics.</p
Ductal Flow Ratio as Measure of Transition in Preterm Infants After Birth
No full textBackground: Cardiovascular changes during the transition from intra- to extrauterine life, alters the pressure gradient across the ductus arteriosus (DA). DA flow ratio (R-L/L-R) has been suggested to reflect the infant's transitional status and could potentially predict neonatal outcomes after preterm birth. Aim: Determine whether DA flow ratio correlates with oxygenation parameters in preterm infants at 1 h after birth. Methods: Echocardiography was performed in preterm infants born <32 weeks gestational age (GA), as part of an ancillary study. DA flow was measured at 1 h after birth. DA flow ratio was correlated with FiO2, SpO2, and SpO2/FiO2 (SF) ratio. The DA flow ratio of infants receiving physiological-based cord clamping (PBCC) or time-based cord clamping (TBCC) were compared. Results: Measurements from 16 infants were analysed (median [IQR] GA 29 [27–30] weeks; birthweight 1,176 [951–1,409] grams). R-L DA shunting was 16 [17–27] ml/kg/min and L-R was 110 [81–124] ml/kg/min. The DA flow ratio was 0.18 [0.11–0.28], SpO2 94 [93–96]%, FiO2 was 23 [21–28]% and SF ratio 4.1 [3.3–4.5]. There was a moderate correlation between DA flow ratio and SpO2 [correlation coefficient (CC) −0.415; p = 0.110], FiO2 (CC 0.384; p = 0.142) and SF ratio (CC −0.356; p = 0.175). There were no differences in DA flow measurements between infants where PBBC or TBCC was performed. Conclusion: In this pilot study we observed a non-significant positive correlation between DA flow ratio at 1 h after birth and oxygenation parameters in preterm infants.</p
Partial volume correction in arterial spin labeling perfusion MRI
No full textThe mismatch in the spatial resolution of Arterial Spin Labeling (ASL) MRI perfusion images and the anatomy of functionally distinct tissues in the brain leads to a partial volume effect (PVE), which in turn confounds the estimation of perfusion into a specific tissue of interest such as gray or white matter. This confound occurs because the image voxels contain a mixture of tissues with disparate perfusion properties, leading to estimated perfusion values that reflect primarily the volume proportions of tissues in the voxel rather than the perfusion of any particular tissue of interest within that volume. It is already recognized that PVE influences studies of brain perfusion, and that its effect might be even more evident in studies where changes in perfusion are co-incident with alterations in brain structure, such as studies involving a comparison between an atrophic patient population vs control subjects, or studies comparing subjects over a wide range of ages. However, the application of PVE correction (PVEc) is currently limited and the employed methodologies remain inconsistent. In this article, we outline the influence of PVE in ASL measurements of perfusion, explain the main principles of PVEc, and provide a critique of the current state of the art for the use of such methods. Furthermore, we examine the current use of PVEc in perfusion studies and whether there is evidence to support its wider adoption. We conclude that there is sound theoretical motivation for the use of PVEc alongside conventional, ‘uncorrected’, images, and encourage such combined reporting. Methods for PVEc are now available within standard neuroimaging toolboxes, which makes our recommendation straightforward to implement. However, there is still more work to be done to establish the value of PVEc as well as the efficacy and robustness of existing PVEc methods.</p
Cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct CSF biomarker profile
No full textBackground: Understanding the changes that occur in the transitional stage between absent and overt amyloid-β (Aβ) pathology within the Alzheimer’s continuum is crucial to develop therapeutic and preventive strategies. The objective of this study is to test whether cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct CSF, structural, and functional neuroimaging biomarker profile. Methods: Cross-sectional study of 318 middle-aged, cognitively unimpaired individuals from the ALFA+ cohort. We measured CSF Aβ42/40, phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100B, and α-synuclein. Participants also underwent cognitive assessments, APOE genotyping, structural MRI, [18F]-FDG, and [18F]-flutemetamol PET. To ensure the robustness of our results, we used three definitions of low burden of Aβ pathology: (1) positive CSF Aβ42/40 and < 30 Centiloids in Aβ PET, (2) positive CSF Aβ42/40 and negative Aβ PET visual read, and (3) 20–40 Centiloid range in Aβ PET. We tested CSF and neuroimaging biomarker differences between the low burden group and the corresponding Aβ-negative group, adjusted by age and sex. Results: The prevalence and demographic characteristics of the low burden group differed between the three definitions. CSF p-tau and t-tau were increased in the low burden group compared to the Aβ-negative in all definitions. CSF neurogranin was increased in the low burden group definitions 1 and 3, while CSF NfL was only increased in the low burden group definition 1. None of the defined low burden groups showed signs of atrophy or glucose hypometabolism. Instead, we found slight increases in cortical thickness and metabolism in definition 2. Conclusions: There are biologically meaningful Aβ-downstream effects in individuals with a low burden of Aβ pathology, while structural and functional changes are still subtle or absent. These findings support considering individuals with a low burden of Aβ pathology for clinical trials. Trial registration: NCT02485730</p
Relationship between perceived risks of using mhealth applications and the intention to use them among older adults in the netherlands
No full textBackground: Considering the increasing demand for health services by older people and the ongoing COVID-19 pandemic, digital health is commonly viewed to offer a pathway to provide safe and affordable health services for older adults, thus enabling self-management of their health while health care systems are struggling. However, several factors cause older people to be particularly reluctant to adopt digital health technologies such as mobile health (mHealth) tools. In addition to previously studied technology acceptance factors, those related to perceived risks of mHealth use (eg, leakage of sensitive information or receiving incorrect health recommendations) may further diminish mHealth adoption by older adults. Objective: The aim of this study was to explore the relationship between perceived risks of using mHealth applications and the intention to use these applications among older adults. Methods: We designed a cross-sectional study wherein a questionnaire was used to collect data from participants aged 65 years and older in the Netherlands. Perceived risk was divided into four constructs: Privacy risk, performance risk, legal concern, and trust. Linear regression analyses were performed to determine the associations between these perceived risk constructs and the intention to use mHealth applications. Results: Linear regression per perceived risk factor showed that each of the four constructs is significantly associated with the intention to use mobile medical applications among older adults (adjusted for age, sex, education, and health status). Performance risk (β=-.266; P=<.001), legal concern (β=-.125; P=.007), and privacy risk (β=-.100; P=.03) were found to be negatively correlated to intention to use mHealth applications, whereas trust (β=.352; P=<.001) was found to be positively correlated to the intention to use mHealth applications. Conclusions: Performance risk, legal concern, and privacy risk as perceived by older adults may substantially and significantly decrease their intention to use mHealth applications. Trust may significantly and positively affect this intention. Health care professionals, designers of mHealth applications, and policy makers can use these findings to diminish performance risks, and tailor campaigns and applications to address legal and privacy concerns and promote mHealth uptake and health care access for older adults, especially during the COVID-19 pandemic.</p
Fascial closure in giant ventral hernias after preoperative botulinum toxin a and progressive pneumoperitoneum
No full textBackground: The primary objective was to assess the perioperative efficacy of the preoperative use of progressive pneumoperitoneum or Botulinum Toxin A injections in ventral hernia repair. Methods: Embase, Medline Ovid, Web of Science, Cochrane Central, and Google Scholar were systematically searched. Studies in English reporting on fascial closure, indications, complications or postoperative outcomes in adult patients that had undergone progressive pneumoperitoneum, Botulinum Toxin A injections, or both before ventral hernia repair were included. Study quality was assessed with the Oxford Levels of Evidence guidelines and the Methodological Index for Non-Randomized Studies criteria. A pooled fascial closure rate and recurrence rate were calculated with random effects models. Results: Twenty studies were included from the 905 identified, comprising the use progressive pneumoperitoneum (n = 11), Botulinum Toxin A (n = 6), and both techniques (n = 3). The overall fascial closure rate was 0.94 (95% confidence interval 0.89–0.98). Indications for the use of progressive pneumoperitoneum or Botulinum Toxin A were based on objective (eg, computed tomography measurements) or subjective measures (eg, foreseen surgical problems). In contrast to the use of Botulinum Toxin A, reported complications with the use of progressive pneumoperitoneum were ample and sometimes severe. The cumulative reported recurrence rate was 0.03 (95% confidence interval 0.01–0.06). Conclusion: Preoperative progressive pneumoperitoneum and Botulinum Toxin A can facilitate fascial closure without causing significant numbers of adverse events. Botulinum Toxin A qualifies for low-threshold use, yet progressive pneumoperitoneum should be used cautiously owing to a larger number of complications. Definitive recommendations cannot be made as the quality of included studies is low, bias is present, and comparative information is scarce. Registration number Information about the design and conduct of this systematic review has been registered on PROSPERO, registration number CRD42020181679.</p
Outcome of early-onset fetal growth restriction with or without abnormal umbilical artery Doppler flow
No full textIntroduction: Early-onset fetal growth restriction is a pregnancy complication often coinciding with abnormal Doppler flow in the umbilical artery. Absent or reversed end-diastolic flow in the umbilical artery is associated with adverse perinatal outcome. As the optimal management of this condition is unclear, the objective of this study was to analyze the time interval from admission to delivery of pregnancies with early-onset fetal growth restriction, while pursuing a policy of postponing delivery unless active management of labor would be required because of fetal distress or maternal condition. We also assessed short- and long-term perinatal outcome. Material and methods: In this historical cohort study, all pregnant women with singleton pregnancies, admitted during 2004–2015 with early-onset fetal growth restriction were included. Pregnancies with absent or reversed end-diastolic flow (AREDF) were compared with pregnancies with a positive end-diastolic Doppler flow (PEDF). Time until delivery was determined and perinatal outcome was assessed for both groups. Results: In our study, 111 women were allocated to the PEDF group and 109 to the AREDF group. In the AREDF group, fetal distress was more often an indication for delivery, in comparison with the PEDF group (p =.004). Median time until delivery in patients admitted between 26 and 28 weeks’ gestation was 6+5 weeks in the PEDF group and 1+4 weeks in the AREDF group (p =.001). No statistically significant difference was found between the Doppler groups in the composite adverse neonatal outcome, which includes at least one of the following outcomes: infant respiratory distress syndrome, sepsis, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage >grade 2, periventricular leukomalacia and perinatal death (p =.63). Conclusions: In this study, comprising pregnancies with early-onset fetal growth restriction, fetal distress was observed more frequently in the AREDF group with the consequence of delivery at an earlier stage of gestation, compared with the PEDF group. AREDF was not associated with increased perinatal morbidity and mortality compared with PEDF.</p
Improvements in PCOS characteristics and phenotype severity during a randomized controlled lifestyle intervention
No full textResearch question: What is the effect of weight loss through different interventions (three-component lifestyle intervention with short message service [SMS+] versus three-component lifestyle intervention without SMS [SMS–] versus care as usual [CAU]) on polycystic ovary syndrome (PCOS) characteristics (ovulatory dysfunction, hyperandrogenism, polycystic ovarian morphology [PCOM]) and phenotype distribution? Design: Analysis of secondary outcome measures of a randomized controlled trial. Women diagnosed with PCOS (n = 183), who wished to become pregnant, with a body mass index above 25 kg/m², were assigned to a 1-year three-component (cognitive behavioural therapy, diet, exercise) lifestyle intervention group, with or without SMS, or to CAU (advice to lose weight). Results: The prevalence of biochemical hyperandrogenism was 30.9% less in the SMS- group compared with CAU after 1 year (P = 0.027). Within-group analyses revealed significant improvements in ovulatory dysfunction (SMS+: –39.8%, P = 0.001; SMS–: –30.5%, P = 0.001; CAU: –32.1%, P < 0.001), biochemical hyperandrogenism (SMS–: –27.8%, P = 0.007) and PCOM (SMS–: –14.0%, P = 0.034). Weight loss had a significantly favourable effect on the chance of having ovulatory dysfunction (estimate 0.157 SE 0.030, P < 0.001) and hyperandrogenism (estimate 0.097 SE 0.027, P < 0.001). Conclusions: All groups demonstrated improvements in PCOS characteristics, although these were more profound within the lifestyle intervention groups. Weight loss per se led to an amelioration of diagnostic characteristics and in the phenotype of PCOS. A three-component lifestyle intervention aimed at a 5–10% weight loss should be recommended for all women with PCOS before they become pregnant.</p
STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk)
No full textBACKGROUND: Healthcare professionals are often reluctant to deprescribe fall-risk-increasing drugs (FRIDs). Lack of knowledge and skills form a significant barrier and furthermore, there is no consensus on which medications are considered as FRIDs despite several systematic reviews. To support clinicians in the management of FRIDs and to facilitate the deprescribing process, STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) and a deprescribing tool were developed by a European expert group. METHODS: STOPPFall was created by two facilitators based on evidence from recent meta-analyses and national fall prevention guidelines in Europe. Twenty-four panellists chose their level of agreement on a Likert scale with the items in the STOPPFall in three Delphi panel rounds. A threshold of 70% was selected for consensus a priori. The panellists were asked whether some agents are more fall-risk-increasing than others within the same pharmacological class. In an additional questionnaire, panellists were asked in which cases deprescribing of FRIDs should be considered and how it should be performed. RESULTS: The panellists agreed on 14 medication classes to be included in the STOPPFall. They were mostly psychotropic medications. The panellists indicated 18 differences between pharmacological subclasses with regard to fall-risk-increasing properties. Practical deprescribing guidance was developed for STOPPFall medication classes. CONCLUSION: STOPPFall was created using an expert Delphi consensus process and combined with a practical deprescribing tool designed to optimise medication review. The effectiveness of these tools in falls prevention should be further evaluated in intervention studies.</p
Correction to: Validation of a novel patient reported tool to assess the impact of treatment in erythropoietic protoporphyria: the EPP-QoL
No full textFollowing publication of the original article [1], the authors identified an error in the author name of G. Biolcati. The incorrect author name is: G. Biolcatti The correct author name is: G. Biolcati The author group has been updated above and the original article [1] has been corrected.</p