Pharyngolaryngeal semiology and prognostic factors in multiple system atrophy.

INTRODUCTION: Multiple system atrophy (MSA) is a rare degenerative neurological disorder in adults. It induces parkinsonian and/or cerebellar syndrome associated with dysautonomia. Pharyngolaryngeal symptoms are common. Our aim is to describe the Pharyngolaryngeal semiology on one hand, and to ascertain whether the presence of these symptoms represents a prognostic factor for MSA on the other. METHODS: Thus, we carried out a retrospective, single-centre study, on a cohort receiving care at the centre of reference for MSA. The patients were referred for otorhinolaryngology assessment. The data was collected over the year 2020 with the help of computer software from the university hospital centre (UHC). Firstly, we described the Pharyngolaryngeal semiology specific to MSA by questioning patients, and by the results of nasofibroscopic examinations and swallowing tests. We then used multivariate analysis of variance to describe the prognostic factors of MSA progression (in UMSARS I and II points per month of progression) and survival (number of years between the first symptoms and death). RESULTS: This study included a hundred and one patients and made it possible to define a Pharyngolaryngeal semiology profile of MSA, which is: a reduction in laryngeal mobility (primarily vocal cord abduction defects), abnormal movements (particularly at rest or when initiating a movement) and a defect in the protection mechanisms of the upper airways. The swallowing difficulties are moderate and the main mechanisms are delayed pharyngeal swallow and/or an oro-pharyngeal transport defect. In the multivariate analyses, the contributing factors are laryngeal anomalies, modification of solid food to fluid food and nutritional complication. CONCLUSION: ENT specialists should pay close attention to problems in the Pharyngolaryngeal dynamic and then consider a neurological cause. They can also itemize the clinical factors that could have a negative effect on the prognosis of the patient with MSA. Indeed, early detection makes it possible to provide care for respiratory and nutritional complications.

Increase of Diversity of Mumps Virus Genotype G SH Variants Circulating Among a Highly Immunized Population: Spain, 2007-2019.

MuV caused three epidemic waves in Spain since genotype G emerged in 2005, despite high vaccination coverage. SH gene sequencing according to WHO protocols allowed the identification of seven relevant variants and 88 haplotypes. While the originally imported MuVi/Sheffield.GBR/1.05/-variant prevailed during the first two waves, it was subsequently replaced by other variants originated by either local evolution or importation, according to the additional analysis of hypervariable NCRs. The time of emergence of the MRCA of each MuV variant clade was concordant with the data of the earliest sequence. The analysis of Shannon entropy showed an accumulation of variability on six particular positions as the cause of the increase on the number of circulating SH variants. Consequently, SH gene sequencing needs to be complemented with other more variable markers for mumps surveillance immediately after the emergence of a new genotype, but the subsequent emergence of new SH variants turns it unnecessary.

ENgage YOung people earlY (ENYOY): a mixed-method study design for a digital transdiagnostic clinical - and peer- moderated treatment platform for youth with beginning mental health complaints in the Netherlands.

BACKGROUND: The onset of mental disorders typically occurs between the ages of 12 and 25, and the burden of mental health problems is the most consequential for this group. Indicated prevention interventions to target individuals with subclinical symptoms to prevent the transition to clinical levels of disorders, even leading to suicide, have shown to be effective. However, the threshold to seek help appears to be high. Digital interventions could offer a solution, especially during the Covid-19 pandemic. This implementation study will investigate the digital indicated prevention intervention ENgage YOung people Early (ENYOY), the Dutch version of the original Moderated Online Social Therapy Platform (MOST+) from Australia. In addition, the relationship between stress biomarkers, symptoms and outcome measures of youth using the platform will be investigated in this study. METHODS: The MOST+ platform will be adapted, translated and developed for the situation in the Netherlands in collaboration with a Youth Panel. A prospective cohort of 125 young people (16-25 years) with beginning mental health complaints will be on the platform and followed for a year, of which 10 participants will have an additional smart watch and 10 participants will be asked to provide feedback about the platform. Data will be collected at baseline and after 3, 6 and 12 months. Outcome measures are Psychological Distress assessed with the Kessler Psychological Distress Scale (K10), Social and occupational functioning (measures by the SOFAS), positive mental health indicators measured by the Positive Health Instrument, stress biomarkers with a smart-watch, website journeys of visitors, and feedback of youth about the platform. It will be a mixed-method study design, containing qualitative and quantitative measures. DISCUSSION: This trial will specifically address young people with emerging mental health complaints, and offers a new approach for treatment in the Netherlands. Considering the waiting lists in (child and adolescent)-psychiatry and the increase in suicides among youth, early low-threshold and non-stigmatizing help to support young people with emerging psychiatric symptoms is of crucial importance. Moreover, this project aims to bridge the gap between child and adolescent and adult psychiatry. TRIAL REGISTRATION: Netherlands Trial Register ID NL8966 , retrospectively registered on the 19th of October 2020.

Seroepidemiology of varicella zoster virus infection in Vojvodina, Serbia.

The present cross-sectional serosurvey constitutes the first effort to describe the varicella zoster virus (VZV) seroepidemiology in Serbia. An age-stratified serum bank of 3570 residual samples collected between 2015 and 2016 in each of the seven districts of the Vojvodina Province was tested for IgG anti-VZV antibodies with an enzyme immunoassay. Results were standardised into common units according to the European Sero-Epidemiology Network (ESEN2) methodology. Univariable and multivariable analyses were used to examine the relationships between standardised anti-VZV positivity or logarithmically transformed antibody titres and demographic features of study subjects. Seropositivity (85% overall) increased with age, in parallel with geometric mean titres. By the time of school entry, 68% of children were immune. The slower subsequent acquisition of immunity leaves epidemiologically relevant proportions of adolescents (7%), young adults (6%) and especially females of reproductive age (6%) prone to more severe forms of varicella. In the ongoing pre-vaccine era, natural infection provides a high level of collective immunity, with the highest VZV transmission in children of preschool age. The detected gaps in VZV immunity of the Serbian population support the adoption of the official recommendations for varicella immunisation of non-immune adolescents and young adults, including non-pregnant women of childbearing age.

In utero negativization of Zika virus in a foetus with serious central nervous system abnormalities.

We describe a case of a pregnant woman with Zika virus (ZIKV) infection and a foetus with severe brain malformations. ZIKV tested positive in amniotic fluid at 19 weeks but was negative at delivery. The newborn did not meet the case definition of congenital ZIKV syndrome because neither ZIKV RNA nor IgM antibodies were detected; however, prenatal brain lesions were confirmed after birth (Graphical Abstract).

Prevalence of anti-rubella, anti-measles and anti-mumps IgG antibodies in neonates and pregnant women in Catalonia (Spain) in 2013: susceptibility to measles increased from 2003 to 2013.

Non-immune neonates and non-immune pregnant women are at risk of developing rubella, measles and mumps infections, including congenital rubella syndrome. We describe the seroepidemiology of measles, mumps and rubella (MMR) in neonates and pregnant women in Catalonia (Spain). Anti-rubella, anti-measles and anti-mumps serum IgG titres were assessed using enzyme-linked immunosorbent assay (ELISA) tests in 353 cord blood samples from neonates of a representative sample of pregnant women obtained in 2013. The prevalence of protective antibody titres in neonates was 96 % for rubella IgG (≥8 IU/ml), 90 % for measles IgG (>300 IU/ml) and 84 % for mumps IgG (>460 EU/ml). Slightly lower prevalences of protective IgG titres, as estimated from the cord blood titres, were found in pregnant women: 95 % for rubella IgG, 89 % for measles IgG and 81 % for mumps IgG. The anti-measles and anti-mumps IgG titres and the prevalences of protective IgG titres against measles and mumps increased significantly (p < 0.001) with maternal age. The prevalence of protective anti-measles IgG titres decreased by 7 % [odds ratio (OR) = 0.15, p < 0.001), the prevalence of protective anti-rubella IgG titres increased by 3 % (OR = 1.80, p < 0.05) and the MMR vaccination coverage (during childhood) in pregnant women increased by 54 % (OR = 2.09, p < 0.001) from 2003 to 2013. We recommend to develop an MMR prevention programme in women of childbearing age based on mass MMR vaccination or MMR screening and vaccination of susceptible women to increase immunity levels against MMR.

Estimating seroprevalence of vaccine-preventable infections: is it worth standardizing the serological outcomes to adjust for different assays and laboratories?

The aim of the European Sero-Epidemiology Network 2 (ESEN2) project was to estimate age-specific seroprevalence for a number of vaccine-preventable diseases in Europe. To achieve this serosurveys were collected by 22 national laboratories. To adjust for a variety of laboratory methods and assays, all quantitative results were transformed to a reference laboratory's units and were then classified as positive or negative to obtain age-specific seroprevalence. The aim of this study was to assess the value of standardization by comparing the crude and standardized seroprevalence estimates. Seroprevalence was estimated for measles, mumps, rubella, diphtheria, varicella zoster and hepatitis A virus (HAV) and compared before and after serological results had been standardized. The results showed that if no such adjustment had taken place, seroprevalence would have differed by an average of 3·2% (95% bootstrap interval 2·9-3·6) although this percentage varied substantially by antigen. These differences were as high as 16% for some serosurveys (HAV) which means that standardization could have a considerable impact on seroprevalence estimates and should be considered when comparing serosurveys performed in different laboratories using different assay methods.

Molecular characterization of enteroviruses associated with neurological infections in Spain, 2008.

In order to investigate the etiology of viral neurological infections in Spain, a national study was performed in 2008. The results obtained have been published. Enteroviruses were the most frequent cause of the aseptic meningitis and infant febrile syndromes. The present report supplements the previous study with the genotyping of the detected enteroviruses. Typing was by amplification of partial VP1 region and sequencing in 70 (53%) of the 132 available cerebrospinal fluid samples positive for enteroviruses. Twelve different genotypes within the B species were identified. Echovirus 4 was predominant (24%), followed by echovirus 30 (19%), echovirus 9 (17%), and echovirus 6 (14%). In summary, a co-circulation of several enterovirus types associated with meningitis in children under 15 years old was observed. Although infrequently detected, echovirus 4 was the predominant genotype identified due to an aseptic meningitis outbreak which occurred in the Canary Islands in 2008.

Seroepidemiology of mumps in Europe (1996-2008): why do outbreaks occur in highly vaccinated populations?

Mumps outbreaks have recently been recorded in a number of highly vaccinated populations. We related seroprevalence, epidemiological and vaccination data from 18 European countries participating in The European Sero-Epidemiology Network (ESEN) to their risk of mumps outbreaks in order to inform vaccination strategies. Samples from national population serum banks were collected, tested for mumps IgG antibodies and standardized for international comparisons. A comparative analysis between countries was undertaken using age-specific mumps seroprevalence data and information on reported mumps incidence, vaccine strains, vaccination programmes and vaccine coverage 5-12 years after sera collection. Mean geometric mumps antibody titres were lower in mumps outbreak countries [odds ratio (OR) 0·09, 95% confidence interval (CI) 0·01-0·71)]. MMR1 vaccine coverage ⩾95% remained protective in a multivariable model (P < 0·001), as did an interval of 4-8 years between doses (OR 0·08, 95% CI 0·01-0·85). Preventing outbreaks and controlling mumps probably requires several elements, including high-coverage vaccination programmes with MMR vaccine with 4-8 years between doses.

Viral infections of the central nervous system in Spain: a prospective study.

The aim of the study was to determine the incidence of viruses causing aseptic meningitis, meningoencephalitis, and encephalitis in Spain. This was a prospective study, in collaboration with 17 Spanish hospitals, including 581 cases (CSF from all and sera from 280): meningitis (340), meningoencephalitis (91), encephalitis (76), febrile syndrome (7), other neurological disorders (32), and 35 cases without clinical information. CSF were assayed by PCR for enterovirus (EV), herpesvirus (herpes simplex [HSV], varicella-zoster [VZV], cytomegalovirus [CMV], Epstein-Barr [EBV], and human herpes virus-6 [HHV-6]), mumps (MV), Toscana virus (TOSV), adenovirus (HAdV), lymphocytic choriomeningitis virus (LCMV), West Nile virus (WNV), and rabies. Serology was undertaken when methodology was available. Amongst meningitis cases, 57.1% were characterized; EV was the most frequent (76.8%), followed by VZV (10.3%) and HSV (3.1%; HSV-1: 1.6%; HSV-2: 1.0%, HSV non-typed: 0.5%). Cases due to CMV, EBV, HHV-6, MV, TOSV, HAdV, and LCMV were also detected. For meningoencephalitis, 40.7% of cases were diagnosed, HSV-1 (43.2%) and VZV (27.0%) being the most frequent agents, while cases associated with HSV-2, EV, CMV, MV, and LCMV were also detected. For encephalitis, 27.6% of cases were caused by HSV-1 (71.4%), VZV (19.1%), or EV (9.5%). Other positive neurological syndromes included cerebellitis (EV and HAdV), seizures (HSV), demyelinating disease (HSV-1 and HHV-6), myelopathy (VZV), and polyradiculoneuritis (HSV). No rabies or WNV cases were identified. EVs are the most frequent cause of meningitis, as is HSV for meningoencephalitis and encephalitis. A significant number of cases (42.9% meningitis, 59.3% meningoencephalitis, 72.4% encephalitis) still have no etiological diagnosis.

Circulation of mumps virus genotypes in Spain from 1996 to 2007.

Although the WHO recommends the use of genotyping as a tool for epidemiological surveillance for mumps, limited data on mumps virus (MV) genotype circulation that may be used to trace the patterns of virus spread are available. We describe the first complete series of data from Spain. The small hydrophobic region was sequenced from 237 MV-positive samples from several regions of Spain collected between 1996 and 2007. Six different genotypes were identified: A, C, D (D1), G (G1, G2), H (H1, H2), and J. Genotype H1 was predominant during the epidemic that occurred from 1999 to 2003 but was replaced by genotype G1 as the dominant genotype in the epidemic that occurred from 2005 to 2007. The same genotype G1 strain caused concomitant outbreaks in different parts of the world (the United States, Canada, and the United Kingdom). The remaining genotypes (genotypes A, C, D, and J) appeared in sporadic cases or small limited outbreaks. This pattern of circulation seems to reflect continuous viral circulation at the national level, despite the high rates of vaccine coverage.

Uterine rupture in The Netherlands: a nationwide population-based cohort study.

OBJECTIVE: To assess incidence of uterine rupture in scarred and unscarred uteri and its maternal and fetal complications in a nationwide design. DESIGN: Population-based cohort study. SETTING: All 98 maternity units in The Netherlands. POPULATION: All women delivering in The Netherlands between August 2004 and August 2006 (n = 371,021). METHODS: Women with uterine rupture were prospectively collected using a web-based notification system. Data from all pregnant women in The Netherlands during the study period were obtained from Dutch population-based registers. Results were stratified by uterine scar. MAIN OUTCOME MEASURES: Population-based incidences, severe maternal and neonatal morbidity and mortality, relative and absolute risk estimates. RESULTS: There were 210 cases of uterine rupture (5.9 per 10,000 pregnancies). Of these women, 183 (87.1%) had a uterine scar, incidences being 5.1 and 0.8 per 10,000 in women with and without uterine scar. No maternal deaths and 18 cases of perinatal death (8.7%) occurred. The overall absolute risk of uterine rupture was 1 in 1709. In univariate analysis, women with a prior caesarean, epidural anaesthesia, induction of labour (irrespective of agents used), pre- or post-term pregnancy, overweight, non-Western ethnic background and advanced age had an elevated risk of uterine rupture. The overall relative risk of induction of labour was 3.6 (95% confidence interval 2.7-4.8). CONCLUSION: The population-based incidence of uterine rupture in The Netherlands is comparable with other Western countries. Although much attention is paid to scar rupture associated with uterotonic agents, 13% of ruptures occurred in unscarred uteri and 72% occurred during spontaneous labour.

Differential diagnosis of hepatitis E virus, cytomegalovirus and Epstein-Barr virus infection in patients with suspected hepatitis E.

BACKGROUND: The accuracy of the diagnosis of hepatitis E in the clinical setting relies mainly on the performance of assays for hepatitis E virus (HEV)-specific IgM (anti-HEV IgM) testing in serum. OBJECTIVES: Identification of factors influencing the specificity of the results obtained with these assays is an important issue in regard to the accuracy of the diagnosis. STUDY DESIGN: Anti-HEV IgM and HEV RNA were studied in samples from 153 patients with acute hepatitis of unknown aetiology received during a two-year period. Fifteen patients were positive for anti-HEV IgM, and eight of them were also positive for HEV RNA. Investigation of CMV and Epstein-Barr virus (EBV) infection markers among the remaining seven patients, and of HEV infection markers among 18 patients with infectious mononucleosis, was performed. RESULTS: The results obtained showed that acute infection by CMV or EBV may cause false reactivity for anti-HEV IgM, likely because of polyclonal B-cell stimulation. CONCLUSIONS: Since infection by these herpesviruses may produce acute hepatitis, such event can cause diagnostic mistakes and should be investigated in patients positive for anti-HEV IgM and negative for HEV RNA.

The European Sero-Epidemiology Network 2 (ESEN2): standardization of assay results for hepatitis A virus (HAV) to enable comparisons of seroprevalence data across 15 countries.

The European Sero-Epidemiology Network 2 (ESEN2) aimed to compare serological results of vaccine-preventable diseases across Europe. To ensure direct inter-country comparability of hepatitis A virus antibody (anti-HAV) measurements, a standardization panel of 150 sera was developed by a designated reference laboratory and tested by participating national laboratories using assays of choice; each country's results were subsequently regressed against those of the reference laboratory. Quantitatively, the assays were generally highly correlated (R2>0.90). Nevertheless, qualitative comparisons indicated that results obtained with different assays may differ despite the usage of well-established international and local standards. To a great extent standardization successfully alleviated such differences. The generated standardization equations will be used to convert national serological results into common units to enable direct international comparisons of HAV seroprevalence data. The results of this study are expected to contribute to the evaluation and potential improvement of the currently employed immunization strategies for hepatitis in Europe.

Asthma beliefs among mothers and children from different ethnic origins living in Amsterdam, the Netherlands.

BACKGROUND: Doctors and patients hold varying beliefs concerning illness and treatment. Patients' and families' explanatory models (EMs) vary according to personality and sociocultural factors. In a multi-ethnic society, it is becoming increasingly significant that doctors understand the different beliefs of their patients in order to improve patient/doctor communication as well as patient adherence to treatment. METHODS: Twelve focus groups were formed, consisting of 40 children diagnosed with asthma, as well as 28 mothers of these children. These groups included mothers and children of different ethnicities who were living in Amsterdam, the Netherlands. In order to understand the beliefs that both mothers and children hold regarding asthma and its treatment, the explanatory models were analysed and compared. RESULTS: Study findings show that mothers and children, regardless of ethnicity and age, have their own EMs. Overall, there is a great deal of uncertainty related to the causes, consequences, problems, and symptoms of asthma and its treatment. It also seems that many concerns and feelings of discomfort are the result of lack of knowledge. For instance, the fact that asthma is not seen as a chronic disease requiring daily intake of an inhaled corticosteroid, but rather as an acute phenomenon triggered by various factors, may be very relevant for clinical practice. This particular belief might suggest an explanation for non-adherent behaviour. CONCLUSION: A thorough understanding of the mothers' and children's beliefs regarding the illness and its treatment is an important aspect in the management of asthma. Gaining an understanding of these beliefs will provide a foundation for a solid clinician-patient/family partnership in asthma care. Although ethnic differences were observed, the similarities between the mothers' and children's beliefs in this multi-ethnic population were striking. In particular, a common belief is that asthma is considered an acute rather than a chronic condition. In addition, there is a lack of knowledge about the course and the self-management of asthma. Health care providers should be aware of these commonly held beliefs, and this information could be shared in educational programs.

Eliminating congenital rubella syndrome in Spain: does massive immigration have any influence?

In this short report we highlight the importance of implementing good immunization programs adapted to the epidemiological situation of rubella and congenital rubella syndrome (CRS), discuss the influence of massive immigration and stress the need to improve surveillance and control by implementing comprehensive national surveillance and promoting awareness among primary healthcare workers and midwives to find out any signs and symptoms compatible with rubella in pregnant women who have recently arrived from countries with high susceptibility to rubella infection.

Internationally adopted children: what vaccines should they receive?

It is of paramount importance to know the vaccination status in internationally adopted children, so that they can be correctly immunized. This study ascertains the seroprotection rate for vaccine-preventable diseases and the validity of the immunization cards in 637 adopted children. The absence of the immunization card (13% of children) correlated with a poor global vaccine protection. Children with immunization records (87%) had a better global seroprotection but the information obtained from the card did not accurately predict seroprotection for each particular antigen. The best variable to predict the status of seroprotection was the country of origin. The highest rate of protection was found in children from Eastern Europe and, in descending order, India, Latin America, China and Africa. General recommendations for immunization of internationally adopted children are difficult to establish. Actions for vaccination have to be mainly implemented on the basis of the existence of the immunization card and of the country of origin.