[Uncertainties with starting new vaccinations: a comparison between polio and covid-19 vaccination]. / Onzekerheden bij invoering nieuwe vaccinaties.

In 1956 The Netherlands experienced a major outbreak of poliomyelitis with over 2200 patients. A vaccine was in reach, and it was used. Now, polio is nearly eradicated globally with vaccinations. In 2020 a similar situation occurred with COVID-19. Large-scale vaccinations form an essential tool to combat the epidemic. This article describes uncertainties to start both mass vaccination campaigns, and reflects on similarities and differences then and now.

Colistin-resistant Enterobacterales among veterinary healthcare workers and in the Dutch population.

Objectives: Plasmid-mediated colistin resistance can be transferred from animals to humans. We investigated the prevalence of carriage of mcr-mediated colistin-resistant Escherichia coli and Klebsiella pneumoniae (ColR-E/K) in veterinary healthcare workers and in the general population in the Netherlands. Methods: Two cross-sectional population studies were performed: one among veterinary healthcare workers and one in the general population. Participants sent in a faecal sample and filled in a questionnaire. Samples were analysed using selective enrichment and culture. Mobile colistin resistance genes (mcr) were detected by PCR and ColR-E/K were sequenced using Illumina and Nanopore technologies. Results: The prevalence of mcr-mediated ColR-E/K was 0.2% (1/482, 95% CI 0.04%-1.17%) among veterinary personnel and 0.8% (5/660, 95% CI 0.3%-1.8%) in the population sample. mcr-1 was found in E. coli from four persons, mcr-8 in K. pneumoniae from one person and another person carried both mcr-1 and mcr-8 in a K. pneumoniae isolate. mcr-1 was found on different plasmid types (IncX4, IncI1 and IncI2), while mcr-8 was found on IncF plasmids only. Conclusions: mcr-mediated ColR-E/K resistance was uncommon in both populations. Professional contact with animals does not increase the chance of carriage of these bacteria in the Netherlands at present. mcr-8 was found for the first time in the Netherlands. Surveillance of colistin resistance and its underlying mechanisms in humans, livestock and food is important in order to identify emerging trends in time.

Ocular complications of oak processionary caterpillar setae in the Netherlands; case series, literature overview, national survey and treatment advice.

During early summer 2019, the Netherlands experienced an outbreak of the exotic oak processionary caterpillar. The vast number of caterpillars, which live in large nests on oak trees before they turn into moths, possess thousands of small, barbed hairs (setae) that are disseminated with the wind. The hairs cause a range of primarily dermatologic problems. However, Dutch ophthalmologists started reporting patients with ophthalmologic complaints caused by the penetrating hairs of the oak processionary caterpillar. This paper focuses on the ophthalmologic complications caused by the caterpillar hairs. We collected a series of four cases with reports ranging from a corneal erosion with hairs lodged into the cornea, to a sterile endophthalmitis in which hairs were found in the vitreous. A literature review for similar cases was performed using the PubMed and Embase database. Together with the Dutch Ophthalmic Society (Nederlands Oogheelkundig Gezelschap, NOG), a national survey was issued to determine the scale of this new problem. This showed that oak processionary caterpillar related complaints are primarily limited to the south of the Netherlands. Suggested ophthalmic treatment guidelines are presented. With the next summer at the doorstep, and limited preventative measures against the caterpillar hairs, we expect a new wave of ophthalmologic complaints coming year as well.

[National Immunisation Programme: is vaccinating less an option?] / Rijksvaccinatieprogramma: is minder vaccineren een optie?

Many people are no longer familiar with the diseases that are part of the Dutch National Immunisation Programme (NIP). The protection given by the NIP has ensured that these diseases, most of them serious, have largely disappeared. The NIP has developed gradually, but in retrospect it was in 1957 that what we now know as the NIP started. Over the years, the NIP has gradually expanded to include various vaccines such as live attenuated vaccines, conjugate vaccines and vaccines that offer protection against chronic viral infections. Currently, the NIP offers protection against twelve different diseases. Occasionally the Netherlands still sees minor outbreaks of those diseases included in the NIP programme, generally among non-vaccinated people. It is important that the NIP is retained; stopping vaccination always leads to the return of the disease. The question is: can good protection be maintained with fewer injections? This subject is on the agenda of the Health Council Of The Netherlands for discussion in 2022.

[No scientific lower threshold for compulsory vaccination]. / Geen wetenschappelijke ondergrens voor verplicht vaccineren.

The national vaccination rate in young children in the Netherlands has decreased in recent years. This has led to social and political discussions, for instance about compulsory vaccination for children in child-care. The national commission on child-care and vaccination has advised that vaccination should be made compulsory when the rate of vaccination has declined to a pre-determined lower threshold, to be determined by the government. A frequently quoted lower threshold is 95%. The idea behind this is the concept of a critical vaccination rate, a threshold needed for elimination of an infection in a large, well-mixed population. In this article we argue why the critical vaccination rate does not offer a scientific basis for a lower threshold to the national vaccination rate.

No evidence found for an increased risk of long-term fatigue following human papillomavirus vaccination of adolescent girls.

INTRODUCTION: In 2013, the Netherlands Pharmacovigilance Center Lareb published an overview of reports of long-lasting fatigue following bivalent HPV-vaccination (2vHPV). After an update of this overview in 2015, concerns regarding the safety of 2vHPV was picked up by the media, which led to further reports of long-lasting fatigue. Therefore, the Dutch National Institute for Public Health and the Environment (RIVM) investigated a possible association between HPV-vaccination and long-term fatigue. METHODS: In this retrospective cohort study conducted in the Integrated Primary Care Information database, we investigated the occurrence of chronic fatigue syndrome (CFS), fatigue ≥6 months and 3-6 months in all girls born in 1991-2000 during the follow-up period January 1st 2007-December 31st 2014 (2007-2008 pre-vaccination and 2009-2014 post-vaccination). Patients with certain fatigue ≥6 m were asked for consent to link their primary care information with vaccination data. Incidence rates per 10,000 person years (PY) for 12-16-year-old girls were compared between pre- and post-HPV-vaccine era. A self-controlled case series (SCCS) analysis was performed using consenting vaccinated cases. A primary high-risk period of 12 months after each dose was defined. RESULTS: The cohort consisted of 69,429 12-16-year-old girls accounting for 2758 PY pre-vaccination and 57,214 PY post-vaccination. Differences between pre- and post-vaccination incidences (CFS: 3.6 (95% CI 0.5-25.7)/10,000 PY and 0.9 (0.4-2.1); certain fatigue ≥6 m: 7.3 (1.8-29.0) and 19.4 (16.1-23.4); certain fatigue 3-6 m: 0.0 and 16.6 (13.6-20.3), respectively) were not statistically significant. SCCS analyses in 16 consenting vaccinated cases resulted in an age-adjusted RR of 0.62 (95%CI 0.07-5.49). CONCLUSIONS: Fatigue ≥6 m and 3-6 m was frequently found among adolescent girls, but CFS was rarely diagnosed. No statistically significant increased incidence rates were found post-vaccination compared to similar age groups of girls pre-vaccination. The SCCS analysis included a low number of cases but revealed no elevated risk of certain fatigue ≥6 m in the high-risk period.

The Influence of End-of-Life Care on Organ Donor Potential.

Many patients with acute devastating brain injury die outside intensive care units and could go unrecognized as potential organ donors. We conducted a prospective observational study in seven hospitals in the Netherlands to define the number of unrecognized potential organ donors outside intensive care units, and to identify the effect that end-of-life care has on organ donor potential. Records of all patients who died between January 2013 and March 2014 were reviewed. Patients were included if they died within 72 h after hospital admission outside the intensive care unit due to devastating brain injury, and fulfilled the criteria for organ donation. Physicians of included patients were interviewed using a standardized questionnaire regarding logistics and medical decisions related to end-of-life care. Of the 5170 patients screened, we found 72 additional potential organ donors outside intensive care units. Initiation of end-of-life care in acute settings and lack of knowledge and experience in organ donation practices outside intensive care units can result in under-recognition of potential donors equivalent to 11-34% of the total pool of organ donors. Collaboration with the intensive care unit and adjusting the end-of-life path in these patients is required to increase the likelihood of organ donation.

Recurrent coma and fever in familial hemiplegic migraine type 2. A prospective 15-year follow-up of a large family with a novel ATP1A2 mutation.

Background Familial hemiplegic migraine (FHM) is a rare monogenic migraine subtype characterised by attacks associated with transient motor weakness. Clinical information is mainly based on reports of small families with only short follow-up. Here, we document a prospective 15-year follow-up of an extended family with FHM type 2. Patients and methods After diagnosing FHM in a patient with severe attacks associated with coma and fever, we identified eight more family members with FHM and one with possible FHM. All family members were prospectively followed for 15 years. In total 13 clinically affected and 21 clinically non-affected family members were genetically tested and repeatedly investigated. Results A novel p.Arg348Pro ATP1A2 mutation was found in 14 family members: 12 with clinical FHM, one with psychomotor retardation and possible FHM, and one without FHM features. In 9/12 (75%) family members with genetically confirmed FHM, attacks were severe, long-lasting, and often associated with impaired consciousness and fever. Such attacks were frequently misdiagnosed and treated as viral meningitis or stroke. Epilepsy was reported in three family members with FHM and in the one with psychomotor retardation and possible FHM. Ataxia was not observed. Conclusion FHM should be considered in patients with recurrent coma and fever.

No relevant excess prevalence of myotonic dystrophy type 2 in patients with suspected fibromyalgia syndrome.

Myotonic dystrophy type 2 (DM2) is a rare, autosomal dominant, multisystem disorder with proximal weakness, myotonia, pain and cataract as important symptoms. Given the assumed underreporting of DM2 in the Netherlands combined with the predominant role of pain in DM2 as well as in fibromyalgia syndrome (FMS), we hypothesized there will be an excess prevalence of DM2 in patients with (suspected) FMS. Our objective was to determine the prevalence of DM2 in patients with suspected FMS. A prevalence of 2% was considered a relevant excess frequency. Between November 2011 and April 2014, 398 patients with suspected FMS who had been assessed by a rheumatologist participated in this cross-sectional study. 95% of the study population was female, with a mean age of 42 years. The final ICD-9 diagnoses were collected, in 96% the diagnosis was FMS. 92% met the 2010 American College of Rheumatology (ACR) diagnostic criteria for FMS. A questionnaire including neuromuscular symptoms was completed. Creatine kinase was determined, and genetic testing for DM2 was conducted in all patients. DM2 was established in only one patient (0.25%, 95% CI 0.04-1.4%), thus disapproving our hypothesis of a relevant prevalence of 2%. Our results suggest that patients with suspected FMS should not routinely be tested for DM2.

In Vivo Quantitative Assessment of Myocardial Structure, Function, Perfusion and Viability Using Cardiac Micro-computed Tomography.

The use of Micro-Computed Tomography (MicroCT) for in vivo studies of small animals as models of human disease has risen tremendously due to the fact that MicroCT provides quantitative high-resolution three-dimensional (3D) anatomical data non-destructively and longitudinally. Most importantly, with the development of a novel preclinical iodinated contrast agent called eXIA160, functional and metabolic assessment of the heart became possible. However, prior to the advent of commercial MicroCT scanners equipped with X-ray flat-panel detector technology and easy-to-use cardio-respiratory gating, preclinical studies of cardiovascular disease (CVD) in small animals required a MicroCT technologist with advanced skills, and thus were impractical for widespread implementation. The goal of this work is to provide a practical guide to the use of the high-speed Quantum FX MicroCT system for comprehensive determination of myocardial global and regional function along with assessment of myocardial perfusion, metabolism and viability in healthy mice and in a cardiac ischemia mouse model induced by permanent occlusion of the left anterior descending coronary artery (LAD).

Social inequality and age-specific gender differences in overweight and perception of overweight among Swedish children and adolescents: a cross-sectional study.

BACKGROUND: Overweight among children and adolescents related to social inequality, as well as age and gender differences, may contribute to poor self-image, thereby raising important public health concerns. This study explores social inequality in relation to overweight and perception of overweight among 263 boys and girls, age 7 to 17, in Växjö, Sweden. METHODS: Data were obtained through a questionnaire and from physical measurements of height, weight and waist circumference [WC]. To assess social, age and gender differences in relation to overweight, the independent sample t- and chi-square tests were used, while logistic regression modeling was used to study determinants for perception of overweight. RESULTS: Social inequality and gender differences as they relate to high ISO-BMI [Body Mass Index for children] and WC were associated with low maternal socioeconomic status [SES] among boys < 13 years [mean age = 10.4; n = 65] and with low paternal education level among boys ≥ 13 years [mean age = 15.0; n = 39] [p < 0.05]. One suggested explanation for this finding is maternal impact on boys during childhood and the influence of the father as a role model for adolescent boys. The only association found among girls was between high ISO-BMI in girls ≥ 13 years [mean age = 15.0; n = 74] and low paternal occupational status. Concerning perception of overweight, age and gender differences were found, but social inequality was not the case. Among boys and girls < 13 years, perception of overweight increased only when overweight was actually present according to BMI or WC [p < 0.01]. Girls ≥ 13 years [mean age = 15.0] were more likely to unrealistically perceive themselves as overweight or "too fat," despite factual measurements to the contrary, than boys [p < 0.05] and girls < 13 years [mean age = 10.4; n = 83] [p < 0.001]. CONCLUSIONS: The association between social inequality and overweight in adolescence in this study is age- and gender-specific. Gender differences, especially in perception of overweight, tend to increase with age, indicating that adolescence is a crucial period. When planning interventions to prevent overweight and obesity among children and adolescents, parental SES as well as age and gender-specific differences in social norms and perception of body weight status should be taken into account.

Comparison of automated 4-chamber cardiac views versus axial views for measuring right ventricular enlargement in patients with suspected pulmonary embolism.

PURPOSE: Compare the right ventricle to left ventricle (RV/LV) diameter ratio obtained from axial pulmonary CT angiograms (CTPA) with those derived from automatically generated 4-chamber (4-CH) reformats in patients with suspected pulmonary embolism (PE). METHODS: In this institutional review board-approved study we included 120 consecutive non ECG-gated CTPA from 3 institutions (mean age 60 ± 16 years; 71 women). Twenty 64-slice CTPA with PE and 20 without PE were selected per institution. For each patient the RV/LV diameter ratio was obtained from both axial CTPA images and automatically generated 4-CH reformats. Measurements were performed twice in two separated sessions by 2 experienced radiologists and 2 residents. The differences between the measurements on both views were evaluated. RESULTS: The 4-CH view was successfully obtained in 113 patients. The mean axial and 4-CH diameter ratios were comparable for three of the four readers (p = 0.56, p = 0.13, p = 0.08). Although the mean diameters (1.0 and 1.03 respectively) for one resident were significantly different (p = 0.013), the difference of 0.03 seems negligible in clinical routine. Three readers achieved equally high intra-reader agreements with both measurements (ICCs of 0.94, 0.95 and 0.96), while one reader showed a different variability with ICCs of 0.96 for the axial view and 0.91 for the 4-CH view. The inter-reader agreement was equally high for both measurement types with ICCs of 0.95 and 0.94, respectively. CONCLUSION: In patients with suspected PE, RV/LV diameters ratio can be measured with the same reproducibility and accuracy using an automatically generated 4-CH view compared to the axial view.

[Effects of ageing on infectious disease]. / Effecten van vergrijzing op infectieziekten.

Expectations are that 25% of the Dutch population will be aged 65 years or older in 2050 whilst in 2008 this proportion was only 15%. As a consequence the annual absolute number of new cases of specific infectious diseases will increase. Elderly people often have less clear symptoms of infection, making it harder for clinicians to recognize the disease. Morbidity and mortality caused by infections increase with age. Ageing will possibly cause an increase in levels of antibiotic resistance. There will be more elderly people in hospitals and nursing homes, where more antibiotics are used. This development will come in addition to other developments in the field of antibiotic resistance. There will be more elderly people with chronic HIV and viral hepatitis B and C infection and their complications because patients who are presently infected with those pathogens are ageing. Policy makers should more often consider introducing vaccination of older age groups against certain infectious diseases.

Characterization of the methylation patterns of MS4A2 in atopic cases and controls.

BACKGROUND: It is largely unknown whether epigenetic modifications of key genes may contribute to the reported maternal effects in atopy. The aim of this study was to characterize the methylation patterns of the membrane-spanning 4-domains, subfamily A, member 2 gene (MS4A2) (beta-chain of the IgE high-affinity receptor), a key gene in the allergic cascade. METHODS: Mass spectrometry and bisulphite sequencing were used to measure the methylation of two potential substrates for epigenetic regulation of MS4A2, namely a predicted promoter and a CpG-rich AluSp repeat. Methylation was measured in DNA extracted from peripheral blood lymphocytes of 38 atopic cases and 37 controls. Cases were positive for atopy, asthma, bronchial hyper-responsiveness and had high IgE levels. Both parents of eight atopic cases were also tested. RESULTS: The AluSp element was highly methylated across all individuals (mean 0.92, range 0.87-0.94), a pattern inconsistent with classical imprinting. Variation in methylation at this locus was not associated with age, sex, daily steroid use or atopic status, and there were no differences in methylation between mothers and fathers of atopic cases. Bisulphite sequencing analysis of the promoter region showed that it was also not imprinted, and there was no evidence for allele-specific methylation, but we were unable to test for association with atopy status. CONCLUSIONS: Methylation levels at the AluSp repeat analysed in MS4A2 were inconsistent with classical imprinting mechanisms and did not associate with atopy status. The promoter region was less methylated but further analysis of this region in larger cohorts is warranted to investigate its role in allergic disease.

[Changes in the duty of notification of infectious diseases via the Dutch Public Health Act]. / Veranderingen in de meldingsplicht voor infectieziekten door de Wet Publieke Gezondheid.

The Dutch Public Health Act, which came into force on 1 December 2008, replaces the existing laws concerning the combating of infectious diseases. Important changes have been incorporated in the new Public Health Act in comparison with the previous law on infectious diseases. Diseases which are probably infectious in nature and caused by as yet unknown pathogens are now notifiable, laboratories also have a nominal duty of notification and the list of notifiable diseases has been extended with 10 new infectious diseases. The provisions in the law comply with the International Health Regulations of the World Health Organization. The Centre for Infectious Disease Control Netherlands at the Dutch National Institute for Public Health and the Environment (RIVM) has issued a booklet for all Dutch physicians and laboratories providing background information on notifiable diseases. This can be useful in daily practice for helping to decide whether a disorder or cluster of infections is notifiable.

Dysphagia is present but mild in myotonic dystrophy type 2.

The phenotype of myotonic dystrophy type 2 (DM2) shows similarities as well as differences to that of myotonic dystrophy type 1 (DM1). Dysphagia, a predominant feature in DM1, has not yet been examined in DM2. In a recent nationwide questionnaire survey of gastrointestinal symptoms in DM2, 12 out of 29 DM2 patients reported to have difficulty in swallowing for solid food. The aim of the study was to investigate the presence of dysphagia in patients with genetically proven DM2 who reported difficulty in swallowing for solid food at the questionnaire survey. Swallowing function and fiberoptic endoscopic evaluation of swallowing (FEES) were examined by a speech therapist and otorhinolaryngologist, respectively. In DM2 patients who reported difficulty in swallowing the presence of dysphagia could be confirmed (clinically in 100%, by FEES in 88%). A correlation exists between Dysphagia Outcome and Severity Score (DOSS) and age (p=0.05). None of the patients was underweight, and none of the patients had suffered aspiration pneumonia in the past. Dysphagia is present among DM2 patients and is more severe in older patients. However, dysphagia is generally mild, and do not lead to weight loss, or aspiration pneumonia.

Waist circumference in relation to body perception reported by Finnish adolescent girls and their mothers.

AIM: To study how waist circumference (WC) relates to body perception in adolescent girls and to maternal perception of the girl's body size. METHODS: Three hundred and four girls, 11-18 years, were measured for height, weight and WC. 294 girls provided self-report data on weight, height and body image before anthropometric measurements. Paired data from 237 girls and mothers on perception of the girls' body size were collected. RESULTS: In girls, self-reported weight indicated awareness of actual body size. The girls' body perception showed an overestimation of body size relative to international reference values for body mass index (BMI) (p < 0.05), but not for WC. Girls' body perception exceeded that of their mothers (p < 0.05). Maternal perception agreed better than the girls' perception with international reference values for BMI (p < 0.05). No significant difference between mothers and girls were found concerning agreement of body perception with international reference values for WC. CONCLUSION: WC rather than BMI agrees with perception of body size, possibly due to its relation to abdominal fat at different ages. For effective prevention and treatment programmes for weight-related health problems among adolescent girls, we recommend measuring WC to diminish the discrepancy between measured and perceived body size.

A conjunctival mass in the deep superior fornix after a long retained hard contact lens in a patient with keloids.

PURPOSE: To report a case of an upper eyelid mass induced by a rigid contact lens retained for more than 3 years in the eye of a patient with a general history of keloids and to provide a review of the literature on retained contact lenses. METHODS: Case report. RESULTS: A 45-year-old woman with an ophthalmologic history of dry eyes and follicular chronic conjunctivitis presented at our department complaining of irritation, mucous discharge, and contact lens intolerance in her left eye. The ophthalmic examination revealed a visual acuity of 20/20 in both eyes and bilateral blepharitis. A pseudoptosis and an impressive mass growing from the superior tarsal conjunctiva with a lot of mucous discharge were present in the left eye. After a delay of 3.5 years with persisting complaints, a double lid eversion revealed the presence of a hard contact lens retained in the deep fornix of the left eye. After removing the lens and a short period of treatment with local corticosteroids, the mass and the symptoms disappeared. CONCLUSIONS: In patients who wear or wore contact lenses and present with one-sided chronic irritation and tissue proliferation, the possibility of a retained contact lens should be considered. The previous history of dry eyes and chronic conjunctivitis led us to miss the diagnosis at the first visits, despite persisting complaints. No other cases about the effects of a retained contact lens in a patient with keloids have been previously reported.