Validation of the clinical performance and reproducibility of the NeuMoDx HPV assay self-sample workflow.

BACKGROUND: Human papillomavirus (HPV) testing on self-samples is a valid tool for cervical cancer screening. HPV self-sample workflows need to be clinically validated to ensure safe use in screening. OBJECTIVE: This study evaluated the fully automated NeuMoDx HPV Assay self-sample workflow that is compiled of the NeuMoDx HPV assay and the NeuMoDx 96/288 Molecular Systems, for clinical performance and reproducibility on Evalyn Brush-collected self-samples. METHODS: The clinical performance of the NeuMoDx HPV Assay self-sample workflow for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+ was evaluated on 987 self-samples obtained from women attending national organized HPV-based cervical cancer screening by a noninferiority analysis relative to reference workflows using either HPV-Risk Assay or high-risk HPV GP5+/6+-PCR. Intra- and inter-laboratory reproducibility of the NeuMoDx HPV Assay self-sample workflow using both NeuMoDx 96 and 288 Molecular Systems was assessed on 520 self-samples in three laboratories. RESULTS: The clinical sensitivity and specificity of the NeuMoDx HPV Assay self-sample workflow for the detection of CIN2+ and CIN3+ were found to be non-inferior to the reference workflows using either HPV-Risk Assay or high-risk HPV GP5+/6+-PCR, with all p-values <0.034. The NeuMoDx HPV Assay self-sample workflow exhibited an intra-laboratory reproducibility of 94.4 % (95 %CI:92.5-96.1 %) with kappa value 0.86 (95 %CI:0.81-0.91). Inter-laboratory agreement was high (all ≥93.4 % and all kappa values ≥0.83). CONCLUSIONS: The NeuMoDx HPV Assay self-sample workflow demonstrated high clinical accuracy for CIN2+/3+ and high reproducibility. The NeuMoDx HPV Assay self-sample workflow can be considered suitable for cervical cancer screening purposes.

Construct validity of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) treatment target cut-offs in a BASDAI treat-to-target axial spondyloarthritis cohort: a cross-sectional study.

OBJECTIVE: In axial spondyloarthritis (axSpA), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) are recommended for use in treat-to-target (T2T) strategies. However, BASDAI disease states may be a less suitable T2T instrument than ASDAS, since BASDAI contains non-disease activity related items. The objective of our study was to investigate the construct validity of BASDAI and ASDAS disease states. METHOD: We performed a single-centre cross-sectional study on BASDAI and ASDAS construct validity in long-term BASDAI T2T-treated axSpA patients. Our hypothesis was that BASDAI is less representative of disease activity than ASDAS owing to the focus on pain and fatigue, and missing an objective item, e.g. C-reactive protein (CRP). This was operationalized using several subhypotheses. RESULTS: The study included 242 axSpA patients. BASDAI and ASDAS disease states showed a similar relation to Patient Acceptable Symptom State and T2T protocol adherence. The proportions of patients with high BASDAI and ASDAS disease activity fulfilling Central Sensitization Inventory and fibromyalgia syndrome criteria were similar. The correlation with fatigue was moderate for both BASDAI (Spearman's rho 0.64) and ASDAS (Spearman's rho 0.54) disease states. A high ASDAS was strongly correlated with increased CRP (relative risk 6.02, 95% CI 3.0-12.09), while this correlation was not seen for BASDAI (relative risk 1.13, 95% CI 0.74-1.74). CONCLUSION: Our study showed moderate and comparable construct validity for BASDAI- and ASDAS-based disease activity states, with the expected exception of association with CRP. Therefore, no strong preference can be given for either measure, although the ASDAS seems marginally more valid.

Human brain mapping using co-registered fUS, fMRI and ESM during awake brain surgeries: A proof-of-concept study.

Accurate, depth-resolved functional imaging is key in both understanding and treatment of the human brain. A new sonography-based imaging technique named functional Ultrasound (fUS) uniquely combines high sensitivity with submillimeter-subsecond spatiotemporal resolution available in large fields-of-view. In this proof-of-concept study we show that: (A) fUS reveals the same eloquent regions as found by fMRI while concomitantly visualizing in-vivo microvascular morphology underlying these functional hemodynamics and (B) fUS-based functional maps are confirmed by Electrocortical Stimulation Mapping (ESM), the current gold-standard in awake neurosurgical practice. This unique cross-modality experiment was performed using motor, visual and language-related functional tasks in patients undergoing awake brain tumor resection. The current work serves as an important milestone towards further maturity of fUS as well as a novel avenue to increase our understanding of hemodynamics-based functional brain imaging.

Steps towards implementation of protocolized dose reduction of adalimumab, etanercept and ustekinumab for psoriasis in daily practice.

BACKGROUND: Dose reduction (DR) of adalimumab, etanercept and ustekinumab has proven to be (cost-)effective in psoriasis patients with low disease activity. Further implementation is needed to establish application of DR for eligible patients. OBJECTIVES: To evaluate the implementation of protocolized biologic DR in daily practice. METHODS: A pilot implementation study was performed in 3 hospitals during 6 months. By combining education and protocol development, involved healthcare providers (HCPs) were directed toward the adoption of protocolized DR. DR of adalimumab, etanercept, and ustekinumab was achieved by stepwise injection interval prolongation. Implementation outcomes (fidelity, feasibility) were assessed. Factors for optimizing implementation were explored in interviews with HCPs. Uptake was measured in patients by chart review. RESULTS: The implementation strategy was executed as planned. Implementation fidelity was less than 100% as not all provided tools were used across study sites. HCPs indicated the feasibility of implementing protocolized DR, although time investment was needed. Identified additional factors for successful implementation included support for patients, uptake of DR into guidelines, and supportive electronic health record systems. During the 6 months intervention period, 52 patients were eligible for DR of whom 26 (50%) started DR. The proposed DR protocol was followed in 22/26 patients (85%) on DR. CONCLUSION: Additional staff for support, extra time during consultations, education on DR for HCPs and patients, and effective tools such as a feasible protocol can lead to more patients on biologic DR.

Patients' perspectives towards biologic dose reduction in psoriasis: a qualitative study.

Dose reduction of biologics for psoriasis could contribute to more efficient use of these expensive medicines. Evidence on opinions of patients with psoriasis regarding dose reduction is sparse. The objective of this study was therefore to explore patients' perspectives towards dose reduction of biologics for psoriasis. A qualitative study was conducted, comprising semi-structured interviews with 15 patients with psoriasis with different characteristics and treatment experiences. Interviews were analyzed by inductive thematic analysis. Perceived benefits of biologic dose reduction according to patients were minimizing medication use, lowering risks of adverse effects and lowering societal healthcare costs. Patients reported to have experienced a large impact of their psoriasis, and expressed concerns about loss of disease control due to dose reduction. Fast access to flare treatment and adequate monitoring of disease activity were among reported preconditions. According to patients, they should have confidence in dose reduction effects and should be willing to change their effective treatment. Moreover, addressing information needs and involvement in decision-making were deemed important among patients. In conclusion, addressing patients' concerns, fulfilling information needs, providing the possibility of resuming standard dose, and involving patients in decision-making are important according to patients with psoriasis when considering biologic dose reduction.

Dose Tapering of Biologics in Patients with Psoriasis: A Scoping Review.

INTRODUCTION: Biologics serve as a cornerstone in psoriasis treatment, with low disease activity or sometimes even clinical remission as a realistic treatment outcome. So far, it is unclear whether biologics should be tapered when this target is achieved. Dose tapering could offer potential benefits by decreasing side effects, the burden of repetitive injections and costs of biological therapy. However, clinical guidelines on dose tapering of biologicals in psoriasis patients are lacking. This scoping review was conducted to provide an overview of the current literature on dose tapering and offer guidance for clinicians in daily clinical practice. METHODS: Dose tapering is defined as the administration of a lower dose per administration, or the prolongation of the regular dose interval, after initial treatment according to the standard dosing. Four electronic databases (PubMed, EMBASE, Cochrane, and Web of Science) were systematically searched for literature on tapering of biologics in adult patients with psoriasis from 1 January 2000. RESULTS: We included 19 original articles on biologic tapering in psoriasis patients: four randomized controlled trials and 15 observational studies. Tapering eligibility criteria, tapering strategies, tapering outcomes, and recapture of response after relapse were assessed. Furthermore, the available evidence on possible predictors for successful tapering, and the effect of tapering on safety, quality of life and costs is summarized. The definition of low disease activity as a measure for tapering eligibility varied widely. Beside tapering criteria, tapering strategies were also heterogeneous. Of note, quality-of-life measurements were barely integrated in the evaluation of tapering outcomes. Literature on regaining response after relapse due to tapering was limited, but restored remission has been described. The included studies did not proclaim a significant effect of tapering on the occurrence of (severe) adverse events. Even though cost savings have been reported, no proper cost-effectiveness analysis has been conducted yet. CONCLUSION: Biologic tapering seems to be effective and safe in psoriasis patients with stable low disease activity or clinical remission. Available data on biologic dose tapering in patients with psoriasis are promising, but more research is warranted to fill the current gaps in knowledge.

Biologics are effective in treating psoriasis amongst other diseases, such as rheumatoid arthritis and Crohn's disease. However, biologics are costly, and can cause side effects, such as an increased risk of infection. In patients with rheumatoid arthritis, it is not uncommon to lower the dose of these biologics (also called "dose tapering"), once stable low disease activity, or even remission, is reached. However, in psoriasis patients, dose tapering of biologics is not common practice. In this "scoping review," we provide an overview of the available literature on dose tapering of biologics in adult patients with plaque psoriasis in order to address the current gaps in literature. We found 19 studies that addressed dose tapering. These studies used different criteria to determine which patients were eligible for tapering, which led to various interpretations of tapering success. This made it difficult for us to draw general conclusions on which tapering criteria and strategies should be further investigated. Dose tapering seems to be effective and safe in patients with a stable low disease activity, although more (high-quality) research is needed. Future studies should focus on generating more data on long-term safety, finding predictors for successful tapering, calculating the cost-effectiveness of dose tapering, and evaluating dose tapering in the newest generation of biologics.

Surveillance of infections in long-term care facilities (LTCFs): The impact of participation during multiple years on health care-associated infection incidence.

We studied trends in the incidence of health care-associated infections (HAIs) in LTCFs between 2009 and 2015 and determined the effect of participation in our network. Elder-care physicians reported weekly the number of cases of influenza-like illness, gastroenteritis, (probable) pneumonia, urinary tract infections (UTIs) and all-cause mortality. Trends in the incidence of infection and mortality in relation to LTCF characteristics were calculated using multilevel univariate and multivariate logistic regression. Thirty LTCF participated for 3 years or more, 16 for 2 years and the remaining 12 LTCF for 1 year. During the study period, the median number of beds decreased from 158 to 139, whereas the percentage of residents with private bedrooms increased from 14% to 87%. UTIs were the most frequently reported infections, followed by (probable) pneumonia and gastroenteritis. Adjusted for calendar year and season, we observed a statistically significant decrease in the incidence of influenza-like illness (odds ratio (OR) = 0.8, P < 0.01) and (probable) pneumonia (OR = 0.8, P < 0.01) for each extra year an LTCF participated. Although there are other likely contributors, such as more private rooms and enhanced infection control measures, the decreasing trend of HAI in LTCFs participating in surveillance implies that surveillance is a valuable addition to current strategies to optimise infection control.

Cost-effectiveness of five different anti-tumour necrosis factor tapering strategies in rheumatoid arthritis: a modelling study.

Objective: To investigate the cost-effectiveness of five different tumour necrosis factor inhibitor tapering strategies in patients with rheumatoid arthritis (RA) and stable low disease activity, using a modelling design.Method: Using Markov models based on data from the DRESS and STRASS randomized controlled trials, and the Nijmegen RA cohort, five tapering strategies for etanercept and adalimumab were tested against continuation: 1, four-step tapering (DRESS strategy); 2, five-step tapering; 3, tapering without withdrawal; 4, use of a stricter flare criterion; and 5, use of a theoretical predictor for successful tapering. We also examined how well a biomarker should be able to predict in order for strategy 5 to become cost-effective compared to the other strategies.Results: All examined tapering strategies were cost saving (range: EUR 5128 to 7873) but yielded more short-lived flares compared to continuation. The change in utilities compared to continuation was minimal and not clinically relevant (range: -0.005 to 0.007 quality-adjusted life-years). Strategy 1 was cost-effective compared to all other strategies [highest incremental net monetary benefit (iNMB)]. However, there was a large overlap in credible intervals, especially between strategies 1 and 2. Scenario analyses showed that 50% reduction of drug prices would result in the highest iNMB for strategy 2. A biomarker only becomes cost-effective when it is inexpensive and has a sensitivity and specificity of at least 84%.Conclusion: Because our study showed a comparable iNMB for tapering in four or five steps (including discontinuation), we recommend a choice between these strategies, based on shared decision making.

Iatrogenic endometriosis harbors somatic cancer-driver mutations.

STUDY QUESTION: Does incisional endometriosis (IE) harbor somatic cancer-driver mutations? SUMMARY ANSWER: We found that approximately one-quarter of IE cases harbor somatic-cancer mutations, which commonly affect components of the MAPK/RAS or PI3K-Akt-mTor signaling pathways. WHAT IS KNOWN ALREADY: Despite the classification of endometriosis as a benign gynecological disease, it shares key features with cancers such as resistance to apoptosis and stimulation of angiogenesis and is well-established as the precursor of clear cell and endometrioid ovarian carcinomas. Our group has recently shown that deep infiltrating endometriosis (DE), a form of endometriosis that rarely undergoes malignant transformation, harbors recurrent somatic mutations. STUDY DESIGN, SIZE, DURATION: In a retrospective study comparing iatrogenically induced and endogenously occurring forms of endometriosis unlikely to progress to cancer, we examined endometriosis specimens from 40 women with IE and 36 women with DE. Specimens were collected between 2004 and 2017 from five hospital sites in either Canada, Germany or the Netherlands. IE and DE cohorts were age-matched and all women presented with histologically typical endometriosis without known history of malignancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Archival tissue specimens containing endometriotic lesions were macrodissected and/or laser-capture microdissected to enrich endometriotic stroma and epithelium and a hypersensitive cancer hotspot sequencing panel was used to assess for presence of somatic mutations. Mutations were subsequently validated using droplet digital PCR. PTEN and ARID1A immunohistochemistry (IHC) were performed as surrogates for somatic events resulting in functional loss of respective proteins. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, we detected somatic cancer-driver events in 11 of 40 (27.5%) IE cases and 13 of 36 (36.1%) DE cases, including hotspot mutations in KRAS, ERBB2, PIK3CA and CTNNB1. Heterogeneous PTEN loss occurred at similar rates in IE and DE (7/40 vs 5/36, respectively), whereas ARID1A loss only occurred in a single case of DE. While rates of detectable somatic cancer-driver events between IE and DE are not statistically significant (P > 0.05), KRAS activating mutations were more prevalent in DE. LIMITATIONS, REASONS FOR CAUTION: Detection of somatic cancer-driver events were limited to hotspots analyzed in our panel-based sequencing assay and loss of protein expression by IHC from archival tissue. Whole genome or exome sequencing, or epigenetic analysis may uncover additional somatic alterations. Moreover, because of the descriptive nature of this study, the functional roles of identified mutations within the context of endometriosis remain unclear and causality cannot be established. WIDER IMPLICATIONS OF THE FINDINGS: The alterations we report may be important in driving the growth and survival of endometriosis in ectopic regions of the body. Given the frequency of mutation in surgically displaced endometrium (IE), examination of similar somatic events in eutopic endometrium, as well as clinically annotated cases of other forms of endometriosis, in particular endometriomas that are most commonly linked to malignancy, is warranted. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a Canadian Cancer Society Impact Grant [701603, PI Huntsman], Canadian Institutes of Health Research Transitional Open Operating Grant [MOP-142273, PI Yong], the Canadian Institutes of Health Research Foundation Grant [FDN-154290, PI Huntsman], the Canadian Institutes of Health Research Project Grant [PJT-156084, PIs Yong and Anglesio], and the Janet D. Cottrelle Foundation through the BC Cancer Foundation [PI Huntsman]. D.G. Huntsman is a co-founder and shareholder of Contextual Genomics Inc., a for profit company that provides clinical reporting to assist in cancer patient treatment. R. Aguirre-Hernandez, J. Khattra and L.M. Prentice have a patent MOLECULAR QUALITY ASSURANCE METHODS FOR USE IN SEQUENCING pending and are current (or former) employees of Contextual Genomics Inc. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Incidence of pneumonia in nursing home residents with dementia in the Netherlands: an estimation based on three differently designed studies.

Pneumonia leads to considerable morbidity and mortality in nursing home residents with dementia. We assessed pneumonia incidence based on data from three different studies: (1) real-time national surveillance of healthcare-associated infections in nursing home residents in 2009-2015; (2) a randomized controlled trial in 2012-2015 to assess effects of a practical guideline in nursing home residents with dementia and pneumonia; and (3) a study in 2007-2010 to assess quality of dying in newly admitted nursing home residents with dementia. In national surveillance data, pneumonia incidence was calculated separately for psychogeriatric and somatic beds, as a proxy for residents with and without dementia. Weekly pneumonia incidence was significantly lower per 1000 psychogeriatric beds (3·9; 95% confidence interval (CI) 3·2-4·6) compared with 1000 somatic beds (5·7; 95% CI 5·1-6·3). Annual incidence per 1000 psychogeriatric beds was similar in national surveillance (range 78·9-117·1) and the trial (range 71·0-94·3), and significantly higher in newly admitted dementia residents (range 267·3-363·2). The incidence was highest during the first months after admission when compared with residents with longer stay. In conclusion, follow-up of pneumonia in newly admitted dementia residents may result in higher incidence, possibly due to higher risk in this population.

Implementation of protocolized tight control and biological dose optimization in daily clinical practice: results of a pilot study.

OBJECTIVES: To assess the effects of education, guideline development, and individualized treatment advice on rheumatologist adherence to tight control-based treatment and biological dose optimization in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondyloarthropathy (SpA) patients. METHOD: This pilot study, among two rheumatologists and two specialized nurses in a general hospital, combined education, feedback, local guideline development, and individualized treatment advice. Outcomes (baseline and 1 year post-intervention) were the percentage of patients with a Disease Activity Score in 28 joints (DAS28) or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) measured during the visit, mean DAS28/BASDAI, and the percentage of patients using a reduced biological dose. DAS28 outcomes only applied to RA and PsA patients, BASDAI outcomes only applied to SpA patients whereas outcomes on biological dose applied to all patients. RESULTS: A total of 232 patients (67% RA, 15% PsA, 18% SpA; 58% female, mean age 56 ± 15 years) were included in the study. The percentage of DAS28 and BASDAI measurements performed increased after the intervention [DAS28 15-51%, odds ratio (OR) 3.3, 95% confidence interval (CI) 2.1-5.5; BASDAI 23-50%, OR 2.2, 95% CI 1.0-5.5], with mean DAS28 and BASDAI scores remaining similar (DAS28: mean difference 0.1, 95% CI -0.3 to 0.5; BASDAI: mean difference 0.03, 95% CI -1.8 to 1.9). Use of a reduced biological dose increased from 10% to 61% (OR 3.9, 95% CI 2.4-6.5). CONCLUSIONS: A multicomponent intervention strategy aimed at rheumatologists can lead to improved adherence to tight control-based treatment and a reduction in the use of biologicals in RA, SpA, and PsA patients.

Large and prolonged food-borne multistate hepatitis A outbreak in Europe associated with consumption of frozen berries, 2013 to 2014.

In May 2013, Italy declared a national outbreak of hepatitis A, which also affected several foreign tourists who had recently visited the country. Molecular investigations identified some cases as infected with an identical strain of hepatitis A virus subgenotype IA. After additional European Union/European Economic Area (EU/EEA) countries reported locally acquired and travel-related cases associated with the same outbreak, an international outbreak investigation team was convened, a European outbreak case definition was issued and harmonisation of the national epidemiological and microbiological investigations was encouraged. From January 2013 to August 2014, 1,589 hepatitis A cases were reported associated with the multistate outbreak; 1,102 (70%) of the cases were hospitalised for a median time of six days; two related deaths were reported. Epidemiological and microbiological investigations implicated mixed frozen berries as the vehicle of infection of the outbreak. In order to control the spread of the outbreak, suspected or contaminated food batches were recalled, the public was recommended to heat-treat berries, and post-exposure prophylaxis of contacts was performed. The outbreak highlighted how large food-borne hepatitis A outbreaks may affect the increasingly susceptible EU/EEA general population and how, with the growing international food trade, frozen berries are a potential high-risk food.

Laboratory-based surveillance in the molecular era: the TYPENED model, a joint data-sharing platform for clinical and public health laboratories.

Laboratory-based surveillance, one of the pillars of monitoring infectious disease trends, relies on data produced in clinical and/or public health laboratories. Currently, diagnostic laboratories worldwide submit strains or samples to a relatively small number of reference laboratories for characterisation and typing. However, with the introduction of molecular diagnostic methods and sequencing in most of the larger diagnostic and university hospital centres in high-income countries, the distinction between diagnostic and reference/public health laboratory functions has become less clear-cut. Given these developments, new ways of networking and data sharing are needed. Assuming that clinical and public health laboratories may be able to use the same data for their own purposes when sequence-based testing and typing are used, we explored ways to develop a collaborative approach and a jointly owned database (TYPENED) in the Netherlands. The rationale was that sequence data - whether produced to support clinical care or for surveillance -can be aggregated to meet both needs. Here we describe the development of the TYPENED approach and supporting infrastructure, and the implementation of a pilot laboratory network sharing enterovirus sequences and metadata.

The estimated disease burden of norovirus in The Netherlands.

Noroviruses are an important cause of acute gastroenteritis in humans. We incorporated new insights gained over the past decade in an updated estimate of the disease burden of (foodborne) norovirus illness in The Netherlands in 2009. The disease outcomes - non-consulting cases, visiting a general practitioner, hospitalization and mortality - and the foodborne proportion were derived from cohort studies, surveillance data and literature. Age-specific incidence estimates were applied to the population age distribution in The Netherlands in 2009. The general population incidence was 3800/100 000 (95% CI 2670­5460), including 0.4 fatal cases/100 000,resulting in 1622 (95% CI 966­2650) disability-adjusted life-years in a population of 16.5 million [corrected].The updated burden of norovirus is over twofold higher than previously estimated, due in particular to the new insights in case-fatality ratios. Results suggest that the burden of norovirus institutional outbreaks is relatively small compared to the burden of community-acquired norovirus infections.

Assessing potential introduction of universal or targeted hepatitis A vaccination in the Netherlands.

In many industrialized countries, hepatitis A incidence rates have declined steadily in the past decades. Since future cohorts of non-vaccinated elderly will lack protection against disease and the burden of hepatitis A is higher with increasing age, this could be an argument in favour of taking preventive measures such as including hepatitis A vaccine into the National Immunisation Program, or offering hepatitis A vaccine to the elderly only. Using a vaccination evaluation scheme, we assessed the potential benefits and drawbacks of introducing hepatitis A vaccine in the National Immunisation Program in the Netherlands. The average number of annual hepatitis A notifications is declining, from 957 in the period 1991 to 1995 to 211 over the period 2006 to 2010. The direct health care costs and costs due to productivity losses per patient are rising, because the age at infection increases and older patients require a relatively higher number of hospitalizations. Initiating a vaccination program would most likely not be cost-effective yet. The annual costs of mass-vaccination are large: about €10 million for infants and €13 million for older people (and only in the first year €210 million), based on current retail prices. The annual effects of mass-vaccination are small: the cost-of-illness in recent years attributed to hepatitis A infection is estimated to be €650,000 per year, and the disease burden is on average 17 DALYs. Given the current low hepatitis A incidence, and the continuing decline in incidence, targeted preventive measures such as vaccinating travellers and other high-risk groups and timely vaccination of close contacts of hepatitis A patients are adequate. However, because susceptibility to hepatitis A is increasing in the group with the highest risk of developing severe complications upon infections, careful monitoring of the epidemiology of hepatitis A remains important.

Seroprevalence of hepatitis E antibodies and risk profile of HEV seropositivity in The Netherlands, 2006-2007.

SHepatitis E virus (HEV) is now considered an endemic pathogen in industrialized countries, leading to acute and sometimes chronic hepatitis, mostly in vulnerable people. The endemic sources are unclear. A survey in The Netherlands in 2006-2007 showed a 1·9% seroprevalence of HEV antibodies measured by ELISA and confirmed by immunoblot in a nationwide sample. Overall, in 134/7072 (1·9%) seropositive individuals, older age (P<0·01), being male (P<0·01), working with patients (P=0·03), working with animals (P=0·07), recent diarrhoeal complaints (P=0·07) and adhering to a religion that considers pigs unclean (P<0·01) were independently associated with seropositivity in multivariate analysis. Sub-analysis of 59/4022 (1·5%) anti-HEV antibody-positive subjects with probable endemic exposure showed independent association with youngest household member being aged <5 years or between 19 and <65 years (P=0·05) in multivariate analysis. These findings may contribute to a better understanding of the sources of endemic HEV exposure, and also highlight the need for systematic epidemiological and serological evaluation of new cases.

Changing risk profile of hepatitis A in The Netherlands: a comparison of seroprevalence in 1995-1996 and 2006-2007.

The prevalence of antibodies to hepatitis A virus (HAV) was assessed in a nationwide sample (n=6229) in The Netherlands in 2006-2007, and compared to the seroprevalence in a similar study in 1995-1996 (n=7376). The overall seroprevalence increased from 34% in 1995-1996 to 39% in 2006-2007, mainly due to vaccination of travellers and an increased immigrant population. Risk factors remain travelling to, and originating from, endemic regions, and vaccination is targeted currently at these risk groups. Our results show a trend of increasing age of the susceptible population. These people would also benefit from HAV vaccination because they are likely to develop clinically serious symptoms after infection, and are increasingly at risk of exposure through imported viruses through foods or travellers. The cost-effectiveness of adding elderly people born after the Second World War as a target group for prophylactic vaccination to reduce morbidity and mortality after HAV infection should be assessed.

Norovirus disease associated with excess mortality and use of statins: a retrospective cohort study of an outbreak following a pilgrimage to Lourdes.

Although norovirus infection is generally known to be a mild disease, there is some evidence for severe outcome. An outbreak in a Dutch psychiatric institution, originating from pilgrims returning from Lourdes (France), provided an opportunity for performing a retrospective cohort study in order to identify risk factors for norovirus disease and excess mortality. Relative risks (RR) including 95% confidence intervals (CI) showed that attending the pilgrimage (RR 2·0, 95% CI 1·4-3·0) and age >70 (RR 1·7, 95% CI 1·2-2·2) were risk factors for symptomatic infection. In a subset of patients, for whom more detailed information was available, the use of statins was associated with norovirus disease when adjusted for underlying condition (adjusted odds ratio 3·9, 95% CI 1·2-13·0). Mortality was higher in cases infected during the pilgrimage compared to other residents (RR 20·9, 95% CI 4·7-93·8). Norovirus disease can lead to severe outcome. The newly identified risk of statins for contracting norovirus disease may have considerable consequences for the Western world and needs prospective confirmation.