Comment on Jones et al. Application of a Novel Algorithm for Expanding Newborn Screening for Inherited Metabolic Disorders across Europe. Int. J. Neonatal Screen. 2022, 8, 20.

With innovations in both the screening methodologies and treatment of diseases, newborn screening (NBS) programmes are confronted with an increasing number of candidate diseases [...].

Critical evaluation of the newborn screening for congenital hypothyroidism in the Netherlands.

OBJECTIVE: Congenital hypothyroidism (CH) is defined as thyroid hormone deficiency at birth due to disorders of the thyroid gland (thyroidal CH, CH-T), or the hypothalamus or pituitary (central CH, CH-C). The Dutch Newborn Screening (NBS) strategy is primarily based on determination of thyroxine (T4) concentrations in dried blood spots followed, if necessary, by thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) measurement enabling detection of both CH-T and CH-C. A calculated T4/TBG ratio serves as an indirect measure for free T4. A T4/TBG ratio ≤ 17 in a second heel puncture is suggestive of CH-C. DESIGN AND METHODS: In the present study, we evaluated 11 years of Dutch CH NBS using a database of referred cases by assessing the contribution of each criterion in the unique stepwise T4-TSH-TBG NBS algorithm. RESULTS: Between 2007 and the end of 2017, 1 963 465 newborns were screened in the Netherlands. Use of the stepwise algorithm led to 3044 referrals and the identification of 612 CH cases, consisting of 496 CH-T, 86 CH-C, and 30 CH of unknown origin diagnoses. We detected 62.8% of CH-C cases by the T4/TBG ratio in the second heel puncture. The positive predictive value (PPV) of the stepwise T4-TSH-TBG NBS algorithm was 21.0%. CONCLUSION: This evaluation shows that the Dutch stepwise T4-TSH-TBG NBS algorithm with a calculated T4/TBG ratio is of great value for the detection of both CH-T and CH-C in the Netherlands, at the cost of a lower PPV compared to TSH-based NBS strategies.

Parental perspectives on retention and secondary use of neonatal dried bloodspots: a Dutch mixed methods study.

BACKGROUND: Neonatal bloodspot screening (NBS) identifies conditions to offer early intervention and minimize irreversible damage. NBS policies guide a comprehensive system including processes for storage of neonatal dried blood spots (NDBS). NDBS retention and secondary use policies have been subject of public debates internationally, suggesting that the public's perceptions of NDBS policy are not always on par with existing policies. The current study aims to provide insight in relevant factors for new parents in the Netherlands regarding retention and secondary use of NDBS. These factors can be taken into account when developing or updating NDBS policies. METHODS: A mixed methods design was used combining an online survey (n = 753), focus groups (6 groups, 37 participants), and individual in-depth interviews (n = 7). The discussed topics included: parental information, obtaining informed consent, support for retention, and support for secondary use. The study population consisted of Dutch-speaking new parents: pregnant women (≥20 weeks) and/or their partner, and parents of at least one child (≤5 years). RESULTS: New parents expressed needs for easily accessible information, adequate communication on the retention and (potential) use of NDBS, clearly described safeguards for privacy, a more active consent process, regulation for the actors conducting NDBS research, and parental involvement in decisions on secondary use. Overall, participants were positive about prolonged retention and different types of secondary use if those needs were met. CONCLUSIONS: While parental involvement is a challenge, our study is an example of gauging parent's perspectives on NDBS policy and contributes to including these perspectives in the current policy discussion on longer retention. Prolonged retention could be a feasible option in the Netherlands if several prerequisites are met. Therefore, implementation studies involving parents are needed.

The value of models in informing resource allocation in colorectal cancer screening: the case of The Netherlands.

In May 2011, the Dutch government decided to implement a national programme for colorectal cancer (CRC) screening using biennial faecal immunochemical test screening between ages 55 and 75. Decision modelling played an important role in informing this decision, as well as in the planning and implementation of the programme afterwards. In this overview, we illustrate the value of models in informing resource allocation in CRC screening using the role that decision modelling has played in the Dutch CRC screening programme as an example.

Pandemic influenza A(H1N1)pdm09 improves vaccination routine in subsequent years: a cohort study from 2009 to 2011.

BACKGROUND: In 2009 the pandemic influenza virus A(H1N1)pdm09 emerged with guidance that people at risk should be vaccinated. It is unclear how this event affected the underlying seasonal vaccination rate in subsequent years. PURPOSE: To investigate the association of pandemic influenza A(H1N1)pdm09 and seasonal flu vaccination status in 2009 with vaccination rates in 2010 and 2011. METHODS: Data were collected in 40 Dutch family practices on patients at risk for influenza during 2009-2011; data analysis was conducted in 2012. RESULTS: A multilevel logistic regression model (n=41,843 patients) adjusted for practice and patient characteristics (age and gender, as well as those patient groups at risk), showed that people who were vaccinated against A(H1N1)pdm09 in 2009 were more likely to have been vaccinated in 2010 (OR 6.02; 95%CI 5.62-6.45, p<.0001). This likelihood was even more for people who were vaccinated against seasonal flu in 2009 (OR 13.83; 95%CI 12.93-14.78, p<.0001). A second analysis on the uptake rate in 2011 (n=39,468 patients) showed that the influence of the vaccination state in 2009 declined after two years, but the diminishing effect was smaller for people vaccinated against A(H1N1)pdm09 than for seasonal flu (OR 5.50; 95%CI 5.13-5.90, p<.0001; OR 10.98; 95%CI 10.26-11.75, p<.0001, respectively). CONCLUSION: Being vaccinated against A(H1N1)pdm09 and seasonal influenza in the pandemic year 2009 enhanced the probability of vaccination in the next year and this was still effective in 2011. This suggests that peoples' vaccination routines were not changed by the rumor around the outbreak of A(H1N1)pdm09, but rather confirmed underlying behavior.

High vaccination rates for seasonal and pandemic (A/H1N1) influenza among healthcare workers in Dutch general practice.

In previous years, the influenza vaccination rate among Dutch general practitioners (GPs) was low (36% during the 2007/2008 season). Since 2008, yearly influenza vaccination has been actively recommended for GPs in The Netherlands. Moreover, in 2009 the Dutch government urged healthcare workers to receive additional vaccination against the pandemic influenza (A/H1N1). The effects of these recommendations are unknown. In February 2010, a questionnaire was mailed to random samples of GPs (n=810) and GP-trainees (n=300). Vaccination rates were determined and motives and barriers for vaccination were assessed. The response rates for GPs and GP-trainees were 83% and 90%, respectively. In total, 63% of the GPs were vaccinated against seasonal influenza and 85% against pandemic (A/H1N1) influenza. For GP-trainees, these percentages were 47% and 77%, respectively. With regard to the medical staff working in the respondents' practices, 60% received the seasonal and 76% the pandemic (A/H1N1) influenza vaccine. Reducing the risk of transmitting the virus to vulnerable patients and the individual's personal protection were the most frequently reported motives for vaccination. Having no medical indication for influenza vaccination and the conviction of being protected against influenza because of frequent professional exposure to the virus were the most frequently mentioned reasons for not being vaccinated. In conclusion, the seasonal influenza vaccination rate among Dutch GPs has risen considerably since the previous survey and the vaccination rate against pandemic (A/H1N1) influenza was very high. Moreover, Dutch GPs were convinced that influenza vaccination will reduce the risk of transmitting the virus to their patients.

Risk factors for acute respiratory tract infections in general practitioner patients in The Netherlands: a case-control study.

BACKGROUND: Acute respiratory tract infections (ARTI) are an important public health problem. Improved identification of risk factors might enable targeted intervention. Therefore we carried out a case-control study with the aim of identifying environmental risk factors for ARTI consultations in the Dutch general population. METHODS: A subset of patients visiting their GP in the period of 2000-2003 with an ARTI (cases) and age-matched controls (visiting for other complaints) were included in a case-control study. They were asked to complete a questionnaire about potential risk factors. Conditional logistic regression was used to calculate odds ratio's (OR) and 95% confidence intervals (CI) to estimate the independent effect of potential risk factors. RESULTS: A total of 493 matched pairs of case and control subjects were enrolled. Exposure to persons with respiratory complaints, both inside and outside the household, was found to be an independent risk factor for visiting a GP with an ARTI (respectively ORadj = 1.9 and ORadj = 3.7). Participants exposed to dampness or mould at home (ORadj=0.5) were significantly less likely to visit their GP. In accordance with the general risk of consultations for ARTI, participants with a laboratory-confirmed ARTI who were exposed to persons with respiratory complaints outside the household were also significantly more likely to visit their GP (ORadj=2.5). CONCLUSION: This study confirmed that heterogeneity in the general population as well as in pathogens causing ARTI makes it complicated to detect associations between potential risk factors and respiratory infections. Whereas it may be difficult to intervene on the risk posed by exposure to persons with respiratory complaints, transmission of ARTI in the general population might be reduced by improved hygienic conditions.

A case-control study of acute respiratory tract infection in general practice patients in The Netherlands.

BACKGROUND: Acute respiratory tract infections (ARTIs) are responsible for considerable morbidity in the community, but little is known about the presence of respiratory pathogens in asymptomatic individuals. We hypothesized that asymptomatic persons could have a subclinical infection and thus act as a source of transmission. METHODS: During the period of 2000-2003, all patients with ARTI who visited their sentinel general practitioner had their data reported to estimate the incidence of ARTI in Dutch general practices. A random selection of these patients (case patients) and an equal number of asymptomatic persons visiting for other complaints (control subjects) were included in a case-control study. Nose and throat swabs of participants were tested for a broad range of pathogens. RESULTS: The overall incidence of ARTI was 545 cases per 10,000 person-years, suggesting that, in the Dutch population, an estimated 900,000 persons annually consult their general practitioner for respiratory complaints. Rhinovirus was most common in case patients (24%), followed by influenza virus type A (11%) and coronavirus (7%). Viruses were detected in 58% of the case patients, beta -hemolytic streptococci group A were detected in 11%, and mixed infections were detected in 3%. Pathogens were detected in approximately 30% of control subjects, particularly in the youngest age groups. CONCLUSION: This study confirms that most ARTIs are viral and supports the reserved policy of prescribing antibiotics. In both case and control subjects, rhinovirus was the most common pathogen. Of bacterial infections, only group A beta-hemolytic streptococci were more common in case patients than in control subjects. Furthermore, we demonstrated that asymptomatic persons might be a neglected source of transmission.

The expected number of hospitalisations and beds needed due to pandemic influenza on a regional level in the Netherlands.

In order to minimise the effects of a potential influenza pandemic on the population, regional authorities in the Netherlands are in the process of development of a plan to be prepared to cope with mass illness and to ensure health care services. The objective of this study is to calculate the expected numbers of hospitalisations and the maximum number of beds needed per day on a regional level. As many uncertainties are involved in this type of studies, we have performed a scenario analysis of the expected number of hospitalisations and beds needed during an influenza pandemic. The analysis gives insight into the impact of the pandemic in terms of how many will be hospitalised, how many beds are needed during the pandemic and in the effect of a possible intervention by therapeutic use of antivirals in terms of hospitalisations and beds needed. It can be concluded that our scenario analysis will be helpful in designing and planning on a regional level.

A prospective, community-based study on virologic assessment among elderly people with and without symptoms of acute respiratory infection.

BACKGROUND/OBJECTIVES: Community-based elderly studies concerning microbiology of acute respiratory infections are scarce. Data on subclinical infections are even totally absent, although asymptomatic persons might act as a source of respiratory infections. METHODS: In a 1-year community-based study, we prospectively investigated the possible virologic cause of acute respiratory infections in 107 symptomatic case episodes and 91 symptom-free control periods. Participants, persons >/=60 years, reported daily the presence of respiratory symptoms in a diary. Virologic assessment was performed by polymerase chain reaction (PCR) and serology. RESULTS: In 58% of the case episodes a pathogen was demonstrated, the most common being rhinoviruses (32%), coronaviruses (17%), and influenzaviruses (7%). The odds ratio for demonstrating a virus in cases with symptoms vs. controls without symptoms was 30.0 (95% confidence interval 10.2-87.6). In 4% of the symptom-free control periods a virus was detected. CONCLUSIONS: This study supports the importance of rhinovirus infections in community-dwelling elderly persons, whereas asymptomatic elderly persons can also harbor pathogens as detected by PCR, and thus might be a source of infection for their environment.

Pandemic influenza and healthcare demand in the Netherlands: scenario analysis.

In accordance with World Health Organization guidelines, the Dutch Ministry of Health, Welfare and Sports designed a national plan to minimize effects of pandemic influenza. Within the scope of the Dutch pandemic preparedness plan, we were asked to estimate the magnitude of the problem in terms of the number of hospitalizations and deaths during an influenza pandemic. Using scenario analysis, we also examined the potential effects of intervention options. We describe and compare the scenarios developed to understand the potential impact of a pandemic (i.e., illness, hospitalizations, deaths), various interventions, and critical model parameters. Scenario analysis is a helpful tool for making policy decisions about the design and planning of outbreak control management on a national, regional, or local level.

Pharmacoeconomics of elderly vaccination against invasive pneumococcal infections: cost-effectiveness analyses and implications for The Netherlands.

We performed a review of cost-effectiveness of elderly pneumococcal vaccination to prevent invasive disease. It concerns studies in the USA, Canada, Netherlands and Spain and a multinational study of five European countries. Cost-effectiveness of elderly vaccination against invasive pneumococcal infections varies from cost-saving to EUR 33,000 per life-year gained. The Dutch study estimates cost-effectiveness at EUR 10,100 per life-year gained (price level: 1995). This is below the level that has recently been defined for treatment of high cholesterol (EUR 20,000 per life-year gained) and may therefore be considered as favorable. Almost all studies base their estimate of vaccine efficacy on the same case-control study from the USA. We identify a need for a systematic review on the efficacy of the pneumococcal vaccine. Also, we suggest further analysis with respect to potential effects on cost-effectiveness of extended influenza vaccination for the Dutch elderly in recent years and inclusion of pneumococcal re-vaccination. Pending this additional information, we conclude that cost-effectiveness of vaccination against invasive pneumococcal infections for Dutch elderly is favorable (as in several other countries) and justifies implementation from a pharmacoeconomic point of view.

Pharmacoeconomics of influenza vaccination for healthy working adults: reviewing the available evidence.

A favourable pharmacoeconomic profile has been well established for influenza vaccination in the elderly. For employers relevant benefits seem to exist for vaccinating healthy working adults to avert absenteeism and related production losses. From a pharmacoeconomic point of view it is relevant to consider whether societal benefits of vaccination for healthy working adults is worthwhile given the costs of vaccination for the community. We searched Medline and Embase using the key words influenza (vaccination) in combination with cost, cost-benefit, cost-effectiveness, efficiency, economic evaluation, health-policy and pharmacoeconomics. From this primary search, we selected 11 studies concerned with the group of healthy working adults. We reviewed these studies according to several criteria: benefit-to-cost (B/C) ratio;vaccine effectiveness, influenza incidence, number of days of work absence due to illness; and relative cost of the vaccine. Three studies on vaccinating healthy working adults found costs exceeding the benefits (B/C-ratio <1). The remaining eight pharmacoeconomic studies found a B/C-ratio of almost two or more. Cost savings are strongly related to the inclusion of indirect benefits related to averted production losses. After exclusion of indirect costs and benefits of production gains/losses, only one of the eight studies remains cost saving. Considering the available pharmacoeconomic evidence, vaccination of healthy working adults in Western countries may be an intervention with favourable cost-effectiveness and cost-saving potentials if indirect benefits of averted production losses are included. Excluding indirect benefits and costs of production losses/gains, cost-saving potentials are limited. Recent international guidelines for pharmacoeconomic research advise the inclusion of production gains and losses in the preferred societal perspective. Hence, on the basis of the available evidence, influenza vaccination of healthy working adults may be recommended from pharmacoeconomic point of view. Pharmacoeconomics do, however, present only one argument for consideration aside from ethical issues, budgetary limits and psychosocial aspects.