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DNA barcoding is an important molecular methodology for species identification that was developed over the last two decades and it should be covered in the biology bachelor curriculum. Here, we present an example of DNA barcoding by sequencing a segment of the 28S nuclear ribosomal large subunit rRNA gene of wild mushrooms and framing the education in a project form for undergraduate students in biology. Students perform this project in 6-8 weeks, which also includes preparing a poster, writing a report and presenting a paper related to the work in a journal club format. First, fieldwork in the Netherlands was carried out, during which students collected mushrooms under supervision of a professional mycologist with the goal to (a) verify morphologically based identifications with a molecular method and (b) assess phylogenetic relationships of the different species collected. Next, DNA extractions and quantitation were performed, PCR amplification was done, and samples were sent out for Sanger sequencing. Students aligned and analyzed the sequences using BLAST and Geneious and subsequently created a phylogenetic tree. In case of collecting DNA barcodes of an earlier sequenced species, students could upload the data to a repository established for facilitation of future research projects. The method described is very robust, reagents and equipment are readily available, and costs are relatively low. In addition, the results can be compared to published fungal phylogenetic trees.

Background: Cystitis is commonly treated with antibiotics, although non-antibiotic options could be considered for healthy non-pregnant women. Shared decision making (SDM) can be used in cystitis management to discuss the various treatment options but is not frequently applied in general practice. Aim: To identify barriers and facilitators for applying SDM in cystitis management in general practice. Design & setting: Qualitative explorative research in general practice with healthcare professionals (HCPs; GPs and GP assistants) and healthy non-pregnant women with a recent history of cystitis (patients). Method: Individual semi-structured interviews were conducted between May and October 2022. We applied a combination of thematic and framework analysis. Results: Ten GPs, seven GP assistants, and 15 patients were interviewed. We identified the following three main barriers and one key facilitator: (1) applying SDM is deemed inefficient; (2) HCPs assume that patients expect antibiotic treatment and some HCPs consider non-antibiotic treatment inferior; (3) patients are largely unaware of the various non-antibiotic treatment options for cystitis; and (4) HCPs recognise some benefits of applying SDM in cystitis management, including reduced antibiotic use and improved patient empowerment, and patients appreciate involvement in treatment decisions, but preferences for SDM vary. Conclusion: SDM is infrequently applied in cystitis treatment in general practice owing to the current focus on efficient cystitis management that omits patient contact, HCPs' perceptions, and patient unawareness. Nevertheless, both HCPs and patients recognise the long-term benefits of applying SDM in cystitis management. Our findings facilitate the development of tailored interventions to increase the application of SDM, which should be co-created with HCPs and patients, and fit into the current efficient cystitis management. [ABSTRACT FROM AUTHOR]

Background: In out-of-hours primary care (OHS-PC), semi-automatic decision support tools are often used during telephone triage. In the Netherlands, the Netherlands Triage Standard (NTS) is used. The NTS is mainly expert-based and evidence on the diagnostic accuracy of the NTS' urgency allocation against clinically relevant outcomes for patients calling with shortness of breath (SOB) is lacking. Methods: We included data from adults (≥18 years) who contacted two large Dutch OHS-PC centres for SOB between 1 September 2020 and 31 August 2021 and whose follow-up data about final diagnosis could be retrieved from their own general practitioner (GP). The diagnostic accuracy (sensitivity and specificity with corresponding 95% confidence intervals (CI)) of the NTS' urgency levels (high (U1/U2) versus low (U3/U4/U5) and 'final' urgency levels (including overruling of the urgency by triage nurses or supervising general practitioners (GPs)) was determined with life-threatening events (LTEs) as the reference. LTEs included, amongst others, acute coronary syndrome, pulmonary embolism, acute heart failure and severe pneumonia. Results: Out of 2012 eligible triage calls, we could include 1833 adults with SOB who called the OHS-PC, mean age 53.3 (SD 21.5) years, 55.5% female, and 16.6% showed to have had a LTE. Most often severe COVID-19 infection (6.0%), acute heart failure (2.6%), severe COPD exacerbation (2.1%) or severe pneumonia (1.9%). The NTS urgency level had a sensitivity of 0.56 (95% CI 0.50–0.61) and specificity of 0.61 (95% CI 0.58–0.63). Overruling of the NTS' urgency allocation by triage nurses and/or supervising GPs did not impact sensitivity (0.56 vs. 0.54, p = 0.458) but slightly improved specificity (0.61 vs. 0.65, p < 0.001). Conclusions: The semi-automatic decision support tool NTS performs poorly with respect to safety (sensitivity) and efficiency (specificity) of urgency allocation in adults calling Dutch OHS-PC with SOB. There is room for improvement of telephone triage in patients calling OHS-PC with SOB. Trial registration: The Netherlands Trial Register, number: NL9682. [ABSTRACT FROM AUTHOR]

Objective: There currently is no disease-modifying therapy for spinocerebellar ataxia type 1 (SCA1). Genetic interventions, such as RNA-based therapies, are being developed but those currently available are very expensive. Early evaluation of costs and benefits is, therefore, crucial. By developing a health economic model, we aimed to provide first insights into the potential cost-effectiveness of RNA-based therapies for SCA1 in the Netherlands. Methods: We simulated disease progression of individuals with SCA1 using a patient-level state-transition model. Five hypothetical treatment strategies with different start and endpoints and level of effectiveness (5–50% reduction in disease progression) were evaluated. Consequences of each strategy were measured in terms of quality-adjusted life years (QALYs), survival, healthcare costs, and maximum costs to be cost effective. Results: Most QALYs (6.68) are gained when therapy starts during the pre-ataxic stage and continues during the entire disease course. Incremental costs are lowest (− €14,048) if therapy is stopped when the severe ataxia stage is reached. The maximum costs per year to be cost-effective are €19,630 in the "stop after moderate ataxia stage" strategy at 50% effectiveness. Discussion: Our model indicates that the maximum price for a hypothetical therapy to be cost-effective is considerably lower than currently available RNA-based therapies. Most value for money can be gained by slowing progression in the early and moderate stages of SCA1 and by stopping therapy upon entering the severe ataxia stage. To allow for such a strategy, it is crucial to identify individuals in early stages of disease, preferably just before symptom onset. [ABSTRACT FROM AUTHOR]

Background: Pulse oximetry as a home or remote monitoring tool accelerated during the pandemic for patients with COVID-19, but evidence on its use is lacking. Aim: To assess the feasibility of home monitoring by pulse oximetry of patients aged ≥40 years with cardiovascular comorbidity and moderate-to-severe COVID-19. Design and setting: A primary care-based, open, pilot randomised controlled trial, with nested process evaluation, was undertaken in the Netherlands. Method: From November 2020 to June 2021, eligible patients presenting to one of 14 participating Dutch general practices were randomly allocated to regular measurement of peripheral oxygen saturation (at least three SpO2 measurements per day for 14 days) with a validated pulse oximeter or usual care. Results: All 41 participants (21 intervention, 20 usual care) completed the 45-day follow-up period. Overall, the intervention group performed 97.6% of protocolised measurements; the median daily measurement per participant was 2.7 (interquartile range 1–4). Hypoxemia (SpO2 <94%) was reported in 10 participants (in 52 measurements); of those, six consulted the GP as instructed. Participants reported a high feeling of safety (0–100 visual analogue scale): 71.8 for the intervention group versus 59.8 for the control (P = 0.09). Primary care consultations were similar across groups: 50 for the intervention versus 51 for the control. Eleven visits by 10 participants were made to the emergency department (eight from the intervention group versus three from usual care), of which six participants were hospitalised (five intervention versus one usual care). No participants were admitted to the intensive care unit or died during follow-up. Conclusion: Home monitoring of patients with moderate-to-severe COVID-19 by pulse oximetry appeared feasible; adherence was high, patients reported a high feeling of safety, while the number of primary care consultations remained similar to usual care. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is the main cause of death in children around the world. The last Dutch epidemiological study described the incidence over 10 years ago. Mechanism of injury seems to change with the age of the child, therefore it is important to appreciate different age groups. To be able to lower the impact of childhood TBI, an understanding of current incidence, mechanism of injury and outcome is necessary. A nationwide retrospective cohort study was conducted. The Dutch National Trauma Database was used to identify all patients 18 years and younger who were admitted to a Dutch hospital with moderate-severe TBI (Abbreviated Injury Score≥3) in the Netherlands, from January 2015 until December 2017. Subanalyses were done for different age groups. In total, 1413 patients were included, of whom 5% died. The incidence rate of moderate-severe TBI was 14/100,000 person years. Median age was 10.4 years. Largest age group was patients <5 years, incidence rate was highest in patients ≥16 years. Falls were more common than road traffic accidents (RTA), but RTAs occurred far more frequently amongst children over 10. RTAs predominantly consisted of bicycle accidents. Mortality rates increased from youngest to oldest age groups, as did the chances of a Glasgow Outcome Scale score of 3. Paediatric moderate-severe TBI represents a significant problem in the Netherlands. Falls are the most common mechanism of injury amongst younger children and RTAs amongst older children. Unique for the Netherlands is the vast amount of bicycle accident related injuries. • Traumatic brain injury main cause of death in children globally. • Incidence rate in the Netherlands 14/100,000 person years from January 2015 until December 2017. • 5% of these children died, mortality rates increase with age as did chances of being dependent on others in daily life. • Falls were the most common trauma mechanism, followed by road traffic accidents. • Bicycle accidents were by far the most common amongst road traffic accidents. [ABSTRACT FROM AUTHOR]

Introduction: Recent reports have highlighted the impact of the COVID-19 pandemic on the incidence of infectious disease illnesses and antibiotic use. This study investigates the effect of the pandemic on childhood incidence of otitis media (OM) and associated antibiotic prescribing in a large primary care-based cohort in the Netherlands. Material and Methods: Retrospective observational cohort study using routine health care data from the Julius General Practitioners' Network (JGPN). All children aged 0-12 registered in 62 practices before the COVID-19 pandemic (1 March 2019 - 29 February 2020) and/or during the pandemic (1 March 2020 - 28 February 2021) were included. Data on acute otitis media (AOM), otitis media with effusion (OME), ear discharge episodes and associated antibiotic prescriptions were extracted. Incidence rates per 1,000 child years (IR), incidence rate ratios (IRR) and incidence rate differences (IRD) were compared between the two study periods. Results: OM episodes declined considerably during the COVID-19 pandemic: IR pre-COVID-19 vs COVID-19 for AOM 73.7 vs 27.1 [IRR 0.37]; for OME 9.6 vs 4.1 [IRR 0.43]; and for ear discharge 12.6 vs 5.8 [IRR 0.46]. The absolute number of AOM episodes in which oral antibiotics were prescribed declined accordingly (IRD pre-COVID-19 vs COVID-19: -22.4 per 1,000 child years), but the proportion of AOM episodes with antibiotic prescription was similar in both periods (47% vs 46%, respectively). Discussion: GP consultation for AOM, OME and ear discharge declined by 63%, 57% and 54% respectively in the Netherlands during the COVID-19 pandemic. Similar antibiotic prescription rates before and during the pandemic indicate that the case-mix presenting to primary care did not considerably change. Our data therefore suggest a true decline as a consequence of infection control measures introduced during the pandemic. [ABSTRACT FROM AUTHOR]

This study combines insights from contact theory and social capital literature to study how ethnic diversity at work is associated to ethnic tolerance. It is argued that workplace ethnic diversity is related to ethnic tolerance in two ways: through interethnic contact and through interethnic social resources. The interrelation between these two mechanisms is also considered. The study relies on unique workplace survey data from the Netherlands (N = 3800) with information on ethnic tolerance, measured as support for immigrant entitlements. The results show that ethnic diversity in the workplace is positively related to interethnic contact and interethnic resources at work, and both of these are positively related to ethnic tolerance. However, the initial positive effect of interethnic contact on support for immigrant entitlements is mediated by interethnic resources, thereby showing that the interethnic resources mechanism is more insightful as to how ethnically diverse workplaces matter for ethnic tolerance. [ABSTRACT FROM AUTHOR]

Background: Acute otitis media (AOM) is among the most common paediatric conditions managed in primary care. Most recent estimates of the cost of AOM date from a decade ago and lack a full societal perspective. We therefore explored the societal cost of childhood AOM in the Netherlands within the setting of a trial comparing the effectiveness of an intervention aimed at educating general practitioners (GPs) about pain management in AOM compared to usual care.Methods: Economic analysis alongside a cluster randomised controlled trial conducted between February 2015 and May 2018 in 37 practices (94 GPs). In total, 224 children with AOM were included of which 223 (99%) completed the trial (intervention: n = 94; control: n = 129). The cost of AOM due to health care costs, patient and family costs, and productivity losses by parent caregivers were retrieved from study diaries and primary care electronic health records, during 28-day follow-up. We calculated mean cost (€ and $) per AOM episode per patient with standard deviations (SD, in €) regardless of study group assignment because there was no clinical effect of the trial intervention. In sensitivity analysis, we calculated cost in the intervention and usual care group, after exclusion of extreme outliers.Results: Mean total AOM cost per patient were €565.93 or $638.78 (SD €1071.01); nearly 90% of these costs were due to productivity losses experienced by parents. After exclusion of outliers, AOM cost was €526.70 or $594.50 (SD €987.96) and similar in the intervention and usual care groups: €516.10 or $582.53 (SD €949.69) and €534.55 or $603.36 (SD €920.55) respectively.Conclusions: At €566 or $639 per episode, societal cost of AOM is higher than previously known and mainly driven by productivity losses by children's parents. Considering its high incidence, AOM poses a significant economic burden that extends beyond direct medical costs.Trial Registration: Netherlands Trial Register no. NTR4920: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4920 . [ABSTRACT FROM AUTHOR]

Background: Pain management in acute otitis media (AOM) is often suboptimal, potentially leading to unnecessary discomfort, GP reconsultation, and antibiotic prescribing.Aim: To assess the effectiveness of a GP-targeted educational intervention to improve pain management in children with AOM.Design and Setting: Pragmatic, cluster randomised controlled trial (RCT). GPs in 37 practices (intervention n = 19; control n = 18) across the Netherlands recruited 224 children with GP-confirmed AOM and ear pain (intervention n = 94; control n = 130) between February 2015 and May 2018.Method: GPs in practices allocated to the intervention group were trained (online and face-to-face) to discuss pain management with parents using an information leaflet, and prompted to prescribe weight-appropriate dosed paracetamol. Ibuprofen was additionally prescribed if pain control was still insufficient. GPs in the control group provided usual care.Results: Mean ear pain scores over the first 3 days were similar between groups (4.66 versus 4.36; adjusted mean difference = -0.05; 95% confidence intervals [CI] = -0.93 to 0.83), whereas analgesic use, in particular ibuprofen, was higher in the intervention group. The total number of antibiotic prescriptions during the 28-day follow-up was similar (mean rate 0.43 versus 0.47; adjusted rate ratio [aRR] 0.97; 95% CI = 0.68 to 1.38). Parents of children in the intervention group were more likely to reconsult for AOM-related complaints (mean rate 0.70 versus 0.41; aRR 1.73; 95% CI = 1.14 to 2.62).Conclusion: An intervention aimed at improving pain management for AOM increases analgesic use, particularly ibuprofen, but does not provide symptomatic benefit. GPs are advised to carefully weigh the potential benefits of ibuprofen against its possible harms. [ABSTRACT FROM AUTHOR]

To assess the performances of three commonly used antigen rapid diagnostic tests used as self-tests in asymptomatic individuals in the Omicron period. We performed a cross-sectional diagnostic test accuracy study in the Omicron period in three public health service COVID-19 test sites in the Netherlands, including 3600 asymptomatic individuals aged ≥ 16 years presenting for SARS-CoV-2 testing for any reason except confirmatory testing after a positive self-test. Participants were sampled for RT-PCR (reference test) and received one self-test (either Acon Flowflex [Flowflex], MP Biomedicals (MPBio), or Siemens-Healthineers CLINITEST [CLINITEST]) to perform unsupervised at home. Diagnostic accuracies of each self-test were calculated. Overall sensitivities were 27.5% (95% CI, 21.3–34.3%) for Flowflex, 20.9% (13.9–29.4%) for MPBio, and 25.6% (19.1–33.1%) for CLINITEST. After applying a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL), sensitivities increased to 48.3% (37.6–59.2%), 37.8% (22.5–55.2%), and 40.0% (29.5–51.2%), respectively. Specificities were >99% for all tests in most analyses. The sensitivities of three commonly used SARS-CoV-2 antigen rapid diagnostic tests when used as self-tests in asymptomatic individuals in the Omicron period were very low. Antigen rapid diagnostic test self-testing in asymptomatic individuals may only detect a minority of infections at that point in time. Repeated self-testing in case of a negative self-test is advocated to improve the diagnostic yield, and individuals should be advised to re-test when symptoms develop. [ABSTRACT FROM AUTHOR]

Background: Most estimates of the incidence of acute otitis media (AOM) are based on general practitioner (GP) or pediatrician diagnoses. It is likely that these figures underestimate the community incidence of AOM since parents do not visit their doctor every time their child suffers from acute ear symptoms. The impact of these symptom episodes may be substantial since they affect the child’s quality of life and parents’ productivity. Methods: To determine AOM symptoms in the community, we measured parent-reported AOM symptoms daily for 12 consecutive months in 1,260 children participating in a prospective birth cohort in the Netherlands. The mean age of these children was at study enrollment 0.9 months (standard deviation 0.6). A parent-reported AOM symptom episode was defined as fever (temperature 38˚C or above) plus at least one of the following symptoms: ear pain and ear discharge. These febrile AOM symptom episodes were linked to GP-consultations and diagnoses in the GP electronic health records. Results: With an estimated 624 parent-reported symptom episodes per 1,000 child-years (95% CI: 577 to 674) incidence of febrile AOM symptoms during the child’s first year is high. The GP was consulted in half of these symptom episodes and AOM was diagnosed in 49% of these consultations. Conclusions and Relevance: The incidence of febrile AOM symptoms in the first year of life is high in Dutch children and leads to a GP-consultation in only half of the cases. This suggests that AOM symptomatology in the community is underestimated when focusing on GP-diagnosed AOM episodes alone, since a considerable proportion of febrile AOM symptom episodes are treated symptomatically by parents at home and do not come to the attention of the GP. Having data on community AOM symptomatology available for each country is important when the potential impact of preventive and therapeutic interventions for AOM are studied. [ABSTRACT FROM AUTHOR]

Background A revised primary care guideline on acute rhinosinusitis (ARS) has been introduced in the Netherlands in 2005, which advocates a more judicious use of antibiotics. Objective To investigate whether consultation and prescription rates for ARS in adults changed over recent years in order to provide information on family physicians' behaviour before and after introduction of the revised guideline. Methods Retrospective cohort study. All adult patients within the computerized database of Utrecht Primary Care Research Network over the years 2000–09 were included. Clinical diagnoses of ARS were recorded according to the International Classification of Primary Care codes (R75 and/or R09) and drug prescriptions according to the Anatomical Therapeutic Chemical Classification System. Results ARS consultation rates revealed a stable pattern, with an average consultation rate of 29 episodes per 1000 person-years. From 2000 to 2005, the antibiotic prescription rate increased from 56 to 62 prescriptions per 100 episodes (P value for time trend <0.05). From 2005 onwards, the antibiotic prescription rate decreased to 56 per 100 episodes in 2009 [rate difference (RD): −6, 95% confidence interval (CI): −10 to −1; P value for difference between 2000–05 and 2005–09 <0.05]. From 2005 to 2009, intranasal corticosteroid (INCS) prescription rate increased from 20 to 31 prescriptions per 100 episodes (RD: 11, 95% CI: 7 to 15; P value for difference between 2000–05 and 2005–09 <0.01). Oral corticosteroid prescription and referral rates remained low. Conclusions Despite strong guideline recommendations to restrict the use of antibiotics and INCS, we found only a modest decrease in antibiotic prescription rates, whereas INCS prescription rates even increased. [ABSTRACT FROM PUBLISHER]

In 2020, the COVID-19 pandemic brought dramatic changes in the delivery of primary health care across the world, presumably changing the number of consultations for infectious diseases and antibiotic use. We aimed to assess the impact of the pandemic on infections and antibiotic prescribing in Dutch primary care. All patients included in the routine health care database of the Julius General Practitioners' Network were followed from March through May 2019 (n = 389,708) and March through May 2020 (n = 405,688). We extracted data on consultations for respiratory/ear, urinary tract, gastrointestinal and skin infections using the International Classification of Primary Care (ICPC) codes. These consultations were combined in disease episodes and linked to antibiotic prescriptions. The numbers of infectious disease episodes (total and those treated with antibiotics), complications, and antibiotic prescription rates (i.e., proportion of episodes treated with antibiotics) were calculated and compared between the study periods in 2019 and 2020. Fewer episodes were observed during the pandemic months than in the same months in 2019 for both the four infectious disease entities and complications such as pneumonia, mastoiditis and pyelonephritis. The largest decline was seen for gastrointestinal infections (relative risk (RR), 0.54; confidence interval (CI), 0.51 to 0.58) and skin infections (RR, 0.71; CI, 0.67 to 0.75). The number of episodes treated with antibiotics declined as well, with the largest decrease seen for respiratory/ear infections (RR, 0.54; CI, 0.52 to 0.58). The antibiotic prescription rate for respiratory/ear infections declined from 21% to 13% (difference −8.0% (CI, −8.8 to −7.2)), yet the prescription rates for other infectious disease entities remained similar or increased slightly. The decreases in primary care infectious disease episodes and antibiotic use were most pronounced in weeks 15–19, mid-COVID-19 wave, after an initial peak in respiratory/ear infection presentation in week 11, the first week of lock-down. In conclusion, our findings indicate that the COVID-19 pandemic has had profound effects on the presentation of infectious disease episodes and antibiotic use in primary care in the Netherlands. Consequently, the number of infectious disease episodes treated with antibiotics decreased. We found no evidence of an increase in complications. [ABSTRACT FROM AUTHOR]

Despite significant efforts, the COVID-19 pandemic has put enormous pressure on health care systems around the world, threatening the quality of patient care. Telemonitoring offers the opportunity to carefully monitor patients with a confirmed or suspected case of COVID-19 from home and allows for the timely identification of worsening symptoms. Additionally, it may decrease the number of hospital visits and admissions, thereby reducing the use of scarce resources, optimizing health care capacity, and minimizing the risk of viral transmission. In this paper, we present a COVID-19 telemonitoring care pathway developed at a tertiary care hospital in the Netherlands, which combined the monitoring of vital parameters with video consultations for adequate clinical assessment. Additionally, we report a series of medical, scientific, organizational, and ethical recommendations that may be used as a guide for the design and implementation of telemonitoring pathways for COVID-19 and other diseases worldwide. [ABSTRACT FROM AUTHOR]

[Display omitted] • It has been suggested that patients with diabetes who experience an ACS present with a broad variety of symptoms which could hamper the urgency allocation during telephone triage. • Among males and females who called OHS-PC with acute chest discomfort, those with diabetes versus those without: • Reported relatively lower rates of chest pain and higher rates of shortness of breath; • Did not receive a high urgency more often; • Had higher odds for ACS and 'ACS or other LTE'. • Triage nurses at the OHS-PC should always ask for diabetes in callers with acute chest discomfort as this helps triage given the substantial increase in risk of ACS and 'ACS or other LTE'. We investigated the differences in prevalence of acute coronary syndrome (ACS) by presence versus absence of diabetes in males and females with chest discomfort who called out-of-hours primary care (OHS-PC). A cross-sectional study performed in the Netherlands. Patients who called the OHS-PC in the Utrecht region, the Netherlands between 2014 and 2017 with acute chest discomfort were included. We compared those with diabetes with those without diabetes. Multivariable logistic regression was used to determine the relation between diabetes and (i) high urgency allocation and (ii) ACS. Of the 2,195 callers with acute chest discomfort, 180 (8.2%) reported having diabetes. ACS was present in 15.3% of males (22.0% in those with diabetes) and 8.4% of females (18.8% in those with diabetes). Callers with diabetes did not receive a high urgency more frequently (74.4% vs. 67.8% (OR: 1.38; 95% CI 0.98–1.96). However, such callers had a higher odds for ACS (OR: 2.17; 95% CI 1.47–3.19). These differences were similar for females and males. Diabetes holds promise as diagnostic factor in callers to OHS-PC with chest discomfort. It might help triage in this setting given the increased risk of ACS in those with diabetes. [ABSTRACT FROM AUTHOR]

Background: Acute remote home monitoring of acutely ill patients with COVID-19 holds potential for early detection of deterioration and thus subsequentearly intervention that may prevent or mitigate progression to severe illness and need for respiratory support. Our aim was to describe common features of acute remote home monitoring programs for acutely ill patients with COVID-19 in the Netherlands., Methods: We performed literature searches (both grey and academic) between 1st March 2020 and 1st March 2023 to identify Dutch acute remote home monitoring initiatives, excluding studies on early hospital discharge. From the available protocols, we extracted relevant information on patient eligibility, organization of acute remote home monitoring and home management., Results: We identified and approached ten acute remote home monitoring initiatives for information regarding their used protocols. Seven out of ten protocols were retrieved and assessed. All initiatives focused on adult patients with COVID-19 who where at risk of developing severe COVID-19, and all initiatives provided close follow-up through remote home monitoring using medically certified pulse oximeters. Daily measurements included peripheral oxygen saturation (all initiatives, n = 7), body temperature (n = 6), heart frequency per minute (n = 4) and breathing rate per minute (n = 4). For follow-up and review of measured values, in most initiatives (n = 6) the physician (general practitioner or hospital physician) in charge was supported by a dedicated monitoring center. In 5 out of 7 initiatives, the general practitioner (GP) was responsible for supervising the patients and monitoring staff., Conclusion: The acute remote home monitoring initiatives that emerged in the Netherlands during the first wave of the COVID-19 pandemic were similarly organized. Common building blocks for home monitoring include daily check of peripheral oxygen saturation, monitoring through a dedicated remote monitoring center alongside healthcare personnel and a supervising physician., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in compliance with applicable laws and regulations, including the World Health Organization’s “Code of Conduct for Responsible Research,” and the EU GDPR (General Data Protection Regulation). This study does not fall under the scope of the Dutch Medical Research Involving Human Subjects Act (WMO). It therefore does not require approval from an accredited medical ethics committee in the Netherlands. Ethical review was waived by the Medical Ethics Review Committee Utrecht, the waiver of this study is registered under 22–482. However, in the UMC Utrecht, an independent quality check has been carried out to ensure compliance with legislation and regulations (regarding data management, privacy aspects and legal aspects). Informed consent was not taken because the EU GDPR does not apply, since no personal data is collected. Informed consent procedure was waived by the Medical Ethics Review Committee Utrecht, the waiver of this study is registered under 22–482. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: There is a paucity of prognostic models for COVID-19 that are usable for in-office patient assessment in general practice (GP)., Objectives: To develop and validate a risk prediction model for hospital admission with readily available predictors., Methods: A retrospective cohort study linking GP records from 8 COVID-19 centres and 55 general practices in the Netherlands to hospital admission records. The development cohort spanned March to June 2020, the validation cohort March to June 2021. The primary outcome was hospital admission within 14 days. We used geographic leave-region-out cross-validation in the development cohort and temporal validation in the validation cohort., Results: In the development cohort, 4,806 adult patients with COVID-19 consulted their GP (median age 56, 56% female); in the validation cohort 830 patients did (median age 56, 52% female). In the development and validation cohort respectively, 292 (6.1%) and 126 (15.2%) were admitted to the hospital within 14 days, respectively. A logistic regression model based on sex, smoking, symptoms, vital signs and comorbidities predicted hospital admission with a c-index of 0.84 (95% CI 0.83 to 0.86) at geographic cross-validation and 0.79 (95% CI 0.74 to 0.83) at temporal validation, and was reasonably well calibrated (intercept -0.08, 95% CI -0.98 to 0.52, slope 0.89, 95% CI 0.71 to 1.07 at geographic cross-validation and intercept 0.02, 95% CI -0.21 to 0.24, slope 0.82, 95% CI 0.64 to 1.00 at temporal validation)., Conclusion: We derived a risk model using readily available variables at GP assessment to predict hospital admission for COVID-19. It performed accurately across regions and waves. Further validation on cohorts with acquired immunity and newer SARS-CoV-2 variants is recommended.

Background: Anecdotal reports suggest that missed diagnosis in general practice during the first wave of the COVID-19 pandemic contributed to a drop in life-threatening events (LTEs) detected in hospitals., Objectives: To investigate the impact of the COVID-19 pandemic on the accuracy of urgency allocation by telephone triage of patients with shortness of breath and/or chest discomfort in out-of-hours primary care (OHS-PC). Accuracy is defined as the correct allocation of high urgency to patients with LTEs and low urgency to those without., Methods: Retrospective observational study with data from callers contacting OHS-PC for shortness of breath and/or chest discomfort, between 1 March and 1 June 2019 (pre-pandemic) and 1 March to 1 June 2020 (first wave COVID-19 pandemic). Sensitivity and specificity of telephone urgency allocation were compared during both periods with LTEs, including acute coronary syndrome, and pulmonary embolism, as the reference., Results: 3,064 adults (1,840 COVID-19 pandemic and 1,224 pre-pandemic, p  < 0.001) were included in the study. The sensitivity of urgency allocation was similar during and before the COVID-19 pandemic (0.68, 95% CI 0.59 to 0.75 vs. 0.68, 95% CI 0.60 to 0.75, p  = 0.944). Specificity was slightly higher during the COVID-19 pandemic (0.52, 95% CI 0.50 to 0.55 vs. 0.45, 95% CI 0.42 to 0.48, p  < 0.001)., Conclusion: Despite a surge in calls from adults with shortness of breath and/or chest discomfort during the COVID-19 pandemic, the accuracy of telephone triage for LTEs in OHS-PC remained similar to the pre-pandemic era. Improvement of telephone triage seems necessary in both periods.

Background: Current guidance suggests oral antibiotics can be considered for children with acute otitis media (AOM) and ear discharge, but there is an absence of evidence regarding the relative effectiveness of antibiotic-corticosteroid eardrops., Aim: To establish whether antibiotic-corticosteroid eardrops are non-inferior to oral antibiotics in children with AOM and ear discharge., Design and Setting: Open randomized controlled non-inferiority trial set in Dutch primary care., Methods: Children were randomized to hydrocortisone-bacitracin-colistin eardrops (five drops, three times per day in the discharging ear(s)) or amoxicillin suspension (50 mg per kilogram of body weight per day, divided over three doses administered orally) for 7 days. The primary outcome was the proportion of children with resolution of ear pain and fever at day 3., Results: Between December 2017 and March 2023, 58 of the planned 350 children were recruited due to slow accrual for various reasons. Children assigned to eardrops (n = 26) had lower resolution rates of ear pain and fever at 3 days compared to those receiving oral antibiotics (n = 31): 42% vs 65%; adjusted risk difference 20.3%, 95% confidence interval -5.3% to 41.9%), longer parent-reported ear discharge (6 vs 3 days; P = .04), and slightly higher mean ear pain scores (Likert scale 0-6) over days 1-3 (2.1 vs 1.4, P = .02), but received fewer oral antibiotic courses in 3months (11 for 25 children vs 33 for 30 children), and had less GI upset and rash (12% vs 32% and 8% vs 16%, respectively)., Conclusion: Early termination stopped us from determining non-inferiority of antibiotic-corticosteroid eardrops. Our limited data, requiring confirmation, suggest that oral antibiotics may be more effective than antibiotic-corticosteroid eardrops in resolving symptoms and shortening the duration of ear discharge., (© The Author(s) 2024. Published by Oxford University Press.)

Importance: Atherogenesis starts during childhood, making childhood and adolescence an important window of opportunity to prevent atherosclerotic cardiovascular disease later in life., Objective: To identify early-life risk factors for preclinical atherosclerosis in adolescence., Design, Setting, and Participants: This cohort study is part of the ongoing Wheezing Illness Study in Leidsche Rijn (WHISTLER) prospective birth cohort study, which includes 3005 healthy newborns born between December 2001 and December 2012 in the Leidsche Rijn area of Utrecht, the Netherlands. Eligible participants included those from the WHISTLER cohort who visited the clinic between March 2019 and October 2020 for adolescent follow-up. This study's analyses were performed in January 2024., Exposures: Early-life growth was assessed at birth to 6 months, 5 years, and 12 to 16 years. Abdominal ultrasonography determined abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) depth. Blood pressure (BP) percentiles and body mass index (BMI) z scores were used., Main Outcomes and Measures: Carotid ultrasonography was performed at age 12 to 16 years to assess carotid intima-media thickness (cIMT) and the distensibility coefficient (DC), established measures of preclinical atherosclerosis. Multivariable linear regression models were used to identify early-life risk factors for cIMT and DC in adolescence., Results: In total, 232 adolescents (median [IQR] age, 14.9 [13.7-15.8] years; 121 female [52.2%]) were included. More postnatal weight gain (B = 12.34; 95% CI, 2.39 to 22.39), higher systolic BP at 5 years (B = 0.52; 95% CI, 0.02 to 1.01), more VAT at 5 years (B = 3.48; 95% CI, 1.55 to 5.40), and a larger change in VAT between 5 and 12 to 16 years (B = 3.13; 95% CI, 1.87 to 4.39) were associated with a higher cIMT in adolescence. A higher BMI (B = -2.70, 95% CI,-4.59 to -0.80) and VAT at 5 years (B = -0.56; 95% CI, -0.87 to -0.25), as well as a larger change in BMI between 5 and 12 to 16 years (B = -3.63; 95% CI, -5.66 to -1.60) were associated with a higher carotid stiffness in adolescence. On the contrary, a larger change in SAT between 5 and 12 to 16 years (B = 0.37; 95% CI, 0.16 to 0.58) was associated with a higher carotid DC in adolescence., Conclusions and Relevance: In this cohort study of 232 participants, early-life growth parameters, and particularly abdominal VAT development, were associated with a higher cIMT and carotid stiffness in adolescence. These findings suggest that assessment of adipose tissue development during childhood can aid characterization of lifetime risk trajectories and tailoring of cardiovascular prevention and risk management strategies.

Background: People with chronic kidney disease (CKD) are at high risk of polypharmacy. However, no previous study has investigated international prescribing patterns in this group. This article aims to examine prescribing and polypharmacy patterns among older people with advanced CKD across the countries involved in the European Quality (EQUAL) study., Methods: The EQUAL study is an international prospective cohort study of patients ≥65 years of age with advanced CKD. Baseline demographic, clinical and medication data were analysed and reported descriptively. Polypharmacy was defined as ≥5 medications and hyperpolypharmacy as ≥10. Univariable and multivariable linear regressions were used to determine associations between country and the number of prescribed medications. Univariable and multivariable logistic regression were used to determine associations between country and hyperpolypharmacy., Results: Of the 1317 participants from five European countries, 91% were experiencing polypharmacy and 43% were experiencing hyperpolypharmacy. Cardiovascular medications were the most prescribed medications (mean 3.5 per person). There were international differences in prescribing, with significantly greater hyperpolypharmacy in Germany {odds ratio (OR) 2.75 [95% confidence interval (CI) 1.73-4.37]; P < 0.001, reference group UK}, the Netherlands [OR 1.91 (95% CI 1.32-2.76); P = 0.001] and Italy [OR 1.57 (95% CI 1.15-2.15); P = 0.004]. People in Poland experienced the least hyperpolypharmacy [OR 0.39 (95% CI 0.17-0.87); P = 0.021]., Conclusions: Hyperpolypharmacy is common among older people with advanced CKD, with significant international differences in the number of medications prescribed. Practice variation may represent a lack of consensus regarding appropriate prescribing for this high-risk group for whom pharmacological treatment has great potential for harm as well as benefit., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: The effectiveness of inactivated influenza vaccine (IIV) immunization in preventing all cause respiratory illness (RI) in children with pre-existing medical conditions has not been fully established and varies from season to season. This study aims to quantify the overall impact of IIV immunization on primary care attended RI episodes in children with pre-existing medical conditions, using robust observational data spanning twelve influenza seasons., Methods: Electronic records of IIV eligible children aged 6 months to 18 years were extracted from primary care databases over the years 2004-2015. IIV eligibility criteria according to Dutch guidelines included (chronic) respiratory and cardiovascular disease and diabetes mellitus. For each year, information on IIV immunization status, primary care attended RI episodes (including influenza, acute respiratory tract infections and asthma exacerbations) and potential confounders were collected. Generalized estimating equations were used to model the association between IIV status and occurrence of at least one RI episode during the influenza epidemic period with "current year immunized" as reference group. Robustness of findings were assessed by performing various sensitivity analyzes in which (i) seasons with a mismatch between the dominant circulating influenza virus and vaccine strain were excluded, (ii) influenza periods were further restricted to weeks with at least 30% influenza virus positive specimens in sentinel surveillance (instead of 5%), (iii) propensity scores were used to adjust for confounding., Results: In total, 11,797 children (follow-up duration: 38,701 child-years) were eligible for IIV for ≥ one season with 29% immunized at least once. The adjusted odds for primary care attended RI episodes during the influenza epidemic period did not differ between current season immunized versus not immunized children (adjusted OR:1.01; 95%CI:0.90-1.13). The various sensitivity analysis showed comparable results., Conclusions: IIV immunization in children with pre-existing medical conditions does not reduce all cause RI episodes encountered in primary care during the influenza season., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Annual influenza immunization in medical risk groups is recommended in many countries. Recent evidence suggests that repeated inactivated influenza vaccine (IIV) immunization throughout childhood may impair long-term immunity against influenza. We assessed whether prior immunization altered the effect of IIV in children with preexisting medical conditions on primary care-diagnosed respiratory illness (RI) episodes during the influenza season., Methods: Electronic records of IIV-immunized children who met the criteria for annual IIV immunization according to Dutch guidelines were extracted from a primary care database from 2004 to 2015. For each year, we collected information on IIV immunization status, primary care-attended RI episodes (including influenza-like illness, acute RI, and asthma exacerbation), and potential confounders. Generalized estimating equations were used to model the association between prior IIV and occurrence of at least one RI episode during the influenza season, with "current year immunized but without IIV history" as reference group., Results: A total of 4,183 children (follow-up duration: 11,493 child-years) were IIV immunized at least once. Adjusted estimates showed lower odds for RI in current year-immunized children with prior IIV compared with those without (odds ratio [OR] = 0.61; 95% CI, 0.47-0.78 for "current year immunized and one IIV in previous 2 years"; OR = 0.85; 95% CI, 0.68-1.07 for "current year immunized and ≥2 IIVs in previous 3 years, including prior year")., Conclusion: Repeated IIV immunization in children with preexisting medical conditions has no negative impact on, and may even increase, long-term protection against RI episodes diagnosed during the influenza season in primary care., (© 2019 Annals of Family Medicine, Inc.)

Background: Whilst current guidelines highlight the importance of pain management for children with acute otitis media (AOM), there is evidence to suggest that this is not implemented in everyday practice. We have developed a primary care-based multifaceted educational intervention to optimise pain management in children with AOM, and we trial its clinical and cost effectiveness., Methods: This cluster randomised controlled trial aims to recruit 250 children aged 6 months to 10 years presenting with AOM to general practitioners (GPs) in 30 primary care centres (PCCs) across the Netherlands. GPs in the PCCs allocated to the intervention group receive a blended GP educational programme (online and face-to-face training). The intervention asks GPs to proactively discuss pain management with parents using an information leaflet, and to prescribe paracetamol and ibuprofen according to current guidelines. GPs in both groups complete an online module illustrating various otoscopic images to standardise AOM diagnosis. GPs in the PCCs allocated to the control group do not receive any further training and provide 'care as usual'. During the 4-week follow-up, parents complete a symptom diary. The primary outcome is the difference in parent-reported mean earache scores over the first 3 days. Secondary outcomes include both number of days with earache and fever, GP re-consultations for AOM, antibiotic prescriptions, and costs. Analysis will be by intention-to-treat., Discussion: The optimal use of analgesics through the multifaceted intervention may provide symptom relief and thereby reduce re-consultations and antibiotic prescriptions in children with AOM., Trial Registration: Netherlands Trial Register, NTR4920 . Registered on 19 December 2014.

Objective: This population-based cohort study assesses the impact of switching from a 7-valent pneumococcal conjugate vaccine (PCV) to a 10-valent PCV on outpatient antibiotic use in Dutch infants, and whether geographical vaccination coverage modifies this association., Setting and Participants: We extracted 2006-2013 anonymised antibiotic purchase data of 255 154 Dutch infants aged below 2 years from Achmea Health, a health insurance fund covering 28% of the national population., Design and Main Outcome Measure: Changes in monthly antibiotic use from 2006-2011 (PCV7) to 2011-2013 (PCV10) were estimated using time-series analysis accounting for seasonality and autocorrelation. Interaction terms for vaccination coverage (categorised into seven groups) and period were added to the model to test whether this association was vaccination coverage-dependent., Results: 275 337 antibiotic courses were used by 119 078 infants (461 352 person-years). PCV10 introduction was associated with a modest 1.6% overall reduction in antibiotic use (purchase rate ratio: 0.98, 95% CI: 0.98 to 0.99). Our model showed a significant difference in time trend in antibiotic use after PCV10 introduction (p = 0.0084) with an increase in prescriptions in the PCV7 period (slope: 0.0023/month, 95% CI: -0.0001 to 0.0047) versus a decline in the PCV10 period (slope: -0.0089/month, 95% CI: -0.0150 to -0.0029). There was no evidence that PCV vaccination coverage affected this association, but since the largest rate ratios were observed in municipalities with the lowest vaccine coverage and had very wide accompanying CIs, our study might have insufficient power to detect such an association., Conclusions: Switching from PCV7 to PCV10 was associated with a modest decline in outpatient antibiotic use in Dutch infants., Competing Interests: Competing interests: ACF is an employee of Seqirus Netherlands B.V., Amsterdam, The Netherlands. Seqirus was not involved in any aspect of the submitted work. EAMS reports independent research grants from GlaxoSmithKline and Pfizer. AWH is chair of a large (around 600 employees) research and teaching institute within our University Medical Center. The Institute performs both investigator-driven and industry-driven research projects with a number of pharmaceutical and diagnostic companies. In addition, some of the members of staff receive unrestricted grants for research projects from a number of companies. It is the institute’s explicit policy to work with several companies and not to focus on one or two industrial partners. AWH received no personal payment from any industrial partner. AMS and the evidENT team at University College London have been supported by a NIHR Research Professorship award with the remit to develop a UK infrastructure and programme of clinical trials in ENT Hearing and Balance. The other authors have indicated they have no potential conflicts of interest to disclose., (© Author(s) (or their employer(s)) [2018]. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Although common in children with tympanostomy tubes, the current incidence of tympanostomy tube otorrhea (TTO) is uncertain. TTO is generally a sign of otitis media, when middle ear fluid drains through the tube. Predictors for otitis media are therefore suggested to have predictive value for the occurrence of TTO., Objective: To determine the incidence of TTO and its predictors., Methods: We performed a cohort study, using a parental web-based questionnaire to retrospectively collect data on TTO episodes and its potential predictors from children younger than 10 years of age with tympanostomy tubes., Results: Of the 1,184 children included in analyses (total duration of time since tube placement was 768 person years with a mean of 7.8 months per child), 616 children (52%) experienced one or more episodes of TTO. 137 children (12%) had TTO within the calendar month of tube placement. 597 (50%) children had one or more acute TTO episodes (duration <4 weeks) and 46 children (4%) one or more chronic TTO episodes (duration ≥4 weeks). 146 children (12%) experienced recurrent TTO episodes. Accounting for time since tube placement, 67% of children developed one or more TTO episodes in the year following tube placement. Young age, recurrent acute otitis media being the indication for tube placement, a recent history of recurrent upper respiratory tract infections and the presence of older siblings were independently associated with the future occurrence of TTO, and can therefore be seen as predictors for TTO., Conclusions: Our survey confirms that otorrhea is a common sequela in children with tympanostomy tubes, which occurrence can be predicted by age, medical history and presence of older siblings.