Clinical prediction models for serious infections in children: external validation in ambulatory care.

BACKGROUND: Early distinction between mild and serious infections (SI) is challenging in children in ambulatory care. Clinical prediction models (CPMs), developed to aid physicians in clinical decision-making, require broad external validation before clinical use. We aimed to externally validate four CPMs, developed in emergency departments, in ambulatory care. METHODS: We applied the CPMs in a prospective cohort of acutely ill children presenting to general practices, outpatient paediatric practices or emergency departments in Flanders, Belgium. For two multinomial regression models, Feverkidstool and Craig model, discriminative ability and calibration were assessed, and a model update was performed by re-estimation of coefficients with correction for overfitting. For two risk scores, the SBI score and PAWS, the diagnostic test accuracy was assessed. RESULTS: A total of 8211 children were included, comprising 498 SI and 276 serious bacterial infections (SBI). Feverkidstool had a C-statistic of 0.80 (95% confidence interval 0.77-0.84) with good calibration for pneumonia and 0.74 (0.70-0.79) with poor calibration for other SBI. The Craig model had a C-statistic of 0.80 (0.77-0.83) for pneumonia, 0.75 (0.70-0.80) for complicated urinary tract infections and 0.63 (0.39-0.88) for bacteraemia, with poor calibration. The model update resulted in improved C-statistics for all outcomes and good overall calibration for Feverkidstool and the Craig model. SBI score and PAWS performed extremely weak with sensitivities of 0.12 (0.09-0.15) and 0.32 (0.28-0.37). CONCLUSIONS: Feverkidstool and the Craig model show good discriminative ability for predicting SBI and a potential for early recognition of SBI, confirming good external validity in a low prevalence setting of SBI. The SBI score and PAWS showed poor diagnostic performance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02024282. Registered on 31 December 2013.

Cost-effectiveness of point-of-care interventions to tackle inappropriate prescribing of antibiotics in high- and middle-income countries: a systematic review.

BACKGROUND: Antimicrobial resistance (AMR) is propagated by widespread inappropriate use of antibiotics. In response, point-of-care interventions (POCIs) have been developed in primary care to preserve antibiotic effectiveness. Many of these POCIs are adopted based on their clinical value. However, assessment of their cost-effectiveness is crucial as well. OBJECTIVES: To summarize the evidence on cost-effectiveness of POCIs aimed at tackling inappropriate antibiotic prescriptions in primary care in middle- and high-income countries. We also evaluate the quality of the evidence with particular attention to how these economic evaluations faced the challenge of capturing the impact of these POCIs on AMR. METHODS: Six scientific databases (MEDLINE, Embase, Web of Science, NHS EED, NHS HTA, the Cochrane Library) were searched for eligible articles published from 1999 to 2022. Their quality was appraised by means of the Drummond and CHEERS checklist. RESULTS: Twenty-nine articles met the selection criteria. Using their own (implicit) definitions of cost-effectiveness, evidence reported that point-of-care testing, scoring tools, electronic interventions, communication training, and multidimensional and educational interventions are more cost-effective than standard care. In contrast, studies found dipstick testing and audit-and-feedback interventions to be not cost-effective. Data synthesis took a narrative approach as eligible studies were not similar and/or reliable enough to pool their results through meta-analysis. CONCLUSIONS: More high-quality evidence is needed to attain a thorough understanding of the cost-effectiveness of POCIs. Heterogeneity in terms of interventions and efficiency measures complicates comparing and generalizing results. Methodological recommendations are urgently needed to economically evaluate POCIs, focusing on how AMR should be accounted for.

Point-of-care tests for pediatric urinary tract infections in general practice: a diagnostic accuracy study.

BACKGROUND: Early diagnosis of pediatrics urinary tract infections in the outpatient settings is challenging but essential to prevent hospitalization and kidney damage. OBJECTIVE: We aimed to evaluate the diagnostic test accuracy of a selection of point-of-care tests for pediatric urinary tract infections in general practice. METHODS: A prospective cross-sectional study in 26 general practices in Flanders, Belgium (clinicaltrials.gov, NCT03835104). Urine was sampled systematically from children between 3 months to 18 years presenting with an acute illness of maximum 10 days. Samples were analyzed at the central laboratory with a routine dipstick test, the Utriplex test, the Uriscreen test and the Rapidbac as index tests, and with urine culture showing more than 105 colony-forming units per milliliter of one pathogen as reference standard. For each test, we calculated sensitivity, specificity, positive and negative likelihood ratios, and predictive values with 95% confidence intervals. RESULTS: Three-hundred urine samples were available for analysis of which 30 samples were culture positive (10%). Sensitivities and specificities were 32% (95% CI 16%-52%) and 86% (95% CI 82%-90%) for the dipstick test, 21% (95% CI 8%-40%) and 94% (95% CI 91%-97%) for the Utriplex test, 40% (95% CI 16%-68%) and 83% (95% CI 75%-88%) for the Rapidbac test, and 67% (95% CI 38%-88%) with 69% (95% CI 60%-76%) for the Uriscreen test. CONCLUSION: All 4 point-of-care tests were suboptimal for use in the broad range of children presenting with acute illnesses to general practice. General practitioners need novel methods for obtaining reliable urine samples during the time of the consultation, especially for children not yet toilet-trained.

Using Belgian pharmacy dispensing data to assess antibiotic use for children in ambulatory care.

BACKGROUND: The desired effect of antibiotics is compromised by the rapid escalation of antimicrobial resistance. Children are particularly at high-risk for unnecessary antibiotic prescribing, which is owing to clinicians' diagnostic uncertainty combined with parents' concerns and expectations. Recent Belgian data on ambulatory antibiotic prescribing practices for children are currently lacking. Therefore, we aim to analyse different aspects of antibiotic prescriptions for children in ambulatory care. METHODS: Pharmacy dispensing data on antibiotics for systematic use referring from 2010 to 2019 were retrieved from Farmanet, a database of pharmaceutical dispensations in community pharmacies. Population data were obtained from the Belgian statistical office (Statbel). Descriptive statistics were performed in Microsoft Excel. The Mann-Kendall test for trend analysis and the seasplot function for seasonality testing were conducted in R. RESULTS: The past decade, paediatric antibiotic use and expenditures have relatively decreased in Belgian ambulatory care with 35.5% and 44.3%, respectively. The highest volumes of antibiotics for children are prescribed by GPs working in Walloon region and rural areas, to younger children, and during winter. The most prescribed class of antibiotics for children are the penicillins and the biggest relative reduction in number of packages is seen for the sulfonamides and trimethoprim and quinolone antibacterials. CONCLUSIONS: Paediatric antibiotic use has decreased in Belgian ambulatory care. Further initiatives are needed to promote prudent antibiotic prescribing in ambulatory care.

Point-of-care C-reactive protein test results in acute infections in children in primary care: an observational study.

BACKGROUND: Acute infections are a common reason for children to consult primary care. Serious infections are rare but differentiating them from self-limiting illnesses remains challenging. This can lead to inappropriate antibiotic prescribing. Point-of-care C-reactive protein testing is used to guide antibiotic prescribing in adults. However, in children its use remains unclear. The purpose of this study was to assess point-of-care CRP test levels with respect to patients' characteristics, care setting, preliminary diagnosis, and management. METHODS: A prospective observational study was performed in children with an acute infection presenting to ambulatory care in Belgium. RESULTS: In this study 8280 cases were analysed, of which 6552 had a point-of-care CRP value available. A total of 276 physicians participated. The median patient age was 1.98 years (IQR 0.97 to 4.17), 37% of children presented to a general practitioner, 33% to a paediatric out-patient clinic, and 30% to the emergency department. A total of 131 different preliminary diagnoses were found, with acute upper airway infection as the most frequent. In 6% (n = 513) patients were diagnosed with a serious infection. The most common serious infection was pneumonia. Antibiotics were prescribed in 28% (n = 2030) of all episodes. The median CRP over all infectious episodes was 10 mg/L (IQR < 5-29). Children below 5 years of age and those presenting to a paediatrician had a higher median CRP. Median CRP in patients with serious infections was 21 mg/L (IQR 6 to 63.5). Pneumonia had a median CRP of 48 mg/L (IQR 13-113). In the episodes with antibiotics prescription, median CRP level was 29 mg/L (IQR 10-58) compared to 7 mg/L (IQR < 5-19) when they were not prescribed. CONCLUSION: A low POC CRP as a standalone tool did not seem to be sufficient to rule out serious infections, but its potential in assessing serious infections could increase when integrated in a clinical decision rule. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02024282 (registered on 31/12/2013).

Changes in social, psychological and physical well-being in the last 5 years of life of older people with cancer: a longitudinal study.

BACKGROUND: older people with cancer are at risk of complex and fluctuating health problems, but little is known about the extent to which their well-being changes in the last years of life. OBJECTIVE: to examine changes in physical, psychological and social well-being in the last 5 years of life of older people with cancer. DESIGN: prospective cohort study. SETTING: Belgium, the Netherlands. PARTICIPANTS: people with a new primary diagnosis of breast, prostate, lung or gastrointestinal cancer, aged ≥70 years, life expectancy >6 months, were recruited from nine hospitals. We analysed data of deceased patients. METHODS: data were collected from participants around diagnosis, and after 6 months, 1, 3 and 5 years through structured questionnaires administered through interviews or as self-report. Outcomes were physical, emotional, social, role functioning (EORTC QLQ-C30), depressive symptoms (GDS-15), emotional and social loneliness (Loneliness Scale). We conducted linear mixed model analyses. RESULTS: analysing 225 assessments from 107 deceased participants (assessments took place between 1,813 and 5 days before death), mean age at baseline 77 years (standard deviation: 5.2), we found statistically significant deterioration in physical functioning (b = 0,016 [95%confidence interval 0.009-0.023]), depressive symptoms (b = -0,001 [-0.002 to 0.000]) and role functioning (b = 0.014 [0.004-0.024]). Changes over time in emotional and social functioning and in social and emotional loneliness were smaller and statistically non-significant. CONCLUSIONS: care towards the end of life for older people with cancer needs to put their social and psychological well-being at the centre, alongside physical needs. Future research should focus on understanding inter-individual variation in trajectories.

Using Liminality and Subjunctivity to Better Understand How Patients With Cancer Experience Uncertainty Throughout Their Illness Trajectory.

Uncertainty is a central theme in the illness experiences of older cancer patients throughout their illness trajectory. Mishel's popular theory on uncertainty during illness approaches uncertainty as an outcome and is characterized by the patient's inability to find meaning in illness events. This study used the concepts of liminality and subjunctivity to explore uncertainty throughout the illness trajectory of cancer patients. We interviewed 18 older (age range = 57-92 years) patients with breast cancer or gastro-intestinal cancer 3 to 4 years post diagnosis. Our analysis is based on the QUAGOL guide that draws on elements of grounded theory such as constant comparison. We found that liminality and subjunctivity provide a useful frame for understanding uncertainty with a specific focus on its productive potential and meaning making. Health care professionals should be open to acquiring a complete picture of patients' diverse and dynamic experiences of uncertainty in the different stages of their illness trajectory.

The influence of coping strategies on subsequent well-being in older patients with cancer: A comparison with 2 control groups.

OBJECTIVE: To evaluate dispositional coping strategies as predictors for changes in well-being after 1 year in older patients with cancer (OCP) and 2 control groups. METHODS: OCP were compared with 2 control groups: middle-aged patients with cancer (MCP) (aging effect) and older patients without cancer (ONC) (cancer effect). Patients were interviewed shortly after a cancer diagnosis and 1 year later. Dispositional coping was measured with the Short Utrecht Coping List. For well-being, we considered psychological well-being (depression, loneliness, distress) and physical health (fatigue, ADL, IADL). Logistic regression analyses were performed to study baseline coping as predictor for subsequent well-being while controlling for important baseline covariates. RESULTS: A total of 1245 patients were included in the analysis at baseline: 263 OCP, 590 ONC, and 392 MCP. Overall, active tackling was employed most often. With the exception of palliative reacting, OCP utilized each coping strategy less frequently than MCP. At 1-year follow-up, 833 patients (66.9%) were interviewed. Active coping strategies (active tackling and seeking social support) predicted subsequent well-being only in MCP. Avoidance coping strategies did not predict well-being in any of the patient groups. Palliative reacting predicted distress in OCP; depression and dependency for ADL in MCP. CONCLUSIONS: Coping strategies influence subsequent well-being in patients with cancer, but the impact is different in the age groups. Palliative reacting was the only coping strategy that predicted well-being (ie, distress) in OCP and is therefore, especially in this population, a target for coping skill interventions.

Design, synthesis and evaluation against Chikungunya virus of novel small-molecule antiviral agents.

Chikungunya virus is a re-emerging arbovirus transmitted to humans by mosquitoes, responsible for an acute flu-like illness associated with debilitating arthralgia, which can persist for several months or become chronic. In recent years, this viral infection has spread worldwide with a previously unknown virulence. To date, no specific antivirals treatments nor vaccines are available against this important pathogen. Starting from the structures of two antiviral hits previously identified in our research group with in silico techniques, this work describes the design and preparation of 31 novel structural analogues, with which different pharmacophoric features of the two hits have been explored and correlated with the inhibition of Chikungunya virus replication in cells. Structure-activity relationships were elucidated for the original scaffolds, and different novel antiviral compounds with EC50 values in the low micromolar range were identified. This work provides the foundation for further investigation of these promising novel structures as antiviral agents against Chikungunya virus.

Prevalence and predictors of psychosocial problems in informal caregivers of older cancer survivors - A systematic review: Still major gaps in current research.

Despite the abundance of studies concerning caring for patients with cancer, less is known about caring for an older cancer survivor (≥65 years). We aimed to systematically gather literature about the psychosocial well-being of caregivers of older cancer survivors and to identify possible risk factors for developing psychosocial problems. Fourteen articles met the following inclusion criteria: articles about (a) cancer, (b) informal caregivers, (c) older survivors and a (d) curative setting. After critical appraisal, nearly all were considered to be of moderate-to-strong quality. This results mainly from the specific study population, the valid and reliable measurement instruments and the appropriate statistical methods used in the articles. Main outcomes were burden, depression, anxiety, self-esteem, distress, communication issues, stress and QoL. For all these outcomes, measurement instruments and timing of measurements vary. Also, the results on studied predictors vary widely or not all of them were described in the reviewed articles. There seems to be a higher prevalence of distress, lower QoL and more anxiety in informal caregivers of older cancer survivors compared with the general population, but all were understudied. Based on these results and more focused future research, specific and qualitative support for this group of caregivers can be developed.

Point-of-care CRP matters: normal CRP levels reduce immediate antibiotic prescribing for acutely ill children in primary care: a cluster randomized controlled trial.

OBJECTIVE: Antibiotics are prescribed too often in acutely ill children in primary care. We examined whether a Point-of-Care (POC) C-reactive Protein (CRP) test influences the family physicians' (FP) prescribing rate and adherence to the Evidence Based Medicine (EBM) practice guidelines. DESIGN: Cluster randomized controlled trial. SETTING: Primary care, Flanders, Belgium. INTERVENTION: Half of the children with non-severe acute infections (random allocation of practices to perform POC CRP or not) and all children at risk for serious infection were tested with POC CRP. SUBJECTS: Acutely ill children consulting their FP. MAIN OUTCOME MEASURE: Immediate antibiotic prescribing. RESULTS: 2844 infectious episodes recruited by 133 FPs between 15 February 2013 and 28 February 2014 were analyzed. A mixed logistic regression analysis was performed. Compared to episodes in which CRP was not tested, the mere performing of POC CRP reduced prescribing in case EBM practice guidelines advise to prescribe antibiotics (adjusted odds ratio (aOR) 0.54 (95% Confidence Interval (CI) 0.33-0.90). Normal CRP levels reduced antibiotic prescribing, regardless of whether the advice was to prescribe (aOR 0.24 (95%CI 0.11-0.50) or to withhold (aOR 0.31 (95%CI 0.17-0.57)). Elevated CRP levels did not increase antibiotic prescribing. CONCLUSION: Normal CRP levels discourage immediate antibiotic prescribing, even when EBM practice guidelines advise differently. Most likely, a normal CRP convinces FPs to withhold antibiotics when guidelines go against their own gut feeling. Future research should focus on whether POC CRP can effectively identify children that benefit from antibiotics more accurately, without increasing the risks of under-prescribing. Key points What is previously known or believed on this topic •Antibiotics are prescribed too often for non-severe conditions. Point-of-care (POC) C-reactive Protein (CRP) testing without guidance does not reduce immediate antibiotic prescribing in acutely ill children in primary care. What this research adds •FPs clearly consider CRP once available: normal CRP levels discourage immediate antibiotic prescribing, even when EBM practice guidelines advise differently. Most likely, a normal CRP convinces FPs to withhold antibiotics when guidelines go against their own gut feeling. •Future research should focus on whether POC CRP can effectively identify children that benefit from antibiotics more accurately, without increasing the risks of under-prescribing.

The utilization of formal and informal home care by older patients with cancer: a Belgian cohort study with two control groups.

BACKGROUND: The purpose of this paper is to analyse the utilization of formal and informal home care among older patients with cancer (OCP) and to compare this with middle-aged patients with cancer (MCP) and older patients without cancer (ONC). Additionally, we examined predictors of transitions towards formal care one year after a cancer diagnosis. METHODS: OCP and MCP had to be recruited within three months after a cancer diagnosis and have an estimated life expectancy over six months. ONC consisted of patients without known cancer, seen by the general practitioner. Formal and informal care were compared between the patient groups at baseline, i.e. shortly after a cancer diagnosis and changes in care were studied after one year. RESULTS: A total of 844 patients were evaluable for formal care at baseline and 469 patients (56%) at follow-up. At baseline, about half of older adults and 18% of MCP used formal care, while about 85% of cancer patients and 57% ONC used informal care. Formal care increased for all groups after one year though not significantly in OCP. The amount of informal care only changed in MCP which decreased after one year. Cancer-related factors and changes in need factors predict a transition towards formal care after a cancer diagnosis. CONCLUSIONS: A cancer diagnosis has a different impact on the use of formal and informal care than ageing as such. The first year after a cancer diagnosis is an important time to follow-up on the patients' needs for home care.

Should all acutely ill children in primary care be tested with point-of-care CRP: a cluster randomised trial.

BACKGROUND: Point-of-care blood C-reactive protein (CRP) testing has diagnostic value in helping clinicians rule out the possibility of serious infection. We investigated whether it should be offered to all acutely ill children in primary care or restricted to those identified as at risk on clinical assessment. METHODS: Cluster randomised controlled trial involving acutely ill children presenting to 133 general practitioners (GPs) at 78 GP practices in Belgium. Practices were randomised to undertake point-of-care CRP testing in all children (1730 episodes) or restricted to children identified as at clinical risk (1417 episodes). Clinical risk was assessed by a validated clinical decision rule (presence of one of breathlessness, temperature ≥ 40 °C, diarrhoea and age 12-30 months, or clinician concern). The main trial outcome was hospital admission with serious infection within 5 days. No specific guidance was given to GPs on interpreting CRP levels but diagnostic performance is reported at 5, 20, 80 and 200 mg/L. RESULTS: Restricting CRP testing to those identified as at clinical risk substantially reduced the number of children tested by 79.9 % (95 % CI, 77.8-82.0 %). There was no significant difference between arms in the number of children with serious infection who were referred to hospital immediately (0.16 % vs. 0.14 %, P = 0.88). Only one child with a CRP < 5 mg/L had an illness requiring admission (a child with viral gastroenteritis admitted for rehydration). However, of the 80 children referred to hospital to rule out serious infection, 24 (30.7 %, 95 % CI, 19.6-45.6 %) had a CRP < 5 mg/L. CONCLUSIONS: CRP testing should be restricted to children at higher risk after clinical assessment. A CRP < 5 mg/L rules out serious infection and could be used by GPs to avoid unnecessary hospital referrals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02024282 (registered on 14th September 2012).

Design, synthesis, optimization and antiviral activity of a class of hybrid dengue virus E protein inhibitors.

The ß-OG pocket is a cavity in the flavivirus envelope (E) protein that was identified by Proc. Natl. Acad. Sci. U.S.A.2003, 100, 6986 as a promising site for the design of antiviral agents that interfere with virus entry into the host cell. The availability of the X-ray crystal structure of the dengue virus (DENV) E protein provided an opportunity for in silico drug design efforts to identify candidate inhibitors. The present study was set up to explore whether it is possible to generate a novel class of molecules that are hybrids between two hit compounds that have been reported previously by ACS. Chem. Biol.2008, 3, 765 following an in silico screening effort against the DENV E protein. First, a library of twenty hybrid molecules were designed and synthesized to explore the feasibility of this strategy. Antiviral evaluation in a virus-cell-based assay for DENV proved this approach to be successful, after which another twenty-four molecules were produced to further explore and optimize the potency of this novel class of hybrid inhibitors. In the end, a molecule was obtained with an EC50 against dengue virus serotype 2 in the low micromolar range (23, 1.32±0.41µM).

Diagnosing serious infections in acutely ill children in ambulatory care (ERNIE 2 study protocol, part A): diagnostic accuracy of a clinical decision tree and added value of a point-of-care C-reactive protein test and oxygen saturation.

BACKGROUND: Acute illness is the most common presentation of children to ambulatory care. In contrast, serious infections are rare and often present at an early stage. To avoid complications or death, early recognition and adequate referral are essential. In a recent large study children were included prospectively to construct a symptom-based decision tree with a sensitivity and negative predictive value of nearly 100%. To reduce the number of false positives, point-of-care tests might be useful, providing an immediate result at bedside. The most probable candidate is C-reactive protein, as well as a pulse oximetry. METHODS: This is a diagnostic accuracy study of signs, symptoms and point-of-care tests for serious infections. Acutely ill children presenting to a family physician or paediatrician will be included consecutively in Flanders, Belgium. Children testing positive on the decision tree will get a point-of-care C-reactive protein test. Children testing negative will randomly either receive a point-of-care C-reactive protein test or usual care. The outcome of interest is hospital admission more than 24 hours with a serious infection within 10 days. Aiming to include over 6500 children, we will report the diagnostic accuracy of the decision tree (+/- the point-of-care C-reactive protein test or pulse oximetry) in sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values. New diagnostic algorithms will be constructed through classification and regression tree and multiple logistic regression analysis. DISCUSSION: We aim to improve detection of serious infections, and present a practical tool for diagnostic triage of acutely ill children in primary care. We also aim to reduce the number of investigations and admissions in children with non-serious infections. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02024282.

Optimizing antibiotic prescribing for acutely ill children in primary care (ERNIE2 study protocol, part B): a cluster randomized, factorial controlled trial evaluating the effect of a point-of-care C-reactive protein test and a brief intervention combined with written safety net advice.

BACKGROUND: Despite huge public campaigns, there is still overconsumption of antibiotics in children with self-limiting diseases. Possible explanations may be the physicians' and parents' uncertainty about the gravity of the disease and inadequate communication between physicians and parents leading to lack of reassurance for the parents. In this paper we describe the design and methods of a trial aiming to rationalize antibiotic prescribing by decreasing this uncertainty and parental anxiety. METHODS/DESIGN: Acutely ill children without suspected serious disease consulting their family physician will be consecutively included in a four-armed cluster randomized factorial controlled trial. The intervention will consist a Point-of-Care C-reactive protein test and/or a brief intervention with safety net advice. The control group will receive usual care. We intend to include 2560 patients in 88 family practices. Patients will be followed up until cure. The primary outcome measure is the immediate antibiotic prescribing rate. Secondary outcomes are: comparison between groups of speed of clinical recovery, parental concern, parental perception of the quality of the communication, parental satisfaction, use of medication, use of diagnostic tests and medical services during the illness episode, and cost-effectiveness of the interventions. Besides this, we will observationally analyse data of the children included in the large ERNIE2-trial, but excluded in the cluster randomized trial, namely children suspected of serious disease presenting in primary care and children who initially present at the out-patient paediatric clinic or emergency department. We will search for predictors of antibiotic prescribing, speed of clinical recovery, parental concern, parental perception of communication, parental satisfaction, use of medication, diagnostic tests and medical services. DISCUSSION: This is a unique multifaceted intervention, in that it targets both physicians and parents by aiming specifically at their uncertainty and concerns during the consultation. Both interventions are easy to implement without special training. When proven effective, they could offer a feasible way to decrease inappropriate antibiotic prescribing for children in family practice and thus avoid emergence of bacterial resistance, side effects and unnecessary healthcare costs. Moreover, the observational part of the study will increase our insight in the course, management and parent's concern of acute illness in children. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02024282.

Vaccine hesitancy for the COVID-19 vaccine booster dose among nursing home staff fully vaccinated with the primary vaccination course in Belgium.

In Belgium, nursing home (NH) staff (NHS) and residents were prioritised for the initial COVID-19 vaccination and successive booster doses. The vaccination campaign for the first booster started in September 2021 in Belgian NH. Our first study about vaccine hesitancy towards the COVID-19 vaccine in Belgian NHS already showed a degree of fear for the primary vaccination course (T1). This new study aims to evaluate vaccine hesitancy to get the first booster (T2) in a population of fully vaccinated (with two doses) NHS. A random stratified sample of NHS who received the primary vaccination course (N = 954) completed an online questionnaire on COVID-19 booster hesitancy (between 25/11/2021 and 22/01/2022). NHS who hesitated or refused the booster were asked for the main reason for their hesitation/refusal. Overall, 21.0 % of our population hesitated before, were still hesitating or refused the booster, NHS that were not hesitant at T1 being 5.7 times less likely to hesitate to get the first booster dose (Adjusted OR 0.179, 95 % CI: 0.120, 0.267). Although there was a slight reduction (23.5 % to 20.1 %) in the proportion of NHS who hesitated/refused vaccination at T1 compared to T2 (p = 0.034), the fear of unknown effects was the principal reason for hesitation/refusal, already mentioned in our first study. NHS were not reassured concerning their initial fears. Given the likelihood that booster vaccinations will be necessary over the coming years, a communication strategy specific to NHS should be implemented.

Prevalence of SARS-CoV-2 antibodies among Belgian nursing home residents and staff during the primary COVID-19 vaccination campaign.

BACKGROUND: Nursing home residents (NHR) and staff have been disproportionally affected by the COVID-19 pandemic and were therefore prioritised in the COVID-19 vaccination strategy. However, frail older adults, like NHR, are known to have decreased antibody responses upon vaccination targeting other viral antigens. OBJECTIVES: As real-world data on vaccine responsiveness, we assessed the prevalence of SARS-CoV-2 antibodies among Belgian NHR and staff during the primary COVID-19 vaccination campaign. METHODS: In total, we tested 1629 NHR and 1356 staff across 69 Belgian NHs for the presence of SARS-CoV-2 IgM/IgG antibodies using rapid tests. We collected socio-demographic and COVID-19-related medical data through questionnaires. Sampling occurred between 1 February and 24 March 2021, in a randomly sampled population that received none, one or two BNT162b2 vaccine doses. RESULTS: We found that during the primary vaccination campaign with 59% of the study population fully vaccinated, 74% had SARS-CoV-2 antibodies. Among fully vaccinated individuals only, fewer residents tested positive for SARS-CoV-2 antibodies (77%) than staff (98%), suggesting an impaired vaccine-induced antibody response in the elderly, with lowest seroprevalences observed among infection naïve residents. COVID-19 vaccination status and previous SARS-CoV-2 infection were predictors for SARS-CoV-2 seropositivity. Alternatively, age ≥ 80 years old, the presence of comorbidities and high care dependency predicted SARS-CoV-2 seronegativity in NHR. CONCLUSION: These findings highlight the need for further monitoring of SARS-CoV-2 immunity upon vaccination in the elderly population, as their impaired humoral responses could imply insufficient protection against COVID-19. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrials.gov (NCT04738695).