Tine De Burghgraeve

A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro.

ABSTRACT A doxorubicin derivate, SA-17, that carries a squaric acid amide ester moiety at the carbohydrate (α-l-daunosaminyl) group was identified as a selective inhibitor of in vitro dengue virus (DENV) serotype 2 replication (50% effective concentration [EC50] = 0.34 ± 0.20 μg/ml [0.52 ± 0.31 μM]). SA-17 is markedly less cytostatic than the parent compound, resulting in a selectivity index value of ∼100. SA-17 also inhibits yellow fever virus 17D (YFV-17D) replication (EC50 = 3.1 ± 1.0 μg/ml [4.8 ± 1.5 μM]), although less efficiently than DENV replication, but proved inactive against a variety of enveloped and nonenveloped viruses. SA-17 inhibits in vitro flavivirus replication in a dose-dependent manner, as was assessed by virus yield reduction assays and quantification of viral RNA by means of real-time quantitative reverse transcriptase PCR (RT-qPCR) (∼2 to 3 log reduction). The anti-DENV activity was confirmed using a Renilla luciferase-expressing dengue reporter virus. Time-of-drug-addition studies revealed that SA-17 acts at the very early stages of the viral replication cycle (i.e., virus attachment and/or virus entry). This observation was corroborated by the observation that SA-17, unlike the nucleoside analogue ribavirin, does not inhibit the replication of DENV subgenomic replicons. Preincubation of high-titer stocks of DENV or YFV-17D with ≥5 μg/ml SA-17 resulted in 100% inhibition of viral infectivity (≥3 log reduction). SA-17, however, did not prove virucidal.

Validating a decision tree for serious infection: diagnostic accuracy in acutely ill children in ambulatory care

Objective Acute infection is the most common presentation of children in primary care with only few having a serious infection (eg, sepsis, meningitis, pneumonia). To avoid complications or death, early recognition and adequate referral are essential. Clinical prediction rules have the potential to improve diagnostic decision-making for rare but serious conditions. In this study, we aimed to validate a recently developed decision tree in a new but similar population. Design Diagnostic accuracy study validating a clinical prediction rule. Setting and participants Acutely ill children presenting to ambulatory care in Flanders, Belgium, consisting of general practice and paediatric assessment in outpatient clinics or the emergency department. Intervention Physicians were asked to score the decision tree in every child. Primary outcome measures The outcome of interest was hospital admission for at least 24 h with a serious infection within 5 days after initial presentation. We report the diagnostic accuracy of the decision tree in sensitivity, specificity, likelihood ratios and predictive values. Results In total, 8962 acute illness episodes were included, of which 283 lead to admission to hospital with a serious infection. Sensitivity of the decision tree was 100% (95% CI 71.5% to 100%) at a specificity of 83.6% (95% CI 82.3% to 84.9%) in the general practitioner setting with 17% of children testing positive. In the paediatric outpatient and emergency department setting, sensitivities were below 92%, with specificities below 44.8%. Conclusions In an independent validation cohort, this clinical prediction rule has shown to be extremely sensitive to identify children at risk of hospital admission for a serious infection in general practice, making it suitable for ruling out. Trial registration number 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.

BackgroundDespite 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/DesignAcutely 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.DiscussionThis 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 registrationClinicalTrials.gov Identifier: NCT02024282.

Point-of-care C reactive protein to identify serious infection in acutely ill children presenting to hospital: prospective cohort study.

Objective Acute infection is the most common presentation of children to hospital. A minority of these infections are serious, but early recognition and adequate management are essential. We aimed to develop improved tools to assess children attending ambulatory hospital care, integrating clinical features with point-of-care C reactive protein (CRP). Design Prospective observational diagnostic study. Setting and patients 5517 acutely ill children (1 month–16 years) presenting to 106 paediatricians at six outpatient clinics and six emergency departments in Belgium. Index test Point-of-care CRP alongside vital signs and objective symptoms measurements. Main outcome Hospital admission for >24 hours with a serious infection <5 days after presentation. Results An algorithm was developed consisting of clinical features and CRP. This achieved 97.1% (95% CI 94.3% to 98.7%) sensitivity and 99.6% (95% CI 99.2% to 99.8%) negative predictive value, excluding serious infections in 36.4% of children. It stratifies patients into three groups based on CRP level: high-risk group with CRP >75 mg/L (26.8% risk of infection), intermediate-risk group with CRP 20–75 mg/L and at least one of seven clinical features (8.1%), and lower risk group with CRP <20 mg/L with at least one of the 11 features (3.8%). Children in intermediate-risk or low-risk groups with normal clinical assessment have 0.6% and 0.4% risk of serious infections, respectively. Conclusions Conducting a CRP test may first enable children to be stratified into three risk groups, guiding assessment of clinical features that could be performed by junior doctors or nurses. In one-third of acutely ill children, the algorithm could exclude serious infection. Prospective validation of the algorithm is needed. Clinical trial registration NCT02024282 (post-results).

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

Abstract 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 influence of coping strategies on subsequent well-being in older patients with cancer: a comparison with two control groups

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.

CRP-test alleen bij acuut zieke kinderen met hoger risico

SamenvattingInleiding Een CRP-sneltest via een vingerprik zou de huisarts kunnen helpen bij het uitsluiten van een ernstige infectie bij kinderen. Wij onderzochten of we de sneltest bij alle kinderen moeten aanbieden of alleen bij kinderen met klinische risicofactoren.Methode We voerden een clustergerandomiseerd onderzoek uit onder acuut zieke kinderen die zich aanmeldden bij 133 huisartsen in 78 huisartspraktijken in België (3147 ziekte-episodes). We randomiseerden praktijken om een CRP-sneltest uit te voeren bij alle kinderen of alleen bij kinderen met klinische risicofactoren (kortademigheid, temperatuur ≥ 40 °C, diarree bij kinderen tussen 12 tot 30 maanden of een niet-pluisgevoel van de arts). De uitkomstmaat was ziekenhuisopname met een ernstige infectie binnen vijf dagen.Resultaten Als kinderen een CRP-test krijgen op basis van klinische risicofactoren, is zo’n test slechts nodig bij 20% van de kinderen. Er was tussen de twee onderzoeksgroepen geen verschil in het aantal kinderen met een ernstige infectie dat de huisartsen dadelijk naar het ziekenhuis verwezen (0,16% versus 0,14%, p = 0,88), of misten bij het eerste contact (0,29% versus 0,14%, p = 0,35). Elf kinderen hadden een ernstige infectie, van hen hadden er zes een CRP van minder dan 20 mg/L. Slechts een kind met een CRP < 5 mg/L had een ziekte die een opname rechtvaardigde.Conclusie De CRP-sneltest is alleen nuttig bij kinderen met klinische risicofactoren. Een CRP < 5 mg/L sluit een ernstige infectie uit en kan de huisarts helpen om onnodige verwijzingen te vermijden. Het klinische oordeel van de arts blijft essentieel, zelfs als een lage CRP-waarde een ernstige infectie lijkt uit te sluiten.

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

BackgroundThe 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.MethodsOCP 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.ResultsA 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.ConclusionsA 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.