Alarming signs and symptoms in febrile children in primary care: An observational cohort study in The Netherlands

__Abstract__ Context: Febrile children in primary care have a low risk for serious infection. Although several alarming signs and symptoms are proposed to have predictive value for serious infections, most are based on research in secondary care. The frequency of alarming signs/symptoms has not been established in primary care; however, in this setting differences in occurrence may influence their predictive value for serious infections. Objective: To determine the frequency of alarming signs/symptoms in febrile children in primary care. Design: Observational cohort study. Clinical information was registered in a semi-structured way and manually recoded. Setting: General practitioners' out-of-hours service. Subjects: Face-to-face patient contacts concerning children (aged ≤16 years) with fever were eligible for inclusion. Main outcome measures: Frequency of 18 alarming signs and symptoms as reported in the literature. Results: A total of 10,476 patient contacts were included. The frequency of alarming signs/symptoms ranged from n = 1 (ABC instability; 40°C as reported by the parents; 12.9%) to 8,647 contacts (parental concern; 82.5%). Conclusion: Although the prevalence of specific alarming signs/symptoms is low in primary care, ≥50% of children have one or more alarming signs/symptoms. There is a need to determine the predictive value of alarming signs/symptoms not only for serious infections in primary care, but as well for increased risk of a complicated course of the illness

The effect of n-3 polyunsaturated fatty acid-rich diets on cognitive and cerebrovascular parameters in chronic cerebral hypoperfusion

Western diets consist to a large part of n-6 polyunsaturated fatty acids (PUFAs). These n-6 PUFAs and their conversion products favor immune and inflammatory reactions and compromise vasoregulation, which can contribute to the development of dementia. Recent epidemiological studies associated dementia, particularly the type accompanied by a vascular component, with high, saturated dietary fat intake. Conversely, high fish consumption (a source of long chain n-3 PUFAs) was related to a reduced risk for cognitive decline. Therefore we studied the effects of long chain n-3 PUFAs in rats with bilateral occlusion of the common carotid arteries (2VO), which mimics cerebral hypoperfusion, a risk factor for dementia. Male Wistar rats received experimental diets with a decreased (n-6)/(n-3) ratio from weaning on. At the age of 3 months, the animals underwent 2VO surgery. The rats were tested in the elevated plus maze, an active avoidance paradigm and the Morris water maze (at different survival times). Following behavioral testing, the animals were sacrificed at the age of 7 months. The frontoparietal cortex was analyzed for capillary ultrastructure with electron microscopy. No effects of cerebral hypoperfusion or diet were found on elevated plus maze and active avoidance, while spatial memory in the Morris maze was compromised due to cerebral hypoperfusion under placebo dietary conditions. n-3 PUFA supplementation in combination with extra additives improved the performance of the 2VO animals. The number of endothelial mitochondria, as well as the ratio of microvessels with degenerative pericytes appeared to be lower due to long chain n-3 PUFAs. These results may indicate an improved condition of the blood–brain barrier.

Efficacy of an implantable cardioverter-defibrillator in a neonate with LQT3 associated arrhythmias

We present a case in which LQTS induced severe prenatal and neonatal arrhythmias. LQT3 was diagnosed (mutation R1623Q). Short-acting beta-blockers were ineffective as well as sotalol and mexiletine in preventing recurrent ventricular arrhythmias. An ICD was implanted at the age of 7 months (weight and length of the infant at implantation 6 kg and 60 cm respectively). Flecainide was prescribed in addition to the ICD implantation. After an appropriate shock the flecainide plasma levels were shown to be subtherapeutic. Readjustment of the flecainide dose resulted in adequate plasma levels. No further shocks occurred during a further 17 months follow-up period. The combination of an active can with a subcutaneous patch proved feasible, and lifesaving shocks occurred at 7 months after implantation. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserve

Translation of clinical prediction rules for febrile children to primary care practice: an observational cohort study

Background Clinical prediction rules (CPRs) to identify children with serious infections lack validation in low-prevalence populations, which hampers their implementation in primary care practice. Aim To evaluate the diagnostic value of published CPRs for febrile children in primary care. Design and setting Observational cohort study among febrile children (<16 years) who consulted five GP cooperatives (GPCs) in the Netherlands. Method Alarm signs of serious infection and clinical management were extracted from routine clinical practice data and manually recoded with a structured electronic data-entry program. Eight CPRs were selected from literature. CPR-variables were matched with alarm signs and CPRs were applied to the GPC-population. 'Referral to emergency department (ED)' was used as a proxy outcome measure for 'serious infection'. CPR performance was assessed by calibration analyses, sensitivity, specificity, and area under the ROC-curve (ROC-area). Results A total of 9794 GPC-contacts were eligible, 54% male, median age 2.3 years (interquartile range 1.0-4.6 years) and 8.1% referred to ED. Frequencies of CPR-variables varied from 0.5% (cyanosis, drowsy) to 25% (temperature = 40 degrees C). Alarm signs frequently included in CPRs were 'ill appearance', 'inconsolable', and 'abnormal circulatory or respiratory signs'. The height of the CPR's predicted risks generally corresponded with being (or not being) referred to the ED in practice. However, calibration-slopes indicated that three CPRs underestimated the risk of serious infection in the GPC-population. Sensitivities ranged from 42% to 54%, specificities from 68% to 89%. ROC-areas ranged from 0.52 to 0.81, with best performance of CPRs for children aged Conclusion Published CPRs performed moderately well in the primary out-of-hours care population. Advice is given on how to improve translation of CPRs to primary care practice

Hepatic Arterial Infusion Pump Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis

Background: Patients with unresectable intrahepatic cholangiocarcinoma (iCCA) have poor survival. This systematic review describes the survival outcomes of hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine for patients with unresectable iCCA. Patients and Methods: A literature search was conducted using the electronic databases PubMed, Medline (Ovid), Embase, Web of Science, Google Scholar, and Cochrane to find studies that reported data on the survival of patients with unresectable iCCA treated with HAIP chemotherapy using floxuridine. The quality of the studies was assessed using the Newcastle–Ottawa quality assessment Scale (NOS). Overall survival (OS) was the primary outcome measure, and progression-free survival (PFS), response rates, resection rates, and toxicity were defined as secondary outcome measures. Results: After removing duplicates, 661 publications were assessed, of which nine studies, representing a total of 478 patients, met the inclusion criteria. Three out of nine studies were phase II clinical trials, one study was a prospective dose-escalation study, and the remaining five studies were retrospective cohort studies. After accounting for overlapping cohorts, 154 unique patients were included for pooled analysis. The weighted median OS of patients with unresectable iCCA treated with HAIP chemotherapy with floxuridine was 29.0 months (range 25.0–39 months). The pooled 1-, 2-, 3-, and 5-year OS were 86.4, 55.5, 39.5, and 9.7%, respectively. Conclusion: HAIP chemotherapy with floxuridine for patients with unresectable iCCA was associated with a 3-year OS of 39.5%, which is favorable compared with systemic chemotherapy for which no 3-year survivors were reported in the Advanced Biliary Cancer (ABC) trials

ASO Visual Abstract: Hepatic Arterial Infusion Pump Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma - A Systematic Review and Meta-analysis

Hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine has been explored as a means to control cancer in the liver. In this systematic review (https://doi.org/10.1245/ s10434-022-11439-x), 478 patients with unresectable intrahepatic cholangiocarcinoma (iCCA) were identified from nine studies; survival outcomes of 154 patients were used in the meta-analysis. HAIP chemotherapy with floxuridine for patients with unresectable iCCA was associated with a pooled 3-year overall survival (OS) of 39.5% (95% confidence interval (CI) 31.5–47.4%) and a weighted median OS of 29.0 months (range 25.0–39 months)

Alarm signs and antibiotic prescription in febrile children in primary care:an observational cohort study

<p>Background</p><p>Although fever in children is often self-limiting, antibiotics are frequently prescribed for febrile illnesses. GPs may consider treating serious infections by prescribing antibiotics.</p><p>Aim</p><p>To examine whether alarm signs and/or symptoms for serious infections are related to antibiotic prescription in febrile children in primary care.</p><p>Design and setting</p><p>Observational cohort study involving five GP out-of-hours services.</p><p>Method</p><p>Clinical information was registered and manually recoded. Children (</p><p>Results</p><p>Of the 8676 included patients (median age 2.4 years), antibiotics were prescribed in 3167 contacts (36.5%). Patient characteristics and alarm signs and/or symptoms positively related to antibiotic prescription were: increasing age (odds ratio [OR] = 1.03; 95% confidence interval [95% CI] = 1.02 to 1.05), temperature measured by GP (OR = 1.72; 95% CI = 1.59 to 1.86), ill appearance (OR = 3.93; 95% CI = 2.85 to 5.42), being inconsolable (OR = 2.27; 95% CI = 1.58 to 3.22), shortness of breath (OR = 2.58; 95% CI = 1.88 to 3.56), duration of fever (OR = 1.31; 95% CI = 1.26 to 1.35). Negative associations were found for neurological signs (OR = 0.45; 95% CI = 0.27 to 0.76), signs of urinary tract infection (OR = 0.63; 95% CI = 0.49 to 0.82), and vomiting and diarrhoea (OR = 0.65; 95% CI = 0.57 to 0.74). These variables explained 19% of the antibiotic prescriptions.</p><p>Conclusion</p><p>Antibiotics are often prescribed for febrile children. These data suggest that treatment of a supposed serious bacterial infection is a consideration of GPs. However, the relatively low explained variation indicates that other considerations are also involved.</p>

Frequency of combined presence of alarming signs and symptoms.

<p>Frequency of combined presence of alarming signs and symptoms.</p

Presence of alarming signs and symptoms.

<p>*Assumption: when not mentioned in the record, it is not present.</p>†<p>Percentage of N registered.</p