Diagnostic Accuracy of a Real-Time Host-Protein Test for Infection.

OBJECTIVE: Determining infection etiology can be difficult because viral and bacterial diseases often manifest similarly. A host protein test that computationally integrates the circulating levels of TNF-related apoptosis-induced ligand, interferon γ-induced protein-10, and C-reactive protein to differentiate between bacterial and viral infection (called MMBV) demonstrated high performance in multiple prospective clinical validation studies. Here, MMBV's diagnostic accuracy is evaluated in febrile children for whom physicians were uncertain about etiology when applied at the physician's discretion. METHODS: Patients aged 3 months to 18 years were retrospectively recruited (NCT03075111; SPIRIT study; 2014-2017). Emergency department physician's etiological suspicion and certainty level were recorded in a questionnaire at blood-draw. MMBV results are based on predefined score thresholds: viral/non-bacterial etiology (0 ≤ score <35), equivocal (35 ≤ score ≤65), and bacterial or coinfection (65 < score ≤100). Reference standard etiology (bacterial/viral/indeterminate) was adjudicated by 3 independent experts based on all available patient data. Experts were blinded to MMBV. MMBV and physician's etiological suspicion were assessed against the reference standard. RESULTS: Of 3003 potentially eligible patients, the physicians were uncertain about infection etiology for 736 of the cases assigned a reference standard (128 bacterial, 608 viral). MMBV performed with sensitivity 89.7% (96/107; 95% confidence interval 82.4-94.3) and specificity 92.6% (498/538; 95% confidence interval 90.0-94.5), significantly outperforming physician's etiological suspicion (sensitivity 49/74 = 66.2%, specificity 265/368 = 72.0%; P < .0001). MMBV equivocal rate was 12.4% (91/736). CONCLUSIONS: MMBV was more accurate in determining etiology compared with physician's suspicion and had high sensitivity and specificity according to the reference standard.

Paediatric hospital visit with laboratory-confirmed influenza improved family members' influenza vaccination.

OBJECTIVES: Vaccination is the primary intervention to prevent influenza infection, yet vaccine uptake remains low among children and other at-risk patients. The aim of the study is to investigate the impact of a paediatric hospital visit with laboratory-confirmed influenza on the influenza vaccination behaviour of participants and their family members in the subsequent influenza season. METHODS: This study compared the influenza vaccination coverage for participants < 18 years of age with a clinical suspicion of influenza in 2017-2018 during a hospital visit, in two subsequent influenza seasons. Data was retrieved from the hospital electronic medical record and a follow-up questionnaire (2018-2019) to ascertain the common reason(s) that families did not vaccinate their children the following year (2018-2019). The children were distributed into positive- (antigen and/or PCR) and negative-influenza groups. RESULTS: A total of 133 children were enrolled in our study. Participants' mean age was 4.6 years and 74 (55.6%) were males. Overall, 47 (35.3%) had confirmed influenza virus. A significant increase in influenza immunization was found among both positive- and negative-influenza participants between 2017-2018 and 2018-2019 (6.4% vs. 27.7%, p < 0.001; 8.1% vs. 29.1%, p < 0.001, respectively), as well as among family members of positive-influenza participants - siblings and parents (6.4% vs. 19.6%, p = 0.003; 0% vs. 17%, p < 0.001, respectively). Common reasons for failure to vaccinate included doubt in vaccine effectiveness, unlikely to get "flu", busy, and side effects. CONCLUSIONS: Our findings suggest that a paediatric hospital visit with laboratory-confirmed influenza increases vaccine uptake among families. Future studies should aim to evaluate evidence-based interventions to improve influenza vaccine uptake among children.

BV score differentiates viral from bacterial-viral co-infection in adenovirus PCR positive children.

Background and objectives: Adenovirus causes acute respiratory illness that can mimic bacterial infection, making it challenging to differentiate adenoviral infection from adenoviral-bacterial co-infection. A host-protein score (BV score) for differentiating bacterial from viral infection that combines the expression levels of TNF-related apoptosis-induced ligand, interferon gamma-induced protein-10, and C-reactive protein exhibited a negative predictive value (NPV) of 98% in prior studies. Here we evaluate BV score's diagnostic accuracy in pediatrics with adenovirus PCR detection. Methods: This is a sub-analysis of children aged 3 months to 20 years with adenovirus PCR-positive infection recruited prospectively in two previous cohort studies. Reference standard diagnosis (bacterial, viral or indeterminate) was based on expert adjudication. BV score ranges from 0 to 100 and provides three results based on predefined cutoffs: viral or other non-bacterial etiology (0 ≤ score < 35), equivocal (35 ≤ score ≤ 65), and bacterial or co-infection (65 < score ≤ 100). Experts were blinded to BV results. Results: Out of 1,779 children, 142 had an adenovirus PCR-positive nasopharyngeal swab. Median age was 1.2 years (interquartile range 0.6-1.8), 50.7% were male and 52.8% were hospitalized. 12 cases were reference standard bacterial, 115 reference standard viral and 15 were indeterminate. BV score attained sensitivity of 100.0% (no false negatives), specificity of 89.5% (95% confidence interval: 83.2-95.8), and NPV of 100.0% (92.6-100.0). Equivocal rate was 19.7%. Conclusions: BV score accurately differentiated between adenoviral and bacterial-adenoviral co-infection in this cohort of children with PCR-positive adenovirus detection. This performance supports a potential to improve appropriate antibiotic use.

The diagnostic value of nasal microbiota and clinical parameters in a multi-parametric prediction model to differentiate bacterial versus viral infections in lower respiratory tract infections.

BACKGROUND: The ability to accurately distinguish bacterial from viral infection would help clinicians better target antimicrobial therapy during suspected lower respiratory tract infections (LRTI). Although technological developments make it feasible to rapidly generate patient-specific microbiota profiles, evidence is required to show the clinical value of using microbiota data for infection diagnosis. In this study, we investigated whether adding nasal cavity microbiota profiles to readily available clinical information could improve machine learning classifiers to distinguish bacterial from viral infection in patients with LRTI. RESULTS: Various multi-parametric Random Forests classifiers were evaluated on the clinical and microbiota data of 293 LRTI patients for their prediction accuracies to differentiate bacterial from viral infection. The most predictive variable was C-reactive protein (CRP). We observed a marginal prediction improvement when 7 most prevalent nasal microbiota genera were added to the CRP model. In contrast, adding three clinical variables, absolute neutrophil count, consolidation on X-ray, and age group to the CRP model significantly improved the prediction. The best model correctly predicted 85% of the 'bacterial' patients and 82% of the 'viral' patients using 13 clinical and 3 nasal cavity microbiota genera (Staphylococcus, Moraxella, and Streptococcus). CONCLUSIONS: We developed high-accuracy multi-parametric machine learning classifiers to differentiate bacterial from viral infections in LRTI patients of various ages. We demonstrated the predictive value of four easy-to-collect clinical variables which facilitate personalized and accurate clinical decision-making. We observed that nasal cavity microbiota correlate with the clinical variables and thus may not add significant value to diagnostic algorithms that aim to differentiate bacterial from viral infections.

Multidomain Cognitive Impairment in Children With Pseudotumor Cerebri Syndrome.

BACKGROUND: Although prompt and suitable treatment of pseudotumor cerebri syndrome (PTCS) leads to an excellent prognosis and can prevent optic nerve atrophy, adults show long-lasting neurocognitive deficits even with prompt treatment. The purpose of our study was to evaluate cognitive outcomes in pediatric patients with PTCS. METHODS: We performed a prospective study on children diagnosed with PTCS and a healthy control group. Children with pre-existing neurological conditions or psychiatric drug use were excluded. Both groups underwent a neurocognitive evaluation, using the NeuroTrax computerized battery of tests. The PTCS group were tested 3 months after the initial diagnosis. RESULTS: We evaluated 82 children (49 females [60%], 6.5-16 years old, mean age 13.3), including 26 diagnosed with idiopathic PTC and 56 controls. Global cognitive score (P < 0.001), verbal memory (P < 0.001), executive function (P < 0.001), attention (P< 0.003), and information processing speed (P < 0.004) were all significantly lower in the PTCS group. No differences were found between children currently being treated and those whose symptoms had resolved and treatment was stopped. CONCLUSIONS: Children with PTCS experience comprehensive cognitive decline that persists after the resolution of the symptoms and treatment.

Evaluation of Israeli healthcare workers knowledge and attitudes toward the COVID-19 vaccine.

OBJECTIVES: Healthcare workers (HCWs) are considered an important target group for the COVID-19 vaccines. The current study assesses the knowledge and attitudes of Israeli HCWs regarding COVID-19 immunization, and how various occupational and demographic factors may underlie COVID-related knowledge and attitudes differences. METHODS: Following a pre-test to validate measures, a cross-sectional online anonymous survey was distributed to HCWs using a snowball sampling method. RESULTS: The survey was completed by 714 participants (mean age 39.9; range 18-74; 447 female), 52% doctors, 32% nurses, and the remainder by paramedical staff. Of the respondents, 553 (77.4%) answered the question are you in favor of getting the COVID-19 vaccine, 105 (14.7%) were not sure, and 56 (7.8%) were not in favor. Doctors had higher odds of agreement as compared to both nurses (p < .025) and paramedical staff (p < .001). Multivariate logistic regression analysis revealed that increased age (OR: 1.075; 95% CI: 1.04-1.11, p < .001), profession (physician vs. nurse; OR: 2.73; 95% CI: 1.32-5.65; p < .007), and getting the current influenza vaccine (OR: 4.96; 95% CI: 2.47-9.95) were significant predictors of agreement. CONCLUSIONS: A high level of HCWs knowledge and in favor attitudes were observed. Yet negative attitudes were also noted, particularly among nurses, paramedical staff, and young employees.

Outcomes of Migraine and Tension-Type Headache in Children and Adolescents.

The aim of our study was to evaluate the long-term outcomes of pediatric migraine and TTH in a clinical setting. We conducted a cohort study. Pediatric patients who visited the pediatric neurology clinic due to diagnoses of migraine or TTH were contacted by phone 8-10 years after their initial diagnosis and interviewed about their outcomes. Of 147 children, we were able to reach 120 (81%) patients. Of these 120 patients, 59 were seen initially due to migraine and 61 due to TTH. For the migraine patients, headaches improved in 48 (81.4%) and worsened in four (6.8%). Regarding diagnosis at follow-up, 59% still had migraine, 17% had TTH, and 23% were headache-free. Aura and photophobia were significantly associated with persistence of a migraine diagnosis. For the TTH patients, headaches improved in 49 (81.7%) and worsened in nine (15.0%). Regarding diagnosis at follow-up, 36.7% still had TTH, 18.3% had migraine, and 45% were headache-free. Of the patients with TTH, 36.7% retained their initial diagnosis compared to 59.3% among the migraine patients. Most pediatric patients presenting with migraine or TTH will experience a favorable outcome over 10 years, with TTH patients having twice the chance of complete resolution.

Pooled saliva CMV DNA detection: A viable laboratory technique for universal CMV screening of healthy newborns.

BACKGROUND: Most infants with congenital cytomegalovirus (cCMV) have no overt manifestations at birth, yet may later develop CMV-related sensorineural hearing loss (SNHL). With targeted screening, many asymptomatic neonates are missed and lose the opportunity for timely anti-viral treatment to ameliorate SNHL. Saliva is the preferred screening specimen given its ease of collection. OBJECTIVES: Assess a pooled saliva CMV DNA detection technique for cCMV screening of healthy full-term neonates. STUDY DESIGN: We conducted a prospective laboratory CMV PCR screening study in a secondary hospital from March-June 2019. Saliva specimens were obtained from 1000 newborns two-four hours after birth. Specimens were analyzed for CMV DNA with a real-time PCR platform (Altona) in pools of 10 and individually (40 µL and 400 µL, respectively). Neonates with positive saliva CMV DNA detection required urine CMV PCR testing to confirm cCMV diagnosis. RESULTS: From the 1000 saliva samples, there were 6 urine-confirmed cCMV cases, yielding a prevalence rate of 0.6 %. The specificity was high for both pooled and individual saliva sampling (99.9 % and 98.1 %, respectively). The positive predictive value of the pooled sample was 85.7 %, compared to 24.0 % for a single saliva sample. CONCLUSIONS: Pooling saliva of healthy newborns appears to be a reliable method to identify asymptomatic cCMV infection when positive results are confirmed by urine CMV DNA. Pooling in sizes appropriate to the cCMV prevalence rate may improve the laboratory workflow and decrease costs. Further studies should evaluate the clinical implications of this widespread cCMV pooled screening technique.

The yield of CSF molecular testing in febrile neonates.

We retrospectively examined the yield of a cerebrospinal fluid (CSF) multiplex real-time PCR assay of febrile young infants undergoing a full sepsis work-up. Eighty infants were included in the study: Forty-nine (61%) neonates and 31 (39%) 29-90 day-old patients were included in the study. A viral pathogen was detected in 59% (47/80) of the samples, human enterovirus in 53% (42/80) and Human parechovirus in 6% (5/80). The CSF of nearly half of the subjects with CNS infection was without pleocytosis; all CSF cultures were negative. Multiplex PCR CSF testing enhances the diagnosis of pathogen-specific viral CNS infection among febrile young infants.

Migraine and Tension-Type Headache Among Children and Adolescents: Application of International Headache Society Criteria in a Clinical Setting.

INTRODUCTION: The International Headache Society criteria were written in order to help physicians establish a headache diagnosis. However, sometimes children with headache do not seem to fit any diagnosis. The purpose of our study was to assess the application of the criteria in a clinical setting. METHODS: Medical records of children referred for primary headache to the pediatric neurology clinic at Bnai Zion Medical Center from 2008 to 2017 were assessed. RESULTS: A total of 989 patients (range 6-18 years; 53% female) were assessed at our neurology clinic. Twenty-four percent (n = 241) were diagnosed with tension-type headache, 26% (n = 256) with migraine, and 4.5% (45) with mixed headache. In 41.5% (410), we were unable to reach a specific diagnosis. No differences in gender or age were found between the groups. Children in the migraine group used more analgesic treatments to stop the headache attacks compared with the tension-type headache group (50% vs 38%, P = .001). Patients diagnosed with tension-type headache reported having more emotional difficulties (P = .001). No significant differences were found in headache characteristics (ie, location, sidedness, character), frequency, or intensity between the younger children (ages 6-11) and the adolescents (ages 12-18) within either the tension-type headache or migraine groups. CONCLUSIONS: Retrospective application of International Headache Society criteria in a large cohort of children with headaches failed to diagnose a specific type of headache in 41.5% of children. Migraine and tension-type headache were equally prevalent, and both constituted a major burden on our patients' everyday lives. We found no major differences in frequency, intensity, and characteristics of pain between younger children and adolescents.

Sensory processing patterns affect headache severity among adolescents with migraine.

OBJECTIVE: To evaluate the relationship between pain catastrophizing level, sensory processing patterns, and headache severity among adolescents with episodic migraine. BACKGROUND: Catastrophizing about pain is a critical variable in how we understand adjustment to pain and has a unique contribution in predicting pain intensity. Recent reports found that migraine is also related to enhanced sensory sensitivity. However, the relationship between pain severity, pain catastrophizing level and sensory sensitivity requires greater study especially among adolescents. METHODS: Participants were 92 adolescents aged 13-18 years, 40 with episodic migraine and 52 healthy controls. The migraine patients were prospectively recruited from outpatient pediatric neurology clinics. All participants completed the Adolescent/Adult Sensory Profile (AASP), and the Pain Catastrophizing Scale for children (PCS-ch). The migraine groups also completed the PedMIDAS, which measures Headache related disability. RESULTS: Adolescents with migraine had significantly lower tendency to seek sensory input than healthy controls. Elevated rumination and helplessness correlated with higher migraine pain severity. Tendency to avoid sensory input predicted the migraine related disability level. They also significantly higher pain catastrophizing level than healthy controls, as seen in enhanced rumination (p ≤ 0.001) and helplessness (p ≤ 0.05). CONCLUSIONS: Sensory processing difficulties are common among adolescents with episodic migraine. Sensory avoidance may be related to pain experience, and pain catastrophizing and disability level. TRIAL REGISTRATION: ISRCTN ISRCTN73824458. Registered 28 September 2014. retrospectively registered.

A Retrospective Study of the Impact of Pneumococcal Conjugate Vaccine-13 Immunization in a Northern Israel Hospital.

BACKGROUND: The introduction of pneumococcal conjugate vaccine-13 (PCV-13) has reduced the burden of invasive pneumococcal disease. OBJECTIVES: To characterize true positive blood cultures of children who presented to our hospital following implementation of the PCV-13 vaccine. METHODS: A retrospective study was conducted on positive blood cultures of children presenting with fever from 2010-2017. Subjects were divided into two age groups: a younger group 3-36 months and an older group 3-18 years. Patients were classified as either having or not having a focus of infection at the time of their bacteremia. Pneumococcal isolates were typed at Israel's Streptococcal Reference Laboratory. RESULTS: The samples included 94 true positive blood cultures. Focal infection with concomitant bacteremia was more common than bacteremia without a focus both overall: 67/94 (71%) vs. 27/94 (28.7%), P <0.001 as well as in the two groups: 32/48 (66%) vs. 16/48 (33%), P = 0.02 in the younger group and 35/46 (76%) vs. 11/46 (24%), P = 0.001 in the older group. Streptococcus pneumoniae was the most common pathogen overall, 27/94 (29%), and in the younger group, 21/48 (44%), but rare in the older group, 6/46 (13%). In the latter, Brucella species predominated, 12/46 (26%), along with Staphylococcus aureus 12/46 (26%). CONCLUSIONS: Our findings are consistent with other studies reporting decreased pneumococcal bacteremia, bacteremia primarily accompanying focal infection, and changing etiological agents among PCV-13-vaccinated children. Brucella species was prominent in older children with osteoarticular infections. Ongoing surveillance is warranted to better understand the implications of PCV-13.

Stroke identification using a portable EEG device - A pilot study.

OBJECTIVE: Changes in EEG patterns during stroke are almost immediate; however, a full EEG test takes time and requires highly qualified staff. In this study, we examined whether a short recording using a portable EEG device can differentiate between a stroke and control group. METHODS: EEG samples were collected from patients with an acute ischemic stroke event. The control group comprised healthy volunteers. EEG recordings were recorded using a portable brain wave sensor device. The Revised Brain Symmetry Index (rsBSI) was used to quantify the symmetry of spectral power between the two hemispheres. RESULTS: The investigation group included 33 patients (ages 46-96, mean age 72 years, 66% male) who were diagnosed with ischemic stroke. The control group included 25 healthy individuals. Scores for the rsBSI of non-stroke patients (M=0.1686, SD=0.10) differed significantly from those of ischemic stroke patients (P<0.05, M=0.363, SD=0.25). CONCLUSIONS: A statistically significant difference was observed between a group of stroke patients and a matched group of healthy controls with a short recording using a portable EEG device.

Cat Scratch Disease Presenting as Fever of Unknown Origin Is a Unique Clinical Syndrome.

BACKGROUND: Fever of unknown origin (FUO) is a rare manifestation of cat scratch disease (CSD). Data regarding CSD-associated FUO (CSD-FUO), particularly in adults, are limited. We aimed to study disease manifestations and long-term clinical outcome. METHODS: A national CSD surveillance study has been conducted in Israel since 1991. Data are obtained using questionnaires, review of medical records, and telephone interviews. FUO was defined as fever of ≥14 days without an identifiable cause. CSD-FUO patients were identified in the 2004-2017 CSD national registry. Follow-up included outpatient clinic visits and telephone/e-mail surveys. RESULTS: The study included 66 CSD-FUO patients. Median age was 35.5 years (range, 3-88). Median fever duration was 4 weeks (range, 2-9). Relapsing fever pattern was reported in 52% of patients, weight loss in 57%, and night sweats in 48%. Involvement of ≥1 organs occurred in 59% of patients; hepatosplenic space-occupying lesions (35%), abdominal/mediastinal lymphadenopathy (20%), ocular disease (18%), and multifocal osteomyelitis (6%) were the most common. Malignancy, particularly lymphoma, was the initial radiological interpretation in 21% of patients; 32% underwent invasive diagnostic procedures. Of the 59 patients available for follow-up (median duration, 31 weeks; range, 4-445), 95% had complete recovery; 3 patients remained with ocular sequelae. CONCLUSION: This is the first attempt to characterize CSD-FUO as a unique syndrome that may be severe and debilitating and often mimics malignancy. Relapsing fever is a common clinical phenotype. Multiorgan involvement is common. Recovery was complete in all patients except in those with ocular disease.

Acute mastoiditis: 20 years of experience with a uniform management protocol.

OBJECTIVES: To characterize the clinical presentation of pediatric patients who, upon AM diagnosis, also had imaging-diagnosed ICCs (ID-ICCs); to define the group of AM patients at risk of developing ID-ICCs; and to update knowledge about organisms causing AM. STUDY DESIGN: Analysis of all AM patients admitted between 1997 and 2018 and treated according to an obligatory protocol including both brain imaging and sampling for bacterial culture upon clinical diagnosis of AM. RESULTS: Of 166 admitted patients (0.5-19 years old) 22 (13%) already had ID-ICCs. In patients who, on admission, had already received antibiotics for acute otitis media (AOM) and also had CRP (C-reactive protein) levels above 93.5 mg/L, the risk of ID-CC was increased by 22.5-fold (P < 0.0001). Bacterial culture results were available for all patients and were positive in 115 (69%). Organisms most commonly found in patients without prior antibiotic treatment were group A Streptococcus pyogenes (53%), Streptococcus pneumoniae (23%), and Haemophylus influenzae (11%), while with prior antibiotic treatment they were Fusobacterium necrophorum (21%), Streptococcus pyogenes (18%) and Pseudomonas aeruginosa (18%). CONCLUSIONS: Since the risk of ID-ICC in patients with the abovementioned CRP and prior antibiotic treatment was significantly higher than in the others, these high-risk patients should undergo diagnostic imaging on admission. Antibiotic treatment prior to AM development may promote growth of non-AOM pathogen.

Sensory Processing Difficulties Correlate With Disease Severity and Quality of Life Among Children With Migraine.

Introduction: Headaches are common among children and about 80% of children reporting them. Migraine and tension type headaches are the most common primary headaches in children and the prevalence of migraine is about 8%. Accompanying sensory symptoms are common before, during and after migraine attacks. They may be a part of a wider symptom constellation called sensory processing disorder or difficulties (SPD). This includes both hyper or hypo sensitivity to sensations. However, the literature regarding sensory processing symptoms of children and youth with headaches as well as its interaction with child's emotional aspects and quality of life is scarce. Materials and Methods: One hundred and thirty-four children between the ages of 8 and 12 participated in this study. Fifty-four children (22 boys and 32 girls) with episodic migraine were prospectively recruited from pediatric neurological clinics during the years 2014-2017. The control group included 80 healthy children. Both groups completed a health and demographic questionnaire, headache assessment including Ped-MIDAS, Short Sensory Profile, State-Trait Anxiety Inventory (STAI) for children, and the Pediatric Quality of Life Inventory. Results: Children with migraine showed significantly higher prevalence of sensory processing difficulties and lower quality of life compared to healthy controls. Among children with migraine, sensory processing difficulties significantly correlated with lower quality of life. Headache-related disability and sensory processing difficulties predicted quality of life. Conclusion: The possible relationship between migraine and sensory processing disorder or difficulties stresses the need to screen for sensory processing difficulties among children with migraine and when found-refer to their impacts on children's daily function and quality of life.

Respiratory Viruses Frequently Mimic Pertussis in Young Infants.

Bordetella pertussis is prevalent among infants, but its diagnosis is complicated by the fact that its signs and symptoms overlap with respiratory viruses. Indeed, when evaluating the etiology of infants less than 1 year of age suspected of having pertussis, we found that respiratory viruses frequently mimic B. pertussis and are more likely to be the causative agent.

Antibiotic misuse in respiratory tract infections in children and adults-a prospective, multicentre study (TAILORED Treatment).

Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults. Surprisingly, little is known about antibiotic use in children as compared to adults with RTI. This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions. We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel. A panel of three experienced physicians adjudicated a reference standard diagnosis (i.e. bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment. The cohort included 284 children and 232 adults with RTI (median age, 1.3 years and 64.5 years, respectively). The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p < 0.001). In case of viral RTI, antibiotics were prescribed (i.e. overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p < 0.001). One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e. underuse); all were mild cases. This international, prospective study confirms major antibiotic overuse in patients with RTI. Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI. Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages.

Does Herpes 6 Infection Have a Role in Bell's Palsy Among Children and Adolescents?

BACKGROUND: Bell's palsy is a peripheral paralysis of the seventh cranial nerve, whose etiology is unknown. Using polymerase chain reaction technology, it is possible to sample accessible body fluids and identify possible viral factors. The purpose of this research is to investigate its connection to the herpes virus family by testing for the presence of the virus in the saliva and tear fluid of Bell's palsy patients. METHODS: Saliva and tears were collected from 42 children and adolescents suffering from idiopathic facial nerve paralysis. Polymerase chain reaction was used to test for the presence of the viruses Epstein-Barr virus, cytomegalovirus, herpes simplex virus 1 and 2, varicella zoster virus and human herpes virus 6 (HHV-6). Samples were also taken from a control group without paralysis. A second specimen was taken from patients who tested positive for HHV-6 several months after their recovery. RESULTS: Of the 42 patients in the study group, 71% (30 patients) tested positive for HHV-6, compared with only 37% of the control group (P = 0.001). The prevalence of the other 5 viruses tested was low-herpes simplex virus 1: 9.5%, Epstein-Barr virus: 9.5%, cytomegalovirus: 4.8%, varicella zoster virus: 2.3% and herpes simplex virus 2: 0%. Twenty-four of the 30 patients who were HHV-6-positive during their illness were reexamined following recovery. Only 13 patients (54.2%) excreted the virus after recovery from the paralysis. CONCLUSIONS: Herpes 6 virus appears to play some role in the etiology of facial nerve paralysis. The virus was detected in the saliva of children during acute illness and decreased with resolution. Our research opens new insights linking HHV-6 to the etiology of Bell's palsy in children.

A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study.

Bacterial and viral infections often present with similar symptoms. Etiologic misdiagnosis can alter the trajectory of patient care, including antibiotic overuse. A host-protein signature comprising tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) was validated recently for differentiating bacterial from viral disease. However, a focused head-to-head comparison of its diagnostic performance against other biomarker candidates for this indication was lacking in patients with respiratory infection and fever without source. We compared the signature to other biomarkers and prediction rules using specimens collected prospectively at two secondary medical centers from children and adults. Inclusion criteria included fever > 37.5 °C, symptom duration ≤ 12 days, and presentation with respiratory infection or fever without source. Comparator method was based on expert panel adjudication. Signature and biomarker cutoffs and prediction rules were predefined. Of 493 potentially eligible patients, 314 were assigned unanimous expert panel diagnosis and also had sufficient specimen volume. The resulting cohort comprised 175 (56%) viral and 139 (44%) bacterial infections. Signature sensitivity 93.5% (95% CI 89.1-97.9%), specificity 94.3% (95% CI 90.7-98.0%), or both were significantly higher (all p values < 0.01) than for CRP, procalcitonin, interleukin-6, human neutrophil lipocalin, white blood cell count, absolute neutrophil count, and prediction rules. Signature identified as viral 50/57 viral patients prescribed antibiotics, suggesting potential to reduce antibiotic overuse by 88%. The host-protein signature demonstrated superior diagnostic performance in differentiating viral from bacterial respiratory infections and fever without source. Future utility studies are warranted to validate potential to reduce antibiotic overuse.