Mycoplasma pneumoniae is thought to be a common cause of respiratory tract infections (RTIs) in children. The diagnosis of M. pneumoniae RTIs currently relies on serological methods and/or the ...detection of bacterial DNA in the upper respiratory tract (URT). It is conceivable, however, that these diagnostic methods also yield positive results if M. pneumoniae is carried asymptomatically in the URT. Positive results from these tests may therefore not always be indicative of a symptomatic infection. The existence of asymptomatic carriage of M. pneumoniae has not been established. We hypothesized that asymptomatic carriage in children exists and investigated whether colonization and symptomatic infection could be differentiated by current diagnostic methods.
This study was conducted at the Erasmus MC-Sophia Children's Hospital and the after-hours General Practitioners Cooperative in Rotterdam, The Netherlands. Asymptomatic children (n = 405) and children with RTI symptoms (n = 321) aged 3 mo to 16 y were enrolled in a cross-sectional study from July 1, 2008, to November 30, 2011. Clinical data, pharyngeal and nasopharyngeal specimens, and serum samples were collected. The primary objective was to differentiate between colonization and symptomatic infection with M. pneumoniae by current diagnostic methods, especially real-time PCR. M. pneumoniae DNA was detected in 21.2% (95% CI 17.2%-25.2%) of the asymptomatic children and in 16.2% (95% CI 12.2%-20.2%) of the symptomatic children (p = 0.11). Neither serology nor quantitative PCR nor culture differentiated asymptomatic carriage from infection. A total of 202 children were tested for the presence of other bacterial and viral pathogens. Two or more pathogens were found in 56% (63/112) of the asymptomatic children and in 55.5% (50/90) of the symptomatic children. Finally, longitudinal sampling showed persistence of M. pneumoniae in the URT for up to 4 mo. Fifteen of the 21 asymptomatic children with M. pneumoniae and 19 of the 22 symptomatic children with M. pneumoniae in this longitudinal follow-up tested negative after 1 mo.
Although our study has limitations, such as a single study site and limited sample size, our data indicate that the presence of M. pneumoniae in the URT is common in asymptomatic children. The current diagnostic tests for M. pneumoniae are unable to differentiate between asymptomatic carriage and symptomatic infection.
Measles causes a transient immune suppression, leading to increased susceptibility to opportunistic infections. In experimentally infected non-human primates (NHPs) measles virus (MV) infects and ...depletes pre-existing memory lymphocytes, causing immune amnesia. A measles outbreak in the Dutch Orthodox Protestant community provided a unique opportunity to study the pathogenesis of measles immune suppression in unvaccinated children. In peripheral blood mononuclear cells (PBMC) of prodromal measles patients, we detected MV-infected memory CD4
and CD8
T cells and naive and memory B cells at similar levels as those observed in NHPs. In paired PBMC collected before and after measles we found reduced frequencies of circulating memory B cells and increased frequencies of regulatory T cells and transitional B cells after measles. These data support our immune amnesia hypothesis and offer an explanation for the previously observed long-term effects of measles on host resistance. This study emphasises the importance of maintaining high measles vaccination coverage.
Abstract
Background
Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics ...may be harmful.
Methods
We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis).
Results
We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis.
Conclusions
Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours.
Prognostic assessments of the mortality of critically ill patients are frequently performed in daily clinical practice and provide prognostic guidance in treatment decisions. In contrast to several ...sophisticated tools, prognostic estimations made by healthcare providers are always available and accessible, are performed daily, and might have an additive value to guide clinical decision-making. The aim of this study was to evaluate the accuracy of students', nurses', and physicians' estimations and the association of their combined estimations with in-hospital mortality and 6-month follow-up.
The Simple Observational Critical Care Studies is a prospective observational single-center study in a tertiary teaching hospital in the Netherlands. All patients acutely admitted to the intensive care unit were included. Within 3 h of admission to the intensive care unit, a medical or nursing student, a nurse, and a physician independently predicted in-hospital and 6-month mortality. Logistic regression was used to assess the associations between predictions and the actual outcome; the area under the receiver operating characteristics (AUROC) was calculated to estimate the discriminative accuracy of the students, nurses, and physicians.
In 827 out of 1,010 patients, in-hospital mortality rates were predicted to be 11%, 15%, and 17% by medical students, nurses, and physicians, respectively. The estimations of students, nurses, and physicians were all associated with in-hospital mortality (OR 5.8, 95% CI 3.7, 9.2, OR 4.7, 95% CI 3.0, 7.3, and OR 7.7 95% CI 4.7, 12.8, respectively). Discriminative accuracy was moderate for all students, nurses, and physicians (between 0.58 and 0.68). When more estimations were of non-survival, the odds of non-survival increased (OR 2.4 95% CI 1.9, 3.1) per additional estimate, AUROC 0.70 (0.65, 0.76). For 6-month mortality predictions, similar results were observed.
Based on the initial examination, students, nurses, and physicians can only moderately predict in-hospital and 6-month mortality in critically ill patients. Combined estimations led to more accurate predictions and may serve as an example of the benefit of multidisciplinary clinical care and future research efforts.
The large, international, randomized controlled NeoPInS trial showed that procalcitonin (PCT)-guided decision making was superior to standard care in reducing the duration of antibiotic therapy and ...hospitalization in neonates suspected of early-onset sepsis (EOS), without increased adverse events. This study aimed to perform a cost-minimization study of the NeoPInS trial, comparing health care costs of standard care and PCT-guided decision making based on the NeoPInS algorithm, and to analyze subgroups based on country, risk category and gestational age.
Data from the NeoPInS trial in neonates born after 34 weeks of gestational age with suspected EOS in the first 72 h of life requiring antibiotic therapy were used. We performed a cost-minimization study of health care costs, comparing standard care to PCT-guided decision making.
In total, 1489 neonates were included in the study, of which 754 were treated according to PCT-guided decision making and 735 received standard care. Mean health care costs of PCT-guided decision making were not significantly different from costs of standard care (€3649 vs. €3616). Considering subgroups, we found a significant reduction in health care costs of PCT-guided decision making for risk category 'infection unlikely' and for gestational age ≥ 37 weeks in the Netherlands, Switzerland and the Czech Republic, and for gestational age < 37 weeks in the Czech Republic.
Health care costs of PCT-guided decision making of term and late-preterm neonates with suspected EOS are not significantly different from costs of standard care. Significant cost reduction was found for risk category 'infection unlikely,' and is affected by both the price of PCT-testing and (prolonged) hospitalization due to SAEs.
The use of lopinavir/ritonavir once-daily (LPV/r QD) has not been approved for children. Good short-term clinical, virologic and immunologic outcomes have been observed in children on LPV/r QD.
We ...evaluated the long-term effectiveness of a LPV/r QD containing regimen in HIV-1-infected children in clinical practice. Selected children (0-18 years of age) with an undetectable HIV-1 RNA viral load (<50 copies/mL) for at least 6 months on a twice-daily LPV/r-containing regimen switched to LPV/r QD. The main outcome measures were the percentage of patients with an undetectable HIV-1 viral load each subsequent year after switch to LPV/r QD (on treatment and last observation carried forward), and virologic failure during follow-up (>400 copies/mL twice within 6 months). Also, the exposure to LPV on the initial once-daily dosing regimen was determined.
Forty children (median age: 6.5 years; range: 1.0-17) were included. Median follow-up was 6.3 years (range: 1.0-10.3). During yearly follow-up, the percentage of children with an undetectable viral load varied between 82% and 100% (on treatment) and 83% and 93% (last observation carried forward). Five children (12.5%) met the criteria for failure. CD4+ and CD8+ counts remained stable at normal values. Geometric mean LPV area under the plasma concentration-time curve (linear up-log down method) over a dosing interval from time 0 to 24 hours after dosing was 169.3 mg x h/L, and last observed drug concentration was 1.35 mg/L. Adverse events were encountered in 8 patients, were mainly gastrointestinal, and in these cases, no reason to stop treatment.
A once-daily LPV/r-containing regimen in HIV-1-infected children with intensive clinical and therapeutic drug monitoring is well tolerated and has good long-term clinical, virologic and immunologic outcomes.
ObjectivesTo be able to truly involve adolescents in decision making about clinical research participation, we need more insight in the perspective of adolescents themselves. To this end, adolescents ...in an ongoing biobank study were consulted to test a tentative decision assessment tool.MethodsThe perspectives of adolescents (n=8) concerning participation in decision making for research participation were explored in interviews with a tentative tool, which covered six topics: information material usage, understanding, disease perceptions, anxiety, decision-making process and role sharing.ResultsAll adolescents unequivocally expressed the desire to be involved in decision making, but also wanted advice from their parents. The extent of the preferred role of adolescent versus parents varied between individuals. In decision making, adolescents relied on parents for information. More than half hardly used the information material.ConclusionsAdolescents in our study preferred a shared decision-making process. The extent of sharing varied between individuals. The decision assessment tool was a fruitful starting point to discuss adolescents’ perspectives and may aid in tailoring the situation to the individual to achieve optimal participation practices.ImplicationsConsulting adolescents about their preferences concerning decision making using the tool will facilitate tailoring of the shared decision-making process and optimising the developing autonomy of minors.
Background Mycoplasma pneumoniae is thought to be a common cause of respiratory tract infections (RTIs) in children. The diagnosis of M. pneumoniae RTIs currently relies on serological methods and/or ...the detection of bacterial DNA in the upper respiratory tract (URT). It is conceivable, however, that these diagnostic methods also yield positive results if M. pneumoniae is carried asymptomatically in the URT. Positive results from these tests may therefore not always be indicative of a symptomatic infection. The existence of asymptomatic carriage of M. pneumoniae has not been established. We hypothesized that asymptomatic carriage in children exists and investigated whether colonization and symptomatic infection could be differentiated by current diagnostic methods. Methods and Findings This study was conducted at the Erasmus MC-Sophia Children's Hospital and the after-hours General Practitioners Cooperative in Rotterdam, The Netherlands. Asymptomatic children (n = 405) and children with RTI symptoms (n = 321) aged 3 mo to 16 y were enrolled in a cross-sectional study from July 1, 2008, to November 30, 2011. Clinical data, pharyngeal and nasopharyngeal specimens, and serum samples were collected. The primary objective was to differentiate between colonization and symptomatic infection with M. pneumoniae by current diagnostic methods, especially real-time PCR. M. pneumoniae DNA was detected in 21.2% (95% CI 17.2%-25.2%) of the asymptomatic children and in 16.2% (95% CI 12.2%-20.2%) of the symptomatic children (p = 0.11). Neither serology nor quantitative PCR nor culture differentiated asymptomatic carriage from infection. A total of 202 children were tested for the presence of other bacterial and viral pathogens. Two or more pathogens were found in 56% (63/112) of the asymptomatic children and in 55.5% (50/90) of the symptomatic children. Finally, longitudinal sampling showed persistence of M. pneumoniae in the URT for up to 4 mo. Fifteen of the 21 asymptomatic children with M. pneumoniae and 19 of the 22 symptomatic children with M. pneumoniae in this longitudinal follow-up tested negative after 1 mo. Conclusions Although our study has limitations, such as a single study site and limited sample size, our data indicate that the presence of M. pneumoniae in the URT is common in asymptomatic children. The current diagnostic tests for M. pneumoniae are unable to differentiate between asymptomatic carriage and symptomatic infection. Please see later in the article for the Editors' Summary
Background: Impairments in arm function are a common problem in stroke survivors and have a large impact on health-related quality of life (HRQoL). Little is known about the longitudinal relationship ...between recovery of upper limb strength and changes in HRQoL.
Objectives: This study aimed to determine to what extent changes in HRQoL are related to changes in upper limb strength after discharge from inpatient rehabilitation.
Methods: 250 patients from an RCT were assessed at discharge from inpatient rehabilitation (baseline) and at 12 weeks post-discharge (follow-up). The Stroke Impact Scale was used to measure HRQoL, and the Motricity Index Arm was used to measure upper limb strength. Hierarchical regression analysis was performed to determine the predictive value of upper limb strength on HRQoL, relative to demographic and clinical characteristics. Regression analysis was used to determine the relation between upper limb strength improvement and HRQoL improvement.
Results: Upper limb strength at baseline was a major predictor of HRQoL at follow-up, after accounting for demographic and clinical characteristics (p < .05). Improvement in HRQoL was positively related to improvement in upper limb strength (F(1, 240) = 18.351, p <.0005).
Conclusions: These findings highlight the importance of upper limb strength in HRQoL, as HRQoL is associated with improvement in upper limb strength recovery. Better monitoring of recovery and treatment of upper limb strength during the outpatient rehabilitation period and beyond, i.e. outside the typical time-window of recovery in the first 3 months post-stroke, might contribute to higher quality of life for stroke survivors.
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