Children with fever without apparent source: diagnosis and dilemmas

Tills thesis describes the results of diagnostic research in young children presenting with fever without apparent source at the emergency department. The study was conducted at the Sophia Children's University Hospital in Rotterdam and the Juliana Children's Hospital in The Hague, both large inner-city paediatric teaching hospitals in the Netherlands. The specific aims of the studies are: 1. To describe trends in the management of children visiting the emergency department with fever without apparent source. 2. To develop a diagnostic prediction rule for referred patients presenting with fever without apparent source, including readily obtainable parameters from the patient's history, physical examination and laboratory tests in order to distinguish the patients with a serious bacterial infection from those without a serious bacterial infection. 3. To externally validate this developed diagnostic prediction rule for referred patients. 4. To obtain a diagnostic prediction rule for self-referred patients presenting with fever without apparent source, including the determination of the generalisability of the previously developed prediction rule for referred patients. 5. To deal with pitfalls with regard to diagnostic research on routine care data. 6. To compare results of internal and external validation of the developed diagnostic prediction rule for referred patients. 7. To develop a computer-based patient record for structured data entry for paediatric practice, in particular for recording data from the patient's history and physical exarnination

Structured data entry for narrative data in a broad specialty: patient history and physical examination in pediatrics.

BACKGROUND: Whereas an electronic medical record (EMR) system can partly address the limitations, of paper-based documentation, such as fragmentation of patient data, physical paper records missing and poor legibility, structured data entry (SDE, i.e. data entry based on selection of predefined medical concepts) is essential for uniformity of data, easier reporting, decision support, quality assessment, and patient-oriented clinical research. The aim of this project was to explore whether a previously developed generic (i.e. content independent) SDE application to support the structured documentation of narrative data (called OpenSDE) can be used to model data obtained at history taking and physical examination of a broad specialty. METHODS: OpenSDE was customized for the broad domain of general pediatrics: medical concepts and its descriptors from history taking and physical examination were modeled into a tree structure. RESULTS: An EMR system allowing structured recording (OpenSDE) of pediatric narrative data was developed. Patient history is described by 20 main concepts and physical examination by 11. In total, the thesaurus consists of about 1800 items, used in 8648 nodes in the tree with a maximum depth of 9 levels. Patient history contained 6312 nodes, and physical examination 2336. User-defined entry forms can be composed according to individual needs, without affecting the underlying data representation. The content of the tree can be adjusted easily and sharing records among different disciplines is possible. Data that are relevant in more than one context can be accessed from multiple branches of the tree without duplication or ambiguity of data entry via "shortcuts". CONCLUSION: An expandable EMR system with structured data entry (OpenSDE) for pediatrics was developed, allowing structured documentation of patient history and physical examination. For further evaluation in other environments, the tree structure for general pediatrics is available at the Erasmus MC Web site (in Dutch, translation into English in progress) 1. The generic OpenSDE application is available at the OpenSDE Web site 2

Mortality, weight loss and quality of life of patients with morbid obesity: evaluation of the surgical and medical treatment after 2 years Mortalidade, perda de peso e qualidade de vida em pacientes com obesidade mórbida: avaliação do tratamento cirúrgico e clínico após 2 anos

CONTEXT: The surgical treatment for morbid obesity is becoming common in this country. Only a few papers reported the long-term results of the surgical approach for morbid obesity, mainly in terms of quality of life. OBJECTIVE: To compare mortality rate, weight loss, improvement of both diabetes and hypertension, and quality of life of patients from the public healthcare in Cuiabá, MT, Brazil, who underwent either medical or surgical interventions after a minimum of 2 years. METHODS: The population of this study was constituted by morbidly obese patients who initiated treatment between June 2002 and December 2006. The casuistic consisted of 89 patients submitted to medical therapy and 76 patients who underwent surgical procedures. The main variables were weight loss, improvement of hypertension and diabetes, quality of life, and mortality. RESULTS: The overall results showed that weight loss was significant in the two groups (P<0.001); however surgical patients showed a greater loss than the medical group (P = 0.05). The improvement of diabetes and hypertension was significantly greater in the surgical group (P<0.001), in which no cases of diabetes persisted. There was an increase in cases of hypertension among patients receiving medical attention. Mortality occurred in six cases (6.7%) of the medical group and in five cases (6.6%) of the surgical group (P = 0.97). The median grade of the quality of life score obtained by surgical patients (2.37 [range: -2.50 to 3.00]) was significantly greater (P<0.001) when compared to the medical group (1.25 [range: -1.50 to 3.00]). CONCLUSION: The surgical group presented better results regarding the weight loss, quality of life and improvement of hypertension and diabetes. There was no significant difference in mortality rate between the two groups after a minimum of 2 years.<br>CONTEXTO: O tratamento cirúrgico da obesidade mórbida, vem se tornando frequente no país. Poucos trabalhos avaliaram os resultados a longo prazo do tratamento cirúrgico da obesidade mórbida, principalmente em termos de qualidade de vida. OBJETIVO: Comparar pacientes usuários do SUS em Cuiabá, MT tratados clínica ou cirurgicamente, observando taxa de mortalidade, perda de peso, evolução do diabetes e hipertensão e qualidade de vida após pelo menos 2 anos do início do tratamento. MÉTODO: A população do estudo foi constituída de obesos mórbidos pacientes da rede pública, tratados no período de junho de 2002 a dezembro de 2006. A casuística consistiu de 89 pacientes tratados clinicamente e 76 pacientes operados. As principais variáveis foram perda de peso, melhora da hipertensão e diabetes, qualidade de vida e mortalidade. RESULTADOS: Houve significativa perda de peso nos dois grupos (P<0.001), porém pacientes operados apresentaram queda significativamente maior do que o grupo clínico (P = 0,05). Diabetes e hipertensão apresentaram melhora significativa apenas no grupo cirúrgico (P<0,001), não se evidenciando mais casos de diabetes entre eles e havendo aumento do número de hipertensos entre os tratados clinicamente. A mortalidade após 2 anos foi de seis casos (6,7%) no grupo clínico e de cinco (6,6%) no cirúrgico (P = 0,97). A média da pontuação de qualidade de vida obtida pelos pacientes cirúrgicos (2,37 [variação: -2,50 a 3,00]) foi significativamente maior (P<0,001) que a obtida pelo grupo clínico (1,25 [variação: -1,50 a 3,00]). CONCLUSÃO: O grupo cirúrgico apresentou melhores resultados quanto à perda de peso, qualidade de vida e melhora da hipertensão e diabetes. Não houve diferença estatisticamente significante quanto a taxa de mortalidade quando comparados pacientes submetidos aos dois tipos de tratamento

The effect of measuring serum doxycycline concentrations on clinical outcomes during treatment of chronic Q fever

Background: First choice treatment for chronic Q fever is doxycycline plus hydroxychloroquine. Serum doxycycline concentration (SDC) >5 mug/mL has been associated with a favourable serological response, but the effect on clinical outcomes is unknown. Objectives: To assess the effect of measuring SDC during treatment of chronic Q fever on clinical outcomes. Methods: We performed a retrospective cohort study, to assess the effect of measuring SDC on clinical outcomes in patients treated with doxycycline and hydroxychloroquine for chronic Q fever. Primary outcome was the first disease-related event (new complication or chronic Q fever-related mortality); secondary outcomes were all-cause mortality and PCR-positivity. Multivariable analysis was performed with a Cox proportional hazards model, with shared-frailty terms for different hospitals included. Results: We included 201 patients (mean age 68 years, 83% male): in 167 patients (83%) SDC was measured, 34 patients (17%) were treated without SDC measurement. First SDC was >5 mug/mL in 106 patients (63%), all with 200 mg doxycycline daily. In patients with SDC measured, dosage was adjusted in 41% (n = 68), concerning an increase in 64 patients. Mean SDC was 4.1 mug/mL before dosage increase, and 5.9 mug/mL afterwards. SDC measurement was associated with a lower risk for disease-related events (HR 0.51, 95% CI 0.26-0.97, P = 0.04), but not with all-cause mortality or PCR-positivity. Conclusions: SDC measurement decreases the risk for disease-related events, potentially through more optimal dosing or improved compliance. We recommend measurement of SDC and striving for SDC >5 mug/mL and <10 mug/mL during treatment of chronic Q fever

Paper versus computer: Feasibility of an electronic medical record in general pediatrics

BACKGROUND. Implementation of electronic medical record systems promises significant advances in patient care, because such systems enhance readability, availability, and data quality. Structured data entry (SDE) applications can prompt for completeness, provide greater accuracy and better ordering for searching and retrieval, and permit validity checks for data quality monitoring, research, and especially decision support. A generic SDE application (OpenSDE) to support documentation of patient history and physical examination findings was developed and tailored for the domain of general pediatrics. OBJECTIVE. To evaluate OpenSDE for its completeness, uniformity of reporting, and usability in general pediatrics. METHODS. Four (trainee) pediatricians documented data for 8 first-visit patients in the traditional, paper-based, medical record and immediately thereafter in OpenSDE (electronic record). The 32 paper records obtained served as the common data source for data entry in OpenSDE by the other 3 physicians (transcribed record). Data entered by 2 experienced users, with all patient information present in the paper record, served as the control record. Data entry times were recorded, and a questionnaire was used to assess users' experiences with OpenSDE. RESULTS. Clinicians documented 44% of all available patient information identically in the paper and electronic records. Twenty-five percent of all patient information was documented only in the paper record, and 31% was present only in the electronic record. Differences were found in patient history and physical examination documentation in the electronic record; more information was missing for patient history (38%) than for physical examination (15%). Furthermore, physical examination contained more additional information (39%) than did patient history (21%). The interobserver agreement of documentation of patient information from the same data source was fair to moderate, with κ values of 0.39 for patient history and 0.40 for physical examination. Data entry times in OpenSDE decreased from 25 minutes to <15 minutes, indicating a learning effect. The questionnaire revealed a positive attitude toward the use of OpenSDE in daily practice. CONCLUSION. OpenSDE seems to be a promising application for the support of physician data entry in general pediatrics. Copyrigh

Chronic Q fever-related complications and mortality: data from a nationwide cohort

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No increased risk of mature B-cell non-Hodgkin lymphoma after Q fever detected: results from a 16-year ecological analysis of the Dutch population incorporating the 2007-2010 Q fever outbreak

BACKGROUND: A causative role of Coxiella burnetii (the causative agent of Q fever) in the pathogenesis of B-cell non-Hodgkin lymphoma (NHL) has been suggested, although supporting studies show conflicting evidence. We assessed whether this association is present by performing a detailed analysis on the risk of mature B-cell NHL after Q fever during and after the largest Q fever outbreak reported worldwide in the entire Dutch population over a 16-year period. METHODS: We performed an ecological analysis. The incidence of mature B-cell NHL in the entire Dutch population from 2002 until 2017 was studied and modelled with reported acute Q fever cases as the determinant. The adjusted relative risk of NHL after acute Q fever as the primary outcome measure was calculated using a Poisson regression. RESULTS: Between January 2002 and December 2017, 266 050 745 person-years were observed, with 61 424 diagnosed with mature B-cell NHL. In total, 4310 persons were diagnosed with acute Q fever, with the highest incidence in 2009. The adjusted relative risk of NHL after acute Q fever was 1.02 (95% CI 0.97-1.06, P = 0.49) and 0.98 (95% CI 0.89-1.07, P = 0.60), 0.99 (95% CI 0.87-1.12, P = 0.85) and 0.98 (95% 0.88-1.08, P = 0.67) for subgroups of diffuse large B-cell lymphoma, follicular lymphoma or B-cell chronic lymphocytic leukaemia, respectively. Modelling with lag times (1-4 years) did not change interpretation. CONCLUSION: We found no evidence for an association between C. burnetii and NHL after studying the risk of mature B-cell NHL after a large Q fever outbreak in Netherlands

Decompaction of G4/DNA complexes using the polysaccharide heparin.

<p>(A) GelStar-stained gel showing the degree of dissociation of G4/DNA complexes (<i>r</i>_charge  = 0.90) for the indicated concentrations of heparin. The 1^st lane shows the linearized plasmid DNA only (25 μg mL⁻¹, control). (B) GelStar fluorescence measured by steady state fluorescence spectroscopy as a function of heparin concentration. Measurements are performed for DNA (2 μg mL⁻¹) with complexes of <i>r</i>_charge  = 0.35 (•), 0.55 (□) and 0.90 (▵). The intensity is normalized to that of free DNA (in the absence of G4) and error bars are smaller or equal to the marker size. Inset shows the concentration ratios of heparin and DNA.</p