Computerized general practice based networks yield comparable performance with sentinel data in monitoring epidemiological time-course of influenza-like illness and acute respiratory illness

<p>Abstract</p> <p>Background</p> <p>Computerized morbidity registration networks might serve as early warning systems in a time where natural epidemics such as the H₁N₁flu can easily spread from one region to another.</p> <p>Methods</p> <p>In this contribution we examine whether general practice based broad-spectrum computerized morbidity registration networks have the potential to act as a valid surveillance instrument of frequently occurring diseases. We compare general practice based computerized data assessing the frequency of influenza-like illness (ILI) and acute respiratory infections (ARI) with data from a well established case-specific sentinel network, the European Influenza Surveillance Scheme (EISS). The overall frequency and trends of weekly ILI and ARI data are compared using both networks.</p> <p>Results</p> <p>Detection of influenza-like illness and acute respiratory illness occurs equally fast in EISS and the computerized network. The overall frequency data for ARI are the same for both networks, the overall trends are similar, but the increases and decreases in frequency do not occur in exactly the same weeks. For ILI, the overall rate was slightly higher for the computerized network population, especially before the increase of ILI, the overall trend was almost identical and the increases and decreases occur in the same weeks for both networks.</p> <p>Conclusions</p> <p>Computerized morbidity registration networks are a valid tool for monitoring frequent occurring respiratory diseases and the detection of sudden outbreaks.</p

Trends in total cholesterol screening and in prescribing lipid-lowering drugs in general practice in the period 1994–2003

<p>Abstract</p> <p>Background</p> <p>General Practitioners (GPs) play a central role in controlling an important risk factor for cardiovascular diseases, i.e. cholesterol levels in serum. In the past few decades different studies have been published on the effect of treating hyperlipidemia with statins. Guidelines for treatment have been adopted. We investigated the consequences on the practice of GPs screening cholesterol levels and on the timing of starting statin prescription.</p> <p>Methods</p> <p>For this descriptive study, data from the Intego database were used, composed with data from the electronic medical records (EMR) of 47 general practices in Flanders. GPs had not received special instructions for testing specific patients. For each patient the mean cholesterol level per year was calculated. A patient belonged to the group with lipid-lowering drugs if there was at least one prescription of the drug in a year in his EMR. Mixed model linear regression models were used to quantify the effect of covariates on total cholesterol values.</p> <p>Results</p> <p>In the period 1994–2003 total cholesterol was tested in 47,254 out of 139,148 different patients. Twelve percent of those tested took lipid-lowering medication. The proportion of patients with at least one cholesterol test a year, increased over a period of ten years in all age groups, but primarily for those over the age of 65.</p> <p>The mean cholesterol level decreased in the treated as well as in the non-treated group. Of the patients with a cardiovascular antecedent who were on lipid-lowering drugs in 2003, 56% had a cholesterol level ≤ 199 mg/dl, 31% between 200–239 and 13% over 240 mg/dl.</p> <p>Conclusion</p> <p>The indications for testing and treating cholesterol levels broadened considerably in the period examined. In 2003 cholesterol was tested in many more patients and patients were already treated at lower cholesterol values than in previous years. Comparisons of cholesterol levels over different years should therefore be interpreted with caution as they are a reflection of changes in medical care, and not necessarily of efficacy of treatment.</p

High-resolution profiling of the LEDGF/p75 chromatin interaction in the ENCODE region

Lens epithelium-derived growth factor/p75 (LEDGF/p75) is a transcriptional coactivator involved in stress response, autoimmune disease, cancer and HIV replication. A fusion between the nuclear pore protein NUP98 and LEDGF/p75 has been found in human acute and chronic myeloid leukemia and association of LEDGF/p75 with mixed-lineage leukemia (MLL)/menin is critical for leukemic transformation. During lentiviral replication, LEDGF/p75 tethers the pre-integration complex to the host chromatin resulting in a bias of integration into active transcription units (TUs). The consensus function of LEDGF/p75 is tethering of cargos to chromatin. In this regard, we determined the LEDGF/p75 chromatin binding profile. To this purpose, we used DamID technology and focused on the highly annotated ENCODE (Encyclopedia of DNA Elements) regions. LEDGF/p75 primarily binds downstream of the transcription start site of active TUs in agreement with the enrichment of HIV-1 integration sites at these locations. We show that LEDGF/p75 binding is not restricted to stress response elements in the genome, and correlation analysis with more than 200 genomic features revealed an association with active chromatin markers, such as H3 and H4 acetylation, H3K4 monomethylation and RNA polymerase II binding. Interestingly, some associations did not correlate with HIV-1 integration indicating that not all LEDGF/p75 complexes on the chromosome are amenable to HIV-1 integration

nsP4 is a major determinant of Alphavirus replicase activity and template selectivity

Alphaviruses have positive-strand RNA genomes containing two open reading frames (ORFs). The first ORF encodes the nonstructural (ns) polyproteins P123 and P1234 that act as precursors for the subunits of the viral RNA replicase (nsP1 to nsP4). Processing of P1234 leads to the formation of a negative-strand replicase consisting of nsP4 (RNA polymerase) and P123 components. Subsequent processing of P123 results in a positive-strand replicase. The second ORF encoding the structural proteins is expressed via the synthesis of a subgenomic RNA. Alphavirus replicase is capable of using template RNAs that contain essential cis-active sequences. Here, we demonstrate that the replicases of nine alphaviruses, expressed in the form of separate P123 and nsP4 components, are active. Their activity depends on the abundance of nsP4. The match of nsP4 to its template strongly influences efficient subgenomic RNA synthesis. nsP4 of Barmah Forest virus (BFV) formed a functional replicase only with matching P123, while nsP4s of other alphaviruses were compatible also with several heterologous P123s. The P123 components of Venezuelan equine encephalitis virus and Sindbis virus (SINV) required matching nsP4s, while P123 of other viruses could form active replicases with different nsP4s. Chimeras of Semliki Forest virus, harboring the nsP4 of chikungunya virus, Ross River virus, BFV, or SINV were viable. In contrast, chimeras of SINV, harboring an nsP4 from different alphaviruses, exhibited a temperature-sensitive phenotype. These findings highlight the possibility for formation of new alphaviruses via recombination events and provide a novel approach for the development of attenuated chimeric viruses for vaccination strategies. </p

The evolution of renal function and the incidence of end-stage renal disease in patients aged

Abstract Background. The prevalence of chronic kidney disease (CKD) is high, especially among older patients. Methods. In order to identify risk factors for the evolution towards end-stage renal disease (ESRD), a cohort of patients !50 years of age for whom at least four serum creatinine measurements were available were selected from a primary care-based database. The slope of changes in estimated glomerular filtration rate (eGFR) (using the Modification of Diet in Renal Disease formula) was calculated, and ESRD was defined as eGFR &lt;15 mL/min. Risk factors for ESRD were analysed using Cox regression analysis. Conclusions. Baseline eGFR, diabetes, high cholesterol, high LDL, hypertension and female gender are independent risk factors for developing ESRD. Older age at baseline predicts a lower risk

Cross-utilisation of template RNAs by alphavirus replicases

Most alphaviruses (family Togaviridae) including Sindbis virus (SINV) and other human pathogens, are transmitted by arthropods. The first open reading frame in their positive strand RNA genome encodes for the non-structural polyprotein, a precursor to four separate subunits of the replicase. The replicase interacts with cis-acting elements located near the intergenic region and at the ends of the viral RNA genome. A trans-replication assay was developed and used to analyse the template requirements for nine alphavirus replicases. Replicases of alphaviruses of the Semliki Forest virus complex were able to cross-utilize each other's templates as well as those of outgroup alphaviruses. Templates of outgroup alphaviruses, including SINV and the mosquito-specific Eilat virus, were promiscuous; in contrast, their replicases displayed a limited capacity to use heterologous templates, especially in mosquito cells. The determinants important for efficient replication of template RNA were mapped to the 5' region of the genome. For SINV these include the extreme 5'- end of the genome and sequences corresponding to the first stem-loop structure in the 5' untranslated region. Mutations introduced in these elements drastically reduced infectivity of recombinant SINV genomes. The trans-replicase tools and approaches developed here can be instrumental in studying alphavirus recombination and evolution, but can also be applied to study other viruses such as picornaviruses, flaviviruses and coronaviruses.</p

Incident somatic comorbidity after psychosis: Results from a retrospective cohort study based on Flemish general practice data

Background: Psychotic conditions and especially schizophrenia, have been associated with increased morbidity and mortality. Many studies are performed in specialized settings with a strong focus on schizophrenia. Somatic comorbidity after psychosis is studied, using a general practice comorbidity registration network. Methods. Hazard ratios are presented resulting from frailty models to assess the risk of subsequent somatic disease after a diagnosis of psychosis compared to people without psychosis matched on practice, age and gender. Diseases studied are cancer, physical trauma, diabetes mellitus, gastrointestinal disorders, joint disorders, irritable bowel syndrome, general infections, metabolic disorders other than diabetes, hearing and vision problems, anemia, cardiovascular disease, alcohol abuse, lung disorders, mouth and teeth problems, sexually transmitted diseases. Results: Significant higher risks after a diagnosis of psychosis were found for the emergence of diabetes, physical trauma, gastrointestinal disorders, alcohol abuse, chronic lung disease and teeth and mouth problems. With regard to diabetes, by including the type of antipsychotic medication it is clear that the significant overall effect was largely due to the use of atypical antipsychotic medication. No significant higher risk was seen for cancer, joint conditions, irritable bowel syndrome, general infections, other metabolic conditions, hearing/vision problems, anaemia, cardiovascular disease or diabetes, in case no atypical antipsychotic medication was used. Conclusion: Significantly higher morbidity rates for some somatic conditions in patients with psychosis are apparent. People with a diagnosis of psychosis benefit from regular assessments for the emergence of somatic disorders and risk factors, including diabetes in case of atypical antipsychotic medication

Readiness of the Belgian network of sentinel general practitioners to deliver electronic health record data for surveillance purposes: results of survey study

<p>Abstract</p> <p>Background</p> <p>In order to proceed from a paper based registration to a surveillance system that is based on extraction of electronic health records (EHR), knowledge is needed on the number and representativeness of sentinel GPs using a government-certified EHR system and the quality of EHR data for research, expressed in the compliance rate with three criteria: recording of home visits, use of prescription module and diagnostic subject headings.</p> <p>Methods</p> <p>Data were collected by annual postal surveys between 2005 and 2009 among all sentinel GPs. We tested relations between four key GP characteristics (age, gender, language community, practice organisation) and use of a certified EHR system by multivariable logistic regression. The relation between EHR software package, GP characteristics and compliance with three quality criteria was equally measured by multivariable logistic regression.</p> <p>Results</p> <p>A response rate of 99% was obtained. Of 221 sentinel GPs, 55% participated in the surveillance without interruption from 2005 onwards, i.e. all five years, and 78% were participants in 2009. Sixteen certified EHR systems were used among 91% of the Dutch and 63% of the French speaking sentinel GPs. The EHR software package was strongly related to the community and only one EHR system was used by a comparable number of sentinel GPs in both communities. Overall, the prescription module was always used and home visits were usually recorded. Uniform subject headings were only sometimes used and the compliance with this quality criterion was almost exclusively related to the EHR software package in use.</p> <p>Conclusions</p> <p>The challenge is to progress towards a sentinel network of GPs delivering care-based data that are (partly) extracted from well performing EHR systems and still representative for Belgian general practice.</p

LEDGF/p75 Proteins with Alternative Chromatin Tethers Are Functional HIV-1 Cofactors

LEDGF/p75 can tether over-expressed lentiviral integrase proteins to chromatin but how this underlies its integration cofactor role for these retroviruses is unclear. While a single integrase binding domain (IBD) binds integrase, a complex N-terminal domain ensemble (NDE) interacts with unknown chromatin ligands. Whether integration requires chromatin tethering per se, specific NDE-chromatin ligand interactions or other emergent properties of LEDGF/p75 has been elusive. Here we replaced the NDE with strongly divergent chromatin-binding modules. The chimeras rescued integrase tethering and HIV-1 integration in LEDGF/p75-deficient cells. Furthermore, chromatin ligands could reside inside or outside the nucleosome core, and could be protein or DNA. Remarkably, a short Kaposi's sarcoma virus peptide that binds the histone 2A/B dimer converted GFP-IBD from an integration blocker to an integration cofactor that rescues over two logs of infectivity. NDE mutants were corroborative. Chromatin tethering per se is a basic HIV-1 requirement and this rather than engagement of particular chromatin ligands is important for the LEDGF/p75 cofactor mechanism

The appropriateness of prescribing antibiotics in the community in Europe: study design

Contains fulltext : 97417.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Over 90% of all antibiotics in Europe are prescribed in primary care. It is important that antibiotics are prescribed that are likely to be effective; however, information about antibiotic resistance in the community is incomplete. The aim of our study is to investigate the appropriateness of antibiotic prescribing in primary care in Europe by collecting and combining patterns of antibiotic resistance patterns and antibiotic prescription patterns in primary care. We will also evaluate the appropriateness of national antibiotic prescription guidelines in relation to resistance patterns. METHODS/DESIGN: Antibiotic resistance will be studied in an opportunistic sample from the community in nine European countries. Resistance data will be collected by taking a nose swab of persons (N = 4,000 per country) visiting a primary care practice for a non-infectious disease. Staphylococcus aureus and Streptococcus pneumoniae will be isolated and tested for resistance to a range of antibiotics in one central laboratory. Data on antibiotic prescriptions over the past 5 years will be extracted from the electronic medical records of General Practitioners (GPs). The results of the study will include the prevalence and resistance data of the two species and 5 years of antibiotic prescription data in nine European countries.The odds of receiving an effective antibiotic in each country will be calculated as a measure for the appropriateness of prescribing. Multilevel analysis will be used to assess the appropriateness of prescribing. Relevant treatment guidelines of the nine participating countries will be evaluated using a standardized instrument and related to the resistance patterns in that country. DISCUSSION: This study will provide valuable and unique data concerning resistance patterns and prescription behaviour in primary care in nine European countries. It will provide evidence-based recommendations for antibiotic treatment guidelines that take resistance patterns into account which will be useful for both clinicians and policy makers. By improving antibiotic use we can move towards controlling the resistance problem globally