249 research outputs found

    Mapping the Spread of Malaria Drug Resistance

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    Tim Anderson discusses a new study of molecular variation in alleles at the dihydropteroate synthase locus, which underlies resistance to sulfadoxine, in over 5,000 parasites from 50 locations

    Rotavirus and illness severity in children presenting with acute gastroenteritis at the primary care out-of-hours service

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    BACKGROUND: Rotavirus is a common cause of acute gastroenteritis in young children in the Netherlands, where rotavirus vaccination has not yet been implemented. OBJECTIVES: To evaluate a difference in illness severity course depending on the presence of rotavirus infection and assess the prevalence of viruses and the referral rate in children with acute gastroenteritis. METHODS: A prospective cohort of children aged 6 months to 6 years presenting with acute gastroenteritis to a primary care out-of-hours service from October 2016 to March 2018. Faeces were sampled and sent to a laboratory where viral pathogens were identified and quantified by real-time polymerase chain reaction. Severe course of acute gastroenteritis was defined as a Modified Vesikari Score of ≥11. In addition, we assessed referral rates. Chi-square tests were used to evaluate differences between groups. RESULTS: We included 75 children (34 boys) with a median age of 1.5 years (interquartile range, 0.9–2.0 years). The prevalence of rotavirus was 65.3% (95% confidence interval, 53.5–76.0) with a median cycle threshold of 16.0. Severe course of acute gastroenteritis was present in 31 of 71 children (4 were lost to follow-up). Those with rotavirus (20/47) did not have a severe course more often than those without (11/24): odds ratio, 0.88 (95% confidence interval, 0.33–2.36). Referral rates were comparable for rotavirus (15.2%) and non-rotavirus (14.3%). CONCLUSION: In out-of-hours primary care, rotavirus is common but not associated with increased severity and higher referral rates in children with acute gastroenteritis

    Course of uncomplicated acute gastroenteritis in children presenting to out-of-hours primary care

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    Background The aim of this article is to describe the courses of vomiting, diarrhea, fever, and clinical deterioration, in children with uncomplicated gastroenteritis at presentation. This study was performed as a 7-day prospective follow-up study in an out-of-hours primary care service. The course of vomiting, diarrhea, and fever was analyzed by generalized linear mixed modeling. Because young children ( 90%). Vomiting and fever decreased rapidly, but diarrhea decreased at a somewhat slower pace, especially among children aged 6-12 months. Children who deteriorated during follow-up had a higher frequency of vomiting at presentation and higher frequencies of vomiting and fever during follow-up. Conclusions The frequency of vomiting, not its duration, appears to be the more important predictor of deterioration. When advising parents, it is important to explain the typical symptom duration and to focus on alarm symptoms. Clinicians should be vigilant for children with higher vomiting frequencies at presentation and during follow-up because these children are more likely to deteriorate

    Cost-effectiveness of oral ondansetron for children with acute gastroenteritis in primary care:a randomised controlled trial

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    BackgroundAcute gastroenteritis is a common childhood condition with substantial medical and indirect costs, mostly because of referral, hospitalisation, and parental absence from work.AimTo determine the cost-effectiveness of adding oral ondansetron to care as usual (CAU) for children with acute gastroenteritis presenting to out-of-hours primary care (OOH-PC).Design and settingA pragmatic randomised controlled trial from December 2015 to January 2018, at three OOH-PC centres in the north of the Netherlands (Groningen, Zwolle, and Assen) with a follow-up of 7 days.MethodChildren were recruited at the OOH-PC and parents kept a parental diary. Inclusion criteria were: aged 6 months-6 years; diagnosis of acute gastroenteritis; at least four reported episodes of vomiting 24 hours before presentation, at least one of which was in the 4 hours before presentation; and written informed consent from both parents. Children were randomly allocated at a 1:1 ratio to either CAU (oral rehydration therapy) or CAU plus one dose of 0.1 mg/kg oral ondansetron.ResultsIn total, 194 children were included for randomisation. One dose of oral ondansetron decreased the proportion of children who continued vomiting within the first 4 hours from 42.9% to 19.5%, (a decrease of 54.5%), with an odds ratio of 0.4 (95% confidence interval [CI] = 0.2 to 0.7; number needed to treat: four). Total mean costs in the ondansetron group were 31.2% lower ((sic)488 [420] pound versus (sic)709 [610]) pound, and the total incremental mean costs for an additional child free of vomiting in the first 4 hours was -(sic)9 (8) pound (95% CI = -(sic)41 [35] pound to (sic)3 [3]) pound.ConclusionA single oral dose of ondansetron for children with acute gastroenteritis, given in OOH-PC settings, is both clinically beneficial and cost-effective.</p

    Diagnostic performance of preoperative CT in differentiating between benign and malignant origin of suspicious gallbladder lesions

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    Purpose: To determine diagnostic performance of preoperative CT in differentiating between benign and malignant suspicious gallbladder lesions and to develop a preoperative risk score. Method: All patients referred between January 2007 and September 2018 for suspicion of gallbladder cancer (GBC) or incidentally found GBC were retrospectively analyzed. Patients were excluded when preoperative CT or histopathologic examination was lacking. Two radiologists, blinded to histopathology results, independently reviewed CT images to differentiate benign disease from GBC. Multivariable analysis and internal validation were used to develop a risk score for GBC. Model discrimination, calibration, and diagnostic performance were assessed. Results: In total, 118 patients with 39 malignant (33 %) and 79 benign (67 %) lesions were included. Sensitivity of CT for diagnosing GBC was 90 % (95 % confidence interval [CI]: 76?97). Specificity rates were 61 % (95 % CI: 49?72) and 59 % (95 % CI: 48?70). Three predictors of GBC (irregular lesion aspect, absence of fat stranding, and locoregional lymphadenopathy) were included in the risk score ranging from -1 to 4. Adequate performance was found (AUC: 0.79, calibration slope: 0.89). In patients allocated >0 points, the model showed higher performance in excluding GBC than the radiologists (sensitivity 92 % [95 % CI: 79?98]). Moreover, when allocated >3 points, the risk score was superior in diagnosing GBC (specificity 99 % [95 % CI: 93?100]). Conclusions: Sensitivity rates of CT for differentiation between benign and malignant gallbladder lesions are high, however specificity rates are relatively low. The proposed risk score may facilitate differentiation between benign and malignant suspicious gallbladder lesions

    Heritability Enrichment Implicates Microglia in Parkinson's Disease Pathogenesis

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    Objective Understanding how different parts of the immune system contribute to pathogenesis in Parkinson's disease is a burning challenge with important therapeutic implications. We studied enrichment of common variant heritability for Parkinson's disease stratified by immune and brain cell types. Methods We used summary statistics from the most recent meta-analysis of genomewide association studies in Parkinson's disease and partitioned heritability using linkage disequilibrium score regression, stratified for specific cell types, as defined by open chromatin regions. We also validated enrichment results using a polygenic risk score approach and intersected disease-associated variants with epigenetic data and expression quantitative loci to nominate and explore a putative microglial locus. Results We found significant enrichment of Parkinson's disease risk heritability in open chromatin regions of microglia and monocytes. Genomic annotations overlapped substantially between these 2 cell types, and only the enrichment signal for microglia remained significant in a joint model. We present evidence suggesting P2RY12, a key microglial gene and target for the antithrombotic agent clopidogrel, as the likely driver of a significant Parkinson's disease association signal on chromosome 3. Interpretation Our results provide further support for the importance of immune mechanisms in Parkinson's disease pathogenesis, highlight microglial dysregulation as a contributing etiological factor, and nominate a targetable microglial gene candidate as a pathogenic player. Immune processes can be modulated by therapy, with potentially important clinical implications for future treatment in Parkinson's disease. ANN NEUROL 202

    Diagnostic accuracy of follow-up tests for detecting colorectal cancer recurrences in primary care:A systematic review and meta-analysis

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    Introduction Traditionally, follow-up of colorectal cancer (CRC) is performed in secondary care. In new models of care, the screening part care could be replaced to primary care. We aimed to synthesise evidence on the diagnostic accuracy of commonly used screeners in CRC follow-up applicable in primary care: carcinoembryonic antigen (CEA), ultrasound and physical examination. Methods Medline, EMBASE, Cochrane Trial Register and Web of Science databases were systematically searched. Studies were included if they provided sufficient data for a 2 × 2 contingency tables. QUADAS-2 was used to assess methodological quality. We performed bivariate random effects meta-analysis, generated a hypothetical cohort, and reported sensitivity and specificity. Results We included 12 studies (n = 3223, median recurrence rate 19.6%). Pooled estimates showed a sensitivity for CEA (≤ 5 μg/l) of 59% [47%–70%] and a specificity of 89% [80%–95%]. Only few studies reported sensitivities and specificities for ultrasound (36–70% and 97–100%, respectively) and clinical examination (23% and 27%, respectively). Conclusion In practice, GPs could perform CEA screening. Radiological examination in a hospital setting should remain part of the surveillance strategy. Personalised algorithms accounting for recurrence risk and changes of CEA-values over time might add to the diagnostic value of CEA in primary care

    Oral ondansetron for paediatric gastroenteritis in primary care:a randomised controlled trial

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    BACKGROUND: Acute gastroenteritis (AGE) affects almost all children aged ≤5 years. In secondary care, ondansetron was found to be effective at reducing vomiting. AIM: To determine the effectiveness of adding oral ondansetron to care as usual (CAU) to treat vomiting in children with AGE attending out-ofhours primary care (OOH-PC). DESIGN AND SETTING: A pragmatic randomised controlled trial at three OOH-PC centres in the north of the Netherlands (Groningen, Zwolle, and Assen), with a follow-up of 7 days. METHOD: Children were included if they were: aged 6 months–6 years; AGE diagnosed by a GP; ≥4 reported episodes of vomiting in the 24 hours before presentation; ≥1 reported episode of vomiting in the 4 hours before presentation; and written informed consent from both parents. Children were randomly allocated to either the control group or the intervention group. The control group received CAU, namely oral rehydration therapy. The intervention group received CAU plus one dose of oral ondansetron (0.1 mg/kg). RESULTS: In total, 194 children were included for randomisation. One dose of oral ondansetron decreased the proportion of children who continued vomiting within 4 hours from 42.9% to 19.5%, with an odds ratio of 0.37 (95% confidence interval [CI] = 0.20 to 0.72, number needed to treat: four). Ondansetron also decreased the number of vomiting episodes within 4 hours (incidence rate ratio 0.51 [95% CI = 0.29 to 0.88]) and improved overall parental satisfaction with treatment (P = 0.027). CONCLUSION: Children with AGE and increased risk of dehydration due to vomiting could be treated with ondansetron in primary care to stop vomiting more quickly and increase parental satisfaction with treatment. These results could be used to improve the quality and efficacy of general practice medicine

    Physiotherapy for Children with Functional Constipation:A Pragmatic Randomized Controlled Trial in Primary Care

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    Objective: To determine the effectiveness of physiotherapy plus conventional treatment compared with conventional treatment alone for the treatment of functional constipation in children age 4-17 years in primary care. Study design: Pragmatic randomized controlled trial with 8 months follow-up. Primary care physicians recruited children diagnosed with functional constipation (n = 234), and pediatricians recruited newly referred children with a diagnosis of functional constipation (n = 11). Conventional treatment comprised toilet training, nutritional advice, and laxative prescribing, whereas physiotherapy focused on resolving dyssynergic defecation. The primary outcome was treatment success over 8 months, defined as the absence of functional constipation (Rome III criteria) without laxative use. Secondary outcomes included the absence of functional constipation irrespective of continuation of laxative use and global perceived treatment effect. Results: Children were allocated to conventional treatment plus physiotherapy or conventional treatment alone (67 per group), mean (SD) age was 7.6 (3.5) years. Results of longitudinal analyses in the intention-to-treat population showed that the treatment success percentage was not statistically improved by adding physiotherapy to conventional treatment (adjusted relative risk [aRR] 0.80, 95% CI 0.44-1.30). At 4 months, fewer children receiving physiotherapy had treatment success (17%) than children receiving conventional treatment alone (28%), but this had equalized by 8 months (42% and 41%, respectively). The percentage of children without functional constipation, irrespective of continuation of laxative use, was not statistically different between groups over 8 months (aRR 1.12, 95% CI 0.82-1.34). Notably, parents reported significantly more global symptom improvement after physiotherapy than after conventional treatment (aRR 1.40; 95% CI 1.00-1.73). Conclusions: We find no evidence to recommend physiotherapy for all children with functional constipation in primary care. Trial registration: Netherlands Trial Registry: NTR4797
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