Tobias N. Bonten

Procalcitonin reflects bacteremia and bacterial load in urosepsis syndrome: a prospective observational study

IntroductionGuidelines recommend that two blood cultures be performed in patients with febrile urinary tract infection (UTI), to detect bacteremia and help diagnose urosepsis. The usefulness and cost-effectiveness of this practice have been criticized. This study aimed to evaluate clinical characteristics and the biomarker procalcitonin (PCT) as an aid in predicting bacteremia.MethodsA prospective observational multicenter cohort study included consecutive adults with febrile UTI in 35 primary care units and 8 emergency departments of 7 regional hospitals. Clinical and microbiological data were collected and PCT and time to positivity (TTP) of blood culture were measured.ResultsOf 581 evaluable patients, 136 (23%) had bacteremia. The median age was 66 years (interquartile range 46 to 78 years) and 219 (38%) were male. We evaluated three different models: a clinical model including seven bed-side characteristics, the clinical model plus PCT, and a PCT only model. The diagnostic abilities of these models as reflected by area under the curve of the receiver operating characteristic were 0.71 (95% confidence interval (CI): 0.66 to 0.76), 0.79 (95% CI: 0.75 to 0.83) and 0.73 (95% CI: 0.68 to 0.77) respectively. Calculating corresponding sensitivity and specificity for the presence of bacteremia after each step of adding a significant predictor in the model yielded that the PCT > 0.25 μg/l only model had the best diagnostic performance (sensitivity 0.95; 95% CI: 0.89 to 0.98, specificity 0.50; 95% CI: 0.46 to 0.55). Using PCT as a single decision tool, this would result in 40% fewer blood cultures being taken, while still identifying 94 to 99% of patients with bacteremia.The TTP of E. coli positive blood cultures was linearly correlated with the PCT log value; the higher the PCT the shorter the TTP (R2 = 0.278, P = 0.007).ConclusionsPCT accurately predicts the presence of bacteremia and bacterial load in patients with febrile UTI. This may be a helpful biomarker to limit use of blood culture resources.

Predicting the need for radiologic imaging in adults with febrile urinary tract infection.

BACKGROUNDnRadiologic evaluation of adults with febrile urinary tract infection (UTI) is frequently performed to exclude urological disorders. This study aims to develop a clinical rule predicting need for radiologic imaging.nnnMETHODSnWe conducted a prospective, observational study including consecutive adults with febrile UTI at 8 emergency departments (EDs) in the Netherlands. Outcomes of ultrasounds and computed tomographs of the urinary tract were classified as urgent urological disorder (pyonephrosis or abscess), nonurgent urologic disorder, normal, and incidental nonurological findings. Urgent and nonurgent urologic disorders were classified as clinically relevant radiologic findings. The data of 5 EDs were used as the derivation cohort, and 3 EDs served as the validation cohort.nnnRESULTSnThree hundred forty-six patients were included in the derivation cohort. Radiologic imaging was performed for 245 patients (71%). A prediction rule was derived, being the presence of a history of urolithiasis, a urine pH ≥7.0, and/or renal insufficiency (estimated glomerular filtration rate, ≤40 mL/min/1.73 m(3)). This rule predicts clinically relevant radiologic findings with a negative predictive value (NPV) of 93% and positive predictive value (PPV) of 24% and urgent urological disorders with an NPV of 99% and a PPV of 10%. In the validation cohort (n = 131), the NPV and PPV for clinically relevant radiologic findings were 89% and 20%, respectively; for urgent urological disorders, the values were 100% and 11%, respectively. Potential reduction of radiologic imaging by implementing the prediction rule was 40%.nnnCONCLUSIONSnRadiologic imaging can selectively be applied in adults with febrile UTI without loss of clinically relevant information by using a simple clinical prediction rule.

Effect of aspirin intake at bedtime versus on awakening on circadian rhythm of platelet reactivity. A randomised cross-over trial.

The risk of acute cardiovascular events is highest during morning hours, and platelet activity peaks during morning hours. The effect of timing of aspirin intake on circadian rhythm and morning peak of platelet reactivity is not known. It was our objective to evaluate the effect of timing of aspirin intake on circadian rhythm and morning peak of platelet reactivity. A randomised open-label cross-over trial in healthy subjects (n=14) was conducted. Participants used acetylsalicylic acid (80 mg) on awakening or at bedtime for two periods of two weeks, separated by a four-week wash-out period. At the end of both periods blood was drawn every 3 hours to measure COX-1-dependent (VerifyNow-Aspirin; Serum Thromboxane B2 [STxB2]) and COX-1-independent (flow cytometry surface CD62p expression; microaggregation) platelet activity. VerifyNow platelet reactivity over the whole day was similar with intake on awakening and at bedtime (mean difference: -9 [95u2009% confidence interval (CI) -21 to 4]). However, the morning increase in COX-1-dependent platelet activity was reduced by intake of aspirin at bedtime compared with on awakening (mean difference VerifyNow: -23 Aspirin Reaction Units [CI -50 to 4]; STxB2: -1.7 ng/ml [CI -2.7 to -0.8]). COX-1-independent assays were not affected by aspirin intake or its timing. Low-dose aspirin taken at bedtime compared with intake on awakening reduces COX-1-dependent platelet reactivity during morning hours in healthy subjects. Future clinical trials are required to investigate whether simply switching to aspirin intake at bedtime reduces the risk of cardiovascular events during the high risk morning hours.

Risk Factors for Bacteremia with Uropathogen Not Cultured from Urine in Adults with Febrile Urinary Tract Infection

In a prospective study involving 642 patients with febrile urinary tract infection (UTI), we found antimicrobial pretreatment (odds ratio [OR], 3.3), an indwelling urinary catheter (OR, 2.8), and malignancy (OR, 2.7) to be independent risk factors for bacteremia with a uropathogen that was not cultured or recognized in the urine. Although the diagnostic value of blood cultures has been questioned in UTI, we advocate performing blood cultures for patients with these risk factors.

Effect of an evidence-based website on healthcare usage: an interrupted time-series study

Objectives Healthcare costs and usage are rising. Evidence-based online health information may reduce healthcare usage, but the evidence is scarce. The objective of this study was to determine whether the release of a nationwide evidence-based health website was associated with a reduction in healthcare usage. Design Interrupted time series analysis of observational primary care data of healthcare use in the Netherlands from 2009 to 2014. Setting General community primary care. Population 912u2005000 patients who visited their general practitioners 18.1 million times during the study period. Intervention In March 2012, an evidence-based health information website was launched by the Dutch College of General Practitioners. It was easily accessible and understandable using plain language. At the end of the study period, the website had 2.9 million unique page views per month. Main outcomes measures Primary outcome was the change in consultation rate (consultations/1000 patients/month) before and after the release of the website. Additionally, a reference group was created by including consultations about topics not being viewed at the website. Subgroup analyses were performed for type of consultations, sex, age and socioeconomic status. Results After launch of the website, the trend in consultation rate decreased with 1.620 consultations/1000 patients/month (p<0.001). This corresponds to a 12% decline in consultations 2u2005years after launch of the website. The trend in consultation rate of the reference group showed no change. The subgroup analyses showed a specific decline for consultations by phone and were significant for all other subgroups, except for the youngest age group. Conclusions Healthcare usage decreased by 12% after providing high-quality evidence-based online health information. These findings show that e-Health can be effective to improve self-management and reduce healthcare usage in times of increasing healthcare costs.

Effect of β-blockers on platelet aggregation: a systematic review and meta-analysis

Platelets play an important role in cardiovascular disease, and β‐blockers are often prescribed for cardiovascular disease prevention. β‐Blockers may directly affect platelet aggregation, because β‐adrenergic receptors are present on platelets. There is uncertainty about the existence and magnitude of an effect of β‐blockers on platelet aggregation. The aim of this study was to perform a systematic review and meta‐analysis of the effect of β‐blockers on platelet aggregation.

Time-Dependent Effects of Aspirin on Blood Pressure and Morning Platelet Reactivity A Randomized Cross-Over Trial

Aspirin is used for cardiovascular disease (CVD) prevention by millions of patients on a daily basis. Previous studies suggested that aspirin intake at bedtime reduces blood pressure compared with intake on awakening. This has never been studied in patients with CVD. Moreover, platelet reactivity and CVD incidence is highest during morning hours. Bedtime aspirin intake may attenuate morning platelet reactivity. This clinical trial examined the effect of bedtime aspirin intake compared with intake on awakening on 24-hour ambulatory blood pressure measurement and morning platelet reactivity in patients using aspirin for CVD prevention. In this randomized open-label crossover trial, 290 patients were randomized to take 100 mg aspirin on awakening or at bedtime during 2 periods of 3 months. At the end of each period, 24-hour blood pressure and morning platelet reactivity were measured. The primary analysis population comprised 263 (blood pressure) and 133 (platelet reactivity) patients. Aspirin intake at bedtime did not reduce blood pressure compared with intake on awakening (difference systolic/diastolic: −0.1 [95% confidence interval, −1.0, 0.9]/−0.6 [95% confidence interval, −1.2, 0.0] mmu2009Hg). Platelet reactivity during morning hours was reduced with bedtime aspirin intake (difference: −22 aspirin reaction units [95% confidence interval, −35, −9]). The intake of low-dose aspirin at bedtime compared with intake on awakening did not reduce blood pressure of patients with CVD. However, bedtime aspirin reduced morning platelet reactivity. Future studies are needed to assess the effect of this promising simple intervention on the excess of cardiovascular events during the high risk morning hours.

Coordination of care for patients with COPD: Clinical points of interest

The management of care of chronic obstructive pulmonary disease improved over the last years but is still very complex. Both over- and underdiagnosis are often reported and misclassification of disease severity is common. Differentiating between chronic obstructive pulmonary disease, asthma and asthma-chronic obstructive pulmonary disease overlap syndrome remains difficult. Much is known about the effectiveness of treatment approaches in chronic obstructive pulmonary disease, but patients are often not treated according to the guidelines, and we need more evidence on effectiveness in phenotypes of chronic obstructive pulmonary disease. Care coordination is of great importance and can help to further improve care for chronic obstructive pulmonary disease patients. Pulmonary rehabilitation and self-management are considered important aspects of chronic obstructive pulmonary disease care. In our opinion, there is a major role for eHealth to improve coordination of care of chronic obstructive pulmonary disease.

Investigating the causal effect of smoking on hay fever and asthma: A Mendelian randomization meta-analysis in the CARTA consortium

Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR)u2009=u20090·68, 95% confidence interval (CI): 0·61, 0·76; Pu2009<u20090·001) and allergic sensitization (ORu2009=u20090·74, 95% CI: 0·64, 0·86; Pu2009<u20090·001), but similar asthma risk (ORu2009=u20091·00, 95% CI: 0·91, 1·09; Pu2009=u20090·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (ORu2009=u20090·958, 95% CI: 0·920, 0·998; Pu2009=u20090·041), a lower risk of allergic sensitization (ORu2009=u20090·92, 95% CI: 0·84, 1·02; Pu2009=u20090·117), but higher risk of asthma (ORu2009=u20091·06, 95% CI: 1·01, 1·11; Pu2009=u20090·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.

Pulmonary function, exhaled nitric oxide and symptoms in asthma patients with obesity: a cross-sectional study

BackgroundObesity is a risk factor for the development of asthma. In patients with obesity the diagnosis of asthma is often based on symptoms, but without objective measurements. Nevertheless, obesity-associated asthma is recognized as a distinct asthma phenotype. Therefore, this study explores lung function and symptoms in asthma patients with and without obesity.MethodsThe Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort study with 6671 participants (aged 45–65xa0years) of whom 472 had asthma. Of this latter group, linear regression analysis was used to examine differences in lung function and symptoms between asthma patients with (nu2009=u2009248) and without obesity (nu2009=u2009224), and between asthma patients with and without increased FeNO. Analyses were adjusted for confounders.ResultsAsthma patients with obesity had lower predicted FEV1 and FVC values than patients without obesity [adjusted mean difference (MD) -3.3% predicted, 95% CI -6.5, −0.2; adjusted MD −5.0% predicted, 95% CI -7.8, −2.1]. The prevalence of symptoms was higher in patients with obesity. Asthma patients with obesity and with increased FeNO had lower FEV1 and FEV1/FVC values compared with those with low FeNO (adjusted MD −6.9% predicted, 95% CI -11.7, −2.0; −2.4%, 95% CI -4.6, −0.2).ConclusionAsthma patients with obesity had lower FEV1 and FVC values than patients without obesity. This suggests that patients with obesity have restrictive lung function changes, rather than obstructive changes. Asthma patients with obesity and increased FeNO showed more obstructive changes. FeNO might help to identify patients with eosinophilic inflammation-driven asthma, whereas patients with low FeNO might have an obesity-associated asthma phenotype in which symptoms are partly caused by the obesity.