Personalised exhaled nitric oxygen fraction (F ENO)-driven asthma management in primary care: a F ENO subgroup analysis of the ACCURATE trial.

BACKGROUND: The aim of this study was to identify patients who benefit most from exhaled nitric oxide fraction (F ENO)-driven asthma management in primary care, based on prespecified subgroups with different levels of F ENO. METHODS: We used data from 179 adults with asthma from a 12-month primary care randomised controlled trial with 3-monthly assessments of F ENO, asthma control, medication usage, costs of medication, severe asthma exacerbations and quality of life. In the original study, patients were randomised to either a symptom-driven treatment strategy (controlled asthma (Ca) strategy) or a F ENO+symptom-driven strategy (FCa). In both groups, patients were categorised by their baseline level of F ENO as low (<25 ppb), intermediate (25-50 ppb) and high (>50 ppb). At 12 months, we compared, for each prespecified F ENO subgroup, asthma control, asthma-related quality of life, medication usage, and costs of medication between the Ca and FCa strategy. RESULTS: We found a difference between the Ca and FCa strategy for the mean dosage of beclomethasone strategy of 223 µg (95% CI 6-439), p=0.04) and for the total costs of asthma medication a mean reduction of US$159 (95% CI US$33-285), p=0.03) in patients with a low baseline F ENO level. No differences were found for asthma control, severe asthma exacerbations and asthma-related quality of life in patients with a low baseline F ENO level. Furthermore, in patients with intermediate or high level of F ENO, no differences were found. CONCLUSIONS: In primary care, F ENO-driven asthma management is effective in patients with a low F ENO level, for whom it is possible to down-titrate medication, while preserving asthma control and quality of life.

Prediction of prolonged treatment course for depressive and anxiety disorders in an outpatient setting: The Leiden routine outcome monitoring study.

OBJECTIVE: The aim of this study was to improve clinical identification of patients with a prolonged treatment course for depressive and anxiety disorders early in treatment. METHOD: We conducted a cohort study in 1.225 adult patients with a depressive or anxiety disorders in psychiatric specialty care setting between 2007 and 2011, with at least two Brief Symptom Inventory (BSI) assessments within 6 months. With logistic regression, we modelled baseline age, gender, ethnicity, education, marital status, housing situation, employment status, psychiatric comorbidity and both baseline and 1st follow-up BSI scores to predict prolonged treatment course (>2 years). Based on the regression coefficients, we present an easy to use risk prediction score. RESULTS: BSI at 1st follow-up proved to be a strong predictor for both depressive and anxiety disorders (OR = 2.17 (CI95% 1.73-2.74); OR = 2.52 (CI95% 1.86-3.23)). The final risk prediction score included BSI 1st follow-up and comorbid axis II disorder for depressive disorder, for anxiety disorders BSI 1st follow-up and age were included. For depressive disorders, for 28% of the patients with the highest scores, the positive predictive value for a prolonged treatment course was60% (sensitivity 0.38, specificity 0.81). For anxiety disorders, for 35% of the patients with the highest scores, the positive predictive value for a prolonged treatment course was 52% (sensitivity 0.55, specificity 0.75). CONCLUSIONS: A high level of symptoms at 2-6 months of follow-up is a strong predictor for prolonged treatment course. This facilitates early identification of patients at risk of a prolonged course of treatment; in a relatively easy way by a self-assessed symptom severity.

Development and Validation of Personalized Prediction to Estimate Future Risk of Severe Exacerbations and Uncontrolled Asthma in Patients with Asthma, Using Clinical Parameters and Early Treatment Response.

BACKGROUND: Current level of asthma control can be easily assessed by validated instruments, but it is currently difficult to assess individuals' level of future risk. OBJECTIVE: Develop, and validate, a risk prediction score for level of future risk, including patient characteristics and information on early treatment response. METHODS: We used data of 304 adult patients with asthma from a 12-month primary care randomized controlled trial with 3-monthly assessments. With logistic regression we modeled the association between the level of future risk and patient characteristics including early treatment response. Future risk was defined as Asthma Control Questionnaire (ACQ) score of 1.5 or more at 12 months or the experience of at least 1 exacerbation during the final 6 months. We developed a risk prediction score on the basis of regression coefficients. RESULTS: Performance of the risk prediction score improved, taking into account data on early treatment response (area under receiver-operating curve [AUROC] = 0.84) compared with a model containing only baseline characteristics (AUROC = 0.78). The score includes 6 easy-to-obtain predictors: sex, ACQ score and exacerbations in the previous year at baseline and at first follow-up, and smoking status and exacerbations in the previous 3 months (indicating early treatment response). External validation yielded an AUROC of 0.77. The risk prediction score classified patients into 3 risk groups: low (absolute risk, 11.7%), intermediate (47.0%), and high (72.7%). CONCLUSIONS: We developed and externally validated a risk prediction score, quantifying both level of current asthma control and the guideline-defined future risk. Patients' individual risk can now be estimated in an easy way, as proposed but not specified, by asthma management guidelines.

Intravenous immunoglobulins in children with new onset dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy is a rare but serious disorder in children. No effective diagnostic or treatment tools are readily available. This study aimed to evaluate the efficacy of intravenous immunoglobulins in children with new onset dilated cardiomyopathy. Methods and results In this retrospective cohort study, 94 children with new onset dilated cardiomyopathy were followed during a median period of 33 months. All patients with secondary dilated cardiomyopathy - for example, genetic, auto-immune or structural defects - had been excluded. Viral tests were performed in all patients and 18 (19%) children met the criteria for the diagnosis "probable or definite viral myocarditis". Intravenous immunoglobulins were administered to 21 (22%) patients. Overall transplant-free survival was 75% in 5 years and did not differ between treatment groups. The treatment was associated with a higher recovery rate within 5 years, compared with non-treated children (70 versus 43%, log rank=0.045). After correction for possible confounders the hazard ratio for recovery with intravenous immunoglobulins was not significant (hazard ratio: 2.1; 95% CI: 1.0-4.6; p=0.056). Administration of intravenous immunoglobulins resulted in a greater improvement in the shortening fraction of the left ventricle. CONCLUSION: In our population of children with new onset dilated cardiomyopathy, of either viral or idiopathic origin, intravenous immunoglobulins were administered to a minority of the patients and did not influence transplant-free survival, but were associated with better improvement of systolic left ventricular function and with better recovery. Our results support the concept that children with new onset dilated cardiomyopathy might benefit from intravenous immunoglobulins.

Evidence Based Weighing Policy during the First Week to Prevent Neonatal Hypernatremic Dehydration while Breastfeeding.

BACKGROUND: Neonatal hypernatremic dehydration is prevented by daily neonatal weight monitoring. We aim to provide evidence-based support of this universally promoted weighing policy and to establish the most crucial days of weighing. METHODS: Weight measurements of 2,359 healthy newborns and of 271 newborns with clinical hypernatremic dehydration were used within the first seven days of life to simulate various weighting policies to prevent hypernatremic dehydration; its sensitivity, specificity and positive predictive value (PPV) of these policies were calculated. Various referral criteria were also evaluated. RESULTS: A policy of daily weighing with a cut-off value of -2.5 Standard Deviation Score (SDS) on the growth chart for weight loss, had a 97.6% sensitivity, 97.6% specificity and a PPV of 2.80%. Weighing at birth and only at days two, four and seven with the same -2.5 SDS cut-off, resulted in 97.3% sensitivity, 98.5% specificity and a PPV of 4.43%. CONCLUSION: A weighing policy with measurements restricted to birth and day two, four and seven applying the -2.5 SDS cut-off seems an optimal policy to detect hypernatremic dehydration. Therefore we recommend to preferably weigh newborns at least on day two (i.e. ~48h), four and seven, and refer them to clinical pediatric care if their weight loss increases below -2.5 SDS. We also suggest lactation support for the mother, full clinical assessment of the infant and weighing again the following day in all newborns reaching a weight loss below -2.0 SDS.

Charts for weight loss to detect hypernatremic dehydration and prevent formula supplementing.

BACKGROUND: Most breast-fed newborns get the milk they need. However, very rarely milk intake is insufficient mostly as a result of poor breastfeeding techniques. Dramatic weight loss and hypernatremic dehydration may occur. Our aim was to construct charts for weight loss. METHODS: A case-control study was performed. Charts with standard deviation score (SDS) lines for weight loss in the first month were constructed for 2,359 healthy breast-fed term newborns and 271 cases with breastfeeding-associated hypernatremic dehydration with serum sodium level > 149 mEq/L. Day 0 was defined as the day of birth. RESULTS: Many cases with (or who will develop) hypernatremic dehydration (84%; +1 SDS line) fell below the -1 SDS line at day 3, the -2 SDS line at day 4, and the -2.5 SDS line at day 5 in the chart of the healthy breast-fed newborns. Weight loss of cases with permanent residual symptoms was far below the -2.5 SDS. CONCLUSIONS: Already at an early age, weight loss differs between healthy breast-fed newborns and those with hypernatremic dehydration. Charts for weight loss are, therefore, useful tools to detect early, or prevent newborns from developing, breastfeeding-associated hypernatremic dehydration, and also to prevent unnecessary formula supplementing.