Time-dependent association between STOPP and START criteria and gastrointestinal bleeding in older patients using routinely collected primary care data.

PURPOSE: Only few studies have assessed the preventive effect of the STOPP/START criteria on adverse events. We aim to quantify 1) the association between nonadherence to STOPP/START criteria and gastrointestinal bleedings, and 2) the association between exposure to the potentially harmful START-medications and gastrointestinal bleedings. DESIGN: A retrospective cohort study using routinely collected data of patients aged ≥ 65 years from the electronic health records (EHR) of 49 general practitioners (GPs) in 6 GP practices, from 2007 to 2014. The database is maintained in the academic research network database (AHA) of Amsterdam UMC, the Netherlands. METHODS: Gastrointestinal bleedings were identified using ICPC codes and free text inspections. Three STOPP and six START criteria pertaining to gastrointestinal bleedings were selected. Cox proportional hazards regression with time-dependent covariate analysis was performed to assess the independent association between nonadherence to the STOPP/START criteria and gastrointestinal bleedings. The analysis was performed with all criteria as a composite outcome, as well as separately for the individual criteria. RESULTS: Out of 26,576 participants, we identified 19,070 Potential Inappropriate Medications (PIM)/Potential Prescribing Omission (PPO) instances for 3,193 participants and 146 gastrointestinal bleedings in 143 participants. The hazard ratio for gastrointestinal bleedings of STOPP/STARTs, taken as composite outcome, was 5.45 (95% CI 3.62-8.21). When analysed separately, two out of nine STOPP/STARTs showed significant associations. CONCLUSION: This study demonstrates a significant positive association between nonadherence to the STOPP/START criteria and gastrointestinal bleeding. We emphasize the importance of adherence to the relevant criteria for gastrointestinal bleeding, which may be endorsed by decision support systems.

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.

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.

Longitudinal outcomes of different asthma phenotypes in primary care, an observational study.

While asthma presentation is heterogeneous, current asthma management guidelines in primary care are quite homogeneous. In this study we aim to cluster patients together into different phenotypes, that may aid the general practitioner in individualised asthma management. We analysed data from the ACCURATE trial, containing 611 adult asthmatics, 18-50 year-old, treated in primary care, with one year follow-up. Variables obtained at baseline (n = 14), were assessed by cluster analysis. Subsequently, established phenotypes were assessed separately on important asthma outcomes after one year follow-up: asthma control (Asthma Control Questionnaire (ACQ)), quality of life (Asthma Quality of Life Questionnaire (AQLQ)), exacerbation-rate and medication-usage. Five distinct phenotypes were identified. The first phenotype was predominantly defined by their early onset atopic form of asthma. The second phenotype mainly consisted of female patients with a late onset asthma. The third phenotype were patients with high reversibility rates after bronchodilator usage. The fourth phenotype were smokers and the final phenotype were frequent exacerbators. The exacerbators phenotype had the worst outcomes for asthma control and quality of life and experienced the highest exacerbation-rate, despite using the most medication. The early onset phenotype patients were relatively well controlled and their medication dosage was low. ASTHMA: INDIVIDUALIZING TREATMENT BY PHENOTYPE: Asthma patients should be characterised according to their individual asthma type to ensure more targeted treatment. Even though asthma manifests itself in a wide variety of forms with differing degrees of severity, treatment of the disease often takes a broad, one-size-fits-all approach. To determine if asthma can indeed be split into distinct phenotypes, Rishi Khusial at the Leiden University Medical Center and co-workers across the Netherlands analysed data from 611 adult asthmatics treated in primary care, and followed them up after one year. The team identified five phenotypes in the primary care cohort, including one group with early onset asthma, another whose asthma responded well to bronchodilators, and a group classed as frequent exacerbators. Further analysis of long-term asthma outcomes showed clear differences between phenotypes, particularly in terms of asthma control and quality of life.

Symptom- and fraction of exhaled nitric oxide-driven strategies for asthma control: A cluster-randomized trial in primary care.

BACKGROUND: Aiming at partly controlled asthma (PCa) instead of controlled asthma (Ca) might decrease asthma medication use. Biomarkers, such as the fraction of exhaled nitric oxide (Feno), allow further tailoring of treatment. OBJECTIVE: We sought to assess the cost-effectiveness and clinical effectiveness of pursuing PCa, Ca, or Feno-driven controlled asthma (FCa). METHODS: In a nonblind, pragmatic, cluster-randomized trial in primary care, adults (18-50 years of age) with a doctor's diagnosis of asthma who were prescribed inhaled corticosteroids were allocated to one of 3 treatment strategies: (1) aiming at PCa (Asthma Control Questionnaire [ACQ] score <1.50); (2) aiming at Ca (ACQ score <0.75); and (3) aiming at FCa (ACQ score <0.75 and Feno value <25 ppb). During 12 months' follow-up, treatment was adjusted every 3 months by using an online decision support tool. Outcomes were incremental cost per quality-adjusted life year gained, asthma control (ACQ score), quality of life (Asthma Quality of Life Questionnaire score), asthma medication use, and severe exacerbation rate. RESULTS: Six hundred eleven participants were allocated to the PCa (n = 219), Ca (n = 203), or FCa (n = 189) strategies. The FCa strategy improved asthma control compared with the PCa strategy (P < .02). There were no differences in quality of life (P ≥ .36). Asthma medication use was significantly lower for the PCa and FCa strategies compared with the Ca strategy (medication costs: PCa, $452; Ca, $551; and FCa, $456; P ≤ .04). The FCa strategy had the highest probability of cost-effectiveness at a willingness to pay of $50,000/quality-adjusted life year (86%; PCa, 2%; Ca, 12%). There were no differences in severe exacerbation rate. CONCLUSION: A symptom- plus Feno-driven strategy reduces asthma medication use while sustaining asthma control and quality of life and is the preferred strategy for adult asthmatic patients in primary care.

Comparison between an online self-administered and an interviewer-administered version of the Asthma Control Questionnaire: a cross-sectional validation study.

BACKGROUND: Online self-management programmes for asthma have recently become available. International guidelines suggest that the Asthma Control Questionnaire (ACQ) can be used in these programmes. In order to assess the current level of control and guide therapy, the same cut-off values are being used as in conventional asthma management. However, results might differ between different types of administration of the ACQ. AIMS: To assess the agreement between an online self-administered version of the ACQ and an interviewer-administered version at a routine visit. METHODS: Cross-sectional data from primary care asthma patients in the Asthma Control Cost Utility Randomized Trial Evaluation (ACCURATE) trial aged 18-50 years and prescribed inhaled steroids were analysed. We selected patients who self-administered an ACQ online and subsequently had an ACQ completed by a nurse practitioner within 7 days at a trial-related control visit. ACQ scores were calculated and agreement assessed by paired t-tests, Pearson's correlation coefficient and a Bland-Altman plot. RESULTS: A total of 351 patients were eligible (68% female, mean age 40 years). The time interval between the two versions was 3.2 days. There was a significant difference of 0.14 (95% CI 0.09 to 0.20; p<0.001) between the results of the online self-administered ACQ (mean 1.04±0.04) and the interviewer-administered ACQ results (0.90±0.04). The Pearson correlation coefficient was 0.79. The limits of agreement (-0.86, 1.14) exceeded the predefined minimal clinically important difference between results (±0.5). The Bland-Altman plot therefore showed insufficient agreement. CONCLUSIONS: Assessment of asthma control by the ACQ is influenced by the type of administration. Our results suggest that better control of asthma is perceived when interacting with a caregiver than by online self-assessment.