Impact of an electronic monitoring intervention for improving adherence to inhaled therapy in patients with asthma and COPD

Asthma bronchiale and chronic obstructive pulmonary disease (COPD) are two of the leading chronic respiratory diseases worldwide and associated with high morbidity, mortality, and a major economic burden. Despite progress in pharmacological and non-pharmacological treatment in recent years, the burden of disease among asthma and COPD patients is high. Reasons for uncontrolled diseases are manifold, but are often associated with poor inhalation technique and non-adherence to the prescribed treatment plan. As observed in many chronic diseases, poor adherence to medication is also a common phenomenon among asthma and COPD patients. This causes deterioration of symptoms and recurrent exacerbations resulting in increased rates of morbidity, physician visits, hospitalizations, mortality, reduced quality of life, and increased healthcare expenditures. However, it has been demonstrated that the frequency of exacerbation can be reduced by the administration of certain medication. Furthermore, high adherence is associated with reduced exacerbation rates in patients with asthma and COPD. As outlined above, maintaining adequate adherence to inhaled medication is of major importance for achieving therapeutic success, in particular for the treatment of chronic diseases. Different interventions and strategies are already described in the literature aiming to enhance adherence. The greatest success was attained with complex interventions combining several strategies. Nevertheless, to date no intervention was determined to be particularly successful. Therefore, this thesis aims to contribute to this challenging but important research field by investigating the impact of two simple interventions on adherence to inhaled therapy in patients with asthma and COPD. Prior to the study start, we provided a training course for each participant regardless of the treatment group to guarantee a comparable level of disease knowledge and inhalation technique. Further, each patient was equipped with an electronic monitoring device, which was used as the method of choice for the assessment of objective adherence. Overall, the performed intervention consisted of a reminder in form of phone calls and a daily alarm clock as well as feedback on patients’ individual adherence profile. The combination of these two common types of interventions has been chosen since they appeared to be easily applicable in daily clinical practice. We considered this to be one of the important factors in order to guarantee an efficient improvement of patients’ adherence. By the intervention, we expected a prolongation of time to next exacerbation, which was defined as the primary endpoint of this study. Moreover, we assumed an improvement of patients’ taking and timing adherence as well as quality of life, determined as the two secondary endpoints. The thesis is divided into the following three parts:   The aim of Part I was to design and write a study protocol taking into account the above-mentioned aims and under consideration of the current state of the literature as well as the studies already conducted in this field. Part II describes a cross-sectional analysis to evaluate baseline data on compliance in accordance with current treatment guidelines (Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines). Furthermore, baseline data is provided on inhaler application after a training course and its impact on quality of life and symptom control in a typical population with chronic lung diseases from the Adherence-Trial. Overall, correct inhalation technique ranged from 55% to 100% depending on the type of inhaler. 112 participants (68%) participants were treated corresponding to the global guidelines. COPD patients with incorrect device application had a higher CAT sum score compared to those with a correct device application (p=.02). Moreover, COPD patients with incorrect device application had to cough more often (p=.03) and were more breathless while walking up hills or one flight of stairs (p=.02). While there was no significance to be found in asthma patients, COPD patients who used their devices correctly had a significantly better mean FEV1% predicted at baseline compared to those who applied their devices incorrectly (p=.04). In the last part of this thesis (Part III), time to next exacerbation - the primary endpoint of the study - was evaluated and compared between the intervention and the control group. Furthermore, the objective adherence was analyzed by evaluating the taking and timing adherence, as well as the gaps during the study period. Patients’ quality of life was assessed by the St. George Respiratory Questionnaire (SGRQ). Time to next exacerbation was longer (172 days [95% CI, 161 to 182] vs. 161 days [95% CI, 149 to 174], p=.27) and the risk for experiencing an exacerbation lower (HR, 0.67 [95% CI, 0.36 to 1.33], p=.14) in the intervention compared to the control group, but failed to reach statistical significance. In the intervention group significantly more days with a taking adherence between 80-100% were observed with both inhalation techniques (puff inhalers: 81.6±14.2 vs.60.1±30.3, p.05). In conclusion this thesis showed: •At baseline, a large number of the participating asthma, COPD or asthma-COPD overlap patients were treated on target based on the GINA and GOLD guidelines valid at the time of the patient’s inclusion into the Adherence-Trial. •Correct handling of inhaler devices was largely dependent on the device used. In the Adherence-Trial population, metered dose inhalers were applied more frequently in an incorrect way compared to dry powder inhalers. This particularly applies to the Ellipta® device, which has just recently been introduced to the market and which showed a very good applicability. •A correct inhalation technique of the prescribed medication had a positive impact on the health status and the lung function of COPD patients. This was achieved by a comprehensive training of correct inhalation technique. •Regular, automatic and personal reminders seem to have caused a significant improvement in taking and timing adherence with regard to the inhalation with puff inhalers and dry powder capsules. Moreover, reminders can help to avoid forgetting the inhalation of the prescribed medication. Patients who experienced support in their adherence had significantly fewer days without inhalation and fewer gaps over several consecutive days compared to patients receiving no support. •Regular, automatic and personal reminders, led to a substantial improvement in patients’ adherence to inhaled medication. However, this was not associated with an improvement in health-related quality of life in patients with chronic airway diseases. •Higher adherence to the prescribed medication plan was not only associated with a trend towards longer time to next exacerbation but also with a reduced risk of experiencing an exacerbation

Derivation and validation of a prediction model to establish nursing-sensitive quality benchmarks in medical inpatients : a secondary data analysis of a prospective cohort study

Background: Hospitals are using nursing-sensitive outcomes (NSOs) based on administrative data to measure and benchmark quality of nursing care in acute care wards. In order to facilitate comparisons between different hospitals and wards with heterogeneous patient populations, proper adjustment procedures are required. In this article, we first identify predictors for common NSOs in acute medical care of adult patients based on administrative data. We then develop and cross-validate an NSO-oriented prediction model. Methods: We used administrative data from seven hospitals in Switzerland to derive prediction models for each of the following NSO: hospital-acquired pressure ulcer (≥stage II), hospital-acquired urinary tract infection, non-ventilator hospital-acquired pneumonia and in-hospital mortality. We used a split dataset approach by performing a random 80:20 split of the data into a training set and a test set. We assessed discrimination of the models by area under the receiver operating characteristic curves. Finally, we used the validated models to establish a benchmark between the participating hospitals. Results: We considered 36,149 hospitalisations, of which 51.9% were male patients with a median age of 73 years (with an interquartile range of 59–82). Age and length of hospital stay were independently associated with all four NSOs. The derivation and validation models showed a good discrimination in the training (AUC range: 0.75–0.84) and in the test dataset (AUC range:0.77–0.81), respectively. Variation among different hospitals was relevant considering the risk for hospital-acquired pressure ulcer (≥ stage II) (adjusted Odds ratio [aOR] range: 0.51 [95% CI: 0.38–0.69] – 1.65 [95% CI:1.33–2.04]), the risk for hospital-acquired urinary tract infection infection (aOR range: 0.46 [95% CI: 0.36–0.58] – 1.45 [95% CI: 1.31–1.62]), the risk for non-ventilator hospital-acquired pneumonia (aOR range: 0.28 [95% CI: 0.09–0.89] – 2.87 [95% CI: 2.27–3.64]), and the risk for in-hospital mortality (aOR range: 0.45 [95% CI: 0.36–0.56] – 1.39 [95% CI: 1.23–1.60]). Conclusion: The application of risk adjustment when comparing nursing care quality is crucial and enables a more objective assessment across hospitals or wards with heterogeneous patient populations. This approach has potential to establish a set of benchmarks that could allow comparison of outcomes and quality of nursing care between different hospitals and wards

Association of Interprofessional Discharge Planning Using an Electronic Health Record Tool With Hospital Length of Stay Among Patients with Multimorbidity: A Nonrandomized Controlled Trial

Whether interprofessional collaboration is effective and safe in decreasing hospital length of stay remains controversial.; To evaluate the outcomes and safety associated with an electronic interprofessional-led discharge planning tool vs standard discharge planning to safely reduce length of stay among medical inpatients with multimorbidity.; This multicenter prospective nonrandomized controlled trial used interrupted time series analysis to examine medical acute hospitalizations at 82 hospitals in Switzerland. It was conducted from February 2017 through January 2019. Data analysis was conducted from March 2021 to July 2022.; After a 12-month preintervention phase (February 2017 through January 2018), an electronic interprofessional-led discharge planning tool was implemented in February 2018 in 7 intervention hospitals in addition to standard discharge planning.; Mixed-effects segmented regression analyses were used to compare monthly changes in trends of length of stay, hospital readmission, in-hospital mortality, and facility discharge after the implementation of the tool with changes in trends among control hospitals.; There were 54 695 hospitalizations at intervention hospitals, with 27 219 in the preintervention period (median [IQR] age, 72 [59-82] years; 14 400 [52.9%] men) and 27 476 in the intervention phase (median [IQR] age, 72 [59-82] years; 14 448 [52.6%] men) and 438 791 at control hospitals, with 216 261 in the preintervention period (median [IQR] age, 74 [60-83] years; 109 770 [50.8%] men) and 222 530 in the intervention phase (median [IQR] age, 74 [60-83] years; 113 053 [50.8%] men). The mean (SD) length of stay in the preintervention phase was 7.6 (7.1) days for intervention hospitals and 7.5 (7.4) days for control hospitals. During the preintervention phase, population-averaged length of stay decreased by -0.344 hr/mo (95% CI, -0.599 to -0.090 hr/mo) in control hospitals; however, no change in trend was observed among intervention hospitals (-0.034 hr/mo; 95% CI, -0.646 to 0.714 hr/mo; difference in slopes, P = .09). Over the intervention phase (February 2018 through January 2019), length of stay remained unchanged in control hospitals (slope, -0.011 hr/mo; 95% CI, -0.281 to 0.260 hr/mo; change in slope, P = .03), but decreased steadily among intervention hospitals by -0.879 hr/mo (95% CI, -1.607 to -0.150 hr/mo; change in slope, P = .04, difference in slopes, P = .03). Safety analyses showed no change in trends of hospital readmission, in-hospital mortality, or facility discharge over the whole study time.; In this nonrandomized controlled trial, the implementation of an electronic interprofessional-led discharge planning tool was associated with a decline in length of stay without an increase in hospital readmission, in-hospital mortality, or facility discharge.; isrctn.org Identifier: ISRCTN83274049

Canakinumab in patients with COVID-19 and type 2 diabetes - A multicentre, randomised, double-blind, placebo-controlled trial

BACKGROUND: Patients with type 2 diabetes and obesity have chronic activation of the innate immune system possibly contributing to the higher risk of hyperinflammatory response to SARS-CoV2 and severe COVID-19 observed in this population. We tested whether interleukin-1β (IL-1β) blockade using canakinumab improves clinical outcome. METHODS: CanCovDia was a multicenter, randomised, double-blind, placebo-controlled trial to assess the efficacy of canakinumab plus standard-of-care compared with placebo plus standard-of-care in patients with type 2 diabetes and a BMI > 25 kg/m$^{2}$ hospitalised with SARS-CoV2 infection in seven tertiary-hospitals in Switzerland. Patients were randomly assigned 1:1 to a single intravenous dose of canakinumab (body weight adapted dose of 450-750 mg) or placebo. Canakinumab and placebo were compared based on an unmatched win-ratio approach based on length of survival, ventilation, ICU stay and hospitalization at day 29. This study is registered with ClinicalTrials.gov, NCT04510493. FINDINGS: Between October 17, 2020, and May 12, 2021, 116 patients were randomly assigned with 58 in each group. One participant dropped out in each group for the primary analysis. At the time of randomization, 85 patients (74·6 %) were treated with dexamethasone. The win-ratio of canakinumab vs placebo was 1·08 (95 % CI 0·69-1·69; p = 0·72). During four weeks, in the canakinumab vs placebo group 4 (7·0%) vs 7 (12·3%) participants died, 11 (20·0 %) vs 16 (28·1%) patients were on ICU, 12 (23·5 %) vs 11 (21·6%) were hospitalised for more than 3 weeks, respectively. Median ventilation time at four weeks in the canakinumab vs placebo group was 10 [IQR 6.0, 16.5] and 16 days [IQR 14.0, 23.0], respectively. There was no statistically significant difference in HbA1c after four weeks despite a lower number of anti-diabetes drug administered in patients treated with canakinumab. Finally, high-sensitive CRP and IL-6 was lowered by canakinumab. Serious adverse events were reported in 13 patients (11·4%) in each group. INTERPRETATION: In patients with type 2 diabetes who were hospitalised with COVID-19, treatment with canakinumab in addition to standard-of-care did not result in a statistically significant improvement of the primary composite outcome. Patients treated with canakinumab required significantly less anti-diabetes drugs to achieve similar glycaemic control. Canakinumab was associated with a prolonged reduction of systemic inflammation. FUNDING: Swiss National Science Foundation grant #198415 and University of Basel. Novartis supplied study medication

Association of kidney function with effectiveness of procalcitonin-guided antibiotic treatment:A patient-level meta-analysis from randomized controlled trials

Patients with impaired kidney function have a significantly slower decrease of procalcitonin (PCT) levels during infection. Our aim was to study PCT-guided antibiotic stewardship and clinical outcomes in patients with impairments of kidney function as assessed by creatinine levels measured upon hospital admission. We pooled and analyzed individual data from 15 randomized controlled trials who were randomly assigned to receive antibiotic therapy based on a PCT-algorithms or based on standard of care. We stratified patients on the initial glomerular filtration rate (GFR, ml/min/1.73 m2) in three groups (GFR >90 [chronic kidney disease; CKD 1], GFR 15-89 [CKD 2-4] and GFR0.05). This individual patient data meta-analysis confirms that the use of PCT in patients with impaired kidney function, as assessed by admission creatinine levels, is associated with shorter antibiotic courses and lower mortality rates

Ein erster Blick auf die neuen europäischen Hypertonie-Guidelines

Im November 2017 publizierten zahlreiche amerikanische Fachgesellschaften neue Richtlinien zur Diagnostik und Behandlung der arteriellen Hypertonie. In den neuen Richtlinien wurde Bluthochdruck als ein Wert von ≥130/80 mm Hg definiert. Über Nacht gab es damit in den USA zusätzlich 32 Millionen Menschen mit arterieller Hypertonie. Das führte weltweit zu zum Teil heftigen Diskussionen. Umso gespannter wurden die neuen europäischen Richtlinien zur Diagnostik und Therapie der arteriellen Hypertonie erwartet