New combination therapies for asthma

Combination products often have useful clinical benefits in asthma. The scientific rationale for combination therapy includes the fact that different agents have complimentary modes of action. Long-acting beta(2)-agonists have effects on airway smooth muscle, and inhaled corticosteroids have potent topical antiinflammatory effect. This combination has been shown to effectively reduce exacerbations and improve symptoms. Substantial clinical trial data provide a rationale for dual-control therapy supported by basic scientific data. Another combined therapy is inhaled steroids plus leukotriene-receptor antagonists, which provides the patient with two effective therapies. Leukotriene-receptor antagonist can also be combined with antihistamines for improved asthma control. Older therapies including theophylline and controlled release albuterol have been effectively added to inhaled corticosteroids, enabling a reduction in the dose of the inhaled steroids. Many other combination therapies are presently being tested.     

Effectiveness of various combination therapies in patients with coronary heart disease

There is only a limited number of studies available comparing the effectiveness of various combinations of anti-ischemic and antianginal substances in the same patients with coronary artery disease and stable angina pectoris and even these are restricted to either only a few drugs or a single point in time for testing. Accordingly, this study was undertaken to determine to what extent the combination of two or three drugs with different anti-ischemic mechanisms of action such as the long-acting form of the beta-blocker metoprolol and isosorbide dinitrate (ISDN) in sustained-release form as well as the calcium channel blockers nisoldipine and diltiazem in sustained-release form, which previously have not been tested in combination, are capable of enhancing effectiveness and prolonging duration of action. In a double-blind, randomized, crossover study in eleven patients with documented coronary artery disease and stable angina pectoris the effects of monotherapy with 200 mg metoprolol in long-acting form were compared with those of combined treatment with 120 mg ISDN sustained-release or 10 mg nisoldipine or 120 mg diltiazem sustained-release as well as ISDN and nisoldipine and finally, ISDN and diltiazem by means of an intraindividual analysis. For assessment of anti-ischemic and antianginal effects, symptom-limited exercise testing was carried out before as well as three, eight, twelve and 24 hours after medication. The parameters analyzed were ST-segment depression at the highest comparable workload, ischemia-free and symptom-free exercise capacity (one minute prior to ST-segment depression of 1 mm or onset of angina pectoris) as well as the systolic blood pressure--heart rate product at the highest comparable workload and at the highest ischemia-free workload, that is one minute prior to an ischemic reaction of 1 mm. Based on the ST-segment depression, all combinations of two drugs (metoprolol and ISDN at three hours; metoprolol and diltiazem at eight hours) led to a significant or at least relative increase of effectiveness. On comparison of the various double combinations, those with nisoldipine showed an early dissipation of action which, twelve hours after administration, was significantly less marked than those with diltiazem. Of the two tested triple combinations, metoprolol, ISDN and diltiazem was either significantly more effective than the various double combinations (metoprolol and ISDN or metoprolol and nisoldipine, both at eight and twelve hours; metoprolol and diltiazem, twelve hours) or relatively more effective and showed clear prolongation of the effects in excess of twelve hours.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effectiveness of an integrative medicine approach to improve cognitive dysfunction and dementia: An observational study

Despite the urgent need to control dementia, an effective treatment has yet to be developed. Along with the Korean government’s policy of cooperation between conventional medicine (CM) and Korean medicine (KM), integrative medical services for dementia patients are being provided. This study aimed to compare the integrative medical clinic (IMC) for dementia used by Dongguk University Hospitals (DUH) with other service models and to review the characteristics and treatment outcomes of patients who had visited DUH over the past 5 years. Patients’ electronic medical records from May 2015 to June 2020 were searched and their data were analyzed to evaluate the IMC’s service model. Patient demographic and clinical characteristics, diagnostic tests, and treatment patterns for CM and KM were collected. The proportion of patients who did not show worsening cognitive function was described in detail. A strength of the DUH integrative medicine clinic is its ability to manage both KM and CM patients in the same space at the same time. Among the 82 patients who visited the clinic during our study period, 56 remained for data analysis after we excluded patients who met the exclusion criteria; nineteen patients had diagnoses of mild cognitive impairment. Among collaboration patterns, the first visit to the IMC had the highest proportion (55.4%). Among diagnosed tests in CM, laboratory tests and neuropsychological tests were used the most. In KM, a heart rate variability test was frequently used. The most common CM treatment prescribed was anticonvulsants, with 22 patients (39.2%) receiving donepezil, whereas the most frequent KM treatments were acupuncture (82.1%) and herbal medicine (78.6%). Twelve patients were followed up with the Mini-Mental State Examination, and 8 demonstrated either no worsening or improved cognition (baseline Mini-Mental State Examination range: 21–26). All 8 patients had mild cognitive impairment including 6 with amnestic, multidomain impairment. This study searched for a way to improve cognitive dysfunction and dementia using an integrative approach, and it shows promising results for mild cognitive impairment. However, more precisely designed follow-up studies are needed to address the present work’s limitations of a retrospective study design and a small sample size.     

Efficacy of Helicobacter pylori eradication therapies: a single centre observational study

Background  

Many Helicobacter pylori eradication regimens have been described. There are little data reporting their efficacy or integration in routine clinical practice. The overall results of eradication therapy in a cohort of patients are described and an algorithm for management outlined.     

Efficacy and safety of the combination fluticasone propionate plus salmeterol in asthmatic preschoolers: An observational study

Background: Inhaled Corticosteroids (ICS) are the cornerstone of asthma management in pediatric patients. However, in some cases, asthma is not adequately controlled on ICS alone. Long-acting beta₂-agonists (LABA) are one of the available additional therapies but their use has rarely been studied among children younger than 5 years. Objective: The aim of this observational study was to evaluate the efficacy and safety of the combination of fluticasone propionate and salmeterol (FP/SA) in asthmatic children younger than 5 years of age. Methods: A retrospective study of 796 children under the age of 5 years (2.87 ± 1.22 years, 64.2% males), who were treated with FP/SA was conducted. Hospitalization rates, frequency of wheezing, exercise induced asthma, nocturnal wheeze and drug-related side-effects were recorded through children's medical records. Results: The children had previously received short-acting β₂-agonists (73%), ICS (17%), montelukast (1%), and ICS with montelukast (2%). Mean duration of therapy with FP/SA was 12.45 ± 9.14 months. After adjusting for age, gender, and duration of treatment, a 89% reduction was recorded in annual hospitalization rates (from 27.13% before treatment to 3.01% after FP/SA therapy, p < 0.001), a 71% reduction in incidence of exercise-induced asthma (36.8% vs. after 10.6%, p < 0.001), a 81% reduction in nocturnal asthma (33.7% vs. after: 6.4%, p < 0.001), as well as in frequency of wheezing (p < 0.01),. No previous treatment carry-on effect was observed. No major drug-related side-effects occurred in the study group. Conclusions: Combination therapy (FP/SA) is well-tolerated and highly effective in asthmatic children under the age of 5 years.     

Economic impact of severe asthma in Spain: multicentre observational longitudinal study

Objective: Estimate the economic impact of severe asthma from the Spanish social perspective through the estimation of the associated annual direct and indirect costs. Methods: Observational, longitudinal, retrospective study carried out in 20 Spanish secondary settings (Pulmonology and Allergy Services) among patients aged ≥18, diagnosed with severe asthma according to European Respiratory Society/American Thoracic Society consensus and who have not experienced an exacerbation in the previous 2 months. Asthma-related healthcare resource utilization as well as asthma-related days off work were collected over a retrospective 12-month period from medical records review (inclusion period: June to November 2016). Total costs were calculated by multiplying the natural resource units used within 1 year by the corresponding unit cost. Costs were expressed in Euros for 2018. Results: A total of 303 patients were included, mean age was 54 years old and 67% were women. There were 5.7 physician visits per patient (3.3 in secondary care). The most common pharmacologic treatment was fixed dose combination of inhaled corticosteroids/long-acting β2-adrenergic agonists (96.7%), followed by leukotriene receptor antagonists (57.1%). 134 patients (44.2%) had at least one severe asthma exacerbation (mean: 1.9 exacerbation/patient), of whom 22 patients required hospitalization, with a mean hospital stay of 10.9 days/patient. Mean sick leave due to severe asthma was 9.1 days per patient per year. Mean annual direct cost (confidence interval 95%) was €7472/patient (€6578–8612). The cost per exacerbation was €1410/patient. When indirect costs were added (€1082/patient [€564–1987]), the total annual mean cost rose to €8554/patient (€7411–10199). Conclusions: Taking the social perspective, the economic impact of severe asthma in Spain was estimated to be €8554/patient/year.     

Hospitalizations for asthma exacerbation in Chilean children: A multicenter observational study

Background

Asthma hospitalization rates in Chilean children have increased in the last 14 years, but little is known about the factors associated with this.

Etanercept in refractory lupus arthritis: An observational study

ObjectiveTo investigate the long-term safety and preliminary efficacy of etanercept in patients with refractory lupus arthritis.MethodsWe evaluated 43 patients in this observational cohort study. All received etanercept (50 mg/week) in addition to concomitant immunosuppressive agents. Patient and disease characteristics were collected. Incidence of adverse events and the effect on autoantibody levels were evaluated. Clinical efficacy was measured by the 28-joint count and the SLEDAI-2K scores. Remission of lupus arthritis was defined by a 28-joint score = 0. Clinically inactive systemic disease was defined by a SLEDAI-2K score <4.ResultsThe total follow-up time was 93 patient-years (median: 2.3 years per patient; range: 0.4–6.8 years). Most side effects were minor and related to local reactions. Only 2 significant adverse events occurred (8%), both were of infectious nature. The rate of autoantibody production was low (18%). A mild increase in titres of ANA (2), IgG anti-dsDNA (3) and IgM anticardiolipin (aCL) (2) antibodies was observed. All anti-dsDNA antibody increments were transient and coincided with systemic flares. No vascular events occurred. In general, disease activity declined during therapy. Most patients (83%) with lupus arthritis achieved clinical remission by week 12. All patients with simultaneous serositis experienced clinical and radiological resolution of this condition. Relapses were frequent (23%), mostly mild and related to etanercept reduction. A total of 24 patients discontinued treatment, 12 of them due to clinical remission.ConclusionsLong-term therapy with etanercept was relatively safe and had remarkable long-term efficacy for refractory lupus arthritis. In view of these results, further controlled trials are warranted.     

An international observational prospective study to determine the cost of asthma exacerbations (COAX)

Asthma is a common chronic condition that places substantial burden on patients and healthcare services. Despite the standards of asthma control that international guidelines recommend should be achieved, many patients continue to suffer sub-optimal control of symptoms and experience exacerbations (acute asthma attacks). In addition to being associated with reduced quality of life, asthma exacerbations are a key cost driver in asthma management. Routine clinical practice for the management of asthma exacerbations varies in different healthcare systems, so healthcare providers require local costs to be able to assess the value of therapies that reduce the frequency and severity of exacerbations. This prospective study, conducted in a total of 15 countries, assessed the local cost of asthma exacerbations managed in either primary or secondary care. Healthcare resources used were costed using actual values appropriate to each country in local currency and in Euros. Results are presented for exacerbations managed in primary care in Brazil, Bulgaria, Croatia, Czech Republic, Hungary, Poland, Russia, Slovakia, Slovenia, Spain and Ukraine, and in secondary care in Croatia, Denmark, Ireland, Latvia, Norway, Poland, Russia, Slovakia, Slovenia and Spain. Multiple regression analysis of the 2052 exacerbations included in the economic analysis showed that the cost of exacerbations was significantly affected by country (P<0.0001). Mean costs were significantly higher in secondary care (euro 1349) than primary care (euro 445, P=0.0003). Age was a significant variable (P=0.0002), though the effect showed an interaction with care type (P<0.0001). As severity of exacerbation increased, so did secondary care costs, though primary care costs remained essentially constant. In conclusion, the study showed that asthma exacerbations are costly to manage, suggesting that therapies able to increase asthma control and reduce the frequency or severity of exacerbations may bring economic benefits, as well as improved quality of life.     

Comparison of respiratory system impedance in asthma and COPD: A prospective observational study

Background and objective

A single assessment of within‐breath variations of respiratory system reactance (Xrs) at 5 Hz (ΔX5) measured by the forced oscillation technique (FOT) has been reported to be useful for the detection of pathophysiological changes in chronic obstructive pulmonary disease (COPD) and asthma. We examined longitudinal changes in respiratory system resistance (Rrs) and Xrs during tidal breathing between stable asthma and COPD patients in order to clarify the features of changes of respiratory system impedance and airflow limitation for these conditions.

Methods

Between April 2013 and September 2013, outpatients with a COPD or asthma diagnosis were recruited. We examined forced expiratory volume in 1 s (FEV₁) and FOT every 6 months until September 2015. Annual changes were estimated from the linear regression curve slope.

Results

We included 57 and 93 subjects with COPD and asthma, respectively. The median follow‐up period was 26 months (range: 24–29 months). Within‐breath analysis showed that the difference between mean Rrs at 5 Hz and 20 Hz was significantly lower, and ΔX5 more negative, in COPD than in asthma patients. With regard to annual changes, only ΔX5 was significantly different, more negative, in COPD than in asthma patients. Comparing between COPD subjects of Global Initiative Chronic Obstructive Lung Disease (GOLD) stage I/II and those with asthma, there were no significant differences in respiratory system impedance at enrolment, while annual change in ΔX5 was significantly more negative in mild COPD than in asthma patients.

Conclusion

ΔX5 may be useful for long‐term assessment of airflow limitation in COPD.

     

An observational study of attending rounds

The authors conducted an observational study of attending rounds to determine the current status of this form of clinical teaching in a university-based internal medicine department. Using two forms of measurement, questionnaires and timed observations, we found that 63% of attending physician time was spent in the conference room, 26% in hallways, and only 11% at the bedside. Significant differences were found between estimated and actual times, particularly in discussing previously admitted patients, patient interactions, data reviews, topic presentations, and the category of “other” activities. These results provide a framework for appraising attending rounds and identifying areas that may be improved with a teaching workshop intervention. Presented at the Mountain West Regional Meeting of the Society of General Internal Medicine, Sante Fe, New Mexico, March 6, 1992. Supported by the Biomedical Research Support Grant Committee, Grant No.BRSG (2S07 RR05675-22).     

Uncontrolled asthma and its risk factors in Chinese children: A cross-sectional observational study

Objective: Asthma afflicts many children in China but information about asthma management among Chinese pediatric asthma patients is limited. This study aims to evaluate asthma control among Chinese pediatric patients and identify risk factors associated with uncontrolled asthma. Methods: A total of 4223 patients with persistent asthma aged 2–16 years from 42 tertiary hospitals across all regions of mainland China except Tibet were surveyed. Asthma Control Test (ACT), Childhood Asthma Control Test (C-ACT) and Global Initiative for Asthma (GINA) criteria were used to assess asthma control for children aged 12–16 years, 4–11 years and 2–3 years, respectively. Uncontrolled asthma was defined as ACT or C-ACT score ≤19 or GINA-defined uncontrolled asthma. Risk factors associated with uncontrolled asthma were identified using multivariate logistic regression models. Results: Asthma was uncontrolled in 19.9% of the subjects. High rates of uncontrolled asthma were found in subjects with treatment non-adherence (44.1%), concomitant allergic rhinitis (AR) (23.3%), disease duration ≥ 1.5 years (22.8%), and first-degree relatives with AR (21.5%). The risk of uncontrolled asthma was much higher in the treatment non-adherence group compared to the complete adherence group (OR = 5.79, p < 0.001). Concomitant AR, disease duration ≥ 1.5 years, and first-degree relatives with AR were also confirmed as risk factors associated with uncontrolled asthma. Conclusions: About 20% of Chinese pediatric asthma patients had uncontrolled asthma. Treatment adherence and AR were the most significant risk factors. Tailored measures aimed at improving treatment adherence and diagnosis and treatment of AR should be adopted to improve the level of asthma control in Chinese children.     

Effectiveness of biologics in Australian patients with rheumatoid arthritis: a large observational study: REAL

Background

The comparative effectiveness of biologic treatment regimens in a real world Australian population is unknown.

Aim

To assess the effectiveness of biological disease‐modifying anti‐rheumatic drugs (bDMARD) as monotherapy or in combination with methotrexate and/or other conventional DMARD (cDMARD) for the treatment of rheumatoid arthritis (RA).

Methods

A retrospective, non‐interventional study was conducted that investigated the use of bDMARD in adult patients with RA in routine clinical practice. Data were extracted from the Optimising Patient Outcomes in Australian Rheumatology – Quality Use of Medicines Initiative database. Real‐world effectiveness was measured using the 28‐joint disease activity score (DAS28) and clinical disease activity index (CDAI) by treatment group at baseline, weeks 12 and 24.

Results

A total of 2970 patients was included with a median (min–max) age of 60.0 (19.0–94.0) years and median (min–max) duration of RA before first bDMARD treatment of 6.0 (0.2–58.3) years. A total of 1177 patients received more than one bDMARD during the analysis period of 1 January 1997 to 15 August 2015. Patients had 4922 treatment ‘episodes’ (defined as a cycle of continuous individual bDMARD prescribing in a single patient). Patients received a mean (SD) of 1.7 (1.0) episodes of treatment with median (min–max) treatment duration of 0.7 (0–11.8) years; median treatment duration was higher with the first treatment episode. bDMARD were most commonly initiated in combination with methotrexate (73.9% of episodes) and least commonly as monotherapy (9.9% of episodes). Median (min–max) baseline DAS28 decreased from 5.3 (0–8.7) with the first bDMARD to 3.7 (0–8.8) with the second. Median baseline CDAI similarly decreased.

Conclusions

Patients tended to persist longer on their first bDMARD treatment. bDMARD as monotherapy or in combination appear to be accepted treatment strategies in the real world.