Trends in oral corticosteroids use in severe asthma: a 14-year population-based study.

BACKGROUND: Oral corticosteroids are important components of pharmacotherapy in severe asthma. Our objective was to describe the extent, trends, and factors associated with exposure to oral corticosteroids (OCS) in a severe asthma cohort. METHODS: We used administrative health databases of British Columbia, Canada (2000-2014) and validated algorithms to retrospectively create a cohort of severe asthma patients. Exposure to OCS within each year of follow-up was measured in two ways: maintenance use as receiving on average ≥ 2.5 mg/day (prednisone-equivalent) OCS, and episodic use as the number of distinct episodes of OCS exposure for up to 14 days. Trends and factors associated with exposure on three time axes (calendar year, age, and time since diagnosis) were evaluated using Poisson regression. RESULTS: 21,144 patients (55.4% female; mean entry age 28.7) contributed 40,803 follow-up years, in 8.2% of which OCS was used as maintenance therapy. Maintenance OCS use declined by 3.8%/calendar year (p < 0.001). The average number of episodes of OCS use was 0.89/year, which increased by 1.1%/calendar year (p < 0.001). Trends remained significant for both exposure types in adjusted analyses. Both maintenance and episodic use increased by age and time since diagnosis. CONCLUSIONS: This population-based study documented a secular downward trend in maintenance OCS use in a period before widespread use of biologics. This might have been responsible for a higher rate of exacerbations that required episodic OCS therapy. Such trends in OCS use might be due to changes in the epidemiology of severe asthma, or changes in patient and provider preferences over time.

Clinical Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction and Chronic Obstructive Pulmonary Disease: Insights From PARADIGM-HF.

Background Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure with reduced ejection fraction, associated with undertreatment and worse outcomes. New treatments for heart failure with reduced ejection fraction may be particularly important in patients with concomitant COPD. Methods and Results We examined outcomes in 8399 patients with heart failure with reduced ejection fraction, according to COPD status, in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Blocker-Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Cox regression models were used to compare COPD versus non-COPD subgroups and the effects of sacubitril/valsartan versus enalapril. Patients with COPD (n=1080, 12.9%) were older than patients without COPD (mean 67 versus 63 years; P<0.001), with similar left ventricular ejection fraction (29.9% versus 29.4%), but higher NT-proBNP (N-terminal pro-B-type natriuretic peptide; median, 1741 pg/mL versus 1591 pg/mL; P=0.01), worse functional class (New York Heart Association III/IV 37% versus 23%; P<0.001) and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (73 versus 81; P<0.001), and more congestion and comorbidity. Medical therapy was similar in patients with and without COPD except for beta-blockade (87% versus 94%; P<0.001) and diuretics (85% versus 80%; P<0.001). After multivariable adjustment, COPD was associated with higher risks of heart failure hospitalization (hazard ratio [HR], 1.32; 95% CI, 1.13-1.54), and the composite of cardiovascular death or heart failure hospitalization (HR, 1.18; 95% CI, 1.05-1.34), but not cardiovascular death (HR, 1.10; 95% CI, 0.94-1.30), or all-cause mortality (HR, 1.14; 95% CI, 0.99-1.31). COPD was also associated with higher risk of all cardiovascular hospitalization (HR, 1.17; 95% CI, 1.05-1.31) and noncardiovascular hospitalization (HR, 1.45; 95% CI, 1.29-1.64). The benefit of sacubitril/valsartan over enalapril was consistent in patients with and without COPD for all end points. Conclusions In PARADIGM-HF, COPD was associated with lower use of beta-blockers and worse health status and was an independent predictor of cardiovascular and noncardiovascular hospitalization. Sacubitril/valsartan was beneficial in this high-risk subgroup. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01035255.

Does pulmonary subspecialty referral from primary care affect the adherence to vaccination recommendations in COPD patients?

The importance of vaccinations for COPD patients has been previously described. However, there is still a gap between guideline recommendations and the implementation of preventive care delivery for these patients. Specially, the rise of SARS-CoV-2 pandemic has made the significance of vaccination adherence more critical to address. Our study showed that referral to pulmonary clinic is associated with increased odds of receiving influenza (OR = 1.97, [95% CI 1.07, 3.65]) and pneumococcal vaccinations (PCV13 OR = 3.55, [1.47, 8.54]; PPSV23 OR = 4.92, [1.51, 16.02]). These data suggest that partnerships between primary care physicians and pulmonologists can potentially improve the vaccination rates for patients with COPD.

Malignant hyperthermia in severe COVID-19: 2 case reports.

Malignant hyperthermia is a rare but potentially fatal condition. We present 2 cases of young patients with coronavirus disease 2019 (COVID-19) requiring intubation for hypoxic respiratory failure who both developed significant hyperthermia post intubation and were suspected to have malignant hyperthermia. However, the 2 patients had different responses to conservative management and dantrolene. These cases highlight the increased challenge imposed by intubation complications when managing patients with COVID-19.

A Systematic Review of Decision-Analytic Models for Evaluating Cost-Effectiveness of Asthma Interventions.

OBJECTIVE: To demonstrate the landscape of model-based economic studies in asthma and highlight where there is room for improvement in the design and reporting of studies. DESIGN: A systematic review of the methodologies of model-based, cost-effectiveness analyses of asthma-related interventions was conducted. Models were evaluated for adherence to best-practice modeling and reporting guidelines and assumptions about the natural history of asthma. METHODS: A systematic search of English articles was performed in MEDLINE, EMBASE, and citations within reviewed articles. Studies were summarized and evaluated based on their adherence to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). We also studied the underlying assumptions about disease progression, heterogeneity in disease course, comorbidity, and treatment effects. RESULTS: Forty-five models of asthma were included (33 Markov models, 10 decision trees, 2 closed-form equations). Novel biological treatments were evaluated in 12 studies. Some of the CHEERS' reporting recommendations were not satisfied, especially for models published in clinical journals. This was particularly the case for the choice of the modeling framework and reporting on heterogeneity. Only 13 studies considered any subgroups, and 2 explicitly considered the impact of comorbidities. Adherence to CHEERS requirements and the quality of models generally improved over time. CONCLUSION: It would be difficult to replicate the findings of contemporary model-based evaluations of asthma-related interventions given that only a minority of studies reported the essential parameters of their studies. Current asthma models generally lack consideration of disease heterogeneity and do not seem to be ready for evaluation of precision medicine technologies.

Extent, trends, and determinants of controller/reliever balance in mild asthma: a 14-year population-based study.

BACKGROUND: The majority of patients with asthma have the mild form of the disease. Whether mild asthma patients receive appropriate asthma medications has not received much attention in the literature. We examined the trends in indicators of controller/reliever balance. METHODS: Using administrative health databases of British Columbia, Canada (2000 to 2013), we created a population-based cohort of adolescents/adults with mild asthma using validated case definition algorithms. Each patient-year of follow-up was assessed based on two markers of inappropriate medication prescription: whether the ratio of controller medications (inhaled corticosteroids [ICS] and leukotriene receptor antagonists [LTRA]) to total asthma-related prescriptions was low (cut-off 0.5 according to previous validation studies), and whether short-acting beta agonists (SABA) were prescribed inappropriately according to previously published criteria that considers SABA in relation to ICS prescriptions. Generalized linear models were used to evaluate trends and to examine the association between patient-, disease-, and healthcare-related factors and medication use. RESULTS: The final cohort consisted of 195,941 mild asthma patients (59.5% female; mean age at entry 29.6 years) contributing 1.83 million patient-years. In 48.8% of patient-years, controller medications were suboptimally prescribed, while in 7.2%, SABAs were inappropriately prescribed. There was a modest year-over-year decline in inappropriate SABA prescription (relative change - 1.3%/year, P < 0.001) and controller-to-total-medications (relative change - 0.5%/year, P < 0.001). Among the studied factors, the indices of type and quality of healthcare (namely respirologist consultation and receiving pulmonary function test) had the strongest associations with improvement in controller/reliever balance. CONCLUSIONS: Large number of mild asthma patients continue to be exposed to suboptimal combinations of asthma medications, and it appears there are modifiable factors associated with such phenomenon.

Optimum cutoff values of anthropometric indices of obesity for predicting hypertension: more than one decades of follow-up in an Iranian population.

We determined cutoff points of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), for predicting hypertension in an Iranian population. Study sample included 6359 (3678 female) participants aged ≥20 and <60 years of a prospective cohort. The sex stratified multivariate hazard ratios (HRs) for all indices were estimated using Cox regression in two age groups (20-39 and 40-59 years). Receiver operating characteristic (ROC) was used to evaluate the predictive ability and determine the optimal cut-off values of the indices. In both genders and two age groups, the confounders adjusted HRs were significant for general and central obesity measures indices. AUCs of the indices were similar in men; however, among women 40-59 years, WC and WHtR had significantly higher AUC compared to BMI. Generally, the optimal cut-off values were higher in the 40-59 year age group. Optimal BMI, WC and WHR and WHtR cut-off values were 24.15 kg/m2, 90.5 cm, 0.90 and 0.49 among men, aged 20-39 years; the corresponding values were 28.41 kg/m2, 86.5 cm, 0.96 and 0.50 in men aged 40-59 years, respectively. In women, the aforementioned values were 26.38 kg/m2, 83.5 cm, 0.79 and 0.51 in the age group of 20-39 years, and 29.57 kg/m2, 90.5 cm, 0.88 and 0.59 in the 40-59 year age group, respectively. Our results suggest that gender and age differences in the association between anthropometric indices and hypertension should be considered.

The impact of comorbidities on productivity loss in asthma patients.

BACKGROUND: Health-related productivity loss is an important, yet overlooked, component of the economic burden of disease in asthma patients of a working age. We aimed at evaluating the effect of comorbidities on productivity loss among adult asthma patients. METHODS: In a random sample of employed adults with asthma, we measured comorbidities using a validated self-administered comorbidity questionnaire (SCQ), as well as productivity loss, including absenteeism and presenteeism, using validated instruments. Productivity loss was measured in 2010 Canadian dollars ($). We used a two-part regression model to estimate the adjusted difference of productivity loss across levels of comorbidity, controlling for potential confounding variables. RESULTS: 284 adults with the mean age of 47.8 (SD 11.8) were included (68 % women). The mean SCQ score was 2.47 (SD 2.97, range 0-15) and the average productivity loss was $317.5 per week (SD $858.8). One-unit increase in the SCQ score was associated with 14 % (95 % CI 1.02-1.28) increase in the odds of reporting productivity loss, and 9.0 % (95 % CI 1.01-1.18) increase in productivity loss among those reported any loss of productivity. A person with a SCQ score of 15 had almost $1000 per week more productivity loss than a patient with a SCQ of zero. CONCLUSIONS: Our study deepens the evidence-base on the burden of asthma, by demonstrating that comorbidities substantially decrease productivity in working asthma patients. Asthma management strategies must be cognizant of the role of comorbidities to properly incorporate the effect of comorbidity and productivity loss in estimating the benefit of disease management strategies.

The impact of smoking status on 9.3 years incidence of cardiovascular and all-cause mortality among Iranian men.

AIM: To examine the association of different smoking groups with cardiovascular disease (CVD), coronary heart diseases (CHD) and CVD attributed death and death due to all causes in a male Tehranian population. METHODS: From a population-based study 3059 male individuals, aged ≥30 years, free of CVD at baseline were evaluated for a median of 9.3 years. The adjusted hazard ratios (HRs) for incident CVD/CHD, total and CVD mortality regarding their smoking status were calculated using Cox proportional regression analysis, considering never smoking as reference. RESULTS: A total of 158 deaths, in which 78 were CVD attributable, occurred. Considering CVD and CHD events, this study identified 299 and 257 events, respectively. Being a past smoker significantly increased the risk of CVD events (HR = 2.42, CI = 1.28-0.56), however, it has no effect on CHD events, total and CVD mortality. Being a current smoker (more than 10 cigarettes a day) dramatically increased the risk of CVD/CHD events and total/CVD mortality. However, smoking less than 10 cigarettes per day only increased the risk of CVD (HR = 2.12, CI = 1.14-3.95) and its mortality (HR = 4.57, CI = 1.32-15.79). CONCLUSION: The findings indicate that smoking increases the risk of incident CVD/CHD, total and CVD mortality, particularly CVD mortality. These outcomes were attributable to the daily amount of cigarettes smoked. Past smokers still had higher risk for CVD events, which cessation may not reduce.

Is Certolizumab Pegol Safe and Effective in the Treatment of Patients with Moderate to Severe Crohn's Disease? A Meta-analysis of Controlled Clinical Trials.

BACKGROUND: Tumor necrosis factor-α (TNF-α) antibodies are currently used in patients with moderate to severe Crohn's disease (CD) who are unresponsive to conventional therapies. Certolizumab pegol (Cp) is one of the anti-TNF-α agents introduced for the management of CD and rheumatoid arthritis. OBJECTIVES: The aim of this meta-analysis is to assess the efficacy of Cp in inducing clinical response and remission in CD and the associated adverse events. The effect of Cp in terms of CD patients' C-reactive protein (CRP) level was also studied. PATIENTS AND METHODS: Literature was searched for studies investigated the efficacy of Cp on inducing clinical response and maintaining remission in the patients with CD between 1966 and July 2012. RESULTS: Among 165 potentially relevant studies, six with a total of 1695 patients met the inclusion criteria and were meta-analyzed. In comparison to control groups, patients who received Cp had a relative risk (RR) of 1.38 with absolute risk reduction (ARR) = 0.12; 95% CI = 0.03 to 0.21), number needed for treatment (NNT) = 9; P < 0.0001 ) for clinical response and RR of 1.54 (ARR = 0.09; 95% CI = -0.0198 to 0.2), (NNT = 12; P < 0.0001) for maintenance of clinical remission and non-significant RR of 1.24 (P = 0.052) for induction of clinical remission. Baseline CRP did not significantly alter the magnitude or response. Adverse events were not significantly different among patients receiving Cp comparing to placebo. CONCLUSIONS: Cp is effective for inducing clinical response and maintenance of clinical remission in patients with moderate to severe CD with similar side-effect profile as the control arms.

Wells' prediction rules for pulmonary embolism: valid in all clinical subgroups?

Pulmonary embolism is major cause of hospital death. Clinical prediction rules such as Wells' prediction rules can help in selection of at-risk patients who need further testing for pulmonary embolism. We evaluated the usefulness of such criteria for detection of patients with diagnosed pulmonary embolism. Patients enrolled in National Research Institute of Tuberculosis and Lung Disease (NRITLD) deep venous thrombosis (DVT) registry were evaluated and those with objective data about presence or absence of pulmonary embolism were selected for this study. Diagnosis of pulmonary embolism was based on computed tomography pulmonary angiography (CTPA). We calculated the embolic burden in those with CTPA-confirmed pulmonary embolism. Eighty-six patients entered the study (58 males, 28 females, mean age = 54.39 ± 1.74 years). Fifty-four cases had coexisting pulmonary embolism (embolic burden score: 10.77 ± 1.181). Embolic burden score was correlated to presence of massive pulmonary embolism (Pearson rho: 0.43, P = 0.002). There was no association between Wells' pulmonary embolism score and the occurrence of pulmonary embolism (Spearman's rho: 0.085, P = 0.51). Dividing the patients into two, or three, risk groups according to Wells' model did not reveal an association with occurrence of pulmonary embolism either (P = 0.99 and P = 0.261, respectively). Tachycardia and hemoptysis were the only parameters from the Wells' pulmonary embolism score correlated to presence of pulmonary embolism (Spearman's rho: 0.373, P < 0.000 and Spearman's rho: 0.297, P = 0.005, correspondingly). Wells' pulmonary embolism score could not predict the occurrence of pulmonary embolism in DVT patients suspected of having coexisting pulmonary embolism. Until further studies shed light on this patient subset, overreliance on Wells' prediction rules as the solo decision making tool should be cautioned.

Chest physicians' knowledge of appropriate thromboprophylaxis: insights from the PROMOTE study.

Venous thromboembolism (VTE) is a major cause of in-hospital mortality. Several international guidelines provide thromboprophylaxis recommendations; however, guidelines adherence is missing worldwide. We evaluated the chest physicians' knowledge regarding VTE prophylaxis, using a systematically developed questionnaire. The Prophylaxis-foR-venOus-throMbOembolism-assessmenT-questionnairE (PROMOTE) questionnaire was developed using an algorithm encompassing the most important VTE prophylaxis topics and included 13 clinical scenarios. Responses were evaluated with reference to the eighth edition of American College of Chest Physicians guidelines for VTE prevention to assess thromboprophylaxis appropriateness. The questionnaires were distributed during the fourth International Congress on Pulmonary Disease, Intensive Care and Tuberculosis. From the 88 received questionnaires (response rate: 39.8%), 82 were acceptable (62 men, 20 women). The most commonly cited VTE risk factors were immobility (79.2%), surgery (68.2%), and cancer (60.9%). The mean correct response ratio to the questions was 67% [95% confidence interval (CI) 64-70%] with highest appropriateness ratios amongst cardiologists (77.1 ±â€Š5.8%) and lowest ratios among thoracic surgeons (59.2 ±â€Š5%). Physicians' specialty had a significant effect on the overall appropriateness (P = 0.04) and most of appropriateness subcategories. Thoracic surgeons had the lowest rate of over-prophylaxis (P = 0.02). Years passed from graduation were inversely associated with overall appropriateness (P = 0.006). Physicians with academic engagements had a higher overall appropriateness (P = 0.04). We found a wide gap between the guideline recommendations and the responses. PROMOTE is the first systematically developed questionnaire that addresses chest physicians' thromboprophylaxis knowledge and could be useful to strategies to improve VTE prophylaxis. Because of the dissimilar prophylaxis pitfalls of different specialists, distinct educational programs seem necessary to improve their knowledge of proper VTE prophylaxis.

A systematic review and meta-analysis of the effects of infliximab on the rate of colectomy and post-operative complications in patients with inflammatory bowel disease.

INTRODUCTION: Use of biological therapies may reduce or delay the surgical procedures in patients with inflammatory bowel disease (IBD). The aim of this meta-analysis and systematic review was to determine the impact of pre-operative infliximab (IFX) use on the rate of surgical interventions in patients with IBD and also the effect of preoperative IFX therapy on post-surgical complications. MATERIAL AND METHODS: Literature was searched for studies that investigated the efficacy of IFX on the rate of colectomy and post-operative complications/side effects in patients with IBD between 1966 and February 2011. RESULTS: Twelve articles were included in the meta-analysis. In comparison to control groups, patients who received IFX had a relative risk (RR) of 1.17 (p = 0.65) for the rate of colectomy, odds ratio of 3.34 (p = 0.09) in seven observational studies and RR of 0.74 (p = 0.79) in clinical trials for mortality. Summary RR of hospitalization was 0.61 (p = 0.005). Infections and anastomotic leak, pouch-related complications, sepsis and thrombotic events were more common in the patients under IFX therapy but post-operational hospitalization was lower. The patients with IBD who were under IFX therapy were most of the times refractive to other therapies and their disease was more severe. CONCLUSIONS: Although IFX does not decrease the rate of colectomy in patients with IBD, it would not increase most of the post-operational side effects in the patients.