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This position statement aims to provide rapid guidance for pulmonary rehabilitation in adults with COVID-19 illness. These recommendations are based on the consensus of the authors, who are members...

Objective This systematic review and meta-analysis were conducted to study the prevalence and pattern of sleep disturbances in children and adolescents during the COVID-19 pandemic. Methods MEDLINE, EMBASE, and Web of Science were searched for original studies describing sleep abnormalities in children and adolescents with or without pre-existing neurobehavioral disorders during the COVID-19 pandemic. The pooled estimates for various sleep abnormalities were calculated using a random-effect model. Results Of 371 articles screened, 16 studies were included. Among these, five studies were in preschool children, two were in children with pre-existing neurobehavioral disorders and the remaining were in school going children and adolescents. The outcome measures used for sleep were markedly heterogeneous across the studies. The pooled prevalence of any sleep disturbance in children during the pandemic was 54%(95%CI:50–57%). Interestingly, the prevalence in pre-school children was lower than pre-pandemic times (RR = 0.87; 95% CI:0.58–1.30) but this was not statistically significant. The pooled prevalence of children not meeting sleep recommendation was 49% (95%CI: 39–58%). Conclusion The prevalence of sleep problems in children and adolescents during the COVID-19 pandemic is alarming. Pre-school children had a trend towards relatively fewer sleep disturbances due to home confinement measures in comparison with pre-pandemic times. Sleep duration recommendations were not met in nearly half of healthy children. However, these conclusions need to be seen in light of limited literature on the topic, few included studies done in heterogenous populations, and dubious quality of inferences drawn from these studies which were predominantly online surveys. Prospero registration id CRD42020213788.

Chronic obstructive pulmonary disease (COPD) has a profound impact on people living with the disease and has a high global economic and social burden. Often, people with COPD are undiagnosed, while those diagnosed are undertreated and undereducated on different aspects of COPD care. Although there are many published evidence-based treatment guidelines from different expert groups and societies, they are frequently not adhered to, which results in significant gaps in care. In particular, ‘flare-ups’ (known as exacerbations of COPD), which accelerate disease progression, are often under-reported, despite guidelines recommending an escalation of maintenance treatment to prevent subsequent flare-ups. Management of COPD should be proactive to prevent worsening of symptoms and to reduce the risk of future flare-ups and premature death, rather than a secondary reaction to a worsening health status. Key to this is patient access to accurate diagnosis, effective treatment and specialist care, which can vary widely due to socioeconomic differences, geographical locations and poor guideline implementation. In addition, the stigma associated with COPD can act as a barrier, which can result in people being reluctant to access treatment or clinicians being nihilistic. As global patient advocates, we have co-developed this patient charter to set a standard of care that people living with COPD should expect, raising awareness and understanding of the causes and consequences of COPD as well as the potential to improve patient care. Patients with COPD should be empowered to live the highest quality of life possible with the least number of flare-ups. We set out six principles in line with current COPD guideline recommendations, that should be implemented by governments, healthcare providers, policymakers, lung health industry partners and patients/caregivers to drive meaningful change in COPD care.

This position statement aims to provide guidance for resumption of pulmonary rehabilitation (PR) services during the post-peak phase of the COVID-19 pandemic (ie, period of low community prevalence...

With the rapid rise in cases of COVID-19 across the world, health systems face unprecedented challenges in the delivery of patient care. This includes constrained capacity for intensive care unit (...

Background Chronic obstructive pulmonary disease (COPD) is one of the most common causes of mortality and morbidity in high-income countries. In addition to the high costs of initial hospitalization, COPD patients frequently return to the emergency department (ED) and are readmitted to hospital within 30 days of discharge. A COPD acute care discharge care bundle focused on optimizing care for patients with an acute exacerbation of COPD has been shown to reduce ED revisits and hospital readmissions. The aim of this study was to explore and understand factors influencing implementation and uptake of COPD discharge care bundle items in acute care facilities from the perspective of health care providers and patients. Methods Qualitative methodology was adopted. Nine focus groups were conducted using a semi-structured guide: seven with acute and primary/community health care providers and two with patients/family members. Focus groups were audiotaped, transcribed verbatim, and coded and analyzed using a thematic approach. Results Forty-six health care providers and 14 patients/family members participated in the focus groups. Health care providers and patients identified four factors that can challenge the implementation of COPD discharge care bundles: process of care complexities, human capacity in care settings, communication and engagement, and attitudes and perceptions towards change. Both health care providers and patients recognized process of care complexity as the most important determinant of the COPD discharge bundle uptake. Processes of care complexity include patient activities in seeking and receiving care, as well as practitioner activities in making a diagnosis and recommending or implementing treatment. Important issues linked to human capacity in care settings included time constraints, high patient volume, and limited staffing. Communication during transitions in care across settings and patient engagement were also broadly discussed. Other important issues were linked to patients’, providers’, and system attitudes towards change and level of involvement in COPD discharge bundle implementation. Conclusions Complexities in the process of care were perceived as the most important determinant of COPD discharge bundle implementation. Early engagement of health providers and patients in the uptake of COPD discharge bundle items as well as clear communication between acute and post-acute settings can contribute positively to bundle uptake and implementation success.

In this guideline update, we highlight important and new findings related to pharmacological therapy of chronic obstructive pulmonary disease (COPD) that should change clinical practice and improve...

RATIONALE: Delivery of pulmonary rehabilitation (PR) varies widely across Canada. There is a need for evidence-based quality indicators (QI) that can be used to identify variations in the quality o...

COPD patients have increased central arterial stiffness and muscle sympathetic nervous activity (MSNA), both of which contribute to cardiovascular (CV) dysfunction and increased CV risk. Previous work suggests that COPD patients have elevated carotid chemoreceptor (CC) activity/sensitivity, which may contribute to the elevated MSNA and arterial stiffness. Accordingly, the effect of CC inhibition on central arterial stiffness, MSNA and CV function at rest in COPD patients was examined in a randomized placebo-controlled study. Thirteen mild-moderate COPD patients (FEV1 predicted ± SD: 83 ± 19%) and 13 age- and risk-matched controls completed resting CV function measurements with either intravenous saline or I.V. dopamine (2 μg kg min−1) while breathing normoxia or hyperoxia (100% O2). On a separate day, a subset of COPD patients and controls completed MSNA measurements while breathing normoxia or hyperoxia. Arterial stiffness was determined by pulse-wave velocity (PWV) and MSNA was measured by microneurography. Brachial blood flow was determined using Doppler ultrasound, cardiac output was estimated by impedance cardiography, and vascular conductance was calculated as flow/mean arterial pressure (MAP). CC inhibition with dopamine decreased central and peripheral PWV, and MAP (P

Heightened arterial stiffness is a marker of cardiovascular risk and is elevated in chronic obstructive pulmonary disease (COPD). Physical activity has been shown to reduce arterial stiffness, and our previous work has shown that arterial stiffness is related to physical activity and exercise tolerance in COPD. The purpose of this study was to evaluate whether baseline physical activity and exercise tolerance influence the cardiovascular benefits associated with standard COPD outpatient pulmonary rehabilitation (PR).A total of 66 patients with COPD were recruited from the G.F. MacDonald Centre for Lung Health, Edmonton, Alberta, prior to entering PR. Another 23 COPD patients not attending the PR program were recruited as time controls (TC). Arterial stiffness (carotid-radial pulse wave velocity, PWV), physical activity (steps taken over three days), and 6-min walk distance (6MWD) were assessed before and after PR, or before and after six weeks of standard care.Thirty-nine PR and 11 TC completed all parts of the study. Following PR, there was no overall change in PWV. However, changes in arterial stiffness with PR were dependent on baseline exercise tolerance, with those patients with a 6MWD350 m showing a significant reduction in PWV following PR (6MWD350 m: 8.2 ± 1.6 to 8.5 ± 1.7 versus 6MWD350 m: 9.2 ± 0.6 to 7.3 ± 2.0 m/s, p 0.05). The PWV response to PR was not influenced by baseline physical activity levels.COPD patients with low exercise tolerance appear to derive the greatest cardiovascular benefits from PR.

RATIONALE: Since the last published Canadian Thoracic Society (CTS) COPD guideline in 2007 and the 2008 update – highlights for primary care, many new clinical trials have challenged COPD treatment...

Background Patients with chronic obstructive pulmonary disease (COPD) have an exaggerated ventilatory response to exercise, contributing to exertional dyspnea and exercise intolerance. We recently demonstrated enhanced activity and sensitivity of the carotid chemoreceptor (CC) in COPD which may alter ventilatory and cardiovascular regulation and negatively affect exercise tolerance. We sought to determine whether CC inhibition improves ventilatory and cardiovascular regulation, dyspnea and exercise tolerance in COPD. Methods Twelve mild-moderate COPD patients (FEV1 83 ± 15 %predicted) and twelve age- and sex-matched healthy controls completed two time-to-symptom limitation (TLIM) constant load exercise tests at 75% peak power output with either intravenous saline or low-dose dopamine (2 μg·kg−1·min−1, order randomized) to inhibit the CC. Ventilatory responses were evaluated using expired gas data and dyspnea was evaluated using a modified Borg scale. Inspiratory capacity maneuvers were performed to determine operating lung volumes. Cardiac output was estimated using impedance cardiography and vascular conductance was calculated as cardiac output/mean arterial pressure (MAP). Results At a standardized exercise time of 4-min and at TLIM; ventilation, operating volumes and dyspnea were unaffected by dopamine in COPD patients and controls. In COPD, dopamine decreased MAP and increased vascular conductance at all time points. In controls, dopamine increased vascular conductance at TLIM, while MAP was unaffected. Conclusion There was no change in time to exhaustion in either group with dopamine. These data suggest that the CC plays a role in cardiovascular regulation during exercise in COPD; however, ventilation, dyspnea and exercise tolerance were unaffected by CC inhibition in COPD patients.

Background Asthma is a complex disease with variable course. Efforts to identify biomarkers to predict asthma severity, the course of disease and response to treatment have not been very successful so far. We have previous suggested that PAR-2 and CRTh2 expression on specific peripheral blood cell subtypes may be biomarkers of asthma severity. We reasoned that parameters that remain stable when asthma symptoms are controlled would be the most appropriate to evaluate for their utility to predict loss of asthma control and/or severity of the disease. Methods Nineteen stable asthmatics were recruited from the University of Alberta Asthma clinic and followed in clinic every 3 months for a total of 4 visits. Patients had spirometry and completed the ACQ questionnaire in every visit. Blood was drawn in every visit and analyzed for a number of immune parameters by flow cytometry. These parameters included PAR-2 and CRTh2 expression on monocyte subgroups and T lymphocytes respectively, as well as numbers of eosinophils, innate lymphoid type-2 cells (ILC2) and dendritic cells. Within person stability of immune and physiological parameters was calculated using the intraclass correlation (ICC) using R version 3.4.0. Results FEV1 (% predicted), FEV1/FVC ratio, ACQ5 and ACQ7 did not differ significantly over the 4 visits, as would be expected for patients with stable asthma. Peripheral blood eosinophil numbers by Kimura stain and by flow cytometry showed ICC scores of 0.44 and 0.52 respectively, indicating moderate stability. The % of ILC2 cells in peripheral blood also showed moderate stability [ICC score of 0.45 (0.14–0.67)]. The stability for all other immune parameters was poor. Conclusion Among the peripheral blood immune parameters we studied, only numbers of eosinophils and ILC2 in peripheral blood were moderately stable over a year in stable asthmatics. Further studies are required to understand the reasons for the variability of the other cell types.

Background Previous work suggests that mild chronic obstructive pulmonary disease (COPD) patients have greater lung dysfunction than previously appreciated from spirometry alone. There is evidence of pulmonary microvascular dysfunction in mild COPD, which may reduce diffusing capacity (DLCO) and increase ventilatory inefficiency during exercise. The purpose of this study was to determine if DLCO, pulmonary capillary blood volume (Vc), and membrane diffusing capacity (Dm) are diminished during exercise in mild COPD, and whether this is related to ventilatory inefficiency and dyspnea. Methods Seventeen mild COPD patients (FEV1/FVC: 64 ± 4%, FEV1 = 94 ± 11%pred) and 17 age- and sex-matched controls were recruited. Ten moderate COPD patients were also tested for comparison (FEV1 = 66 ± 7%pred). DLCO, Vc, and Dm were determined using the multiple-fraction of inspired oxygen (FIO2) DLCO method at baseline and during steady-state cycle exercise at 40W, 50%, and 80% of V ˙ O 2 peak . Using expired gas data, ventilatory inefficiency was assessed by V ˙ E / V ˙ CO 2 . Results Compared to controls, mild COPD had lower DLCO at baseline and during exercise secondary to diminished Vc (P V ˙ E / V ˙ CO 2 (i.e. ≥34) had lower Vc and greater dyspnea ratings compared to control at 40W. Moderate COPD patients were unable to increase Vc with increasing exercise intensity, suggesting further pulmonary vascular impairment with increased obstruction severity. Conclusion Despite relatively minor airflow obstruction, mild COPD patients exhibit a diminished DLCO and capillary blood volume response to exercise, which appears to contribute to ventilatory inefficiency and greater dyspnea.

Dyspnea has been reported to be a main contributor to exercise avoidance in asthma. While traditional markers of ventilation do not explain the heightened dyspnea during exercise in patients with asthma, this study proposed that exertional dyspnea in asthma was due to high-operating lung volumes, which may be improved with a short-acting β2-agonist. On two separate days, 16 patients with asthma and 16 controls completed a lung function test and incremental exercise tests to exhaustion. On one of the days (order randomized), 400 µg salbutamol was administered before exercise. Inspiratory capacity (IC), inspiratory reserve volume (IRV), and dyspnea (modified Borg scale) were evaluated throughout exercise. Compared with controls, patients with asthma reported greater dyspnea at the same absolute submaximal workloads. Furthermore, patients with asthma demonstrated altered breathing responses to exercise, characterized by reduced IC and IRV throughout exercise compared with controls. The reduced IRV was associated with increased dyspnea in patients with asthma. Salbutamol did not affect dyspnea or operating lung volumes in either group. The increased perception of dyspnea during incremental exercise in patients with asthma appears to be secondary to a reduction in IRV, which is unaffected by an inhaled β2-agonist. NEW & NOTEWORTHY Increased exertional dyspnea in asthma appears to be due to high operating lung volumes and is not affected by salbutamol.

Background Variation in hospital management of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) may prolong length of stay, increasing the risk of hospital-acquired complications and worsening quality of life. We sought to determine whether an evidence-based computerized AECOPD admission order set could improve quality and reduce length of stay. Methods The order set was designed by a provincial COPD working group and implemented voluntarily among three physician groups in a Canadian tertiary-care teaching hospital. The primary outcome was length of stay for patients admitted during order set implementation period, compared to the previous 12 months. Secondary outcomes included length of stay of patients admitted with and without order set after implementation, all-cause readmissions, and emergency department visits. Results There were 556 admissions prior to and 857 admissions after order set implementation, for which the order set was used in 47%. There was no difference in overall length of stay after implementation (median 6.37 days (95% confidence interval 5.94, 6.81) pre-implementation vs. 6.02 days (95% confidence interval 5.59, 6.46) post-implementation, p = 0.26). In the post-implementation period, order set use was associated with a 1.15-day reduction in length of stay (95% confidence interval − 0.5, − 1.81, p = 0.001) compared to patients admitted without the order set. There was no difference in readmissions. Conclusions Use of a computerized guidelines-based admission order set for COPD exacerbations reduced hospital length of stay without increasing readmissions. Interventions to increase order set use could lead to greater improvements in length of stay and quality of care. Electronic supplementary material The online version of this article (10.1186/s12890-018-0657-x) contains supplementary material, which is available to authorized users.

COPD is a common disease with substantial associated morbidity and mortality. Patients with COPD usually have a progression of airflow obstruction that is not fully reversible and can lead to a history of progressively worsening breathlessness, affecting daily activities and health-related quality of life.1-3 COPD is the fourth leading cause of death in Canada4 and the third leading cause of death in the United States where it claimed 133,965 lives in 2009.5 In 2011, 12.7 million US adults were estimated to have COPD.6 However, approximately 24 million US adults have evidence of impaired lung function, indicating an underdiagnosis of COPD.7 Although 4% of Canadians aged 35 to 79 years self-reported having been given a diagnosis of COPD, direct measurements of lung function from the Canadian Health Measures Survey indicate that 13% of Canadians have a lung function score indicative of COPD.4 COPD is also costly. In 2009, COPD caused 8 million office visits, 1.5 million ED visits, 715,000 hospitalizations, and 133,965 deaths in the United States.8 In 2010, US costs for COPD were projected to be approximately $49.9 billion, including $29.5 billion in direct health-care expenditures, $8.0 billion in indirect morbidity costs, and $12.4 billion in indirect mortality costs.9 Exacerbations account for most of the morbidity, mortality, and costs associated with COPD. The economic burden associated with moderate and severe exacerbations in Canada has been estimated to be in the range of $646 million to $736 million per annum.10 This value may be an underestimate given that the prevalence of moderate exacerbations is not well documented, COPD is underdiagnosed, and the rate of hospitalization due to COPD is increasing.11 Exacerbations are to COPD what myocardial infarctions are to coronary artery disease: They are acute, trajectory-changing, and often deadly manifestations of a chronic disease. Exacerbations cause frequent hospital admissions, relapses, and readmissions12; contribute to death during hospitalization or shortly thereafter12; reduce quality of life dramatically12,13; consume financial resources12,14; and hasten a progressive decline in pulmonary function, a cardinal feature of COPD. Hospitalization due to exacerbations accounts for > 50% of the cost of managing COPD in North America and Europe.15,16 COPD exacerbation has been defined as an event in the natural course of the disease characterized by a baseline change in the patient’s dyspnea, cough, and/or sputum that is beyond the normal day-to-day variations, is acute in onset, and may warrant a change in regular medication in a patient with underlying COPD.17,18 Exacerbation in clinical trials has been defined for operational reasons on the basis of whether an increase in treatment beyond regular or urgent care is required in an ED or a hospital. Exacerbation treatment in clinical trials usually is defined by the use of antibiotics, systemic corticosteroids, or both.19 The severity of the exacerbation is then ranked or stratified according to the outcome: mild, when the clinical symptoms are present but no change in treatment or outcome is recorded; moderate, when the event results in a change in medication, such as the use of antibiotics and systemic corticosteroids; or severe, when the event leads to a hospitalization.1 Two-thirds of exacerbations are associated with respiratory tract infections or air pollution, but one-third present without an identifiable cause.17 Exacerbations remain poorly understood in terms of not only cause but also treatment and prevention. Although the management of an acute exacerbation has been the primary focus of clinical trials, the prevention of acute exacerbations has not been a major focus until recently. Most current COPD guidelines focus on the general diagnosis and evaluation of the patient with COPD, the management of stable disease, and the diagnosis and management of acute exacerbations.1,20 Although current COPD guidelines state that prevention of exacerbations is possible, little guidance is provided to the clinician regarding current available therapies for the prevention of COPD exacerbations.1,20 Moreover, new therapies have promise in preventing acute exacerbations of COPD (AECOPD) and would benefit from critical review of their efficacy in the exacerbation prevention management.21-23 The American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) jointly commissioned this evidence-based guideline on the prevention of COPD exacerbations to fill this important void in COPD management. The overall objective of this CHEST and CTS joint evidence-based guideline (AECOPD Guideline) was to create a practical, clinically useful document describing the current state of knowledge regarding the prevention of AECOPD according to major categories of prevention therapies. We accomplished this by using recognized document evaluation tools to assess and choose the most appropriate studies and evidence to extract meaningful data and to grade the level of evidence supporting the recommendations in a balanced and unbiased fashion. The AECOPD Guideline is unique not only for its topic but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in the field of COPD would lead to a series of recommendations to assist clinicians in their management of the patient with COPD. This guideline is unique because a group of interdisciplinary clinicians who have special expertise in COPD clinical research and care led the development of the guideline process with the assistance of methodologists.

BACKGROUND:COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. METHODS:In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. RESULTS:The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in the field of COPD would lead to a series of recommendations to assist clinicians in their management of the patient with COPD. CONCLUSIONS:This guideline is unique because it provides an up-to-date, rigorous, evidence-based analysis of current randomized controlled trial data regarding the prevention of COPD exacerbations.

BACKGROUND: Pulmonary rehabilitation (PR) is a recommended intervention in the management of individuals with chronic lung disease. It is important to study the characteristics and capacity of programs in Canada to confirm best practices and identify future areas of program improvement and research.OBJECTIVE: To identify all Canadian PR programs, regardless of setting, and to comprehensively describe all aspects of PR program delivery. The present article reports the results of the survey related to type of program, capacity and program characteristics.METHODS: All hospitals in Canada were contacted to identify PR programs. A representative from each program completed a 175-item online survey encompassing 16 domains, 10 of which are reported in the present article.RESULTS: A total of 155 facilities in Canada offered PR, of which 129 returned surveys (83% response rate). PR programs were located in all provinces, but none in the three territories. Most (60%) programs were located in hospital settings, 24% were in public health units and 8% in recreation centres. The national capacity of programs was estimated to be 10,280 patients per year, resulting in 0.4% of all Canadians with chronic obstructive pulmonary disease (COPD) and 0.8% of Canadians with moderate to severe COPD having access to PR. COPD, interstitial lung disease, and asthma were the most common diagnoses of patients. The majority of programs had at least four health care professionals involved; 9% had only one health care professional involved.CONCLUSION: The present comprehensive survey of PR in Canada reports an increase in the number of programs and the total number of patients enrolled since the previous survey in 2005. However, PR capacity has not kept pace with demand, with only 0.4% of Canadians with COPD having access.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) and asthma depend on inhalers for management, but critical errors committed during inhaler use can limit drug effectiveness. Outpatient education in inhaler technique remains inconsistent due to limited resources and inadequate provider knowledge.OBJECTIVE: To determine whether a simple, two-session inhaler education program can improve physician attitudes toward inhaler teaching in primary care practice.METHODS: An inhaler education program with small-group hands-on device training was instituted for family physicians (FP) in British Columbia and Alberta. Sessions were spaced one to three months apart. All critical errors were corrected in the first session. Questionnaires surveying current inhaler teaching practices and attitudes toward inhaler teaching were distributed to physicians before and after the program.RESULTS: Forty-one (60%) of a total 68 participating FPs completed both before and after program questionnaires. Before the program, only 20 (49%) reported providing some form of inhaler teaching in their practices, and only four (10%) felt fully competent to teach patients inhaler technique. After the program, 40 (98%) rated their inhaler teaching as good to excellent. Thirty-four (83%) reported providing inhaler teaching in their practices, either by themselves or by an allied health care professional they had personally trained. All stated they could teach inhaler technique within 5 min. Observation of FPs during the second session by certified respiratory educators found that none made critical errors and all had excellent technique.CONCLUSION: A physician inhaler education program can improve attitudes toward inhaler teaching and facilitate implementation in clinical practices.

Purpose The objective of this systematic review was to assess the clinical efficacy, safety, tolerability, and health-related quality of life outcomes associated with management of moderate-to-severe chronic pain with oxycodone/naloxone and tapentadol, focusing on the effect of these treatments on patients’ daily functioning. Methods Literature from a wide range of sources, including Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Central Register of Controlled Trials, was searched to identify randomized controlled trials investigating tapentadol or oxycodone/naloxone for the treatment of patients with chronic pain. A network meta-analysis was conducted to determine the relative efficacy and safety profiles of these treatments. Findings Oxycodone/naloxone was significantly better than tapentadol with respect to the Patient Assessment of Constipation Symptoms total score (risk ratio = –3.60; 95% credible interval, −5.36 to −2.11) and revealed a significantly lower risk of dizziness (risk ratio = 0.72; 95% credible interval, 0.42–0.98). Oxycodone/naloxone was directionally favored, although not significantly superior to tapentadol for headache, fatigue, dry mouth, dyspepsia, and withdrawals due to lack of efficacy. For the AE outcomes of constipation, nausea, and vomiting, as well as pain efficacy and all-cause withdrawals from studies, tapentadol was directionally favored without any statistical difference from oxycodone/naloxone. However, the two treatments were not wholly comparable for the evaluation of pain efficacy because of differences in on-study rescue medication and a higher baseline pain severity in the tapentadol studies. Implications Oxycodone/naloxone offers significant improvements in Patient Assessment of Constipation Symptoms total score and dizziness and was directionally favored for fatigue and headache compared with extended-release tapentadol, which may translate to improved patient daily functioning and health-related quality of life.

To be considered bioequivalent to their branded counterparts, generic drugs must meet the standards for bioequivalence (BE) described by the regulatory agencies. While BE of generic inhalational drugs can be evaluated using a similar approach as that for oral dosage from products or drugs that are delivered systemically, the approach is insufficient to address the complexities of inhalational products (e.g., localized site of action, device–patient interface). Therefore, more considerations are needed and caution should be applied when evaluating BE of inhaled compounds. The purpose of this review is to highlight the considerations and challenges in establishing BE of inhaled compounds by (1) outlining the current regulatory approaches (from Health Canada, the U.S. Food and Drug Administration, and the European Medicines Agency) to assess BE for subsequent entry inhaled products (SEIPs) and (2) reviewing the literature pertaining to testing considerations of SEIPs to establish BE.

Adenoid cystic carcinoma (ACC) accounts for less than 1% of laryngeal tumors. Surgery is the treatment of choice which can be combined with adjuvant radiotherapy. We present a rare case of ACC of glottis and subglottis presented to us with respiratory distress. How to cite this article Verma H, Dass A, Punia RS, Singhal SK, Gupta N, Bhutani M. Adenoid Cystic Carcinoma of Larynx: A Case Report and Rare Experience. Int J Phonosurg Laryngol 2016;6(2):86-88.

BACKGROUND: Although underused, written asthma action plans (AAPs) are associated with reduced numbers of emergency department (ED) visits and hospitalizations.OBJECTIVE: To describe the frequency of use and contents of any AAPs reported by patients presenting with exacerbations to three urban Canadian EDs.METHODS: Prospective data were collected through ED interview and chart review. Descriptive analyses used proportions and medians with interquartile range; multivariable logistic regression was used for the adjusted analyses.RESULTS: Among 176 enrolled patients, the median age was 27 years (interquartile range 23 to 39 years) and 97 (55%) were female. Few (n=42 [24%]) reported having AAPs at ED presentation and only six were written. Most (n=35 [75%]) patients with any AAP took action before the ED visit; none used a valid anti-inflammatory strategy. The first step of 27 plans was to increase asthma medication; no patients appropriately increased inhaled corticosteroids (ICS). In multivariable analyses, only the use of either ICS or ICS/long-acting β-agonist combination agents (31% had AAPs versus 12% did not have AAPs (adjusted OR 3.0 [95% CI 1.14 to 8.07]) and asthma education (47% had AAPs versus 21% did not have AAPs, adjusted OR 3.2 [95% CI 1.13 to 9.19]) were independently associated with AAP possession.CONCLUSION: Possession of AAPs among patients presenting to the ED with acute asthma was low, and only one in 10 AAPs were written. Patients who reported having any AAP used ineffective strategies to abort or mitigate the severity of an ED visit. Increasing frequency of written AAPs and improving their contents holds immediate promise in improving outcomes related to asthma.

Frequent exacerbations of COPD are associated with accelerated loss of lung function, declining health status, increased mortality, and increased health care costs. Thus, a key objective in the management of COPD is preventing exacerbations or at least reducing their number and severity. When new interventions are examined, their value is sometimes assessed in reference to the minimal clinically important difference (MCID), a theoretical construct that may be defined and estimated numerically in several different ways. There have been limited attempts to calculate the MCID for COPD exacerbations but a figure of 20% reduction in exacerbation frequency is occasionally cited as the "established" MCID from a single manuscript reviewing six clinical trials. Our review suggests that defining and calculating the MCID for COPD exacerbations is problematic, not only because the methodology around developing endpoints for MCIDs is inconsistent, but because the impact of exacerbation reduction is likely to be influenced dramatically by the definitions of exacerbation severity used and the population's baseline status. Reference to current literature shows that at least one other estimate for exacerbation MCID as low as 4%. MCID is sometimes estimated by expert consensus; a review of articles used to shape COPD guidelines shows frequent reference to articles in which interventions yielded exacerbation differences as low as 11%. We find no evidence of an established MCID but suggest that interventions reducing exacerbations by as little as 11% appear to be regarded widely as clinically important.

Background A COPD discharge bundle is a set of evidence-based practices aimed at improving patient outcomes after discharge from acute care settings following an exacerbation. We conducted a systematic review on the effectiveness of COPD discharge bundles and summarised their individual care elements. Methods Biomedical electronic databases and clinical trial registries were searched from database inception through April 2016 to identify experimental studies evaluating care bundles offered to patients with COPD at discharge. Random-effects meta-analyses of clinical trials data were conducted for hospital readmissions, mortality, and quality of life (QoL). Results The review included 14 studies (5 clinical trials, 7 uncontrolled trials, and 2 interrupted time series). A total of 26 distinct elements of care were included in the bundles of individual studies. Evidence from four clinical trials with moderate-to-high risk of bias showed that COPD discharge bundles reduced hospital readmissions (pooled risk ratio (RR): 0.80; 95% CI 0.65 to 0.99). There was insufficient evidence that care bundles influence long-term mortality (RR: 0.74; 95% CI 0.43 to 1.28; four trials) or QoL (mean difference in St. George9s Respiratory Questionnaire: 1.84; 95% CI −2.13 to 5.8). Conclusions Discharge bundles for patients with COPD led to fewer readmissions but did not significantly improve mortality or QoL. Future studies should employ higher quality research methods, fully report care bundle elements, implementation strategies and intervention fidelity to better evaluate the effectiveness of packaging evidence-based interventions together to improve outcomes of patients with COPD discharged from acute care settings.

The development of intrapulmonary shunts with increased cardiac output during exercise in healthy humans has been reported in several recent studies, but mechanisms governing their recruitment remain unclear. Dobutamine and dopamine are inotropes commonly used to augment cardiac output; however, both can increase venous admixture/shunt fraction (Qs/Qt). It is possible that, as with exercise, intrapulmonary shunts are recruited with increased cardiac output during dobutamine and/or dopamine infusion that may contribute to the observed increase in Qs/Qt. The purpose of this study was to examine how dobutamine and dopamine affect intrapulmonary shunt and gas exchange. Nine resting healthy subjects received serial infusions of dobutamine and dopamine at incremental doses under normoxic and hyperoxic (inspired O2fraction = 1.0) conditions. At each step, alveolar-to-arterial Po2difference (A-aDo2) and Qs/Qt were calculated from arterial blood gas samples, intrapulmonary shunt was evaluated using contrast echocardiography, and cardiac output was calculated by Doppler echocardiography. Both dobutamine and dopamine increased cardiac output and Qs/Qt. Intrapulmonary shunt developed in most subjects with both drugs and paralleled the increase in Qs/Qt. A-aDo2was unchanged due to a concurrent rise in mixed venous oxygen content. Hyperoxia consistently eliminated intrapulmonary shunt. These findings contribute to our present understanding of the mechanisms governing recruitment of these intrapulmonary shunts as well as their impact on gas exchange. In addition, given the deleterious effect on Qs/Qt and the risk of neurological complications with intrapulmonary shunts, these findings could have important implications for use of dobutamine and dopamine in the clinical setting.

Introduction: Social desirability bias is a systematic error in self-report measures resulting from the desire of respondents to avoid embarrassment and project a favourable image of themselves to others. This bias may decrease the accuracy of self-reported health outcomes collected in health research compromise the validity of research findings. This study compared outcomes obtained by patient self-report vs. the same outcomes after undergoing verification and external adjudication, in trial involving patients with acute asthma. Methods: Cross-sectional analysis of outcome data obtained in a randomized controlled trial conducted in 6 Canadian emergency departments (ED). Adult patients were allocated to receive usual care (UC), opinion leader [OL] guidance to their primary care provider (PCP), or OL guidance+nurse case-management [OL+CM] for patients (NCT01079000). Asthma relapses and PCP follow-up visits were blindly assessed through patient self-report 30 and 90 days after their ED presentation for acute asthma. Each reported event was verified through the provincial electronic medical record, the ED Information Systems, and by calling the PCPs’ offices. Two study investigators, blinded to the study interventions, independently reviewed and adjudicated the verified outcomes. Disagreements were resolved by consensus prior to un-blinding. Results: Overall, 367 patients were enrolled; more were female (64%) and the median age was 28 years. Overall, patient follow-up was obtained in 85% of cases. The proportion of asthma relapses occurring within the first 90 days were lower when considering patient self-report than when considering the adjudicated outcomes (17%[39/227] vs. 19%[70/367]). The proportion of PCP follow-up visits occurring within the first 30 days were higher when considering patient self-report than when considering the adjudicated outcomes (47%[139/290] vs. 40%[146/367]). The pattern was similar, regardless of the arm of the study (UC vs. OL vs. OL+CM arms); outcome disagreement did not influence the direction of magnitude of the treatment effect. Conclusion: Social desirability bias could have influenced the outcomes obtained by patient self-report in this ED-based study. The direction of the bias was the same for both outcomes; however, the variation did not change the study results. This bias may play a role in studies with smaller sample sizes.

Thyroglossal duct cysts (TDC) are commonly encountered in ENT practice. They are treated by Sistrunk’s operation in which the cyst along with the entire tract and part of hyoid bone is excised to prevent any recurrence. Very rarely TDCs may harbour malignancy. In that situation the management protocol is different. We present the case of a 33-year-old female with the unexpected finding of a papillary carcinoma arising in a submental TDC and is described with special regard to the rarity of the localization and the different options in the management strategy when carcinoma is found incidentally following surgery.

Curcumin, a yellow pigment extracted from rhizomes of the plant Curcuma longa (turmeric), has been widely used as food additive and also as a herbal medicine throughout Asia. The present study was designed to study the pharmacological, biochemical and neurochemical effects of daily administration of curcumin to rats subjected to chronic unpredictable stress. Curcumin treatment (20 and 40 mg/kg, i.p., 21 days) significantly reversed the chronic unpredictable stress-induced behavioral (increase immobility period), biochemical (increase monoamine oxidase activity) and neurochemical (depletion of brain monoamine levels) alterations. The combination of piperine (2.5 mg/kg, i.p., 21 days), a bioavailability enhancer, with curcumin (20 and 40 mg/kg, i.p., 21 days) showed significant potentiation of its anti-immobility, neurotransmitter enhancing (serotonin and dopamine) and monoamine oxidase inhibitory (MAO-A) effects as compared to curcumin effect per se. This study provided a scientific rationale for the use of curcumin and its co-administration with piperine in the treatment of depressive disorders.

Background Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) is a receptor for PGD2 and expressed by T cells, eosinophils, basophils, and ILC2 cells. CRTh2 expression by CD4(+) T cells identifies the Th2 subset, and these cells have been characterized as allergen-specific central memory Th2 cells. Recently, activation of the PGD2 -CRTh2 pathway in the lungs was associated with severe asthma. Objective To assess circulating levels of Th2 cells and related mediators in severe asthma and those who experience asthma exacerbations. Methods Peripheral blood cells expressing CRTh2 were characterized by flow cytometry and qRT-PCR. Serum IL-13 and PGD2 were measured by ELISA and compared with asthma severity and tendency to exacerbate. Results Severe asthmatics had more circulating CD4(+) CRTh2(+) T cells, CRTh2 and GATA3 mRNA, and a higher level of serum IL-13 compared to mild/moderate asthmatics. The proportion of CD4(+) CRTh2(+) T cells was associated with lower lung function and was highest in severe asthmatics that exacerbated in the last year. Circulating CD4(+) CRTh2(+) T cells, unlike eosinophils, were positively correlated with inhaled steroid dose. Conclusions and clinical relevance Elevated levels of circulating CD4(+) CRTh2(+) T cells are a feature of severe asthma, despite high-dose corticosteroids. Tracking the systemic level of these cells may help identify type 2 severe asthmatics at risk of exacerbation.

Background: Chronic obstructive pulmonary disease (COPD) is common among patients with cardiovascular disease (CVD), and in fact nearly a third of patients with COPD die of CV causes. Thus, increased screening and evaluation of patients with comorbid COPD and CVD is important and has the potential to improve CVD outcomes. Aims and objectives: This online point-of-care program aimed to empower cardiologists to screen and evaluate their CV patients both at risk of COPD or with COPD. The goals were to ensure COPD was correctly diagnosed, identify patients needing improved COPD control, and prompt cardiologists to refer to a respirologist when appropriate. Methods: 36 Canadian cardiologists completed surveys on up to 20 patients at risk of COPD (age ≥40 years, a smoking history of ≥10 pack-years, and ≥1 positive answer on the Canadian Lung Health Test), or with a current diagnosis, during routine visits. After entering a patient profile, the program prompted physicians with relevant information and recommendations. Results: Cardiologists entered 588 patients into the online program. Compared to the group with COPD, patients at risk of COPD were more likely to present with new or worsening CV symptoms (38% vs. 21%). Of the 143 patients at risk of COPD, 62 were newly referred for spirometry, and 43 were referred to an HCP for evaluation/confirmation of COPD. Out of 445 patients with COPD, 134 had not had spirometry to confirm diagnosis, while 42 were newly referred for confirmation of COPD. Conclusion: Increased awareness of the presence of or potential for COPD among cardiologists9 patients led to positive clinical change in the form of referrals for diagnosis or management of COPD.