ERS statement: a core outcome set for clinical trials evaluating the management of COPD exacerbations.

Clinical trials evaluating the management of acute exacerbations of COPD assess heterogeneous outcomes, often omitting those that are clinically relevant or more important to patients. We have developed a core outcome set, a consensus-based minimum set of important outcomes that we recommend are evaluated in all future clinical trials on exacerbations management, to improve their quality and comparability. COPD exacerbations outcomes were identified through methodological systematic reviews and qualitative interviews with 86 patients from 11 countries globally. The most critical outcomes were prioritised for inclusion in the core outcome set through a two-round Delphi survey completed by 1063 participants (256 patients, 488 health professionals and 319 clinical academics) from 88 countries in five continents. Two global, multi-stakeholder, virtual consensus meetings were conducted to 1) finalise the core outcome set and 2) prioritise a single measurement instrument to be used for evaluating each of the prioritised outcomes. Consensus was informed by rigorous methodological systematic reviews. The views of patients with COPD were accounted for at all stages of the project. Survival, treatment success, breathlessness, quality of life, activities of daily living, the need for a higher level of care, arterial blood gases, disease progression, future exacerbations and hospital admissions, treatment safety and adherence were all included in the core outcome set. Focused methodological research was recommended to further validate and optimise some of the selected measurement instruments. The panel did not consider the prioritised set of outcomes and associated measurement instruments to be burdensome for patients and health professionals to use.

Core outcome set for the management of acute exacerbations of chronic obstructive pulmonary disease: the COS-AECOPD ERS Task Force study protocol.

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations. For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus. Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS.

Prevalence of anxiety and depressive symptoms among medical residents in Tunisia: a cross-sectional survey.

OBJECTIVE: To assess the prevalence of anxiety and depressive symptoms and the associated risk factors among Tunisian medical residents. DESIGN: Cross-sectional survey. SETTING: Faculty of Medicine, Tunis. PARTICIPANTS: All Tunisian medical residents brought together between 14 and 22 December 2015 to choose their next 6-month rotation. INTERVENTION: The items of the Hospital Anxiety and Depression (HAD) questionnaire were employed to capture the prevalence of anxiety and/or depression among the residents. The statistical relationships between anxiety and depression (HAD score) and sociodemographic and work-related data were explored by Poisson regression. RESULTS: 1700 out of 2200 (77%) medical residents (mean age: 28.5±2 years, female: 60.8%) answered the questionnaire. The mean working hours per week was 62±21 hours; 73% ensured a mean of 5.4±3 night shifts per month; and only 8% of them could benefit from a day of safety rest. Overall, 74.1% of the participating residents had either definite (43.6%) or probable (30.5%) anxiety, while 62% had definite (30.5%) or probable (31.5%) depression symptoms, with 20% having both definite anxiety and definite depression. The total HAD score was significantly associated with the resident's age (OR=1.014, 95% CI 1.006 to 1.023, p=0.001); female gender (OR=1.114, 95% CI 1.083 to 1.145, p<0.0001); and the heavy burden of work imposed on a weekly or monthly basis, as reflected by the number of night shifts per month (OR=1.048, 95% CI 1.016 to 1.082, p=0.03) and the number of hours worked per week (OR=1.008, 95% CI 1.005 to 1.011, p<0.0001). Compared with medical specialties, the generally accepted difficult specialties (surgical or medical-surgical) were associated with a higher HAD score (OR=1.459, 95% CI 1.172 to 1.816, p=0.001). CONCLUSION: Tunisian residents experience a rate of anxiety/depression substantially higher than that reported at the international level. This phenomenon is worrying as it has been associated with an increase in medical errors, work dissatisfaction and attrition. The means of improving the well-being of Tunisian medical residents are explored, emphasising those requiring immediate implementation.

Noninvasive ventilation with helium-oxygen mixture in hypercapnic COPD exacerbation: aggregate meta-analysis of randomized controlled trials.

When used as a driving gas during NIV in hypercapnic COPD exacerbation, a helium-oxygen (He/O2) mixture reduces the work of breathing and gas trapping. The potential for He/O2 to reduce the rate of NIV failure leading to intubation and invasive mechanical ventilation has been evaluated in several RCTs. The goal of this meta-analysis is to assess the effect of NIV driven by He/O2 compared to air/O2 on patient-centered outcomes in hypercapnic COPD exacerbation. Relevant RCTs were searched using standard procedures. The main endpoint was the rate of NIV failure. The effect size was computed by a fixed-effect model, and estimated as odds ratio (OR) with 95% confidence interval (CI). Additional endpoints were ICU mortality, NIV-related side effects, and the length and costs of ICU stay. Three RCTs fulfilled the selection criteria and enrolled a total of 772 patients (386 patients received He/O2 and 386 received air/O2). Pooled analysis showed no difference in the rate of NIV failure when using He/O2 mixture compared to air/O2: 17 vs 19.7%, respectively; OR 0.84, 95% CI 0.58-1.22; p = 0.36; I 2 for heterogeneity = 0%, and no publication bias. ICU mortality was also not different: OR 0.8, 95% CI 0.45-1.4; p = 0.43; I 2 = 5%. However, He/O2 was associated with less NIV-related adverse events (OR 0.56, 95% CI 0.4-0.8, p = 0.001), and a shorter length of ICU stay (difference in means = -1.07 day, 95% CI -2.14 to -0.004, p = 0.049). Total hospital costs entailed by hospital stay and NIV gas were not different: difference in means = -279$, 95% CI -2052-1493, p = 0.76. Compared to air/O2, He/O2 does not reduce the rate of NIV failure in hypercapnic COPD exacerbation. It is, however, associated with a lower incidence of NIV-related adverse events and a shortening of ICU length of stay with no increase in hospital costs.

Acetaminophen-Induced Changes in Systemic Blood Pressure in Critically Ill Patients: Results of a Multicenter Cohort Study.

OBJECTIVES: We sought to assess the incidence of acetaminophen-induced hypotension. Our secondary objectives were to describe systemic hemodynamic changes and factors associated with this complication. DESIGN: Prospective observational study. SETTING: Three ICUs. PATIENTS: Adult patients requiring IV acetaminophen infusion. Arterial pressure was monitored via an arterial catheter for 3 hours. Hypotension was defined as a decrease in the mean arterial pressure of greater than or equal to 15% compared with the baseline. RESULTS: Overall, 160 patients were included in this study. Eighty-three patients (51.9%) experienced acetaminophen-induced hypotension according to our definition. In patients with acetaminophen-induced hypotension, the nadir mean arterial pressure was 64 mm Hg (95% CI, 54-74). Hypotension was observed 30 minutes (95% CI, 15-71) after acetaminophen infusion. Changes in mean arterial pressure were closely correlated with decreases in the diastolic arterial pressure (r = 0.92) and to a lesser extent with changes in the pulse pressure (r = 0.18) and heart rate (r = 0.09). Changes in the body temperature were not correlated with changes in mean arterial pressure (r = 0.0002; p = 0.85). None of the patients' baseline characteristics (shock, use of angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, lactates, renal replacement therapy, chronic heart disease, and indication for acetaminophen infusion) or clinically relevant characteristics (baseline severity according to Logistic Organ Dysfunction score, need for vasopressors, use of antihypertensive agents, need for mechanical ventilation, or changes in the body temperature) were independently associated with acetaminophen-induced hypotension. Among patients with acetaminophen-induced hypotension, 29 (34.9%) required therapeutic intervention. CONCLUSIONS: Half of the patients who received IV injections of acetaminophen developed hypotension, and up to one third of the observed episodes necessitated therapeutic intervention. Adequately powered randomized studies are needed to confirm our findings, provide an accurate estimation of the consequences of acetaminophen-induced hypotension, and assess the pathophysiologic mechanisms involved.

Incidence of contrast-induced acute kidney injury in a pediatric setting: a cohort study.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is a common pathology among adult patients, with an incidence ranging from 3-25 % depending on risk factors. Little information is available regarding CI-AKI incidence, risk factors, and prognostic impact in the pediatric population. METHODS: We performed a retrospective study of pediatric patients who underwent computed tomography (CT) scan with iodinated contrast media injection between 2005 and 2014 in five pediatric units of a university hospital. CI-AKI was defined according to Kidney Disease/Improving Global Outcomes (KDIGO) criteria. RESULTS: Of 346 identified patients, 233 had renal function follow-up and were included in our analyses. CI-AKI incidence was 10.3 % [95 % confidence interval (CI) 6.4-14.2 %]. CI-AKI was associated with 30-day unfavorable outcome before (45.8 % vs. 19.7 %, P = 0.007) and after [odds ratio (OR) 3.6; 95 % CI 1.4-9.5] adjustment for confounders. No independent risk factors of CI-AKI were identified. CONCLUSIONS: CI-AKI incidence was as high as 10.3 % following intravenous contrast media administration in the pediatric setting. As reported among adults, CI-AKI was associated with unfavorable outcome after adjustment for confounders. Although additional studies are needed in the pediatric setting, our data suggest that physicians should maintain a high degree of suspicion toward this complication among pediatric patients.

Systemic corticosteroids in acute exacerbation of COPD: a meta-analysis of controlled studies with emphasis on ICU patients.

Guidelines on systemic corticosteroids in chronic obstructive pulmonary disease (COPD) exacerbation rely on studies that excluded patients requiring ventilatory support. Recent publication of studies including ICU patients allows estimation of the level of evidence overall and in patients admitted to the ICU. We included RCTs evaluating the efficacy and safety of systemic corticosteroids in COPD exacerbation, compared to placebo or standard treatment. The effect size on treatment success was computed by a random effects model overall and in subgroups of non-ICU and ICU patients. Effects on mortality and on the rate of adverse effects of corticosteroids were also computed. Twelve RCTs (including 1,331 patients) were included. Pooled analysis showed a statistically significant increase in the treatment success rate when using systemic corticosteroids: odds ratio (OR) = 1.72, 95% confidence interval (CI) = 1.15 to 2.57; p = 0.01. Subgroup analysis showed different patterns of effect in ICU and non-ICU subpopulations: a non-significant difference of effect in the subgroup of ICU patients (OR = 1.34, 95% CI = 0.61 to 2.95; p = 0.46), whereas in the non-ICU patients, the effect was significant (OR = 1.87, 95% CI = 1.18 to 2.99; p = 0.01; p for interaction = 0.72). Among ICU patients, there was no difference in the success whether patients were ventilated with tracheal intubation (OR = 1.85, 95% CI = 0.14 to 23.34; p = 0.63) or with non-invasive ventilation (OR = 4.88, 95% CI = 0.31 to 75.81; p = 0.25). Overall, there was no difference in the mortality rate between the steroid-treated group and controls: OR = 1.07, 95% CI = 0.67 to 1.71; p = 0.77. The rate of adverse events increased significantly with corticosteroid administration (OR = 2.36, 95% CI = 1.67 to 3.33; p < 0.0001). In particular, treatment with systemic corticosteroids significantly increased the risk of hyperglycemic episodes requiring initiation or alteration of insulin therapy (OR = 2.96, 95% CI = 1.69 to 5; p < 0.0001). We found corticosteroids to be beneficial in the whole population (non-critically ill and critically ill patients) in terms of treatment success rate. However, subgroup analysis showed that this effect of corticosteroids was only observed in non-critically ill patients whereas critically ill patients derived no benefit from systemic corticosteroids regardless of the chosen ventilatory mode (invasive or non-invasive ventilation). Further analyses showed no effect on mortality of corticosteroids, but higher side effects, such as hyperglycemic episodes requiring the initiation or alteration of insulin therapy.