Anna Bornefalk-Hermansson

Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study.

Objective To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD). Design Population based longitudinal consecutive cohort study. Setting Centres prescribing long term oxygen therapy in Sweden. Patients 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register. Main outcome measures Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs. Results 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation. No patient was lost to follow-up. Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively. Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend. Opioids also had a dose response relation with mortality: lower dose opioids (≤30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44). Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99). Associations were not modified by being naive to the drugs or by hypercapnia. Conclusions Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease.

The identification of complex interactions in epidemiology and toxicology: a simulation study of boosted regression trees

BackgroundThere is a need to evaluate complex interaction effects on human health, such as those induced by mixtures of environmental contaminants. The usual approach is to formulate an additive statistical model and check for departures using product terms between the variables of interest. In this paper, we present an approach to search for interaction effects among several variables using boosted regression trees.MethodsWe simulate a continuous outcome from real data on 27 environmental contaminants, some of which are correlated, and test the method’s ability to uncover the simulated interactions. The simulated outcome contains one four-way interaction, one non-linear effect and one interaction between a continuous variable and a binary variable. Four scenarios reflecting different strengths of association are simulated. We illustrate the method using real data.ResultsThe method succeeded in identifying the true interactions in all scenarios except where the association was weakest. Some spurious interactions were also found, however. The method was also capable to identify interactions in the real data set.ConclusionsWe conclude that boosted regression trees can be used to uncover complex interaction effects in epidemiological studies.

Cardiovascular and antacid treatment and mortality in oxygen-dependent pulmonary fibrosis : A population-based longitudinal study

Severe idiopathic pulmonary fibrosis is associated with an increased risk of cardiovascular disease and gastro‐oesophageal reflux, which may influence prognosis. We evaluated associations between cardiovascular and antacid medications, and mortality, in oxygen‐dependent pulmonary fibrosis (PF) of unknown cause.

Long-Term Oxygen Therapy 24 vs 15 h/day and Mortality in Chronic Obstructive Pulmonary Disease

Long-term oxygen therapy (LTOT) ≥ 15 h/day improves survival in hypoxemic chronic obstructive pulmonary disease (COPD). LTOT 24 h/day is often recommended but may pose an unnecessary burden with no clear survival benefit compared with LTOT 15 h/day. The aim was to test the hypothesis that LTOT 24 h/day decreases all-cause, respiratory, and cardiovascular mortality compared to LTOT 15 h/day in hypoxemic COPD. This was a prospective, observational, population-based study of COPD patients starting LTOT between October 1, 2005 and June 30, 2009 in Sweden. Overall and cause-specific mortality was analyzed using Cox and Fine-Gray regression, controlling for age, sex, prescribed oxygen dose, PaO2 (air), PaCO2 (air), Forced Expiratory Volume in one second (FEV1), WHO performance status, body mass index, comorbidity, and oral glucocorticoids. A total of 2,249 included patients were included with a median follow-up of 1.1 years (interquartile range, 0.6–2.1). 1,129 (50%) patients died and no patient was lost to follow-up. Higher LTOT duration analyzed as a continuous variable was not associated with any change in mortality rate (hazard ratio [HR] 1.00; (95% confidence interval [CI], 0.98 to 1.02) per 1 h/day increase above 15 h/day. LTOT exactly 24 h/day was prescribed in 539 (24%) patients and LTOT 15–16 h/day in 1,231 (55%) patients. Mortality was similar between the groups for all-cause, respiratory and cardiovascular mortality. In hypoxemic COPD, LTOT 24 h/day was not associated with a survival benefit compared with treatment 15–16 h/day. A design for a registry-based randomized trial (R-RCT) is proposed.

Low-dose opioids should be considered for symptom relief also in advanced chronic obstructive pulmonary disease (COPD).

We read with interest the comments by Dr Vozoris1 on our paper “Safety of benzodiazepines and opioids in very severe respiratory disease.”2 We are concerned that his comments might give the impression that opioids should not be used in patients with severe chronic obstructive pulmonary disease (COPD). This could contribute to symptomatic undertreatment and unnecessary suffering. The main finding of the study should be emphasised: treatment with regular, low-dose opioids (≤30 mg oral morphine equivalents per day) was not associated with increased rates of …

Use of bibloc and monobloc oral appliances in obstructive sleep apnoea: a multicentre, randomized, blinded, parallel-group equivalence trial

Summary Background The clinical benefit of bibloc over monobloc appliances in treating obstructive sleep apnoea (OSA) has not been evaluated in randomized trials. We hypothesized that the two types of appliances are equally effective in treating OSA. Objective To compare the efficacy of monobloc versus bibloc appliances in a short-term perspective. Patients and methods In this multicentre, randomized, blinded, controlled, parallel-group equivalence trial, patients with OSA were randomly assigned to use either a bibloc or a monobloc appliance. One-night respiratory polygraphy without respiratory support was performed at baseline, and participants were re-examined with the appliance in place at short-term follow-up. The primary outcome was the change in the apnoea–hypopnea index (AHI). An independent person prepared a randomization list and sealed envelopes. Evaluating dentist and the biomedical analysts who evaluated the polygraphy were blinded to the choice of therapy. Results Of 302 patients, 146 were randomly assigned to use the bibloc and 156 the monobloc device; 123 and 139 patients, respectively, were analysed as per protocol. The mean changes in AHI were −13.8 (95% confidence interval −16.1 to −11.5) in the bibloc group and −12.5 (−14.8 to −10.3) in the monobloc group. The difference of −1.3 (−4.5 to 1.9) was significant within the equivalence interval (P = 0.011; the greater of the two P values) and was confirmed by the intention-to-treat analysis (P = 0.001). The adverse events were of mild character and were experienced by similar percentages of patients in both groups (39 and 40 per cent for the bibloc and monobloc group, respectively). Limitations The study shows short-term results with a median time from commencing treatment to the evaluation visit of 56 days and long-term data on efficacy and harm are needed to be fully conclusive. Conclusion In a short-term perspective, both appliances were equivalent in terms of their positive effects for treating OSA and caused adverse events of similar magnitude. Trial registration Registered with ClinicalTrials.gov (#NCT02148510).

Spirometric volumes and breathlessness across levels of airflow limitation: The CopDGene study

Spirometric Volumes and Breathlessness Across Levels of Airflow Limitation : The COPDGene Study.