Reported Severe Hypersensitivity Reactions after Intravenous Iron Administration in the European Economic Area (EEA) Before and After Implementation of Risk Minimization Measures.

INTRODUCTION: Severe hypersensitivity reactions (HSRs) such as anaphylaxis are of great clinical concern because of their life-threatening potential. The adverse events attributable to intravenous iron products include HSRs. An investigation by the European Medicines Agency presented in late 2013 resulted in the implementation of risk minimization measures (RMMs). OBJECTIVE: This study evaluated the number of severe HSRs reported for intravenous iron substances related to exposure for the 4-year periods before and after this implementation. METHODS: This was a retrospective pharmacoepidemiologic study with a case-population design. We obtained information from the safety surveillance database EudraVigilance on spontaneously reported severe HSRs using the Medical Dictionary for Regulatory Activities preferred terms "anaphylactic reaction/shock" and "anaphylactoid reaction/shock". Exposure was estimated using IQVIA MIDAS sales data in European economic area countries. RESULTS: Reporting rates for individual products were heterogenous, and the implementation of RMMs appeared to have no clear impact. Reporting rates remained low for the full study period for iron sucrose (0.03-0.20) and ferric gluconate (0.02-0.14) and were higher at the beginning and lower at the end of the study period for ferric carboxymaltose (1.47-0.18). No clear trend was detected for iron dextran (range 0.22-2.80) and iron (III) isomaltoside 1000 (range 0-7.94). CONCLUSIONS: Future research is needed to investigate whether the wide variability in reporting rates for severe HSRs associated with these intravenous iron products are due to potential differences in the safety profiles of these substances.

Evaluation of the Reported Rates of Severe Hypersensitivity Reactions Associated with Ferric Carboxymaltose and Iron (III) Isomaltoside 1000 in Europe Based on Data from EudraVigilance and VigiBase™ between 2014 and 2017.

INTRODUCTION: Hypersensitivity reactions (HSRs) are among the known adverse events of intravenous (i.v.) iron products. Of these, particularly severe HSRs such as anaphylaxis are of great clinical concern due to their life-threatening potential. METHODS: This was a retrospective pharmacoepidemiological study with a case-population design evaluating the number of reported severe HSRs following administration of the two i.v. iron products-ferric carboxymaltose and iron (III) isomaltoside 1000-in relation to exposure in European countries from January 2014 to December 2017. Exposure to both products was estimated using IQVIA MIDAS sales data in European countries. Information on spontaneously reported severe HSRs was obtained from and analysed separately for the two established safety surveillance databases EudraVigilance and VigiBase™ using the MedDRA® Preferred Terms anaphylactic reaction, anaphylactic shock, anaphylactoid reaction and anaphylactoid shock associated with administration of either product. RESULTS: Between 2014 and 2017, the reporting rate of severe HSRs per 100,000 defined daily doses (100 mg dose equivalents of iron) varied from 0.3 to 0.5 for ferric carboxymaltose and from 2.4 to 5.0 for iron (III) isomaltoside 1000. The reporting rate ratio for iron (III) isomaltoside 1000 versus ferric carboxymaltose was between 5.6 (95% CI 3.5-9.0) and 16.2 (95% CI 9.4-27.8). CONCLUSIONS: Findings suggest that iron (III) isomaltoside 1000 is associated with a higher reporting rate of severe HSRs related to estimated exposure than ferric carboxymaltose in European countries. Future research investigating the occurrence of severe HSRs associated with i.v. ferric carboxymaltose and iron (III) isomaltoside 1000 is needed to broaden the evidence for benefit-risk assessment.

Lung function testing influences the attitude toward smoking cessation.

INTRODUCTION: Smoking cessation is the single most effective way to prevent or delay the development of airflow limitation or to reduce its progression in subjects with chronic obstructive pulmonary disease (COPD). The aim of the study was to explore whether performing a spirometry changes attitudes toward smoking cessation. METHOD: A random sample of 513 smokers, of whom 77 had COPD, answered a questionnaire before, shortly after (less than 4 weeks), and 3 months after performing a lung function test. RESULTS: Prior to spirometry, 57% of the smokers with COPD and 52% of those with normal spirometry claimed that they were not planning to quit smoking within the next 6 months. After the spirometry, 9% (p < .0001) of those with COPD and 38% (p = .009) of those with normal spirometry had no intention to stop smoking. Three months later, corresponding figures were 28% in COPD and 48% in smokers with normal spirometry, and the point prevalence of quitters was 30% for the COPD group and 14% for the normal group (p = .02). DISCUSSION: We conclude that performing spirometry changes the attitude toward smoking for a short time. We hypothesize that smokers may be more susceptible to smoking cessation activities during this period.

A comprehensive workplace intervention and its outcome with regard to lifestyle, health and sick leave: the AHA study.

This study is a prospective multicentre cohort study entitled Work and Health in the Processing and Engineering Industries, the AHA Study (AHA is the Swedish abbreviation for the study). Four large workplaces in Sweden participated during the years from 2000 to 2003. The present report has two objectives: (1) to present a comprehensive occupational health intervention programme and (2) to evaluate this programme with a focus on lifestyle (smoking and exercise), health related quality of life (HRQoL) and sick leave. Interventions were provided on an individual and group level, including evidence-based methods for four health/focus areas (individual level) and a group intervention based on a survey-feedback methodology. The analyses in this report were exclusively employed at an organizational level. The proportion of smokers decreased at three companies and the course of the HRQoL was advantageous at two of the companies as compared to a gainfully employed reference group. A significant decrease in sick leave was revealed at one company, whereas a break in an ascending sick-leave trend appeared at a second company as compared to their respective corporate groups. This comprehensive workplace intervention programme appears to have had positive effects on smoking habits, HRQoL and sick leave.

High rate of smoking abstinence in COPD patients: Smoking cessation by hospitalization.

Chronic obstructive pulmonary disease (COPD) is mainly caused by smoking, and smoking cessation is the single most important intervention to prevent disease progression. Most studies show that many initially successful quitters relapse within 1 year. Our aim was to study the outcome of a smoking cessation program after 1 and 3 years. Abstinence outcomes in a group of COPD patients who participated in a 1-year smoking cessation program (N = 247) were compared with those of a group of COPD patients who received usual care (N = 231). The smoking cessation program included a 2-week period of hospitalization. Nicotine replacement therapy and physical exercise were recommended, and education was given in group sessions. Feedback and encouraging comments by phone from the specially trained staff continued during the full year. Follow-ups were performed 1 and 3 years after the start of the smoking cessation program. In the intervention group, 52% were smoke free after 1 year and 38% after 3 years. Corresponding quit rates in the control group were 7% after 1 year and 10% after 3 years. We found no significant differences between subjects who had low or high baseline scores on the Fagerström Test for Nicotine Dependence in regard to their ability to stop smoking successfully. This comprehensive smoking cessation program with hospitalization and a long follow-up period resulted in high quit rates even after 3 years. Despite high costs for this aggressive smoking cessation program, beneficial economic effects are likely to be obtained in the long run.

Low awareness of COPD among physicians.

INTRODUCTION: Early identification of patients with chronic obstructive pulmonary disease (COPD) in the health care system followed by successful smoking cessation may prevent rapid lung function deterioration, development of severe COPD and respiratory failure. OBJECTIVES: The aim of this study was to determine the frequency of under-diagnosed chronic obstructive lung diseases among current smokers. MATERIALS AND METHODS: The under-diagnosis of COPD among smokers was determined in subjects who participated in a screening procedure aimed at recruiting COPD patients for a smoking cessation programme. In order to identify current smokers, a questionnaire was sent out to persons who had been on sick leave for various reasons certified by a physician for more than 2 weeks. Subjects who stated that they currently smoked more than eight cigarettes per day were invited to perform a lung function test. RESULTS: A total of 3887 subjects performed spirometry, i.e. forced expiratory volume in 1 s and forced expirations, and among these, 674 (17.3%) had COPD according to the European Respiratory Society (ERS) consensus guidelines. Of those, 103 (17.3%) had physician-diagnosed COPD. Productive cough was reported by 16.6% of the COPD subjects. Despite the fact that smokers were on sick leave certified by a physician, more than 80% of those with COPD had no previous diagnosis. As the COPD diagnosis cannot be based on reported symptoms, a spirometry on persons at risk must be performed. CONCLUSION: The awareness of COPD among primary care physicians has to increase and smokers above the age of 40, with and without respiratory symptoms, have to undergo spirometry if it is regarded important to establish the COPD diagnosis at an early stage.

COPD diagnosis related to different guidelines and spirometry techniques.

The aim was to compare the diagnosis of COPD among smokers according to different international guidelines and to compare the outcome when using slow (SVC) and forced vital capacity (FVC). In order to find current smokers a questionnaire was sent to persons who had been on sick leave for more than two weeks. Those who smoked more than 8 cigarettes per day were invited to perform a spirometry. Totally 3,887 spirometries were performed. In this sample 10.2% fulfilled the NICE COPD-criteria, 14.0% the GOLD COPD-criteria and 21.7% the ERS COPD criteria. The diagnosis according to NICE and GOLD guidelines is based on FVC and in the ERS guidelines the best value of either SVC or FVC is used. Thus, substantially more subjects with COPD were found when the best of either SVC or FVC was used. Forced VC tended to be higher than SVC when lung function was normal and in those with mild obstruction prior to bronchodilatation whereas SVC exceeded FVC after bronchodilatation in those who had severe bronchial obstruction.The diagnosis of COPD is highly depending on which guidelines are used for defining the disease. If FVC and not the best of SVC and FVC is used when defining COPD the diagnosis will be missed in a substantial number of patients.

Effects on sick leave of an inpatient rehabilitation programme for asthmatics in a randomized trial.

AIM: Among adult asthmatics a major proportion of the cost of illness is attributed to productivity losses and societal costs in connection with sick leave compensation. The aim of the study was to evaluate an extensive structured four-week inpatient rehabilitation programme for asthmatics. METHODS: A diagnosis of asthma was made in a structured way among people on sick leave due to a respiratory disorder. In total, 197 persons were randomized to either a rehabilitation programme, or to usual care. The main components of the rehabilitation programme were education, pharmacological optimization, physical training, and coping skill acquisition. RESULTS: At the three-year follow-up, the median number of sick leave days in the rehabilitation group was 104, and in the usual care group 167 (p = 0.12). An analysis of a subgroup consisting of persons not currently smoking with a previous diagnosis of asthma by a physician (n = 57) showed a significant effect on sick leave at three years (median number of days 63 in the rehabilitation group vs 361 in the control group, p = 0.02). All analyses were based on intention to treat. CONCLUSIONS: The long-term effects on sick leave of an extensive inpatient asthma rehabilitation programme are most evident for non-smokers and ex-smokers with a previous asthma diagnosis. It is therefore recommended that persons with asthma who are current smokers should be offered participation in smoking cessation programmes instead of asthma rehabilitation programmes.