Regulatory adverse drug reaction analyses support a temporal increase in psychiatric reactions after initiation of cystic fibrosis combination modulator therapies.

INTRODUCTION: Despite improved outcomes for many people with cystic fibrosis, there have been reports of adverse neuropsychiatric effects of modulator therapy. The aim of this research is to define temporal associations in adverse drug reaction (ADR) reports for available CFTR modulators. METHODS: Methods include an analysis of the UK Yellow Card Scheme data for ADRs through accessing interactive Drug Analysis Profiles (iDAPs) to define temporal trends in absolute and proportional counts. RESULTS: Since the introduction of ETI, there has been an increase in the absolute number of psychiatric ADRs reported as well as a statistically significant increase in the proportion of psychiatric ADRs in the pre-ETI and post-ETI periods. CONCLUSION: In the post-ETI period, psychiatric ADRs are the most prevalent ADR reported via the Yellow Card scheme. Despite an unclear mechanism, there is significant clinical relevance in counselling and monitoring regarding psychiatric effects of CFTR modulator therapy.

Cardiovascular and pulmonary complications of recreational drugs: A pictorial review.

Recreational drug abuse constitutes a serious health problem worldwide. Consumption of cocaine, amphetamine-type stimulants, opioids and cannabis can lead to multiple acute and chronic cardiopulmonary complications, resulting in high morbidity and mortality. These complications may be first detected at imaging, since clinical presentation is usually non-specific. Cardiovascular complications include myocardial infarction, endocarditis, aortic dissection, infectious pseudoaneurysm, retained needle fragments, cardiomyopathy and pulmonary arterial hypertension. Pulmonary complications encompass pulmonary oedema, crack lung, pneumonia, septic emboli, barotrauma, airway disease, emphysema and excipient lung disease. Knowledge of the cardiopulmonary imaging manifestations of illicit drug use in conjunction with clinical history and a high grade of suspicion enable an accurate diagnosis and appropriate management plan. In this article we aim to provide a pictorial review of the most frequent cardiopulmonary manifestations of recreational drugs, emphasizing the underlying pathophysiologic mechanisms and the various imaging appearances.

Low-dose azithromycin prophylaxis in patients with atrial fibrillation and chronic obstructive pulmonary disease.

Low-dose azithromycin prophylaxis is associated with improved outcomes in people suffering frequent exacerbations of chronic obstructive pulmonary disease (COPD), but the use of macrolides in patients with cardiovascular disease has been debated. To investigate the risk of adverse events after COPD exacerbations in patients with atrial fibrillation (AF) treated with azithromycin prophylaxis. Retrospective cohort study within the TriNetX Platform, including AF patients with COPD exacerbations. Risks of primary and secondary outcomes were recorded up to 30 days post-COPD exacerbations and compared between azithromycin users and azithromycin non-users. The primary outcomes were the risks for a composite of (1) cardiovascular (all-cause death, heart failure, ventricular arrhythmias, ischemic stroke, myocardial infarction, and cardiac arrest), and (2) hemorrhagic events (intracranial hemorrhage (ICH), and gastro-intestinal bleeding). Cox-regression analyses compared outcomes between groups after propensity score matching (PSM). After PSM, azithromycin users (n = 2434, 71 ± 10 years, 49% females) were associated with a lower 30-day risk of post-exacerbation cardiovascular (HR 0.67, 95% CI 0.61-0.73) and hemorrhagic composite outcome (HR 0.45, 95% CI 0.32-0.64) compared to azithromycin non-users (n = 2434, 72 ± 11 years, 51% females). The beneficial effect was consistent for each secondary outcomes, except ICH. On sensitivity analyses, the reduced risk of adverse events in azithromycin users was irrespective of smoking status, exacerbation severity, and type of oral anticoagulation. Azithromycin prophylaxis is associated with a lower risk of all-cause death, thrombotic and hemorrhagic events in AF patients with COPD. The possible role of azithromycin prophylaxis as part of the integrated care management of AF patients with COPD needs further study.

Prevalence, risk factors and outcomes of cardiac disease in cystic fibrosis: a multinational retrospective cohort study.

BACKGROUND: Although people living with cystic fibrosis (PwCF) often have some risk factors for cardiovascular disease, including diabetes and chronic inflammation, little is known about the long-term cardiac risk in this condition. We aimed to determine the characteristics, rates and outcomes for cardiac disease in CF. METHODS: We looked at rates and outcomes for cardiac disease in 5649 adult PwCF in the UK CF Registry and 6265 adult PwCF in TriNetX (a global federated database of electronic healthcare record data). We used propensity matching to compare risk of major adverse cardiac events (MACE) (myocardial infarction, left-sided heart failure and atrial fibrillation) in PwCF against matched non-CF comparators in the general population and other inflammatory diseases. RESULTS: PwCF had a high prevalence of diabetes but low rates of hypertension and obesity. Some cardiac risk factors (age, diabetes and hypertension) were associated with MACE, but relationships between disease-specific risk factors (lung function and intravenous antibiotic days) were also observed. In propensity score-matched analyses, PwCF had higher risk of MACE than matched general population comparators (hazard ratio (HR) 1.65, 95% CI 1.40-1.95; p<0.001) and an equivalent or higher relative risk compared with other inflammatory conditions considered "high risk" for cardiovascular disease, including systemic lupus erythematosus (HR 0.95, 95% CI 0.82-1.09; p=0.44), rheumatoid arthritis (HR 1.21, 95% CI 1.00-1.48; p<0.001) and HIV (HR 0.93, 95% CI 0.82-1.06; p=0.29). CONCLUSIONS: PwCF are at increased risk of adverse cardiac disease events. Future work should focus on defining determinants of cardiovascular risk such that appropriate risk stratification can be employed.

Does availability of point of care C-reactive protein measurement affect provision of antibiotics in a community respiratory service?

Antibiotic resistance presents a growing threat to health systems and patients at a global scale. Point of care (POC) C-reactive protein (CRP) measurement, as an adjunct to exacerbation assessment, has been studied in primary and secondary care and may represent a useful tool for community teams. A retrospective service review was conducted to determine the effect of CRP measurement on antibiotic provision in a community respiratory setting, with chronic obstructive pulmonary disease (COPD) and bronchiectasis exacerbations. This review compared antibiotic provision for COPD and bronchiectasis patients for those where CRP was measured versus those where it was not. It was found that antibiotic provision dropped by almost 25% points for COPD exacerbations, and almost 59% in bronchiectasis, when a CRP measurement was taken as a component of a respiratory assessment. Antibiotics were also provided at a greater amount based on symptom presentation. Therefore, it is concluded that CRP measurement correlates with a reduction in antibiotic provision, highlighting its use alongside symptom assessment in future work.

European Respiratory Society International Congress, Madrid, 2019: nontuberculous mycobacterial pulmonary disease highlights.

Once overlooked, awareness of nontuberculous mycobacterial pulmonary disease (NTM-PD) is rapidly rising, in line with increasing prevalence worldwide. The European Respiratory Society (ERS) International Congress 2019, held in Madrid, Spain, provided a platform for invigorating discussions and exciting new research in the field. This article explores approaches being taken to combat NTM-PD with a focus not only on novel prevalence and risk factor data, but also on emerging antimicrobials and their routes of delivery, and other potential treatment options in early clinical development.

Oxygen alert wristbands (OxyBand) and controlled oxygen: a pilot study.

Despite the introduction of Oxygen Alert Cards, guidelines and audits, oxygen therapy remains overused in NHS practice, and this may lead to iatrogenic mortality. This pilot study aimed to examine the use of Oxygen Alert Wristbands (OxyBand) designed to alert health professionals who are delivering oxygen to patients to ensure that the oxygen is administered and titrated safely to the appropriate target saturations. Patients at risk of hypercapnic acidosis were asked to wear OxyBands while presenting to paramedics and health professionals in hospitals. Inappropriate prescription of oxygen reduced significantly after the OxyBands were used. A questionnaire-based assessment showed that the clinicians involved had a good understanding of the risks of uncontrolled oxygen. Forty-two patients found the wrist band comfortable to wear, and only two did not. OxyBands may have the potential to improve patient safety over Oxygen Alert Cards.

Reducing admissions with patient group directions.

In times of financial restrictions and reform impediments, health services need to invest in resources that provide value for money and reduce hospital admissions. Improving disease management in the community is a primary target for those trying to reduce costs. The second most common cause of emergency admissions to hospital is chronic obstructive pulmonary disease and it has been suggested that more effective treatments and better management of the condition would likely result in an estimated 5% fewer admissions to hospital, saving around pound 15.5m each year. This article discusses how savings could be made by improving care provided in the community.

The role of respiratory viruses in cystic fibrosis.

BACKGROUND: Previous studies have suggested a role played by respiratory viruses in the exacerbation of cystic fibrosis (CF). However, the impact of respiratory viruses could have been underestimated because of the low detection rate by conventional laboratory methods. METHODS: Children with CF had nasal swabs and sputum samples obtained on a routine basis and when they developed respiratory exacerbations. Nucleic Acid Sequence Based Amplification (NASBA) was used to detect respiratory viruses from nasal swabs. The definition of a respiratory exacerbation was when the symptom score totalled to 4 or more, or if the peak expiratory flow fell by more than 50 l/min from the child's usual best value, or if the parent subjectively felt that the child was developing a cold. RESULTS: 71 patients had 165 reported episodes of respiratory exacerbations. 138 exacerbation samples were obtained of which 63 (46%) were positive for respiratory viruses. In contrast, 23 of 136 asymptomatic nasal swabs (16.9%) were positive for respiratory viruses. There was significantly more viruses being detected during respiratory exacerbations, in particular influenza A, influenza B and rhinovirus (p<0.05). Upper respiratory symptoms significantly correlated with positive respiratory viral detection (p<0.05). This study also showed that viral respiratory exacerbations in CF could be independent from bacterial infections. CONCLUSIONS: Respiratory viruses are associated with exacerbations in CF and upper respiratory symptoms are strong predictors for their presence. 'Real-time' NASBA has a rapid turn-around time and has the potential to aid clinical decision making, such as the use of anti-virals and administration of antibiotics.

Is there a role for influenza vaccination in cystic fibrosis?

BACKGROUND: Influenza vaccination is generally recommended to patients with Cystic Fibrosis (CF). Previous studies have shown that influenza infections cause worsening lung functions, disease progression and increase propensity of bacterial infections in CF. However, the clinical evidence in the effectiveness of influenza vaccination in CF is lacking. AIMS: This study retrospectively reviewed the influenza vaccination status in the patients with CF and compared the influenza infection rates between the vaccinated and non-vaccinated groups. Finally the factors associated with non-adherence with vaccination were determined. METHODS: Nasal swabs were obtained from 63 patients with CF between the age of 6 months to 18 years routinely and during respiratory exacerbations between October 2003 to April 2004. Influenza A and Influenza B were detected using Nucleic Acid Sequence Based Amplification (NASBA). The influenza vaccination status of these patients was retrospectively reviewed. RESULTS: 41 patients (65%) were vaccinated against influenza. For the 22 patients (35%) who were not vaccinated, 7 of them were scared of needles leading to non-adherence. Influenza virus was detected on 5 occasions; 3 were Influenza A (60%) and 2 were Influenza B (40%). 1 virus in the vaccinated group and 4 in the non-vaccinated were detected during the study period (p-value=0.046). CONCLUSIONS: Although the current available evidence to support routine influenza vaccination is limited in CF, this study has shown that such practice may yet play a role in preventing its subsequent acquisition.

The common cold: a review of the literature.

Respiratory viral infections, also known as the common cold, are the most common infections in humans. Despite their benign nature, they are a major cause of morbidity and mortality on a worldwide basis. Several viruses have been associated with such illness, of which rhinovirus is the most common. Symptom production is a combination of viral cytopathic effect and the activation of inflammatory pathways. Therefore, antiviral treatment alone may not be able to prevent these events. The optimal use of such agents also requires earlier initiation; therefore, it is important to develop accurate and rapid diagnostic techniques for respiratory viruses. Before any reliable and effective treatment is available, symptomatic therapies may remain the only possible choice of management.

Respiratory virus infections in cystic fibrosis.

Respiratory virus infections have pronounced and long-lasting effects on patients with cystic fibrosis (CF), resulting in significant declines in FVC, FEV(1) and Shwachman score, significantly increasing both the frequency and duration of hospitalisation. Deleterious effects on patients with CF have been reported for most viruses studied but the effects of respiratory syncytial virus and influenza appear the greatest. There is circumstantial evidence that respiratory virus infections may facilitate bacterial infections, particularly Pseudomonas aeruginosa.