Introduction Risk factors for mortality associated with COVID-19 have been reported to include increased age, male sex and certain comorbidities. Fracture neck of femur (NOF) patients is high-risk surgical patients, often with multiple comorbidities and advanced age. We quantify the 30-day mortality rate in fractured NOF patients with a positive peri-operative COVID-19 antigen test and identify risk factors for increased mortality. Methods This is a retrospective multi-centre review of all patients admitted with a fractured NOF and a confirmed laboratory diagnosis of COVID-19 between 1 March and 26 April 2020. Demographic data, comorbidities, ASA grade and date of death (if applicable) were collected. Results There were 64 patients in the cohort with an overall 30-day mortality rate of 32.8% (n = 21). Thirty-five (55%) were female, and mean age was 83 (SD 9, range 46-100) years. There was significantly increased mortality for those with a history of myocardial infarction (p = 0.03). Sixty-four percent of patients underwent surgery within the 36-h target, which is comparable to previous data for the same time of year. Overall mortality increased to 50% (n = 32) at 45 days post-operatively. Conclusion This is a large review of 30-day mortality in NOF patients with concurrent COVID-19 infection. We report a substantial increase from the pre-COVID-19 mean 30-day mortality rate (6.5% in 2019). We highlight the need for counselling patients when presenting with a NOF in relation to peri-operative COVID-19 infection and the associated increased risks. Keywords COVID-19 • SARS-CoV-2 • Fractured neck of femur • Mortality • Hip fracture All collaborators assisted with data collection, drafting of the paper and reviewing the final article. North West COVID NOF Study Group authors listed in Acknowledgements section.
Indacaterol is the first once-daily, long-acting β2-adrenergic agonist (LABA) approved for the treatment of chronic obstructive pulmonary disease (COPD). Indacaterol was developed using a combination of informed drug design and molecular chemistry to generate a β2-adrenergic agonist with a fast onset and long duration of action, enabling once-daily dosing with an acceptable safety profile. Early preclinical studies with indacaterol demonstrated these characteristics, and this promising molecule was taken into clinical development, originally for asthma treatment. Subsequent safety concerns over LABA monotherapy in patients with asthma redirected indacaterol's development to centre on COPD, where a good evidence base and guideline recommendations for bronchodilator monotherapy existed. Clinical development was initially complicated by different inhaler devices and differing doses of indacaterol. Using a phase III innovative adaptive-design clinical trial (INHANCE), indacaterol 150 and 300 μg once-daily doses were selected to be taken forward into the phase III INERGIZE programme. This programme delivered placebo-controlled and active-comparator data, including comparisons with formoterol, tiotropium and salmeterol/fluticasone, as well as the use of indacaterol in combination with tiotropium. Together, these studies provided a comprehensive assessment of the benefit-risk profile of indacaterol, allowing for regulatory submission. Indacaterol was first approved at once-daily doses of 150 and 300 μg in the European Union in 2009, followed by 150 µg in Japan (2011) and China (2012), and 75 μg in the United States (2011). To date, indacaterol is approved and marketed in more than 100 countries worldwide for once-daily maintenance treatment of COPD.
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