ICAR: endoscopic skull‐base surgery

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ONCE DAILY FIBRINOLYTIC THERAPY IN THE MANAGEMENT OF PLEURAL INFECTION

Introduction and Objectives The use of intrapleural fibrinolytic therapy in patients with pleural infection has been shown to reduce hospital stay and reduce surgical referral rate. However, the logistics and cost of delivering twice-daily dosing may have contributed to its underutilisation. Trials are ongoing to establish the most appropriate dosing regime. We explored the feasibility and outcomes of an alternative, reduced cost, once-daily dosing strategy. Methods We completed a prospective observational study of concurrent dosing with once-daily Alteplase and DNase (Deoxyribonuclease) in adult patients with pleural infection, in a single district general hospital. Patients with iatrogenic infections, pregnancy, life expectancy Results 46 consecutive patients diagnosed with pleural infection were included. Of those, 26 received at least one dose of fibrinolytic therapy via chest tube, 14 received intercostal tube drainage and 6 received aspiration alone. 2 patients, both of whom received fibrinolytics, were referred for surgery, but for indications other than management of pleural infection (lung cancer n=1, persistent pneumothorax n=1). 2 patients died within 3 months of diagnosis- one from aspiration pneumonia and one from post surgical complications. The mortality was similar to what was expected based on the RAPID mortality prediction score for the patients in the cohort. Table 1 also summarises other outcomes. Conclusions This study shows that a cheaper and less onerous once-daily fibrinolytic regime is feasible and achieved acceptable outcomes similar to those expected from standard regimes. Further studies are needed to confirm this.</p

Melioidosis

Burkholderia pseudomallei is a Gram-negative environmental bacterium and the aetiological agent of melioidosis, a life-threatening infection that is estimated to account for ∼89,000 deaths per year worldwide. Diabetes mellitus is a major risk factor for melioidosis, and the global diabetes pandemic could increase the number of fatalities caused by melioidosis. Melioidosis is endemic across tropical areas, especially in southeast Asia and northern Australia. Disease manifestations can range from acute septicaemia to chronic infection, as the facultative intracellular lifestyle and virulence factors of B. pseudomallei promote survival and persistence of the pathogen within a broad range of cells, and the bacteria can manipulate the host's immune responses and signalling pathways to escape surveillance. The majority of patients present with sepsis, but specific clinical presentations and their severity vary depending on the route of bacterial entry (skin penetration, inhalation or ingestion), host immune function and bacterial strain and load. Diagnosis is based on clinical and epidemiological features as well as bacterial culture. Treatment requires long-term intravenous and oral antibiotic courses. Delays in treatment due to difficulties in clinical recognition and laboratory diagnosis often lead to poor outcomes and mortality can exceed 40% in some regions. Research into B. pseudomallei is increasing, owing to the biothreat potential of this pathogen and increasing awareness of the disease and its burden; however, better diagnostic tests are needed to improve early confirmation of diagnosis, which would enable better therapeutic efficacy and survival

Global burden of melioidosis in 2015: a systematic review and data synthesis

Background: Melioidosis is an infectious disease caused by the environmental bacterium Burkholderia pseudomallei. It is often fatal, with a high prevalence in tropical areas. Clinical presentation can vary from abscess formation to pneumonia and sepsis. We assessed the global burden of melioidosis, expressed in disability-adjusted life-years (DALYs), for 2015. Methods: We did a systematic review of the peer-reviewed literature for human melioidosis cases between Jan 1, 1990, and Dec 31, 2015. Quantitative data for cases of melioidosis were extracted, including mortality, age, sex, infectious and post-infectious sequelae, antibiotic treatment, and symptom duration. These data were combined with established disability weights and expert panel discussions to construct an incidence-based disease model. The disease model was integrated with established global incidence and mortality estimates to calculate global melioidosis DALYs. The study is registered with PROSPERO, number CRD42018106372. Findings: 2888 articles were screened, of which 475 eligible studies containing quantitative data were retained. Pneumonia, intra-abdominal abscess, and sepsis were the most common outcomes, with pneumonia occurring in 3633 (35·7%, 95% uncertainty interval [UI] 34·8–36·6) of 10 175 patients, intra-abdominal abscess in 1619 (18·3%, 17·5–19·1) of 8830 patients, and sepsis in 1526 (18·0%, 17·2–18·8) of 8469 patients. We estimate that in 2015, the global burden of melioidosis was 4·6 million DALYs (UI 3·2–6·6) or 84·3 per 100 000 people (57·5–120·0). Years of life lost accounted for 98·9% (UI 97·7–99·5) of the total DALYs, and years lived with disability accounted for 1·1% (0·5–2·3). Interpretation: Melioidosis causes a larger disease burden than many other tropical diseases that are recognised as neglected, and so it should be reconsidered as a major neglected tropical disease. Funding: European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Research Grant 2018, AMC PhD Scholarship, The Netherlands Organisation for Scientific Research (NWO), H2020 Marie Skłodowska-Curie Innovative Training Network European Sepsis Academy.</p