Study protocol: infectious diseases consortium (I3D) for study on integrated and innovative approaches for management of respiratory infections: respiratory infections research and outcome study (RESPIRO).

BACKGROUND: Community-acquired respiratory infections are a leading cause of illness and death globally. The aetiologies of community-acquired pneumonia remain poorly defined. The RESPIRO study is an ongoing prospective observational cohort study aimed at developing pragmatic logistical and analytic platforms to accurately identify the causes of moderate-to-severe community-acquired pneumonia in adults and understand the factors influencing disease caused by individual pathogens. The study is currently underway in Singapore and has plans for expansion into the broader region. METHODS: RESPIRO is being conducted at three major tertiary hospitals in Singapore. Adults hospitalised with acute community-acquired pneumonia or lower respiratory tract infections, based on established clinical, laboratory and radiological criteria, will be recruited. Over the course of the illness, clinical data and biological samples will be collected longitudinally and stored in a biorepository for future analysis. DISCUSSION: The RESPIRO study is designed to be hypothesis generating, complementary to and easily integrated with other research projects and clinical trials. The detailed clinical database and biorepository will yield insights into the epidemiology and outcomes of community-acquired lower respiratory tract infections in Singapore and the surrounding region and offers the opportunity to deeply characterise the microbiology and immunopathology of community-acquired pneumonia.

ERS International Congress 2022: highlights from the Respiratory Intensive Care Assembly.

Early Career Members of Assembly 2 (Respiratory Intensive Care) attended the 2022 European Respiratory Society (ERS) International Congress in Barcelona, Spain. The conference covered acute and chronic respiratory failure. Sessions of interest to our Assembly members and to those interested in respiratory critical care included the state-of-the-art session on respiratory critical care, the journal session (ERS/Lancet) on acute respiratory distress syndrome (ARDS) phenotyping into precision medicine, and sessions on specificity of coronavirus disease 2019 ARDS and its post-critical care. A symposium on treatment of acute respiratory failure in patients with COPD and innovations in mechanical ventilation either in the intensive care unit or at home were also reported upon. These sessions are summarised in this article.

Sepsis, cardiovascular events and short-term mortality risk in critically ill patients.

INTRODUCTION: There is paucity of data on the occurrence of cardiovascular events (CVEs) in critically ill patients with sepsis. We aimed to describe the incidence, risk factors and impact on mortality of CVEs in these patients. METHODS: This was a retrospective cohort study of critically ill patients admitted to the medical intensive care unit (ICU) between July 2015 and October 2016. The primary outcome was intra-hospital CVEs, while the secondary outcomes were in-hospital mortality, ICU and hospital length of stay. RESULTS: Patients with sepsis (n=662) had significantly more CVEs compared to those without (52.9% versus 23.0%, P<0.001). Among sepsis patients, 350 (52.9%) had 1 or more CVEs: 59 (8.9%) acute coronary syndrome; 198 (29.9%) type 2 myocardial infarction; 124 (18.7%) incident atrial fibrillation; 76 (11.5%) new or worsening heart failure; 32 (4.8%) cerebrovascular accident; and 33 (5.0%) cardiovascular death. Factors associated with an increased risk of CVEs (adjusted relative risk [95% confidence interval]) included age (1.013 [1.007-1.019]); ethnicity-Malay (1.214 [1.005-1.465]) and Indian (1.240 [1.030-1.494]) when compared to Chinese; and comorbidity of ischaemic heart disease (1.317 [1.137-1.527]). There were 278 patients (79.4%) who developed CVEs within the first week of hospitalisation. Sepsis patients with CVEs had a longer median (interquartile range [IQR]) length of stay in the ICU (6 [3-12] vs 4 [2-9] days, P<0.001), and hospital (21 [10-42] vs 15 [7-30] days, P<0.001) compared to sepsis patients without CVEs. There was no difference in in-hospital mortality between the 2 groups (46.9% vs 45.8%, P=0.792). CONCLUSION: CVEs complicate half of the critically ill patients with sepsis, with 79.4% of patients developing CVEs within the first week of hospitalisation, resulting in longer ICU and hospital length of stay.

Exercise intolerance due to chronotropic incompetence uncovered by cardiopulmonary exercise test: an often overlooked manifestation of ischaemic heart disease.

A 60-year-old delivery man was referred for evaluation of unexplained exertional dyspnoea despite initial non-diagnostic investigations, including pulmonary function tests and dobutamine stress echocardiography. A symptom-limited cardiopulmonary exercise test (CPET) revealed chronotropic incompetence (CI), reduced oxygen uptake (VO2)/work slope at moderate-high workload, and ST-segment depression on recovery electrocardiogram. Coronary angiogram confirmed severe stenosis in right coronary artery and left anterior descending artery, for which he underwent percutaneous coronary stenting and cardiac rehabilitation. An interval CPET showed improvement in heart rate (HR) response and aerobic capacity. CI is characterized by an attenuated HR response to incremental exercise or an increased HR reserve despite maximal effort. Clinically, it is an independent predictor of adverse cardiovascular events and mortality. CI is frequently overlooked, highlighting the importance of CPET in the diagnostic workup of unexplained dyspnoea.

Reversible platypnea-orthodeoxia in COVID-19 acute respiratory distress syndrome survivors.

Platypnea-orthodeoxia syndrome (POS) is a rare clinical syndrome characterized by orthostatic oxygen desaturation and positional dyspnea from supine to an upright position. We observed POS in 5 of 20 cases of severe 2019 novel coronavirus (COVID-19) pneumonia, which demonstrated persistently elevated shunt fraction even after liberation from mechanical ventilation. POS was first observed during physiotherapy sessions; median oxygen desaturation was 8 % (range: 8-12 %). Affected individuals were older (median 64 vs 53 years old, p = 0.05) and had lower body mass index (median 24.7 vs 27.6 kg/m2, p = 0.03) compared to those without POS. While POS caused alarm and reduced tolerance to therapy, this phenomenon resolved over a median of 17 days with improvement of parenchymal disease. The mechanisms of POS are likely due to gravitational redistribution of pulmonary blood flow resulting in increased basal physiological shunting and upper zone dead space ventilation due to the predominantly basal distribution of consolidative change and reported vasculoplegia and microthrombi in severe COVID-19 disease.

Efficacy and safety of abacavir/lamivudine plus rilpivirine as a first-line regimen in treatment-naïve HIV-1 infected adults.

BACKGROUND: The anti-retroviral combination of abacavir/lamivudine plus rilpivirine (ABC/3TC/RPV) is not recommended by international guidelines as the first-line regimen. However, it is potent, well-tolerated, and affordable, especially in resource-limited settings. This study evaluates the efficacy and safety of ABC/3TC/RPV as an initial regimen for treatment-naïve HIV-1 infected patients. METHODS: A retrospective study was conducted in the largest HIV care centre in Singapore, with data collected June 2011 to September 2017. All treatment-naïve HIV-1 infected adults prescribed ABC/3TC as part of their initial anti-retroviral therapy regimen were included. The third drug was a non-nucleoside reverse-transcriptase inhibitor (NNRTI) such as RPV or efavirenz (EFV), or boosted protease-inhibitor (PI). Patients were followed up for 48 weeks. The primary end-point was the percentage of patients achieving virologic suppression, analysed using on-treatment analysis. Secondary outcomes included CD4-count change, treatment discontinuation and treatment-related adverse events. RESULTS: 170 patients were included in the study, 66 patients in the RPV group, 104 patients in the comparator group (EFV or boosted PI). 96% (n = 24) in the RPV group and 87% (n = 26) in the comparator group achieved viral suppression at 48 weeks (p = 0.28). Median (interquartile range) time to viral suppression was similar: 17 (14-24) weeks in the RPV group, and 21 (13-26) weeks in the comparator group. There were no statistically significant differences in the CD4 count between the two groups. 14% (n = 9) of patients on RPV discontinued treatment before 48 weeks, compared to 30% (n = 31) from the comparator group (p = 0.053). Of these, 23 discontinuations were due to drug adverse effects, and only 1 attributed to RPV (p < 0.01). One patient in each group had virologic failure. CONCLUSION: RPV is effective, safe and considerably more tolerable than compared to NNRTI or boosted PI in ABC/3TC-containing regimens for treatment-naïve patients. It offers an affordable and attractive option, especially in resource-limited settings.

Long-term tolerance of a fractured self-expanding metal stent in a patient with adenoid cystic carcinoma.

Self-expanding metals stent are used for recanalization of malignant CAO. Fracture of such a stent has been described. This prompts its removal. However removal of a metal stent is difficult and can be hazardous. Due to this US FDA advisory was released against their insertion in benign diseases where long life expectancy can expose the patients to the complications of prolonged indwelling time of these stents. We describe a case of adenoid cystic carcinoma who required SEMS placement for tracheal obstruction. However, stent fracture developed soon after its insertion causing patient to cough out stent pieces multiple times. In view of the challenge associated with removal of metal stent fixed to the tracheal walls at its proximal and distal ends, the stent was left in-situ. Patient has tolerated the fractured stent for 1-year and remains on follow-up without any complication or adverse event. This illustrates the long-term tolerance and safety of a fractured stent and helps to allay anxiety associated with this complication.