Singapore tuberculosis (TB) clinical management guidelines 2024: A modified Delphi adaptation of international guidelines for drug-susceptible TB infection and pulmonary disease.

Introduction: Tuberculosis (TB) remains endemic in Singapore. Singapore's clinical practice guidelines for the management of tuberculosis were first published in 2016. Since then, there have been major new advances in the clinical management of TB, ranging from diagnostics to new drugs and treatment regimens. The National TB Programme convened a multidisciplinary panel to update guidelines for the clinical management of drug-susceptible TB infection and disease in Singapore, contextualising current evidence for local practice. Method: Following the ADAPTE framework, the panel systematically reviewed, scored and synthesised English-language national and international TB clinical guidelines published from 2016, adapting recommendations for a prioritised list of clinical decisions. For questions related to more recent advances, an additional primary literature review was conducted via a targeted search approach. A 2-round modified Delphi process was implemented to achieve consensus for each recommendation, with a final round of edits after consultation with external stakeholders. Results: Recommendations for 25 clinical questions spanning screening, diagnosis, selection of drug regimen, monitoring and follow-up of TB infection and disease were formulated. The availability of results from recent clinical trials led to the inclusion of shorter treatment regimens for TB infection and disease, as well as consensus positions on the role of newer technologies, such as computer-aided detection-artificial intelligence products for radiological screening of TB disease, next-generation sequencing for drug-susceptibility testing, and video observation of treatment. Conclusion: The panel updated recommendations on the management of drug-susceptible TB infection and disease in Singapore.

Radiographic features of COVID-19 based on an initial cohort of 96 patients in Singapore.

INTRODUCTION: Chest radiographs (CXRs) are widely used for the screening and management of COVID-19. This article describes the radiographic features of COVID-19 based on an initial national cohort of patients. METHODS: This is a retrospective review of swab-positive patients with COVID-19 who were admitted to four different hospitals in Singapore between 22 January and 9 March 2020. Initial and follow-up CXRs were reviewed by three experienced radiologists to identify the predominant pattern and distribution of lung parenchymal abnormalities. RESULTS: In total, 347 CXRs of 96 patients were reviewed. Initial CXRs were abnormal in 41 (42.7%) out of 96 patients. The mean time from onset of symptoms to CXR abnormality was 5.3 ± 4.7 days. The predominant pattern of lung abnormality was ground-glass opacity on initial CXRs (51.2%) and consolidation on follow-up CXRs (51.0%). Multifocal bilateral abnormalities in mixed central and peripheral distribution were observed in 63.4% and 59.2% of abnormal initial and follow-up CXRs, respectively. The lower zones were involved in 90.2% of initial CXRs and 93.9% of follow-up CXRs. CONCLUSION: In a cohort of swab-positive patients, including those identified from contact tracing, we found a lower incidence of CXR abnormalities than was previously reported. The most common pattern was ground-glass opacity or consolidation, but mixed central and peripheral involvement was more common than peripheral involvement alone.

Chest Radiography in Coronavirus Disease 2019 (COVID-19): Correlation with Clinical Course.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 and was declared a global pandemic by the World Health Organization on 11 March 2020. A definitive diagnosis of COVID-19 is made after a positive result is obtained on reverse transcription-polymerase chain reaction assay. In Singapore, rigorous contact tracing was practised to contain the spread of the virus. Nasal swabs and chest radiographs (CXR) were also taken from individuals who were suspected to be infected by COVID-19 upon their arrival at a centralised screening centre. From our experience, about 40% of patients who tested positive for COVID-19 had initial CXR that appeared "normal". In this case series, we described the temporal evolution of COVID-19 in patients with an initial "normal" CXR. Since CXR has limited sensitivity and specificity in COVID-19, it is not suitable as a first-line diagnostic tool. However, when CXR changes become unequivocally abnormal, close monitoring is recommended to manage potentially severe COVID-19 pneumonia.

Atypical Chest Computed Tomography Finding of Predominant Interstitial Thickening in a Patient with Coronavirus Disease 2019 (COVID-19) Pneumonia.

BACKGROUND Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, SARS-CoV-2, and is associated with severe respiratory disease. There are extensive publications on the chest computed tomography (CT) findings of COVID-19 pneumonia, with ground-glass opacities (GGO) and mixed GGO and consolidation being the most common findings. Those with interstitial thickening manifesting as reticular opacities typically show superimposed ground-glass opacities, giving a crazy-paving pattern. CASE REPORT We report the case of a 77-year-old man with a background of asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) who presented with progressive cough and shortness of breath for 2 days. He was in close contact with a confirmed COVID-19 case. Reverse-transcription polymerase chain reaction analysis of a nasopharyngeal swab was positive for SARS-CoV-2. The initial chest radiograph was negative for lung consolidation and ground-glass opacities. During admission, he had worsening shortness of breath with desaturation, prompting a chest CT examination, which was performed on day 14 of illness. The chest CT revealed an atypical finding of predominant focal subpleural interstitial thickening in the right lower lobe. He was provided supportive treatment along with steroid and antibiotics. He recovered well and subsequently tested negative for 2 consecutive swabs. He was discharged after 34 days. CONCLUSIONS Interstitial thickening or reticular pattern on CT has been described in COVID-19 pneumonia, but largely in association with ground-glass opacity or consolidation. This case demonstrates an atypical predominance of interstitial thickening on chest CT in COVID-19 pneumonia on day 14 of illness, which is the expected time of greatest severity of the disease.

Clinical utility of chest radiography for severe COVID-19.

BACKGROUND: Chest radiography (CXR) is performed more widely and readily than CT for the management of coronavirus disease (COVID-19), but there remains little data on its clinical utility. This study aims to assess the diagnostic performance of CXR, with emphasis on its predictive value, for severe COVID-19 disease. METHODS: A retrospective cohort study was conducted, 358 chest radiographs were performed on 109 COVID-19 patients (median age 44.4 years, 58 males and 30 with comorbidities) admitted between 22 January 2020 and 15 March 2020. Each CXR was reviewed and scored by three radiologists in consensus using a 72-point COVID-19 Radiographic Score (CRS). Disease severity was determined by the need for supplemental oxygen and mechanical ventilation. RESULTS: Patients who needed supplemental oxygen (n=19, 17.4%) were significantly older (P<0.001) and significantly more of them had co-morbidities (P=0.011). They also had higher C-reactive protein (CRP) (P<0.001), higher lactate dehydrogenase (LDH) (P<0.001), lower lymphocyte count (P<0.001) and lower hemoglobin (Hb) (P=0.001). Their initial (CRSinitial) and maximal CRS (CRSmax) were higher (P<0.001). Adjusting for age and baseline hemoglobin, the AUROC of CRSmax (0.983) was as high as CRPmax (0.987) and higher than the AUROC for lymphocyte countmin (0.897), and LDHmax (0.900). The AUROC for CRSinitial was slightly lower (0.930). CRSinitial ≥5 had a sensitivity of 63% and specificity of 92% in predicting the need for oxygen, and 73% sensitivity and 88% specificity in predicting the need for mechanical ventilation. CRS between the 6th and 10th day from the onset of symptoms (CRSD6-10) ≥5 had a sensitivity of 89% and specificity of 95% in predicting the need for oxygen, and 100% sensitivity and 86% specificity in predicting the need for mechanical ventilation. CONCLUSIONS: Adjusting for key confounders of age and baseline Hb, CRSmax performed comparable to or better than laboratory markers in the diagnosis of severe disease. CXR performed between the 6th and 10th days from symptom onset was a better predictor of severe disease than CXR performed earlier at presentation. A benign clinical course was seen in CXR that were normal or had very mild abnormalities.

Variable computed tomography appearances of COVID-19.

The coronavirus disease 2019 (COVID-19) is typically diagnosed by specific assays that detect viral nucleic acid from the upper respiratory tract; however, this may miss infections involving only the lower airways. Computed tomography (CT) has been described as a diagnostic modality in the COVID-19 diagnosis and treatment plan. We present a case series with virologically confirmed COVID-19 pneumonia. Variable CT features were observed: consolidation with ground-glass opacities, ground-glass opacities with subpleural reticular bands, and an anterior-posterior gradient of lung abnormalities resembling that of acute respiratory distress syndrome. Evolution of CT findings was observed in one patient, where there was interval resolution of bilateral lung consolidation with development of bronchiolectasis and subpleural fibrotic bands. While sensitive for detecting lung parenchymal abnormalities in COVID-19 pneumonia, the use of CT for initial diagnosis is discouraged and should be reserved for specific clinical indications. Interpretation of chest CT findings should be correlated with duration of symptoms to better determine the disease stage and aid in patient management.

Radiology Preparedness in the Ongoing Battle against COVID-19: Experiences from Large to Small Public Hospitals in Singapore.

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented challenge to the health care systems of the world. In Singapore, early experiences of the radiology community on managing this pandemic was shaped by lessons learned from the severe acute respiratory syndrome outbreak in 2003. This article surveys the operational responses of radiology departments from six public hospitals in Singapore. © RSNA, 2020.

Impact of an interstitial lung disease service in the diagnosis and management of interstitial lung disease in Singapore.

INTRODUCTION: The current gold standard for diagnosing interstitial lung disease (ILD) involves an ILD clinic evaluation, followed by discussion in a multidisciplinary meeting (MDM). However, there is a paucity of data on the impact of ILD MDMs on the diagnosis and management of ILDs in Southeast Asia. We studied the clinical impact of the ILD service on the diagnosis and management of ILDs at a university-affiliated tertiary hospital in Singapore. METHODS: A single-centre retrospective review was done on 97 consecutive patients referred for evaluation to the ILD service from March 2016 to August 2017. RESULTS: Mean age of the patients was 67 ± 11 years. Gender distribution was almost equal (52% male), with a majority of never-smokers (63%). Mean forced vital capacity (FVC) was 1.81 ± 0.66 L (66% ± 20% predicted). The three commonest referral diagnoses were ILD of uncertain classification (n = 38, 39%), connective tissue disease-associated ILD (CTD-ILD) (n = 24, 25%) and idiopathic pulmonary fibrosis (IPF) (n = 16, 17%). Following evaluation by the ILD service, there was a change of diagnosis in 60 (62%) patients and a change of management in 71 (73%) patients. The majority of consensus MDM diagnoses were IPF (n = 35, 36%), CTD-ILD (n = 30, 30%) and others (n = 15, 15%). There was a significant prognostic separation between the IPF and non-IPF diagnoses made following evaluation by the ILD service. CONCLUSION: The ILD service allowed for more precise subtyping of various ILDs. This is particularly useful for IPF patients, who can benefit from antifibrotic therapies.

A practical and adaptive approach to lung cancer screening: a review of international evidence and position on CT lung cancer screening in the Singaporean population by the College of Radiologists Singapore.

Lung cancer is the leading cause of cancer-related death around the world, being the top cause of cancer-related deaths among men and the second most common cause of cancer-related deaths among women in Singapore. Currently, no screening programme for lung cancer exists in Singapore. Since there is mounting evidence indicating a different epidemiology of lung cancer in Asian countries, including Singapore, compared to the rest of the world, a unique and adaptive approach must be taken for a screening programme to be successful at reducing mortality while maintaining cost-effectiveness and a favourable risk-benefit ratio. This review article promotes the use of low-dose computed tomography of the chest and explores the radiological challenges and future directions.

Ministry of Health Clinical Practice Guidelines: Prevention, Diagnosis and Management of Tuberculosis.

The Ministry of Health (MOH) has developed the clinical practice guidelines on Prevention, Diagnosis and Management of Tuberculosis to provide doctors and patients in Singapore with evidence-based treatment for tuberculosis. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Prevention, Diagnosis and Management of Tuberculosis, for the information of SMJ readers. The chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Comprehensive noninvasive evaluation of bypass grafts and native coronary arteries in patients after coronary bypass surgery: accuracy of 64-slice multidetector computed tomography compared to invasive coronary angiography.

AIMS: We assessed the accuracy of 64-slice multidetector computed tomography (MDCT) compared with that of invasive coronary angiography (ICA) in the evaluation of symptomatic postcoronary artery bypass graft (post-CABG) patients. METHODS: MDCT and ICA were performed in 44 consecutive post-CABG patients with chest pain (mean age 66 +/- 10 years, mean duration post-CABG 9 +/- 5 years). MDCT findings were compared with the corresponding ICA, which was read by an interventional cardiologist blinded to the MDCT findings. Significant stenosis was defined as at least 50% luminal stenosis. RESULTS: One hundred and thirty-seven grafts (31 arterial and 106 venous), all evaluable by MDCT, were assessed. In a 'per graft' analysis, MDCT could detect significant disease in bypass grafts (graft occlusion or stenosis) with a sensitivity of 98% and specificity of 98%. In a 'per segment' analysis, MDCT could detect significant disease in all native coronary arteries with a sensitivity of 91% and specificity of 79% and in clinically relevant native coronary arteries with a sensitivity of 92% and specificity of 84%. In a 'per vessel' analysis, MDCT could differentiate native arterial occlusion from nonocclusive stenosis with a sensitivity of 68% and specificity of 70%. In a 'per patient' analysis, MDCT could detect significant disease in bypass grafts or clinically relevant native coronary arteries with a sensitivity of 100%, specificity of 40% and accuracy of 93%. CONCLUSION: Sixty-four-slice MDCT allows evaluation of bypass grafts and native coronary arteries in post-CABG patients. Although accurate for detecting bypass graft disease, 64-slice MDCT has significant limitations when evaluating native arteries in post-CABG patients.

Prevalence of non-cardiac findings in a large series of patients undergoing cardiac multi-detector computed tomography scans.

The purpose of our study was to determine the prevalence of non-cardiac findings in a large series of patients undergoing contrast-enhanced cardiac multi-detector computed tomography (MDCT) scans. Non-cardiac findings were classified according to the organ of involvement and level of significance. We retrospectively reviewed scans and reports of 1,061 patients performed between 1 April 2004 and 31 April 2006. Non-cardiac findings were considered significant if they warranted further radiological or clinical follow-up. A total of 103 non-cardiac findings were reported in 85 (8.0%) of the 1,061 patients. Of these lesions, 48 (46.7%) were significant and 55 (53.3%) were not. The significant lesions were found in 33 of the 1,061 patients (3.1%). Among the significant abnormalities, the three most common were pulmonary nodules (16.7%), emphysema (16.7%) and possible hepatic carcinomas (12.6%). Patients with non-cardiac findings were significantly older than those without (mean age 60 +/- 6 years vs. 55 +/- 8 years; P < 0.0001). The prevalence of active smoking was significantly higher in patients with non-cardiac findings (28.2 vs. 17.8%; P = 0.03). The prevalence of non-cardiac abnormalities detected by cardiac MDCT was 8% and about half of these findings were deemed significant. These lesions commonly occurred in the lungs and the liver. Age and active smoking were predictive of the presence of non-cardiac abnormalities.

Quality of life and psychological status in survivors of severe acute respiratory syndrome at 3 months postdischarge.

BACKGROUND: Little is known about the long-term consequence of severe acute respiratory syndrome (SARS). We carried out an assessment on SARS patients after their recovery from their acute illness. METHOD: Postal survey comprising Health-Related Quality of Life (HRQoL) questionnaires and anxiety and depression measures was sent to them at 3 months' postdischarge. RESULTS: There was a significant impairment in both the HRQoL and mental functioning. Forty-one percent had scores indicative of a posttraumatic stress disorder (PTSD); about 30% had likely anxiety and depression. CONCLUSION: SARS has significant impact on HRQoL and psychological status at 3 months.

1-year pulmonary function and health status in survivors of severe acute respiratory syndrome.

STUDY OBJECTIVES: To characterize the long-term pulmonary function and health status in a prospectively identified cohort of patients who survived the severe acute respiratory syndrome (SARS). DESIGN: Prospective follow-up cohort study. SETTING: University-affiliated hospital. PATIENTS: Ninety-four patients who recovered from SARS were assessed at a uniform time point of 1 year after hospital discharge. MEASUREMENTS: The study included the measurement of static and dynamic lung volumes, the determination of the diffusing capacity of the lung for carbon monoxide (D(LCO)), and a health status evaluation using the St. George Respiratory Questionnaire (SGRQ). RESULTS: Eleven patients (12%) had mild impairment of FVC, 20 (21%) had mild impairment of FEV1, 5 (5%) had mild impairment of the FEV1/FVC ratio, and 17 (18%) had mild impairment of the D(LCO). There was one patient (1%) who had moderate impairment of FVC, one patient (1%) who had moderate impairment of the FEV1/FVC ratio, and three patients (3%) who had moderate impairment of the D(LCO). No pulmonary function abnormalities were detected in 59 patients (63%). Mean scores were significantly higher (ie, worse) than the population norms in the activity (p < 0.001), impacts (p < 0.001), and total (p < 0.001) domains of the SGRQ. CONCLUSIONS: One year after recovery from SARS, persistent pulmonary function impairment was found in about one third of patients. The health status of SARS survivors was also significantly worse compared with the healthy population. The main determinants of morbidity in recovered SARS patients need to be further defined.

Hypocortisolism in survivors of severe acute respiratory syndrome (SARS).

OBJECTIVE: Following the severe acute respiratory syndrome (SARS) outbreak, many survivors were observed to suffer from psychosomatic symptoms reminiscent of various endocrine disorders. Hence, we sought to determine the existence of any chronic endocrine sequelae in SARS survivors. DESIGN, PATIENTS, MEASUREMENTS: Sixty-one survivors of SARS prospectively recruited were analysed for hormonal derangements 3 months following recovery. Patients with pre-existing endocrine disorders were excluded. Any endocrine abnormalities diagnosed were investigated and treated where indicated up to a year. Serial evaluation facilitated characterization of trends and prognostication of any endocrinological aberrations. RESULTS: Twenty-four (39.3%) patients had evidence of hypocortisolism. The hypothalamic-pituitary-adrenal (HPA) axis dysfunction of the majority resolved within a year. Two (3.3%) of the hypocortisolic cohort had transient subclinical thyrotoxicosis. Four (6.7%) were biochemically hypothyroid, being comprised of three with central hypothyroidism and one with primary hypothyroidism. Two of the three with central hypothyroidism had concomitant central hypocortisolism. Eight had subnormal DHEAS levels. CONCLUSIONS: These preliminary findings highlight a possible aetiologic role of SARS-associated coronavirus in causing a reversible hypophysitis or direct hypothalamic effect, with the HPA axis affected more frequently than the HPT axis.

Analysis of deaths during the severe acute respiratory syndrome (SARS) epidemic in Singapore: challenges in determining a SARS diagnosis.

CONTEXT: An outbreak of severe acute respiratory syndrome (SARS), an infectious disease attributed to a novel coronavirus, occurred in Singapore during the first quarter of 2003 and led to 204 patients with diagnosed illnesses and 26 deaths by May 2, 2003. Twenty-one percent of these patients required admission to the medical intensive care unit. During this period, the Center for Forensic Medicine, Health Sciences Authority, Singapore, performed a total of 14 postmortem examinations for probable and suspected SARS. Of these, a total of 8 were later confirmed as SARS infections. OBJECTIVE: Our series documents the difficulties encountered at autopsy during the initial phases of the SARS epidemic, when the pattern of infection and definitive diagnostic laboratory criteria were yet to be established. DESIGN: Autopsies were performed by pathologists affiliated with the Center for Forensic Medicine, Health Sciences Authority, Singapore. Tissue was accessed and read at the Tan Tock Seng Hospital, Singapore, and at the Armed Forces Institute of Pathology, Washington, DC. Autopsy tissue was submitted to the Virology Department, Singapore General Hospital, for analysis, and in situ hybridization for the SARS coronavirus was carried out at the National Institute of Infectious Diseases, Tokyo, Japan. RESULTS: Thirteen of 14 patients showed features of diffuse alveolar damage. In 8 patients, no precipitating etiology was identified, and in all of these patients, we now have laboratory confirmation of coronavirus infection. Two of the 8 patients presented at autopsy as sudden unexpected deaths, while the remaining 6 patients had been hospitalized with varying lengths of stay in the intensive care unit. In 3 patients, including the 2 sudden unexpected deaths, in situ hybridization showed the presence of virally infected cells within the lung. In 4 of the 8 SARS patients, pulmonary thromboemboli were also recognized on gross examination, while one patient had marantic cardiac valvular vegetations. CONCLUSIONS: It is unfortunate that the term atypical pneumonia has been used in conjunction with SARS. Although nonspecific by itself, the term does not accurately reflect the underlying dangers of viral pneumonia, which may progress rapidly to acute respiratory distress syndrome. We observed that the clinical spectrum of disease as seen in our autopsy series included sudden deaths. This is a worrisome finding that illustrates that viral diseases will have a spectrum of clinical presentations and that the diagnoses made for such patients must incorporate laboratory as well as clinical data.

Severe acute respiratory syndrome (SARS): chest radiographic features in children.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a recently recognized condition of viral origin associated with substantial morbidity and mortality rates in adults. Little information is available on its radiologic manifestations in children. OBJECTIVE: The goal of this study was to characterize the radiographic presentation of children with SARS. MATERIALS AND METHODS: We abstracted data (n=62) on the radiologic appearance and course of SARS in pediatric patients with suspect (n=25) or probable (n=37) SARS, diagnosed in five hospital sites located in three cities: Toronto, Singapore, and Hong Kong. Available chest radiographs and thoracic CTs were reviewed for the presence of the following radiographic findings: airspace disease, air bronchograms, airways inflammation and peribronchial thickening, interstitial disease, pleural effusion, and hilar adenopathy. RESULTS: A total of 62 patients (suspect=25, probable=37) were evaluated for SARS. Patient ages ranged from 5.5 months to 17 years and 11.5 months (average, 6 years and 10 months) with a female-to-male ratio of 32:30. Forty-one patients (66.1%) were in close contact with other probable, suspect, or quarantined cases; 10 patients (16.1%) had recently traveled to WHO-designated affected areas within 10 days; and 7 patients (11.2%) were transferred from other hospitals that had SARS patients. Three patients, who did not have close/hospital contact or travel history to affected areas, were classified as SARS cases based on their clinical signs and symptoms and on the fact that they were living in an endemic area. The most prominent clinical presentations were fever, with a temperature over 38 degrees C (100%), cough (62.9%), rhinorrhea (22.6%), myalgia (17.7%), chills (14.5%), and headache (11.3%). Other findings included sore throat (9.7%), gastrointestinal symptoms (9.7%), rigor (8.1%), and lethargy (6.5%). In general, fever and cough were the most common clinical presentations amongst younger pediatric SARS cases (age<10 years), whereas, in addition to these symptoms, headache, myalgia, sore throat, chills, and/or rigor were common in older patients (age>/=10 years). The chest radiographs of 35.5% of patients were normal. The most prominent radiological findings that were observed in the remaining patients were areas of consolidation (45.2%), often peripheral with multifocal lesions in 22.6%. Peribronchial thickening was noted on chest radiographs of 14.5% of patients. Pleural effusion was observed only in one patient (age 17 years and 11.5 months), whereas interstitial disease was not observed in any patient. CONCLUSION: In pediatric cases, SARS manifests with nonspecific radiographic features making radiological differentiation difficult, especially from other commonly encountered childhood respiratory viral illnesses causing airspace disease. The radiographic presentation of suspected SARS cases ranged from normal to mild perihilar peribronchial thickening. The radiographic presentations, as expected, were relatively more pronounced in the SARS probable cases.