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Diagnostic accuracy of the Xpert® MTB/RIF cycle threshold level to predict smear positivity: a meta-analysis

Lange B, Khan P, Kalmambetova G, Al-Darraji HA, Alland D, Antonenka U, et al.

Int J Tuberc Lung Dis, 2017 05 01;21(5):493-502.
PMID: 28399963 DOI: 10.5588/ijtld.16.0702

SETTING: Xpert® MTB/RIF is the most widely used molecular assay for rapid diagnosis of tuberculosis (TB). The number of polymerase chain reaction cycles after which detectable product is generated (cycle threshold value, CT) correlates with the bacillary burden.OBJECTIVE To investigate the association between Xpert CT values and smear status through a systematic review and individual-level data meta-analysis.
DESIGN: Studies on the association between CT values and smear status were included in a descriptive systematic review. Authors of studies including smear, culture and Xpert results were asked for individual-level data, and receiver operating characteristic curves were calculated.
RESULTS: Of 918 citations, 10 were included in the descriptive systematic review. Fifteen data sets from studies potentially relevant for individual-level data meta-analysis provided individual-level data (7511 samples from 4447 patients); 1212 patients had positive Xpert results for at least one respiratory sample (1859 samples overall). ROC analysis revealed an area under the curve (AUC) of 0.85 (95%CI 0.82-0.87). Cut-off CT values of 27.7 and 31.8 yielded sensitivities of 85% (95%CI 83-87) and 95% (95%CI 94-96) and specificities of 67% (95%CI 66-77) and 35% (95%CI 30-41) for smear-positive samples.
CONCLUSION: Xpert CT values and smear status were strongly associated. However, diagnostic accuracy at set cut-off CT values of 27.7 or 31.8 would not replace smear microscopy. How CT values compare with smear microscopy in predicting infectiousness remains to be seen.
Delays in seeking treatment for symptomatic tuberculosis in Sabah, East Malaysia: factors for patient delay

Rundi C, Fielding K, Godfrey-Faussett P, Rodrigues LC, Mangtani P

Int J Tuberc Lung Dis, 2011 Sep;15(9):1231-8, i.
PMID: 21943851 DOI: 10.5588/ijtld.10.0585

SETTING: The state of Sabah contributes one third of the tuberculosis (TB) cases in Malaysia.
OBJECTIVE: To collect information on factors that affect the time period from the onset of symptoms to first contact with health care providers, whether private or government.
DESIGN: A cross-sectional study using a pre-tested questionnaire was conducted among 296 newly registered smear-positive TB patients in 10 districts in Sabah. Univariable and multivariable analyses were used to determine which risk factors were associated with patient delay (>30 days) and 'extreme' patient delay (>90 days).
RESULTS: The percentage of patients who sought treatment after 30 and 90 days was respectively 51.8% (95%CI 45.7-57.9) and 23.5% (95%CI 18.6-29.0). The strongest factors associated with patient delay and 'extreme' patient delay was when the first choice for treatment was a non-government health facility and in 30-39-year-olds. 'Extreme' patient delay was also weakly associated, among other factors, with comorbidity and livestock ownership.
CONCLUSION: Delay and extreme delay in seeking treatment were more common when the usual first treatment choice was a non-government health facility. Continuous health education on TB aimed at raising awareness and correcting misconceptions is needed, particularly among those who use non-government facilities.
Fulltext Delays in diagnosis and treatment of pulmonary tuberculosis in India: a systematic review

Sreeramareddy CT, Qin ZZ, Satyanarayana S, Subbaraman R, Pai M

Int J Tuberc Lung Dis, 2014 Mar;18(3):255-66.
PMID: 24670558 DOI: 10.5588/ijtld.13.0585

OBJECTIVE: To systematically review Indian literature on delays in tuberculosis (TB) diagnosis and treatment.
METHODS: We searched multiple sources for studies on delays in patients with pulmonary TB and those with chest symptoms. Studies were included if numeric data on any delay were reported. Patient delay was defined as the interval between onset of symptoms and the patient's first contact with a health care provider. Diagnostic delay was defined as the interval between the first consultation with a health care provider and diagnosis. Treatment delay was defined as the interval between diagnosis and initiation of anti-tuberculosis treatment. Total delay was defined as time interval from the onset of symptoms until treatment initiation.
RESULTS: Among 541 potential citations identified, 23 studies met the inclusion criteria. Included studies used a variety of definitions for onset of symptoms and delays. Median estimates of patient, diagnostic and treatment delay were respectively 18.4 (IQR 14.3-27.0), 31.0 (IQR 24.5-35.4) and 2.5 days (IQR 1.9-3.6) for patients with TB and those with chest symptoms combined. The median total delay was 55.3 days (IQR 46.5-61.5). About 48% of all patients first consulted private providers; an average of 2.7 health care providers were consulted before diagnosis. Number and type of provider first consulted were the most important risk factors for delay.
CONCLUSIONS: These findings underscore the need to develop novel strategies for reducing patient and diagnostic delays and engaging first-contact health care providers.
Delay in the diagnosis and treatment of pulmonary tuberculosis in patients attending a university teaching hospital

Liam CK, Tang BG

Int J Tuberc Lung Dis, 1997 Aug;1(4):326-32.
PMID: 9432388

University Hospital, Kuala Lumpur, Malaysia.
Common concerns in managing bronchial asthma during the COVID-19 pandemic

Chai CS, Liam CK

Int J Tuberc Lung Dis, 2020 Jul 01;24(7):750-752.
PMID: 32718416 DOI: 10.5588/ijtld.20.0378
Fulltext Clinical-radiological features and diagnostic modalities for mediastinal melioidosis

Nyanti LE, Lee SSY, Shanmugam V, Muien MZBA, Othman AA, Chia YL, et al.

Int J Tuberc Lung Dis, 2023 Oct 01;27(10):724-728.
PMID: 37749834 DOI: 10.5588/ijtld.23.0079

Melioidosis is a potentially life-threatening infection caused by the Gram-negative bacillus Burkholderia pseudomallei. Mediastinal melioidosis has a range of clinical presentations, making it difficult to diagnose: we therefore reviewed the evidence on the clinical characteristics, radiological features and invasive diagnostic modalities or interventions. An electronic search was conducted on three databases (PubMed, SCOPUS, Google Scholar) from November to December 2022. The initial search yielded 120 results, of which 34 studies met the inclusion criteria, but only 31 full-texts were retrievable. Among these, 4 were cohort studies, 26 case reports or series and 1 a conference abstract. The four main themes covered were mediastinal melioidosis as a diagnostic dilemma, unexpected complications, invasive interventions or an accompanying thoracic feature. Radiological manifestations included matting, necrosis and abscess-like collection. Severe presentations of mediastinal melioidosis included superior vena cava obstruction, sinus tract formation and pericardial tamponade. Transbronchial needle aspiration was the most common invasive diagnostic modality. Further research is needed to understand the relationship between the thoracic features of melioidosis on patient prognosis, its relationship to melioidosis transmission and potential preventive measures.
Fulltext Clinical standards for the diagnosis and management of asthma in low- and middle-income countries

Jayasooriya S, Stolbrink M, Khoo EM, Sunte IT, Awuru JI, Cohen M, et al.

Int J Tuberc Lung Dis, 2023 Sep 01;27(9):658-667.
PMID: 37608484 DOI: 10.5588/ijtld.23.0203

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs).METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards.RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available.CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.
Awareness of the ozone layer and acceptance of a new CFC-free metered dose inhaler among asthmatic patients

Liam CK, Lim KH

Int J Tuberc Lung Dis, 1998 Aug;2(8):683-9.
PMID: 9712285

University of Malaya Medical Centre, Kuala Lumpur, Malaysia.
Fulltext Attitudes towards smoking and tobacco control among pre-clinical medical students in Malaysia

Tee GH, Hairi NN, Hairi F

Int J Tuberc Lung Dis, 2012 Aug;16(8):1126-8.
PMID: 22668450 DOI: 10.5588/ijtld.11.0254

Physicians should play a leading role in combatting smoking; information on attitudes of future physicians towards tobacco control measures in a middle-income developing country is limited. Of 310 future physicians surveyed in a medical school in Malaysia, 50% disagreed that it was a doctor's duty to advise smokers to stop smoking; 76.8% agreed that physicians should not smoke before advising others not to smoke; and 75% agreed to the ideas of restricting the sale of cigarettes to minors, making all public places smoke-free and banning advertising of tobacco-related merchandise. Future physicians had positive attitudes towards tobacco regulations but had not grasped their responsibilities in tobacco control measures.
Fulltext Attitudes and knowledge of newly diagnosed tuberculosis patients regarding the disease, and factors affecting treatment compliance

Liam CK, Lim KH, Wong CM, Tang BG

Int J Tuberc Lung Dis, 1999 Apr;3(4):300-9.
PMID: 10206500

SETTING: An urban university teaching hospital.
OBJECTIVES: To determine patients' attitudes to tuberculosis and their knowledge of the disease, and factors associated with treatment compliance.
DESIGN: All adult patients commenced on treatment for tuberculosis from September 1994 to February 1996 were interviewed on initiation of treatment. To assess patient compliance with treatment, hospital clinical records were reviewed retrospectively.
RESULTS: A total of 135 patients with a mean age (±SD) of 41.9 (±17.4) years (range 15–84 years) were interviewed. The patients had limited understanding and knowledge about tuberculosis. There was a negative correlation between patient age and tuberculosis knowledge score (r = −0.18, P = 0.038). Patients with tertiary education had better knowledge than the others. Of 118 patients who were followed-up in our chest clinic, 80 (67.8%) completed the prescribed treatment. Compliance with treatment and follow-up was not affected by age, sex, ethnic group, educational level, occupation, extent of knowledge, tuberculosis symptoms, hospitalisation for tuberculosis or duration of the prescribed treatment regimen. There was a trend toward poorer compliance among patients who equated disappearance of tuberculosis symptoms with cure of the disease.
CONCLUSIONS: Malaysian patients with newly diagnosed tuberculosis attending a university teaching hospital had misconceptions and limited knowledge about the disease and its treatment. Educational background was an important determinant of a patient's level of knowledge about tuberculosis. Compliance was not affected by patient characteristics. Adequate counselling and education of patients and close relatives on tuberculosis and the necessity for prolonged treatment may help to improve treatment compliance.
Study site: Chest clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
Associations between air pollutants and peak expiratory flow and fractional exhaled nitric oxide in students

Adman MA, Hashim JH, Manaf MRA, Norback D

Int J Tuberc Lung Dis, 2020 02 01;24(2):189-195.
PMID: 32127103 DOI: 10.5588/ijtld.19.0096

BACKGROUND: Studies on the effects of outdoor air pollution on the respiratory health of students in tropical countries such as Malaysia are limited.OBJECTIVE: To assess associations between outdoor air pollutants and peak expiratory flow (PEF) and fractional exhaled nitric oxide (FeNO).METHOD: PEF and FeNO levels of 487 students recruited in Melaka and Putrajaya, Malaysia, were measured in April and June 2014. Multiple linear regression with mutual adjustment was used to analyse the associations between exposure to air pollution and health.RESULTS: PEF was significantly associated with ozone for 1-day exposure (β = -13.3 l/min, 95% CI -22.7 to -3.8), carbon monoxide for 2-day exposure (β = -57.2 l/min, 95% CI -90.7 to -23.7) and particulate matter ≦10 μm in diameter for 3-day exposure (β = -6.0 l/min, 95% CI -9.2 to -2.8) and 7-day exposure (β = -8.6 l/min, 95% CI -13.0 to -4.1). Stratified analysis showed that associations between PEF and outdoor air pollutant exposures were similar in students with and without elevated FeNO levels.CONCLUSION: Outdoor air pollution in Malaysia may cause airway obstruction unrelated to eosinophilic airway inflammation among students as measured using FeNO.
Fulltext Association between diabetes mellitus and mortality among patients with tuberculosis

Brož J, Jarošová B, Salih SFA, Brabec M, Salih FMA

Int J Tuberc Lung Dis, 2019 05 01;23(5):638.
PMID: 31097076 DOI: 10.5588/ijtld.18.0796
A prospective study of mycobacterial viability in refrigerated, unpreserved sputum batched for up to 8 weeks

Rashid Ali MR, Parameswaran U, William T, Bird E, Wilkes CS, Lee WK, et al.

Int J Tuberc Lung Dis, 2015 May;19(5):620-1.
PMID: 25868033 DOI: 10.5588/ijtld.14.0938
Fulltext A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB

Tweed CD, Wills GH, Crook AM, Amukoye E, Balanag V, Ban AYL, et al.

Int J Tuberc Lung Dis, 2021 Apr 01;25(4):305-314.
PMID: 33762075 DOI: 10.5588/ijtld.20.0513

BACKGROUND: Treatment for TB is lengthy and toxic, and new regimens are needed.METHODS: Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa200MZ) or 4 months (4Pa200MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa100MZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation. The non-inferiority margin for between-group differences was 12.0%. Recruitment was paused following three deaths and not resumed.RESULTS: Respectively 4/47 (8.5%), 11/57 (19.3%), 14/52 (26.9%) and 1/53 (1.9%) DS-TB outcomes were unfavourable in patients on 6Pa200MZ, 4Pa200MZ, 4Pa100MZ and controls. There was a 6.6% (95% CI -2.2% to 15.4%) difference per protocol and 9.9% (95%CI -4.1% to 23.9%) modified intention-to-treat difference in unfavourable responses between the control and 6Pa200MZ arms. Grade 3+ adverse events affected 68/203 (33.5%) receiving experimental regimens, and 19/68 (27.9%) on control. Ten of 203 (4.9%) participants on experimental arms and 2/68 (2.9%) controls died.CONCLUSION: PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.

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