Clinical standards for the management of adverse effects during treatment for TB.

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.

Diabetes characteristics and long-term management needs in diabetic TB patients.

BACKGROUND: Diabetes mellitus (DM) is common among patients with TB. We assessed DM characteristics and long-term needs of DM-TB patients after completing TB treatment.METHODS: Newly diagnosed TB patients with DM were recruited for screening in a randomised clinical trial evaluating a simple algorithm to improve glycaemic control during TB treatment. DM characteristics, lifestyle and medication were compared before and after TB treatment and 6 months later. Risk of cardiovascular disease (CVD), albuminuria and neuropathy were assessed after TB treatment.RESULTS: Of 218 TB-DM patients identified, 170 (78%) were followed up. Half were males, the mean age was 53 years, 26.5% were newly diagnosed DM. High glycated haemoglobin at TB diagnosis (median 11.2%) decreased during TB treatment (to 7.4% with intensified management and 8.4% with standard care), but this effect was lost 6 months later (9.3%). Hypertension and dyslipidemia contributed to a high 10-year CVD risk (32.9% at month 6 and 35.5% at month 12). Neuropathy (33.8%) and albuminuria (61.3%) were common. After TB treatment, few patients used CVD-mitigating drugs.CONCLUSION: DM in TB-DM patients is characterised by poor glycaemic control, high CVD risk, and nephropathy. TB treatment provides opportunities for better DM management, but effort is needed to improve long-term care.

Clinical standards for the dosing and management of TB drugs.

BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.

Implementing the 4R and 9H regimens for TB preventive treatment in Indonesia.

BACKGROUND: The implementation of tuberculosis preventive treatment (TPT) is challenging especially in resource-limited settings. As part of a Phase 3 trial on TPT, we described our experience with the use of rifampicin for 4 months (4R) and isoniazid for 9 months (9H) in Indonesia.METHODS: In 2011-2017, children and adults with latent TB infection were randomised to either 4R or 9H and followed until 16 months after randomisation for children and 28 months for adults. The primary outcome was the treatment completion rate. Secondary outcomes were Grade 3-5 adverse events (AEs), active TB occurrence, and health costs.RESULTS: A total of 157 children and 860 adults were enrolled. The 4R treatment completion rate was significantly higher than that of 9H (78.7% vs. 65.5%), for a rate difference of 13.2% (95% CI 7.1-19.2). No Grade 3-5 AEs were reported in children; in adults, it was lower in 4R (0.4%) compared to 9H (2.8%). The incidence of active TB was lower with 4R than with 9H (0.09/100 person-year vs. 0.36/100 person-year) (rate difference: -0.36/100 person-year). The total cost per patient was lower for the 4R regimen than for the 9H regimen (USD151.9 vs. USD179.4 in adults and USD152.9 vs. USD206.5 in children)CONCLUSIONS: Completion and efficacy rates for 4R were better than for 9H. Compared to 9H, 4R was cheaper in all age groups, safer in adults and equally safe in children. The Indonesian TB program could benefit from these benefits of the 4R regimen.

Educational counselling of patients with combined TB and diabetes mellitus: a randomised trial.

SETTING: Newly diagnosed pulmonary TB with diabetes mellitus (DM) comorbidity attending clinics in Bandung City, Indonesia. OBJECTIVE: To describe the effect of educational counselling on patients' knowledge about TB (transmission, treatment, risk factors) and DM (symptoms, treatment, complications, healthy lifestyle), adherence to medication, and to assess characteristics associated with knowledge. DESIGN: All patients received counselling and were then randomised to either structured education on TB-DM, combined with clinical monitoring and medication adjustment (intervention arm), or routine care (control arm). Knowledge and adherence were assessed using a questionnaire. RESULTS: Baseline and 6-month questionnaires were available for 108 of 150 patients randomised (60/76 in the intervention arm and 48/74 in the control arm). Patients knew less about DM than about TB. There was no significant difference in the proportion with knowledge improvement at 6 months, both for TB (difference of differences 14%; P = 0.20) or for DM (10%; P = 0.39) between arms. Intervention arm patients were more likely to adhere to taking DM medication, with fewer patients reporting ever missing oral DM drugs than those in the control arm (23% vs. 48%; P = 0.03). Higher education level was associated with good knowledge of both TB and DM. CONCLUSIONS: Structured education did not clearly improve patients' knowledge. It was associated with better adherence to DM medication, but this could not be attributed to education alone. More efforts are needed to improve patients' knowledge, especially regarding DM.

CONTEXTE: Patients atteints de diabète sucré (DM) ayant récemment reçu un diagnostic de TB pulmonaire consultant dans les cliniques de la ville de Bandung, Indonésie. OBJECTIF: Décrire l'effet de conseils éducatifs sur les connaissances des patients en matière de TB (transmission, traitement, facteurs de risque), de DM (symptômes, traitement, complications, mode de vie sain) et d'observance thérapeutique, et évaluer les caractéristiques associées à ces connaissances. MÉTHODE: Tous les patients ont reçu des conseils et ont ensuite été randomisés dans l'un des deux groupes suivants : programme d'éducation structuré sur la TB-DM associé à un suivi clinique et à un ajustement thérapeutique (groupe d'intervention) ou prise en charge de routine (groupe témoin). Les connaissances et l'observance ont été évaluées par questionnaire. RÉSULTATS: Les questionnaires administrés à l'inclusion et à 6 mois étaient disponibles pour 108 des 150 patients randomisés (60/76 dans le groupe d'intervention et 48/74 dans le groupe témoin). Les connaissances des patients étaient moins bonnes sur le DM que sur la TB. Aucune différence significative n'a été observée entre les groupes dans la proportion de patients dont les connaissances s'étaient améliorées à 6 mois, tant pour la TB (différence des différences 14% ; P = 0,20) que pour le DM (10% ; P = 0,39). Les patients du groupe d'intervention étaient plus susceptibles d'observer correctement leur traitement antidiabétique. Moins de patients ont en effet rapporté avoir manqué une dose de leur traitement antidiabétique oral par rapport au groupe témoin (23% vs. 48% ; P = 0,03). Un niveau d'éducation plus élevé a été associé à de bonnes connaissances sur la TB et le DM. CONCLUSIONS: Le programme d'éducation structuré n'a pas amélioré de manière évidente les connaissances des patients. Ce programme a été associé à une meilleure observance du traitement antidiabétique, mais cela n'a pas pu être attribué au seul programme d'éducation. Davantage d'efforts sont nécessaires pour améliorer les connaissances des patients, notamment sur le DM.

Effect of chronic obstructive pulmonary disease and smoking on the outcome of COVID-19.

OBJECTIVE: To investigate the association between chronic obstructive pulmonary disease (COPD) and smoking with outcome in patients with COVID-19.METHODS: A systematic literature search was performed using PubMed, EuropePMC, SCOPUS and the Cochrane Central Database. A composite of poor outcome, mortality, severe COVID-19, the need for treatment in an intensive care unit (ICU) and disease progression were the outcomes of interest.RESULTS: Data on 4603 patients were pooled from 21 studies. COPD was associated with an increased risk for composite poor outcome (OR 5.01, 95%CI 3.06-8.22; P < 0.001; I² 0%), mortality (OR 4.36, 95%CI 1.45-13.10; P = 0.009; I² 0%), severe COVID-19 (OR 4.62, 95%CI 2.49-8.56; P < 0.001; I² 0%), ICU care (OR 8.33, 95%CI 1.27-54.56; P = 0.03; I² 0%), and disease progression (OR 8.42, 95%CI 1.60-44.27; P = 0.01; I² 0%). Smoking was found to increase the risk of composite poor outcome (OR 1.52, 95%CI 1.16-2.00; P = 0.005; I² 12%), and subgroup analysis showed that smoking was significant for increased risk of severe COVID-19 (OR 1.65, 95%CI 1.17-2.34; P = 0.004; I² 11%). Current smokers were at higher risk of composite poor outcomes (OR 1.58, 95%CI 1.10-2.27; P = 0.01; I² 0%) than former/non-smokers.CONCLUSION: Our systematic review and meta-analysis revealed that COPD and smoking were associated with poor outcomes in patients with COVID-19.

Early chest X-ray in persons with presumptive tuberculosis increases Xpert® MTB/RIF diagnostic yield and efficiency.

Adult presumptive tuberculosis (TB) patients (n = 1690) were screened for TB using a questionnaire, chest X-ray (CXR) and sputum microscopy for acid-fast bacilli (AFB); Mycobacterium tuberculosis culture was performed for 74% of the patients and Xpert® MTB/RIF was done for 17.2%. Among patients recruited, 943 (55.8%) were diagnosed with TB, of whom 870 (92.3%) were bacteriologically confirmed and 73 (7.7%) were clinically diagnosed on the basis of CXR. Using CXR prior to culture or Xpert testing reduces the number needed to screen from 7.6 to 5.0. Using CXR to triage for culture or Xpert testing reduces the number of missed cases and increases the efficiency of culture and Xpert testing.

Des patients adultes présumés atteints de TB (n = 1690) ont été dépistés à l'aide d'un questionnaire, d'une radiographie pulmonaire (CXR) et d'une microscopie de crachats à la recherche des bacilles acido-alcoolo-résistants; une culture de Mycobacterium tuberculosis a été réalisée chez 74% des patients et un test Xpert® MTB/RIF, chez 17,2%. Parmi les patients recrutés, 943 (55,8%) ont eu un diagnostic de TB, dont 870 (92,3%) ont été confirmés par bactériologie et 73 (7,7%) ont été diagnostiqués sur la CXR. Recourir à la CXR avant la culture ou le test Xpert réduit le nombre requis pour dépister un cas de 7,6 à 5,0. L'utilisation de la CXR pour le triage avant la culture ou le test Xpert réduit les cas manqués et augmente l'efficacité de l'utilisation de la culture et de l'Xpert.

Se investigó de la tuberculosis (TB) en pacientes adultos con presunción clínica de la enfermedad (n = 1690) mediante un cuestionario, la radiografía de tórax (CXR) y la baciloscopia del esputo; se practicó el cultivo para Mycobacterium tuberculosis en 74% de los pacientes y la prueba Xpert® MTB/RIF en 17,2%. De los pacientes que participaron se diagnosticó la TB en 943 (55,8%), de los cuales 870 (92,3%) con confirmación bacteriológica y 73 (7,7%) con diagnóstico clínico a partir de la CXR. El hecho de realizar la CXR o la prueba Xpert antes del cultivo disminuye de 7,6 a 5,0 el número de pacientes que deben someterse a detección. El uso de la CXR para seleccionar los casos en que se debe practicar el cultivo o la prueba Xpert disminuye los casos pasados por alto y aumenta la eficiencia del uso del cultivo y la prueba Xpert.

Nomograms of sonographic measurements throughout gestation of the fetal hard palate width, length and area.

OBJECTIVE: To assess the feasibility of sonographic depiction of the fetal hard palate and secondarily to create nomograms throughout gestation of its sonographic width, length and area. METHODS: This was a cross-sectional study of pregnant patients between 15 and 41 weeks' gestation. Inclusion criteria consisted of well-established dates (confirmed by early ultrasound), and singleton, non-anomalous fetuses. Sonographic measurements obtained included biparietal diameter, head circumference, abdominal circumference and femur length. Fetal hard palate measurements included maximum width, maximum length and the calculated area. Tables were prepared depicting the estimated mean +/- SD and 5(th), 50(th) and 95(th) centiles at each gestational week between 15 and 41 weeks. Pearson's correlation coefficient and associated P-values for the relationships between fetal hard palate measurements and other sonographic measurements and coefficients of variation for each of the fetal hard palate measurements were calculated. RESULTS: The study included 602 consecutive patients. The mean maternal age was 28.7 +/- 6.3 years, with median gravidity of 2 (range, 1-12) and parity 1 (range, 0-8). All attempts at obtaining fetal hard palate ultrasound measurements were successful. Mean fetal hard palate width (cm) = -0.73579345 + 0.11370432 x GA - 0.00083919 x GA(2) and SD = -0.017842055 + 0.005142475 x GA, where GA is gestational age in weeks. Mean fetal hard palate length (cm) = -0.82020463 + 0.11767777 x GA - 0.00092801 x GA(2) and SD = -0.043064317 + 0.006378869 x GA. Mean fetal hard palate area (cm(2)) = -2.40090641 + 0.17136556 x GA + 0.00097308 x GA(2) and SD = -0.603647741 + 0.040740282 x GA. Sonographic measurements of the fetal hard palate width, length and area correlated significantly and strongly with gestational age (all P < 0.001) and significantly but less strongly with femur length (P = 0.004). CONCLUSION: The fetal hard palate may be depicted sonographically with relative ease between 15 and 41 weeks' gestation and measurements of the fetal hard palate width, length and area correlate well with gestational age, biparietal diameter, abdominal circumference, sonographic estimated fetal weight, and femur length.