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.

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.

Predictors for treatment outcomes among patients with drug-susceptible tuberculosis in the Netherlands: a retrospective cohort study.

OBJECTIVES: We evaluated treatment outcomes and predictors for poor treatment outcomes for tuberculosis (TB) among native- and foreign-born patients with drug-susceptible TB (DSTB) in the Netherlands. METHODS: This retrospective cohort study included adult patients with DSTB treated from 2005 to 2015 from a nationwide exhaustive registry. Predictors for unsuccessful treatment outcomes (default and failure) and TB-associated mortality were analysed using multivariate logistic regression. RESULTS: Among 5674 identified cases, the cumulative incidence of unsuccessful treatment and mortality were 2.6% (n/N = 146/5674) and 2.0% (112/5674), respectively. Although most patients were foreign-born (71%; 4042/5674), no significant differences in these outcomes were observed between native- and foreign-born patients (p > 0.05). Significant predictors for unsuccessful treatment were aged 18-24 years (odds ratio (OR), 2.04; 95% CI 1.34-3.10), homelessness (OR, 2.56; 95% CI 1.16-5.63), prisoner status (OR, 5.39; 95% CI 2.90-10.05) and diabetes (OR, 2.02; 95% CI 1.03-3.97). Furthermore, predictors for mortality were aged 74-84 years (OR, 5.58; 95% CI 3.10-10.03) or ≥85 years (OR, 9.35, 95% CI 4.31-20.30), combined pulmonary and extra-pulmonary TB (OR, 4.97; 95% CI 1.42-17.41), central nervous system (OR, 120, 95% CI 34.43-418.54) or miliary TB (OR, 10.73, 95% CI 2.50-46.02), drug addiction (OR, 3.56; 95% CI 1.34-9.47) and renal insufficiency/dialysis (OR, 3.23; 95% CI 1.17-8.96). CONCLUSIONS: Native- and foreign-born patients exhibited similar TB treatment outcomes. To further reduce disease transmission and inhibit drug resistance, special attention should be given to high-risk patients.

Cost-utility analysis of high-dose treatment for intermediate-susceptible, dose-dependent tuberculosis patients.

SETTING: We proposed to: 1) introduce an intermediate-susceptible, dose-dependent (ISDD) category for Mycobacterium tuberculosis infection; and 2) treat patients with M. tuberculosis infection in this category with a high dose of rifampicin (RMP) and isoniazid (INH). OBJECTIVE: To examine the impact of our strategy on quality-adjusted life-years (QALY) and costs in a low-income country with a high prevalence of multidrug-resistant tuberculosis (MDR-TB) (Belarus) and a high-income, low MDR-TB prevalence country (The Netherlands). DESIGN: A Markov model comprising 14 health states was used to simulate treatment outcomes and costs accrued over 5 years for a hypothetical cohort of 10 000 patients. One-way sensitivity analysis, probabilistic sensitivity analysis and a scenario analysis were also performed. RESULTS: Our strategy was shown to be cost-effective for Belarus, but not for the Netherlands. At a willingness-to-pay of 50 000 euros per QALY, the probability of our strategy being cost-effective was 50% for the Netherlands and 57% for Belarus. CONCLUSION: The study shows that our strategy could be cost-effective and more efficacious. However, more studies are needed on the outcomes of using higher doses of INH and RMP.