Risk factors for early mortality in patients with pulmonary tuberculosis admitted to the emergency room.

Abstract Background and objectives Mortality of patients with pulmonary tuberculosis (TB) admitted to emergency departments is high. This study was aimed at analysing the risk factors associated with early mortality and designing a risk score based on simple parameters. Methods This prospective case-control study enrolled patients admitted to the emergency department of a referral TB hospital. Clinical, radiological, biochemical and microbiological risk factors associated with death were compared among patients dying within one week from admission (cases) and those surviving (controls). Results Forty-nine of 250 patients (19.6%) experienced early mortality. Multiple logistic regression analysis showed that oxygen saturation (SaO2) ≤90%, severe malnutrition, tachypnoea, tachycardia, hypotension, advanced disease at chest radiography, severe anaemia, hyponatremia, hypoproteinemia and hypercapnia were independently and significantly associated with early mortality. A clinical scoring system was further designed to stratify the risk of death by selecting five simple parameters (SpO2 ≤ 90%, tachypnoea, hypotension, advanced disease at chest radiography and tachycardia). This model predicted early mortality with a positive predictive value of 94.88% and a negative predictive value of 19.90%. Conclusions The scoring system based on simple parameters may help to refer severely ill patients early to a higher level to reduce mortality, improve success rates, minimise the need for pulmonary rehabilitation and prevent post-treatment sequelae

Compassionate use of new drugs in children and adolescents with multidrug-resistant and extensively drug-resistant tuberculosis: early experiences and challenges

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SARS-CoV-2 Infection in Multiple Sclerosis

To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal diseas

Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement.

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) substantially challenges TB control, especially in the European Region of the World Health Organization, where the highest prevalence of MDR/XDR cases is reported. The current management of patients with MDR/XDR-TB is extremely complex for medical, social and public health systems. The treatment with currently available anti-TB therapies to achieve relapse-free cure is long and undermined by a high frequency of adverse drug events, suboptimal treatment adherence, high costs and low treatment success rates. Availability of optimal management for patients with MDR/XDR-TB is limited even in the European Region. In the absence of a preventive vaccine, more effective diagnostic tools and novel therapeutic interventions the control of MDR/XDR-TB will be extremely difficult. Despite recent scientific advances in MDR/XDR-TB care, decisions for the management of patients with MDR/XDR-TB and their contacts often rely on expert opinions, rather than on clinical evidence. This document summarises the current knowledge on the prevention, diagnosis and treatment of adults and children with MDR/XDR-TB and their contacts, and provides expert consensus recommendations on questions where scientific evidence is still lacking

Treatment of drug-susceptible and drug-resistant tuberculosis

The treatment of TB, both drug-susceptible and drug-resistant forms, should be based on two principles: 1) the combination of drugs (at least four) to avoid selection pressure resulting in the emergence of DR-TB strains and 2) the need for prolonged treatment in order to sterilise all infectious sites and thus cure the patient and prevent relapses. The selection of drugs should be based on their bactericidal and sterilising properties, their ability to prevent drug resistance and their safety profile. Based on these principles, and on the mode of action of the different drugs, this chapter describes in detail anti-TB treatment, the most appropriate choice of drugs based on in vitro susceptibility testing, starting withdrug-susceptible TB (DS-TB), and a proposal to standardise as much as possible the difficult-to-manage patients with DR-TB. The chapter delineates the recommended treatment for DS-TB, mono- and polyresistant TB, MDR-TB, XDR-TB and forms of TB beyond XDR-TB. Special attention is given to the 2018 WHO guidelines regarding the revised grouping of second-line TB drugs recommended for use in longer MDR-TB regimens, the shorter MDR-TB regimens, the possibility of designing a standardised pre-XDR and XDR-TB regimen adapted to the country, and some relevant management issues

Treatment of drug-susceptible and drug-resistant tuberculosis

The treatment of TB, both drug-susceptible and drug-resistant forms, should be based on two principles: 1) the combination of drugs (at least four) to avoid selection pressure resulting in the emergence of DR-TB strains and 2) the need for prolonged treatment in order to sterilise all infectious sites and thus cure the patient and prevent relapses. The selection of drugs should be based on their bactericidal and sterilising properties, their ability to prevent drug resistance and their safety profile. Based on these principles, and on the mode of action of the different drugs, this chapter describes in detail anti-TB treatment, the most appropriate choice of drugs based on in vitro susceptibility testing, starting with drug-susceptible TB (DS-TB), and a proposal to standardise as much as possible the difficult-to-manage patients with DR-TB. The chapter delineates the recommended treatment for DS-TB, mono- and polyresistant TB, MDR-TB, XDR-TB and forms of TB beyond XDR-TB. Special attention is given to the 2018 WHO guidelines regarding the revised grouping of second-line TB drugs recommended for use in longer MDR-TB regimens, the shorter MDR-TB regimens, the possibility of designing a standardised pre-XDR and XDR-TB regimen adapted to the country, and some relevant management issues

Classifying new anti-tuberculosis drugs: rationale and future perspectives

The classification of anti-tuberculosis (TB) drugs is important as it helps the clinician to build an appropriate anti-TB regimen for multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases that do not fulfil the criteria for the shorter MDR-TB regimen. The World Health Organization (WHO) has recently approved a revision of the classification of new anti-TB drugs based on current evidence on each drug. In the previous WHO guidelines, the choice of drugs was based on efficacy and toxicity in a step-down manner, from group 1 first-line drugs and groups 2–5 second-line drugs, to group 5 drugs with potentially limited efficacy or limited clinical evidence. In the revised WHO classification, exclusively aimed at managing drug-resistant cases, medicines are again listed in hierarchical order from group A to group D. In parallel, a possible future classification is independently proposed. The aim of this viewpoint article is to describe the evolution in WHO TB classification (taking into account an independently proposed new classification) and recent changes in WHO guidance, while commenting on the differences between them. The latest evidence on the ex-group 5 drugs is also discussed