WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

A combined individual and group-based stabilization and skill training intervention versus treatment as usual for patients with long lasting posttraumatic reactions receiving outpatient treatment in specialized mental health care - a study protocol for a randomized controlled trial.

BACKGROUND: Suffering linked to previous interpersonal trauma is common among patients in mental health care. Diagnostic labels may vary, but the clinical picture is often characterized by long-lasting and complex psychological and somatic symptoms, subjective distress and reduced quality of health and life. A substantial proportion of patients do not recover after individual treatment in ordinary specialized mental healthcare settings, despite the proven usefulness of individual trauma-specific treatments. The therapeutic factors that arise in group settings, such as normalization, shame reduction and corrective relational experiences, may be particularly useful for trauma survivors. However, evidence in support of group treatment for trauma survivors is scarce. This study aims to test whether combining a novel group intervention to individual treatment is superior to conventional individual out-patient treatment in an ordinary community mental health hospital. METHODS: In a single-site, non-blinded, randomized controlled trial (RCT), the effect of a combined group-based stabilization and skill-training (SST) intervention added to individual treatment will be compared to conventional treatment (treatment as usual, TAU) alone. Participants (N = 160) with ongoing and long-lasting reactions related to known adverse life events from the past will be recruited among patients at general outpatient clinics in a community mental health centre at St. Olav's University Hospital, Trondheim, Norway. Following baseline assessment and randomization, participants will complete follow-up measures at 4, 8, 13 and 19 months post-baseline. The primary outcome is personal recovery (The questionnaire about the process of recovery , QPR). Secondary outcomes include (1) self-reported symptoms of posttraumatic stress, general mental and somatic health symptoms, well-being, functional impairment and client satisfaction, (2) immunological and endocrine response measured in blood samples and (3) national registry data on occupational status, use of mental health services and pharmacological treatment. Additionally, mechanisms of change via posttraumatic cognitions will be examined. DISCUSSION: The addition of a group-based intervention to individual treatment for trauma survivors might prove to be an efficient way to meet the need of long-lasting high-intensity treatment in a large group of patients in mental health care, thereby reducing their suffering and increasing their psychosocial functioning. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03887559. Registered on 25 March 2019.

TLR9 gene region polymorphisms and susceptibility to tuberculosis in Vietnam.

Humans exposed to Mycobacterium tuberculosis (Mtb) show variation in susceptibility to infection and differences in tuberculosis (TB) disease outcome. Toll-like receptor 9 (TLR9) is a pattern recognition receptor that mediates recognition of Mtb and modulates Mtb-specific T-cell responses. Using a case-population design, we evaluated whether single nucleotide polymorphisms (SNPs) in the TLR9 gene region are associated with susceptibility to pulmonary or meningeal TB as well as neurologic presentation and mortality in the meningeal TB group. In a discovery cohort (n = 352 cases, 382 controls), three SNPs were associated with TB (all forms, p < 0.05) while three additional SNPs neared significance (0.05 < p < 0.1). When these six SNPs were evaluated in a validation cohort (n = 339 cases, 367 controls), one was significant (rs352142) while another neared significance (rs352143). When the cohorts were combined, rs352142 was most strongly associated with meningeal tuberculosis (dominant model; p = 0.0002, OR 2.36, CI 1.43-3.87) while rs352143 was associated with pulmonary tuberculosis (recessive model; p = 0.006, OR 5.3, CI 1.26-31.13). None of the SNPs were associated with mortality. This is the first demonstration of an association between a TLR9 gene region SNP and tuberculous meningitis. In addition, this extends previous findings that support associations of TLR9 SNPs with pulmonary tuberculosis.

Impact of smear microscopy results and observed therapy on tuberculosis treatment in Mombasa, Kenya.

SETTING: Tuberculosis (TB) treatment center at Coast Provincial General Hospital in Mombasa, Kenya. OBJECTIVES: To describe TB management practices in a facility in coastal Kenya and identify factors associated with poor treatment outcomes. DESIGN: Retrospective review of patient treatment records from January 2008 to June 2009. Treatment outcomes of patients were classified as treatment success (cure or treatment completion) or poor treatment outcome (treatment failure, death or default). Relative risk regression was used to determine the association between exposures of interest and poor treatment outcomes. RESULTS: Records were obtained from a total of 183 patients: 142 (78%) had pulmonary TB, 68 (37%) were human immunodeficiency virus (HIV) infected and 81 (44%) had acid-fast bacilli (AFB) positive smear micros- copy. Most treated individuals (86%) achieved a successful treatment outcome as defined by the World Health Organization. Of those with poor treatment outcomes, 64% defaulted, 32% died, and 4% failed treatment. Initial negative AFB smear and HIV co-infection were associated with poor treatment outcomes (RR 3.32, 95%CI 1.22-8.99 and RR 4.61, 95%CI 1.69- 12.59, respectively). CONCLUSION: Strategies to accelerate accurate diagnosis of smear-negative TB and increase patient retention during treatment, especially in HIV co-infected individuals, are needed to reduce poor treatment outcomes in Kenya.

Salivary testosterone determination in studies of child health and development.

Measurement of hormones in children's saliva has excited interest because of numerous potential applications in developmental studies. Although assays of children's saliva for some hormones (e.g., cortisol) are widely available and used, the availability and use of assays of children's saliva testosterone is restricted. By adapting a commercially available serum testosterone kit, our laboratory has developed a reliable, efficient, and highly sensitive procedure for measuring testosterone in children's saliva that does not require separation or extraction. The minimum detection limit was 0.8 pg/mL. Intraassay coefficients of variation (CV) were between 3.66 and 6. 78% at concentrations 9.25 to 86.41 pg/mL, and interassay CVs were between 5.70 and 6.61% at concentrations of 7.3 to 118.51 pg/mL. The standard curve was highly reproducible (M slope = -0.70 and Mr = 0. 99). Method accuracy, determined by spike recovery, and linearity, determined by serial dilution, were 99.20 and 92.80%, respectively. Values from matched serum and saliva samples showed strong linear relationships. The assay captured near 99.09% of the range of individual differences in boys' (N = 90) and girls' (N = 85), ages 8-12, am and pm salivary testosterone levels. This assay can be easily applied to the investigation of testosterone-behavior relations in the context of studies on child health and development. It may help many child development researchers improve or expand their research activities.