jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB. Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampinresistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided. Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.
Background The study objective was to conduct a systematic review and meta-analysis on the proportion of asymptomatic infection among coronavirus disease 2019 (COVID-19) positive persons and their transmission potential. Methods We searched Embase, Medline, bioRxiv, and medRxiv up to 22 June 2020. We included cohorts or cross-sectional studies which systematically tested populations regardless of symptoms for COVID-19, or case series of any size reporting contact investigations of asymptomatic index patients. Two reviewers independently extracted data and assessed quality using pre-specified criteria. Only moderate/high quality studies were included. The main outcomes were proportion of asymptomatic infection among COVID-19 positive persons at testing and through follow-up, and secondary attack rate among close contacts of asymptomatic index patients. A qualitative synthesis was performed. Where appropriate, data were pooled using random effects meta-analysis to estimate proportions and 95% confidence intervals (95% CI). Results Of 6,137 identified studies, 71 underwent quality assessment after full text review, and 28 were high/moderate quality and were included. In two general population studies, the proportion of asymptomatic COVID-19 infection at time of testing was 20% and 75%, respectively; among three studies in contacts it was 8.2% to 50%. In meta-analysis, the proportion (95% CI) of asymptomatic COVID-19 infection in obstetric patients was 95% (45% to 100%) of which 59% (49% to 68%) remained asymptomatic through follow-up; among nursing home residents, the proportion was 54% (42% to 65%) of which 28% (13% to 50%) remained asymptomatic through follow-up. Transmission studies were too heterogenous to meta-analyse. Among five transmission studies, 18 of 96 (18.8%) close contacts exposed to asymptomatic index patients were COVID-19 positive. Conclusions Despite study heterogeneity, the proportion of asymptomatic infection among COVID-19 positive persons appears high and transmission potential seems substantial. To further our understanding, high quality studies in representative general population samples are required.
For children with or without primary nonsevere reflux, prophylaxis does not reduce the rate of recurrent febrile urinary tract infections after the first episode.
BACKGROUNDTo evaluate the effect of chemotherapy on humoral immunity to vaccine‐preventable disease, the authors investigated the persistence of protective antibody titers in a group of patients who were alive and well after they were treated for pediatric malignancies.METHODSSerum antibody levels were evaluated for polio, tetanus, hepatitis B, rubella, mumps, and measles in 192 children. The terms lack of immunity and loss of immunity, respectively, were used to describe the absence of immunity in patients who were tested only after chemotherapy and in patients who were tested both before and after chemotherapy and determined to have immunity before chemotherapy.RESULTSOverall, the absence of a protective serum antibody titer for hepatitis B, measles, mumps, rubella, tetanus, and polio was detected in 46%, 25%, 26%, 24%, 14%, and 7% of patients, respectively. On univariate analysis, loss of antibodies against rubella, mumps, and tetanus was associated significantly with younger age (P < 0.001, P = 0.02, and P = 0.001, respectively), and loss of antibodies against measles was significantly associated with younger age and female gender (P = 0.0003 and P = 0.008, respectively). The administration of 59 booster vaccinations to 51 patients who had lost ≥ 1 protective antibody titer resulted in an overall response rate of 93%.CONCLUSIONSChemotherapy induced different rates of loss of protective antibody titers depending on the type of vaccination administered. This finding may be responsible for the failure of vaccination programs for patients who have undergone chemotherapy. The administration of a booster dose after the completion of chemotherapy is a simple and cost‐effective way to restore humoral immunity against most vaccine‐preventable diseases. Cancer 2004. © 2004 American Cancer Society.
Among children under the age of 18 years, treatment with 4 months of rifampin had similar rates of safety and efficacy but a better rate of adherence than 9 months of treatment with isoniazid. (Funded by the Canadian Institutes of Health Research and Conselho Nacional de Pesquisa; ClinicalTrials.gov number, NCT00170209 .).
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