4%; with no difference between two positive (250/1555; 16.1%) and one positive (159/945; 16.8%; p 0.3) index blood culture. The number of positive index blood cultures was not associated with 30-day case-fatality after adjustment for confounding variables using logistic regression analysis.
 
  Although approximately one-third of BSI are diagnosed on the basis of a single positive blood culture and are associated with different clinical determinants, whether one or both index blood cultures are positive is not associated with lethal outcome.
 Although approximately one-third of BSI are diagnosed on the basis of a single positive blood culture and are associated with different clinical determinants, whether one or both index blood cultures are positive is not associated with lethal outcome.
  We assessed the prognostic value of phase I IgG titres during treatment and follow-up of chronic Q fever.
 
  We performed a retrospective cohort study to analyse the course of phase I IgG titres in chronic Q fever.  https://www.selleckchem.com/products/mpi-0479605.html  We used a multivariable time-varying Cox regression to assess our primary (first disease-related event) and secondary (therapy failure) outcomes. In a second analysis, we evaluated serological characteristics after 1year of therapy (fourfold decrease in phase I IgG titre, absence of phase II IgM and reaching phase I IgG titre of ≤11024) with multivariable Cox regression.
 
  In total, 337 patients that were treated for proven (n=284, 84.3%) or probable (n=53, 15.7%) chronic Q fever were included. Complications occurred in 190 (56.4%), disease-related mortality in 71 (21.1%) and therapy failure in 142 (42.1%) patients. The course of phase I IgG titres was not associated with first disease-related event (HR 1.00, 95% CI 0.86-1.15) or therapy failure (HR 1.02, 95% CI 0.91-1.15). Similar results were found for the serological characteristics for the primary (HR 0.97, 95% CI 0.62-1.51; HR 1.12, 95% CI 0.66-1.90; HR 0.99, 95% CI 0.57-1.69, respectively) and secondary outcomes (HR 0.86, 95% CI 0.57-1.29; HR 1.37, 95% CI 0.86-2.18; HR 0.80, 95% CI 0.48-1.34, respectively).
 
  Coxiella burnetii serology does not reliably predict disease-related events or therapy failure during treatment and follow-up of chronic Q fever. Alternative markers for disease management are needed, but, for now, management should be based on clinical factors, PCR results, and imaging results.
 Coxiella burnetii serology does not reliably predict disease-related events or therapy failure during treatment and follow-up of chronic Q fever. Alternative markers for disease management are needed, but, for now, management should be based on clinical factors, PCR results, and imaging results.
  A growing amount of evidence suggests that the rifampicin dosing currently recommended for tuberculosis treatment could be associated with inadequate exposure and unfavourable outcomes. We aimed to compare clinical and microbiological efficacy and safety outcomes of standard and higher rifampicin dosing.
 
  Data sources were MEDLINE, Google Scholar and the Cochrane Library. This was a systematic review and meta-analysis that included experimental or observational studies comparing 8-week sputum culture conversion, treatment failure, or safety outcomes in naïve patients with pulmonary tuberculosis treated with standard (10 mg/kg) or higher doses of rifampicin.
 
  Of a total of 9683 citations screened, eight randomized controlled trials were included, accounting for 1897 subjects; the risk of bias was low in three studies, high in two and intermediate in three. At week 8 a higher proportion of patients in the high-dose group obtained a sputum culture conversion than those in the standard dose group (83.7% versuat 8 weeks of treatment, particularly in patients receiving ≥20 mg/kg.
  Genotyping of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been instrumental in monitoring viral evolution and transmission during the pandemic. The quality of the sequence data obtained from these genotyping efforts depends on several factors, including the quantity/integrity of the input material, the technology, and laboratory-specific implementation. The current lack of guidelines for SARS-CoV-2 genotyping leads to inclusion of error-containing genome sequences in genomic epidemiology studies. We aimed to establish clear and broadly applicable recommendations for reliable virus genotyping.
 
  We established and used a sequencing data analysis workflow that reliably identifies and removes technical artefacts; such artefacts can result in miscalls when using alternative pipelines to process clinical samples and synthetic viral genomes with an amplicon-based genotyping approach. We evaluated the impact of experimental factors, including viral load and sequencing depth, on correct sequence determination.
 
  We found that at least 1000 viral genomes are necessary to confidently detect variants in the SARS-CoV-2 genome at frequencies of ≥10%. The broad applicability of our recommendations was validated in over 200 clinical samples from six independent laboratories. The genotypes we determined for clinical isolates with sufficient quality cluster by sampling location and period. Our analysis also supports the rise in frequencies of 20A.EU1 and 20A.EU2, two recently reported European strains whose dissemination was facilitated by travel during the summer of 2020.
 
  We present much-needed recommendations for the reliable determination of SARS-CoV-2 genome sequences and demonstrate their broad applicability in a large cohort of clinical samples.
 We present much-needed recommendations for the reliable determination of SARS-CoV-2 genome sequences and demonstrate their broad applicability in a large cohort of clinical samples.
  Observational studies may provide valuable evidence on real-world causal effects of drug effectiveness in patients with coronavirus disease 2019 (COVID-19). As patients are usually observed from hospital admission to discharge and drug initiation starts during hospitalization, advanced statistical methods are needed to account for time-dependent drug exposure, confounding and competing events. Our objective is to evaluate the observational studies on the three common methodological pitfalls in time-to-event analyses immortal time bias, confounding bias and competing risk bias.
 
  We performed a systematic literature search on 23 October 2020, in the PubMed database to identify observational cohort studies that evaluated drug effectiveness in hospitalized patients with COVID-19. We included articles published in four journals British Medical Journal, New England Journal of Medicine, Journal of the American Medical Association and The Lancet as well as their sub-journals.
 
  Overall, out of 255 articles screened, 11 observational cohort studies on treatment effectiveness with drug exposure-outcome associations were evaluated.