Knowledge and attitudes towards ambulatory treatment of tuberculоsis in Kazakhstan

Background Ambulatory based treatment of tuberculosis has been recently introduced in Kazakhstan. We sought to assess the attitudes of the general population, TB patients and their household members towards ambulatory TB treatment and identify how knowledge of TB is associated with these attitudes. Methods New pulmonary TB cases and their household and community controls were recruited from three regions of Kazakhstan in 2012–2014. 1083 participants completed audio computer-assisted self interviews to assess their knowledge of TB and attitudes towards ambulatory care. Mixed effects logistic regression models were used to identify factors associated with attitudes toward ambulatory TB treatment. Results The proportion of people who considered ambulatory TB treatment as appropriate was very low (24.9%). Positive attitudes towards ambulatory TB treatment were significantly associated with region of residence, higher level of education, family support and experience with TB. The association between sufficient tuberculosis knowledge and favorable attitude toward ambulatory treatment was stronger among community controls compared to TB patients and their family members. Conclusions This study provides insight into attitudes toward ambulatory TB treatment among different groups and the specific influence of TB knowledge on these attitudes. Our findings can inform the process of integration of new TB treatment strategies and the development of appropriate education and advocacy programs in the general population

A Four-kallikrein Panel and β-Microseminoprotein in Predicting High-grade Prostate Cancer on Biopsy : An Independent Replication from the Finnish Section of the European Randomized Study of Screening for Prostate Cancer

Background: A panel of four kallikrein markers (total, free, and intact prostate-specific antigen [PSA] and human kallikrein-related peptidase 2 [hK2]) improves predictive accuracy for Gleason score ≥7 (high-grade) prostate cancer among men biopsied for elevated PSA. A four-kallikrein panel model was originally developed and validated by the Dutch center of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The kallikrein panel is now commercially available as 4Kscore™. Objective: To assess whether these findings could be replicated among participants in the Finnish section of ERSPC (FinRSPC) and whether β-microseminoprotein (MSP), a candidate prostate cancer biomarker, adds predictive value. Design, setting, and participants: Among 4861 biopsied screening-positive participants in the first three screening rounds of FinRSPC, a case-control subset was selected that included 1632 biopsy-positive cases matched by age at biopsy to biopsy-negative controls. Outcome measurements and statistical analysis: The predictive accuracy of prespecified prediction models was compared with biopsy outcomes. Results and limitations: Among men with PSA of 4.0-25. ng/ml, 1111 had prostate cancer, 318 of whom had high-grade disease. Total PSA and age predicted high-grade cancer with an area under the curve of 0.648 (95% confidence interval [CI] 0.614-0.681) and the four-kallikrein panel increased discrimination to 0.746 (95% CI 0.717-0.774). Adding MSP to the four-kallikrein panel led to a significant (Wald test; p = 0.015) but small increase (0.003) in discrimination. Limitations include a risk of verification bias among men with PSA of 3.0-3.99. ng/ml and the absence of digital rectal examination results. Conclusions: These findings provide additional evidence that kallikrein markers can be used to inform biopsy decision-making. Further studies are needed to define the role of MSP. Patient summary: Four kallikrein markers and β-microseminoprotein in blood improve discrimination of high-grade prostate cancer at biopsy in men with elevated prostate-specific antigen. Four kallikrein markers and β-microseminoprotein (MSP) in blood improve discrimination of high-grade cancer at biopsy in men with elevated prostate-specific antigen. These kallikrein markers can be used to inform biopsy decision-making. Further studies are needed to define the role of MSP

Guidelines for reporting of statistics for clinical research in urology

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148242/1/bju14640.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148242/2/bju14640_am.pd

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

The Brier score does not evaluate the clinical utility of diagnostic tests or prediction models

Abstract Background A variety of statistics have been proposed as tools to help investigators assess the value of diagnostic tests or prediction models. The Brier score has been recommended on the grounds that it is a proper scoring rule that is affected by both discrimination and calibration. However, the Brier score is prevalence dependent in such a way that the rank ordering of tests or models may inappropriately vary by prevalence. Methods We explored four common clinical scenarios: comparison of a highly accurate binary test with a continuous prediction model of moderate predictiveness; comparison of two binary tests where the importance of sensitivity versus specificity is inversely associated with prevalence; comparison of models and tests to default strategies of assuming that all or no patients are positive; and comparison of two models with miscalibration in opposite directions. Results In each case, we found that the Brier score gave an inappropriate rank ordering of the tests and models. Conversely, net benefit, a decision-analytic measure, gave results that always favored the preferable test or model. Conclusions Brier score does not evaluate clinical value of diagnostic tests or prediction models. We advocate, as an alternative, the use of decision-analytic measures such as net benefit. Trial registration Not applicable

Comparison Between the Four-kallikrein Panel and Prostate Health Index for Predicting Prostate Cancer.

The four-kallikrein panel and the Prostate Health Index (PHI) have been shown to improve prediction of prostate cancer (PCa) compared with prostate-specific antigen (PSA). No comparison of the four-kallikrein panel and PHI has been presented

Screening for Prostate Cancer Starting at Age 50-54 Years. A Population-based Cohort Study

Background: Current prostate cancer screening guidelines conflict with respect to the age at which to initiate screening. Objective: To evaluate the effect of prostate-specific antigen (PSA) screening versus zero screening, starting at age 50-54 yr, on prostate cancer mortality. Design, setting, and participants: This is a population-based cohort study comparing 3479 men aged 50 yr through 54 yr randomized to PSA-screening in the Göteborg population-based prostate cancer screening trial, initiated in 1995, versus 4060 unscreened men aged 51-55 yr providing cryopreserved blood in the population-based Malmö Preventive Project in the pre-PSA era, during 1982-1985. Outcome measurements and statistical analysis: Cumulative incidence and incidence rate ratios of prostate cancer diagnosis, metastasis, and prostate cancer death. Results and limitations: At 17 yr, regular PSA-screening in Göteborg of men in their early 50s carried a more than two-fold higher risk of prostate cancer diagnosis compared with the unscreened men in Malmö (incidence rate ratio [IRR] 2.56, 95% confidence interval [CI] 2.18, 3.02), but resulted in a substantial decrease in the risk of metastases (IRR 0.43, 95% CI 0.22, 0.79) and prostate cancer death (IRR 0.29, 95% CI 0.11, 0.67). There were 57 fewer prostate cancer deaths per 10. 000 men (95% CI 22, 92) in the screened group. At 17 yr, the number needed to invite to PSA-screening and the number needed to diagnose to prevent one prostate cancer death was 176 and 16, respectively. The study is limited by lack of treatment information and the comparison of the two different birth cohorts. Conclusions: PSA screening for prostate cancer can decrease prostate cancer mortality among men aged 50-54 yr, with the number needed to invite and number needed to detect to prevent one prostate cancer death comparable to those previously reported from the European Randomized Study of Screening for Prostate Cancer for men aged 55-69 yr, at a similar follow-up. Guideline groups could consider whether guidelines for PSA screening should recommend starting no later than at ages 50-54 yr. Patient summary: Guideline recommendations about the age to start prostate-specific antigen screening could be discussed. Guideline recommendations about the age to start prostate-specific antigen screening could be discussed

Association Between Lead Time and Prostate Cancer Grade : Evidence of Grade Progression from Long-term Follow-up of Large Population-based Cohorts Not Subject to Prostate-specific Antigen Screening

Background: Lead time (LT) is of key importance in early detection of cancer, but cannot be directly measured. We have previously provided LT estimates for prostate cancer (PCa) using archived blood samples from cohorts followed for many years without screening. Objective: To determine the association between LT and PCa grade at diagnosis to provide an insight into whether grade progresses or is stable over time. Design, setting, and participants: The setting was three long-term epidemiologic studies in Sweden including men not subject to prostate-specific antigen (PSA) screening. The cohort included 1041 men with PSA of 3–10 ng/ml at blood draw and subsequently diagnosed with PCa with grade data available. Outcome measurements and statistical analysis: Multivariable logistic regression was used to predict high-grade (Gleason grade group ≥2 or World Health Organization grade 3) versus low-grade PCa at diagnosis in terms of LT, defined as the time between the date of elevated PSA and the date of PCa diagnosis with adjustment for cohort and age. Results and limitations: The probability that PCa would be high grade at diagnosis increased with LT. Among all men combined, the risk of high-grade disease increased with LT (odds ratio 1.13, 95% confidence interval [CI] 1.10–1.16; p < 0.0001), with no evidence of differences in effect by age group or cohort. Higher PSA predicted shorter LT by 0.46 yr (95% CI 0.28–0.64; p < 0.0001) per 1 ng/ml increase in PSA. However, there was no interaction between PSA and grade, suggesting that the longer LT for high-grade tumors is not simply related to age. Limitations include the assumption that men with elevated PSA and subsequently diagnosed with PCa would have had biopsy-detectable PCa at the time of PSA elevation. Conclusions: Our data support grade progression, whereby following a prostate over time would reveal transitions from benign to low-grade and then high-grade PCa. Patient summary: Men with a longer lead time between elevated prostate-specific antigen and subsequent prostate cancer diagnosis were more likely to have high-grade cancers at diagnosis. The probability that a cancer will be of high grade at diagnosis increases with the lead time. Our findings provide evidence of grade progression, whereby a prostate followed over time would exhibit transitions from benign to low-grade to high-grade prostate cancer