Left-censored recurrent event analysis in epidemiological studies: a proposal for when the number of previous episodes is unknown

Background When dealing with recurrent events in observational studies it is common to include subjects who became at risk before follow-up. This phenomenon is known as left censoring, and simply ignoring these prior episodes can lead to biased and inefficient estimates. We aimed to propose a statistical method that performs well in this setting. Methods Our proposal was based on the use of models with specific baseline hazards. In this, the number of prior episodes were imputed when unknown and stratified according to whether the subject had been at risk of presenting the event before t = 0. A frailty term was also used. Two formulations were used for this “Specific Hazard Frailty Model Imputed” based on the “counting process” and “gap time.” Performance was then examined in different scenarios through a comprehensive simulation study. Results The proposed method performed well even when the percentage of subjects at risk before follow-up was very high. Biases were often below 10% and coverages were around 95%, being somewhat conservative. The gap time approach performed better with constant baseline hazards, whereas the counting process performed better with non-constant baseline hazards. Conclusions The use of common baseline methods is not advised when knowledge of prior episodes experienced by a participant is lacking. The approach in this study performed acceptably in most scenarios in which it was evaluated and should be considered an alternative in this context. It has been made freely available to interested researchers as R package miRecSurv.

Levels of hepatitis B antibody titers are affected by age and doses gap time in children from a high endemic area of the western Amazon

Background Despite completion of the vaccine schedule for hepatitis B virus (HBV), children may display levels of HBV surface antibodies (anti-HBs) that are considered inadequate for sufficient protection (<10 IU/L). Aims Our aim was to investigate if age and gap time between HBV vaccine doses may negatively affect the levels of anti-HBs in children, and if these relationships are modified by sex. Methods In a high-endemic HBV region of the western Brazilian Amazon we enrolled children who had completed the HBV vaccine schedule. All children underwent analysis of anti-HBs and a clinical examination. Results We included 522 children (mean age 4.3 ± 0.8 years; 50% male). Median anti-HBs was 28.4 [interquartile range (IQR) 5.4 to 128.6] IU/L and 32% had anti-HBs <10 IU/L. The median gap time from last to preceding dose was 2.4 [IQR 2.1 to 3.3] months. Levels of anti-HBs decreased with higher age (-42% per year increase [95%CI -56% to -24%], p<0.001), but not with longer gap time (+23% per month increase [95%CI -16% to +62%], p = 0.249). After adjusting for relevant confounders, gap time became significant (p = 0.032) and age remained a significant predictor of anti-HBs (p<0.001). Conclusion One third of assessed children displayed anti-HBs <10 IU/L. Levels of anti-HBs decreased with higher age and increased with longer gap time between the last two doses.

Stop Sign Gap Assist Application in a Connected Vehicle Simulation Environment

Assessment of the safety and mobility impacts of connected vehicles (CVs) and cooperative automated vehicle applications is critical to the success of these applications. In many cases, there may be trade-offs in the mobility and safety impacts depending on the setting of the parameters of the applications. This study developed a method to evaluate the safety and mobility benefits of the Stop Sign Gap Assist (SSGA) system, a CV-based application at unsignalized intersections, which utilizes a calibrated microscopic simulation tool. The study results confirmed that it was critical to calibrate the drivers’ gap acceptance probability distributions in the utilized simulation model to reflect real-world driver behaviors when assessing SSGA impacts. The simulation models with the calibrated gap parameters were then used to assess the impacts of the SSGA. The results showed that SSGA can potentially improve overall minor approach capacity at unsignalized intersections by approximately 35.5% when SSGA utilization reaches 100%. However, this increase in capacity depended on the setting of the minimum gap time in the SSGA and there was a clear trade-off between capacity and safety. The analysis indicated that as the minimum gap time used in the SSGA increased, the safety of the intersection increased, showing for example that with the utilization of an 8-s gap at a 750 vph main street flow rate, the number of conflicts could decrease by 30% as the SSGA utilization rate increased from 0% to 100%.

Everything counts - a method to determine viral suppression among people living with HIV using longitudinal data for the HIV care continuum - results of two large, German, multi-center real-life cohort studies over 20 years (1999–2018)

Background The aim of this study was to develop a standardized method to reconstruct persons’ individual viral load (VL) courses to determine viral suppression and duration of viremia for the HIV care continuum in Germany using longitudinal cohort data. Methods We analyzed data from two large, multi-center German cohort studies under the direction of the Robert Koch Institute. We included data from 1999 to 2018 of all diagnosed people and of people who initiated antiretroviral treatment (ART). We developed a model generating virtual VL values and an individual VL course corresponding to real VL measurements with a maximum distance of 180 days, considering ART status and VL dynamics. If the distance between VL measurements was > 180 days, the time between was defined as gap time. Additionally, we considered blips, which we defined as a single detectable VL < 1000 copies/ml within 180 days. Results A total of 22,120 people (164,691 person-years, PY) after ART initiation were included in the analyses. The proportion of people with viral suppression (VL < 50 copies/ml) increased from 34% in 1999 to 93% in 2018. The proportion of people with VL < 200 copies/ml increased from 47% in 1999 to 96% in 2018. The proportion of people with viremia > 1000 copies/ml decreased from 37% in 1999 to 3% in 2018. The proportion of people with gap time fluctuated and ranged between 18 and 28%. An analysis of the first VL after gap time showed that 90% showed viral suppression, 5% VL between 50- < 1000 copies/ml and 5% VL > 1000 copies/ml. Conclusion We provide a method for estimating viral suppression and duration of viremia using longitudinal VL data. We observed a continuous and remarkable increase of viral suppression. Furthermore, a notable proportion of those with viremia showed low-level viremia and were therefore unlikely to transmit HIV. Individual health risks and HIV drug resistance among those with low-level viremia are problematic, and viral suppression remains the goal. In 2018, 93 and 96% of people after ART initiation showed VL < 50 copies/ml and VL < 200 copies/ml, respectively. Therefore, using the threshold of VL < 200 copies/ml, Germany reached the UNAIDS 95 target of viral suppression since 2017.

Comparing the Importance of the Factors on Drivers’ Response Time to Lead Vehicle’s Braking

During car-following, drivers respond to the braking or deceleration of a leading vehicle based on their perceived threshold for gap, relative speed, change of the gap, time-to-collision, etc. These measures are widely used to estimate drivers’ response time to the braking of a vehicle ahead. However, it is not clear if their response is driven only by absolute thresholds or also through a comparison of the current situation with any baseline situation to which they have just been exposed. This research explored drivers’ braking response to a lead vehicle’s braking using naturalistic driving data. Two hundred and ninety-six braking events were analyzed. It was found that measures adjusted from a baseline (when the lead vehicle’s brake lights were illuminated) were more important for estimating drivers’ response time than the measures on the absolute thresholds. Predictors adjusted according to the baselines are suggested for better prediction of drivers’ response time.

Everything Counts -- A Method to Determine Viral Suppression Among People Living With Hiv Using Longitudinal Data for the Hiv Care Continuum. - Results of two large, German, multi-center real-life cohort studies over 20 years (1999-2018)

BackgroundThe aim of this study was to develop a standardized method to reconstruct persons' individual VL courses to determine viral suppression and duration of viremia for the HIV care continuum in Germany using longitudinal cohort data.MethodsWe analyzed data from two large, multi-center German cohort studies under the direction of the Robert Koch Institute. We included data from 1999-2018 of all diagnosed people and of people who initiated antiretroviral treatment (ART). We developed a model generating virtual VL values and an individual VL course corresponding to real VL measurements with a maximum distance of 180 days, considering ART status and VL dynamics. If the distance between VL measurements was >180 days, the time between was defined as gap time. Additionally, we considered blips, which we defined as a single detectable VL <1,000 copies/ml within 180 days.ResultsA total of 22,120 people (164,691 person-years, PY) after ART initiation were included in the analyses. The proportion of people with viral suppression (VL <50 copies/ml) increased from 34% in 1999 to 93% in 2018. The proportion of people with VL <200 copies/ml increased from 47% in 1999 to 96% in 2018. The proportion of people with viremia >1,000 copies/ml decreased from 37% in 1999 to 3% in 2018. The proportion of people with gap time fluctuated and ranged between 18% and 28%. An analysis of the first VL after gap time showed that 90% showed viral suppression, 5% VL between 50-<1,000 copies/ml and 5% VL >1,000 copies/ml.ConclusionWe provide a method for estimating viral suppression and duration of viremia using longitudinal VL data. We observed a continuous and remarkable increase of viral suppression. Furthermore, a notable proportion of those with viremia showed low-level viremia and were therefore unlikely to transmit HIV. Individual health risks and HIV drug resistance among those with low-level viremia are problematic, and viral suppression remains the goal. In 2018, 93% and 96% of people after ART initiation showed VL <50 copies/ml and VL <200 copies/ml, respectively. Therefore, using the threshold of VL <200 copies/ml, Germany reached the UNAIDS 95 target of viral suppression since 2017.

Everything Counts -- A Method To Determine Viral Suppression Among People Living With Hiv Using Longitudinal Data For The Hiv Care Continuum. - Results Of Two Large, German, Multi-Center Real-Life Cohort Studies Over 20 Years (1999-2018)

Background The aim of this study was to develop a standardized method to reconstruct persons' individual VL courses to determine viral suppression and duration of viremia for the HIV care continuum in Germany using data longitudinal cohort data. Methods We analyzed data from two large, multi-center German cohort studies under the direction of the Robert Koch Institute. We included data from 1998 to 2018 of all diagnosed people and of people who initiated antiretroviral treatment (ART). We developed a model generating virtual VL points and an individual VL course corresponding to real VL measurements with a maximum distance of 180 days, considering ART status and VL dynamics. If the distance between VL measurements was > 180 days, the time between was defined as gap-time. Additionally, we considered blips, which we defined as a single detectable VL < 1,000 copies/ml within 180 days. Results A total of 22,120 people (164,691 person-years, PY) after ART initiation were included in the analyses. The proportion of people with viral suppression (VL < 50 copies/ml) increased from 34% in 1999 to 93% in 2018. The proportion of people with VL < 200 copies/ml increased from 47% in 1999 to 96% in 2018. The proportion of people with viremia > 1,000 copies/ml decreased from 37% in 1999 to 3% in 2018. The proportion of people with gap-time fluctuated and ranged between 18% and 28%. An analysis of the first VL after gap-time showed that 90% showed viral suppression, 5% VL between 50-<1,000 copies/ml and 5% VL > 1,000 copies/ml. Conclusion We provide a method for estimating viral suppression and duration of viremia using longitudinal VL data. We observed a continuous and remarkable increase of viral suppression. Furthermore, a notable proportion of those with viremia showed low-level viremia and were therefore unlikely to transmit HIV. Individual health risks and HIV drug resistance among those with low-level viremia are problematic, and viral suppression remains the goal. In 2018, 93% and 96% of people after ART initiation showed VL < 50 copies/ml and VL < 200 copies/ml, respectively. Therefore, using the threshold of VL < 200 copies/ml, Germany reached the UNAIDS 95 target of viral suppression since 2017.