5 research outputs found
The Prospective Dutch Colorectal Cancer (PLCRC) cohort: real-world data facilitating research and clinical care
Real-world data (RWD) sources are important to advance clinical oncology research and evaluate treatments in daily practice. Since 2013, the Prospective Dutch Colorectal Cancer (PLCRC) cohort, linked to the Netherlands Cancer Registry, serves as an infrastructure for scientific research collecting additional patient-reported outcomes (PRO) and biospecimens. Here we report on cohort developments and investigate to what extent PLCRC reflects the “real-world”. Clinical and demographic characteristics of PLCRC participants were compared with the general Dutch CRC population (n = 74,692, Dutch-ref). To study representativeness, standardized differences between PLCRC and Dutch-ref were calculated, and logistic regression models were evaluated on their ability to distinguish cohort participants from the Dutch-ref (AU-ROC 0.5 = preferred, implying participation independent of patient characteristics). Stratified analyses by stage and time-period (2013–2016 and 2017–Aug 2019) were performed to study the evolution towards RWD. In August 2019, 5744 patients were enrolled. Enrollment increased steeply, from 129 participants (1 hospital) in 2013 to 2136 (50 of 75 Dutch hospitals) in 2018. Low AU-ROC (0.65, 95% CI: 0.64–0.65) indicates limited ability to distinguish cohort participants from the Dutch-ref. Characteristics that remained imbalanced in the period 2017–Aug’19 compared with the Dutch-ref were age (65.0 years in PLCRC, 69.3 in the Dutch-ref) and tumor stage (40% stage-III in PLCRC, 30% in the Dutch-ref). PLCRC approaches to represent the Dutch CRC population and will ultimately meet the current demand for high-quality RWD. Efforts are ongoing to improve multidisciplinary recruitment which will further enhance PLCRC’s representativeness and its contribution to a learning healthcare system
Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal.
Abstract
Background—The extent to which mortality differs following individual acquired
immunodeficiency syndrome (AIDS)–defining events (ADEs) has not been assessed among
patients initiating combination antiretroviral therapy.
Methods—We analyzed data from 31,620 patients with no prior ADEs who started combination
antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard
ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for
sex, HIV transmission group, number of anti-retroviral drugs initiated, regimen, age, date of
starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation
of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together
to form a “rare ADEs” category.
Results—During a median follow-up period of 43 months (interquartile range, 19–70 months),
2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were
esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and
Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-
Hodgkin’s lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84–22.35) and progressive
multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70–14.92). Three
groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped
confidence intervals: severe (non-Hodgkin’s lymphoma and progressive multifocal
leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55–9.48]), moderate
(cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium
avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76–3.13]), and
mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08–2.00]).
Conclusions—In the combination antiretroviral therapy era, mortality rates subsequent to an
ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in
clinical end point trials, prognostic studies, and patient management
Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal
Abstract
Background—The extent to which mortality differs following individual acquired
immunodeficiency syndrome (AIDS)–defining events (ADEs) has not been assessed among
patients initiating combination antiretroviral therapy.
Methods—We analyzed data from 31,620 patients with no prior ADEs who started combination
antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard
ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for
sex, HIV transmission group, number of anti-retroviral drugs initiated, regimen, age, date of
starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation
of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together
to form a “rare ADEs” category.
Results—During a median follow-up period of 43 months (interquartile range, 19–70 months),
2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were
esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and
Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-
Hodgkin’s lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84–22.35) and progressive
multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70–14.92). Three
groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped
confidence intervals: severe (non-Hodgkin’s lymphoma and progressive multifocal
leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55–9.48]), moderate
(cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium
avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76–3.13]), and
mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08–2.00]).
Conclusions—In the combination antiretroviral therapy era, mortality rates subsequent to an
ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in
clinical end point trials, prognostic studies, and patient management