RESUMO
BACKGROUND: Transmission of SARS-CoV-2 in health care facilities poses a challenge against pandemic control. Health care workers (HCWs) have frequent and high-risk interactions with COVID-19 patients. We undertook a cost-effectiveness analysis to determine optimal testing strategies for screening HCWs to inform strategic decision-making in health care settings. METHODS: We modeled the number of new infections, quality-adjusted life years lost, and net costs related to six testing strategies including no test. We applied our model to four strata of HCWs, defined by the presence and timing of symptoms. We conducted sensitivity analyses to account for uncertainty in inputs. RESULTS: When screening recently symptomatic HCWs, conducting only a PCR test is preferable; it saves costs and improves health outcomes in the first week post-symptom onset, and costs $83,000 per quality-adjusted life year gained in the second week post-symptom onset. When screening HCWs in the late clinical disease stage, none of the testing approaches is cost-effective and thus no testing is preferable, yielding $11 and 0.003 new infections per 10 HCWs. For screening asymptomatic HCWs, antigen testing is preferable to PCR testing due to its lower cost. CONCLUSIONS: Both PCR and antigen testing are beneficial strategies to identify infected HCWs and reduce transmission of SARS-CoV-2 in health care settings. IgG tests' value depends on test timing and immunity characteristics, however it is not cost-effective in a low prevalence setting. As the context of the pandemic evolves, our study provides insight to health-care decision makers to keep the health care workforce safe and transmissions low.
RESUMO
BACKGROUND: Transmission of SARS-CoV-2 in health care facilities poses a challenge against pandemic control. Health care workers (HCWs) have frequent and high-risk interactions with COVID-19 patients. We undertook a cost-effectiveness analysis to determine optimal testing strategies for screening HCWs to inform strategic decision-making in health care settings. METHODS: We modeled the number of new infections, quality-adjusted life years lost, and net costs related to six testing strategies including no tests. We applied our model to four strata of HCWs, defined by the presence and timing of symptoms. We conducted sensitivity analyses to account for uncertainty in inputs. RESULTS: When screening recently symptomatic HCWs, conducting only a PCR test is preferable; it saves costs and improves health outcomes in the first week post-symptom onset, and costs $83,000 per quality-adjusted life year gained in the second week post-symptom onset. When screening HCWs in the late clinical disease stage, none of the testing approaches is cost-effective and thus no testing is preferable, yielding $11 and 0.003 new infections per 10 HCWs. For screening asymptomatic HCWs, antigen testing is preferable to PCR testing due to its lower cost. CONCLUSIONS: Both PCR and antigen testing are beneficial strategies to identify infected HCWs and reduce transmission of SARS-CoV-2 in health care settings. IgG testing clinical value depends on test timing and immunity characteristics, however is not cost-effective in a low prevalence setting. As the context of the pandemic evolves, our study provides insight to health-care decision makers to keep the health care workforce safe and transmissions low.
RESUMO
Aberrations in the components of cell-cycle checkpoints are a common feature of many tumours and several have been shown to have prognostic significance in colorectal cancer. In this study, seven components of cell-cycle control [cyclin D1, retinoblastoma (pRb), p21, p27, p16, p53, and proliferating cell nuclear antigen (PCNA)] were examined in a large series of well-characterized colorectal adenocarcinomas using immunohistochemistry to ascertain co-regulation and influence on survival. The majority (92%) of the tumours had abnormal staining of > or =2 cell-cycle control factors. Expression of cyclin D1 protein was correlated with both p21 (p<0.001) and p27 (p=0.033), suggesting co-regulation of these proteins in colorectal tumours. Only cyclin D1 (p=0.048) and p53 (p=0.025) were directly associated with PCNA levels, suggesting a more important role in the proliferative capacity of tumour cells. Significant associations between cell cycle-related proteins and clinicopathological data were observed: cyclin D1 and p53 proteins were correlated with patient age (p=0.042 and p<0.001, respectively) and p53 (p=0.01) and p21 (p=0.024) proteins were associated with tumour site. Expression of cyclin D1 protein was the only protein examined that was related to improved outcome in these patients (p=0.0266), but it was not an independent predictor of survival. These results suggest that loss of control of cell-cycle checkpoints is a common occurrence in colorectal tumours and may be an important therapeutic target.
