ABSTRACT
COVID-19 has a dramatic impact on human health, besides respiratory system, reproduction system would be impaired by SARS-CoV-2. For male, the virus has various negative impacts on testes, including overheating and hormone level fluctuation, which have impacts on the spermatogenesis or spermatogonia development. For female, COVID-19 may increase the risk of endocrine and metabolic dysfunction. However, the impact of SARS-CoV-2 on the ovaries is not clear, and further researches are needed to clarify it. Nearly 60% of the pregnant women develop symptoms of infection and more attention should be paid to the increased risk of adverse pregnancy outcomes including preeclampsia, eclampsia, and severe infection. For the newborns of infected pregnant women, vertical transmission of SARS-CoV-2 is still unclear, and further evaluation are required. Meantime, the pregnant women's fear of the potential infection may reduce their access to the prenatal genetic test. In this chapter, we summarize the latest basic and clinical researches on COVID-19 impacts on male, female reproduction, and prenatal genetic test, hoping to provide guidance and advice for people of reproductive age and reproductive healthcare practitioners. © 2023 Elsevier Inc. All rights reserved.
ABSTRACT
Facing the more contagious COVID-19 variant, Omicron, nonpharmaceutical interventions (NPIs) were still in place and booster doses were proposed to mitigate the epidemic. However, the uncertainty and stochasticity in individuals' behaviours toward the NPIs and booster dose increase, and how this randomness affects the transmission remains poorly understood. We present a model framework to incorporate demographic stochasticity and two kinds of environmental stochasticity (notably variations in adherence to NPIs and booster dose acceptance) to analyze the effects of different forms of stochasticity on transmission. The model is calibrated using the data from December 31, 2021, to March 8, 2022, on daily reported cases and hospitalizations, cumulative cases, deaths and vaccinations for booster doses in Toronto, Canada. An approximate Bayesian computational (ABC) method is used for calibration. We observe that demographic stochasticity could dramatically worsen the outbreak with more incidence compared with the results of the corresponding deterministic model. We found that large variations in adherence to NPIs increase infections. The randomness in booster dose acceptance will not affect the number of reported cases significantly and it is acceptable in the mitigation of COVID-19. The stochasticity in adherence to NPIs needs more attention compared to booster dose hesitancy. © 2023 American Institute of Mathematical Sciences. All rights reserved.
ABSTRACT
BACKGROUND: Among hospitalized US Veterans, the rate of non-ventilator associated hospital acquired pneumonia (NV-HAP) decreased between 2015 and 2020 then increased following the onset of 2019-nCoV (COVID-19). METHODS: Veterans admitted to inpatient acute care for ≥48 hours at 135 Department of Veterans Affairs Medical Centers between 2015 and 2021 were identified (n = 1,567,275). Non-linear trends in NV-HAP incidence were estimated using generalized additive modeling, adjusted for seasonality and patient risk factors. RESULTS: The incidence rate (IR) of NV-HAP decreased linearly by 32% (95% CI: 63-74) from 10/1/2015 to 2/1/2020, translating to 337 fewer NV-HAP cases. Following the US onset of the COVID-19 pandemic in February 2020, the NV-HAP IR increased by 25% (95% CI: 14-36) among Veterans without COVID-19 and 108% (95% CI: 178-245) among Veterans with COVID-19, resulting in an additional 50 NV-HAP cases and $5,042,900 in direct patient care costs 12-months post admission. DISCUSSION: This increase in NV-HAP rates could be driven by elevated risk among Veterans with COVID-19, decreased prevention measures during extreme COVID-19 related system stress, and increased patient acuity among hospitalized Veterans during the first year of the pandemic. CONCLUSIONS: Basic nursing preventive measures that are resilient to system stress are needed as well as population surveillance to rapidly identify changes in NV-HAP risk.
ABSTRACT
Many countries have adopted border closures and other jurisdictions (provinces, states, cities, etc.) to control the spread of SARS-CoV-2. Such measures have significantly restricted population movement and have thus led to immense economic and social fallouts. We build a Susceptible-Exposed-Asymptomatic- Infectious (prodromal phase)- Infectious (with symptoms) -Recovered (SEAIR) model with a household structure to investigate the potential of a safe reopening of a border, which can control disease spread but also allow for economic growth. We focus on the Ontario-USA border, considering an opening date of September 21, 2020. In addition to the instantaneous reproduction number, we also define a novel risk indicator by calculating daily new infections’ percentile to inform risk levels promptly. Under ideal conditions, assuming extremely efficient border testing and strict traveler adherence to quarantine policy, the Ontario-USA can be reopened for a maximum daily number of 500 travelers entering Canada. A number exceeding 500 will stem an uncontrollable spread of the virus. Additionally, the current quarantine policy may not be sufficient under specific scenarios;hence testing measures at the border must be extremely efficient. Reopening of the Ontario-USA must consider the potential for disease spread (which can overburden healthcare resources) and economic growth. If a reopening plan is implemented, the local government must limit the number of daily entrances to 500 and enforce a mandatory quarantine, which may need to be stricter than current policy practice. © 2022, Springer Nature Switzerland AG.
ABSTRACT
Background: Currently, there are no standard ≥3 line regimens recommended for HER2-positive (IHC 3+, or IHC 2+/FISH+) advanced or metastatic breast cancer, and no recommended HER2-targeting treatment for HER2-low expressing (IHC 2+/FISH-, or IHC 1+) population. RC48-ADC is an innovative HER2-targeting antibody-drug conjugate with a cleavable linker and a potent microtubule inhibitor payload MMAE that has a bystanding effect in tumor cell killing. Methods: C001 CANCER (NCT02881138) was a dose-escalation phase I study (0.5, 1.0, 1.5, 2.0, and 2.5 mg/kg) with the 3+3 design among HER2-positive patients. C003 CANCER (NCT03052634) was a phase Ib study with 1.5, 2.0, and 2.5 mg/kg doses in the HER2-positive subgroup and 2.0 mg/kg dose in both IHC 2+/FISH-, and IHC 1+ HER2-low expressing subgroup. C003 CANCER is currently ongoing for IHC 1+ patients. Pooled analysis of the two studies was conducted for the efficacy and safety of RC48-ADC in HER2-positive or HER2-low expressing subgroups. Results: At the time of data cutoff (December 31, 2020), 118 female breast cancer patients were enrolled and treated with RC48-ADC. 70 patients (59.3%) were HER2-positive and 48 patients (40.7%) were HER2-low expressing. At baseline, 77 patients (65.3%) had liver metastases, 50 patients (42.4%) were ECOG PS 1, 47 patients (39.8%) had received ≥3 prior chemotherapy regimens. In the HER2-positive subgroup, ORRs for 1.5, 2.0, and 2.5 mg/kg doses were 22.2% (95% CI: 6.4%, 47.6%), 42.9% (95% CI: 21.8%, 66.0%), and 40.0% (95% CI: 21.1%, 61.3%). mPFSs for 1.5, 2.0, and 2.5 mg/kg cohorts were 4.0 months (95% CI: 2.6, 7.6), 5.7 months (95% CI: 5.3, 8.4) and 6.3 months (95% CI: 4.3, 8.8). In the HER2-low expressing subgroup, the ORR and mPFS were 39.6% (95% CI: 25.8%, 54.7%) and 5.7 months (95% CI: 4.1, 8.3). ORR and mPFS for IHC2+/FISH-patients were 42.9% (15/35) and 6.6 months (95% CI: 4.1, 8.5). For IHC1+ patients, even though the COVID-19 pandemic led to treatment postpone for some patients, ORR and mPFS reached 30.8% (4/13) and 5.5 months (95% CI: 2.7, 11.0). The common treatmentrelated adverse events (TRAEs) were AST increased (64.4%), ALT increased (59.3%), hypoesthesia (58.5%), white blood cell count decreased (48.3%), and neutrophil count decreased (47.5%);most were grade 1-2 in severity. Neutrophil count decreased (16.9%), GGT increased (12.7%), and fatigue (11.9%) were the grade 3 and above TRAEs occurring in ≥ 10% of the overall population. Conclusions: RC48-ADC showed consistent efficacy in HER2-positive and HER2-low expressing subgroups. The 2.0 mg/kg Q2W showed a more favorable benefit-risk ratio than other dose levels. No new safety signals were observed. Further studies are initiated to evaluate the efficacy and safety of RC48-ADC in various settings.