A stochastic contact network model for assessing outbreak risk of COVID-19 in workplaces

The COVID-19 pandemic has drastically shifted the way people work. While many businesses can operate remotely, a large number of jobs can only be performed on-site. Moreover as businesses create plans for bringing workers back on-site, they are in need of tools to assess the risk of COVID-19 for their employees in the workplaces. This study aims to fill the gap in risk modeling of COVID-19 outbreaks in facilities like offices and warehouses. We propose a simulation-based stochastic contact network model to assess the cumulative incidence in workplaces. First-generation cases are introduced as a Bernoulli random variable using the local daily new case rate as the success rate. Contact networks are established through randomly sampled daily contacts for each of the first-generation cases and successful transmissions are established based on a randomized secondary attack rate (SAR). Modification factors are provided for SAR based on changes in airflow, speaking volume, and speaking activity within a facility. Control measures such as mask wearing are incorporated through modifications in SAR. We validated the model by comparing the distribution of cumulative incidence in model simulations against real-world outbreaks in workplaces and nursing homes. The comparisons support the model’s validity for estimating cumulative incidences for short forecasting periods of up to 15 days. We believe that the current study presents an effective tool for providing short-term forecasts of COVID-19 cases for workplaces and for quantifying the effectiveness of various control measures. The open source model code is made available at github.com/abhineetgupta/covid-workplace-risk.

Risk of Cardiometabolic Risk Factors in Women With and Without a History of Breast Cancer: The Pathways Heart Study

PURPOSE The incidence of cardiometabolic risk factors in breast cancer (BC) survivors has not been well described. Thus, we compared risk of hypertension, diabetes, and dyslipidemia in women with and without BC. METHODS Women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California (KPNC) were identified and matched 1:5 to noncancer controls on birth year, race, and ethnicity. Cumulative incidence rates of hypertension, diabetes, and dyslipidemia were estimated with competing risk of overall death. Subdistribution hazard ratios (sHRs) were estimated by Fine and Gray regression, adjusted for cardiovascular disease–related risk factors, and stratified by treatment and body mass index (BMI). RESULTS A total of 14,942 BC cases and 74,702 matched controls were identified with mean age 61.2 years and 65% non-Hispanic White. Compared with controls, BC cases had higher cumulative incidence rates of hypertension (10.9% v 8.9%) and diabetes (2.1% v 1.7%) after 2 years, with higher diabetes incidence persisting after 10 years (9.3% v 8.8%). In multivariable models, cases had higher risk of diabetes (sHR, 1.16; 95% CI, 1.07 to 1.26) versus controls. Cases treated with chemotherapy (sHR, 1.23; 95% CI, 1.11 to 1.38), left-sided radiation (sHR, 1.29; 95% CI, 1.13 to 1.48), or endocrine therapy (sHR, 1.23; 95% CI, 1.12 to 1.34) continued to have higher diabetes risk. Hypertension risk was higher for cases receiving left-sided radiation (sHR, 1.11; 95% CI, 1.02 to 1.21) or endocrine therapy (sHR, 1.10; 95% CI, 1.03 to 1.16). Normal-weight (BMI < 24.9 kg/m2) cases had higher risks overall and within treatment subgroups versus controls. CONCLUSION BC survivors at KPNC experienced elevated risks of diabetes and hypertension compared with women without BC depending on treatments received and BMI. Future studies should examine strategies for cardiometabolic risk factor prevention in BC survivors.

Oncological Outcomes After Hippocampus-Sparing Whole-Brain Radiotherapy in Cancer Patients With Newly Diagnosed Brain Oligometastases: A Single-Arm Prospective Observational Cohort Study in Taiwan

BackgroundPromisingly, the technique of hippocampus sparing during WBRT (HS-WBRT) might preserve NCFs. In this research, we examined oncological outcomes, with emphasis on neurologic/non-neurologic causes of death, CNS progression, and leptomeningeal disease (LMD) recurrence in cancer patients who underwent HS-WBRT.MethodsOne hundred and fourteen cancer patients with newly diagnosed brain oligometastases underwent HS-WBRT were consecutively enrolled. The cumulative incidence of cancer-specific deaths (neurologic or non-neurologic), LMD recurrence, and the composite endpoint of CNS progression (CNS-CE) as the first event were computed with a competing-risks approach to characterize the oncological outcomes after HS-WBRT.ResultsPatients with intact brain metastases had a significantly increased likelihood of dying from non-neurologic causes of death associated with early manifestation of progressive systemic disease (hazard ratio for non-neurologic death, 1.78; 95% CI, 1.08–2.95; p = 0.025; competing-risks Fine–Gray regression), which reciprocally rendered them unlikely to encounter LMD recurrence or any pattern of CNS progression (HR for CNS-CE as the first event, 0.13; 95% CI, 0.02–0.97; p = 0.047; competing-risks Fine–Gray regression). By contrast, patients with resection cavities post-craniotomy had reciprocally increased likelihood of CNS progression which might be associated with neurologic death eventually.ConclusionsPatterns of oncological endpoints including neurologic/non-neurologic death and cumulative incidence of CNS progression manifesting as LMD recurrence are clearly clarified and contrasted between patients with intact BMs and those with resection cavities, indicating they are clinically distinct subgroups.Trial RegistrationClinicalTrials.gov, Identifier: NCT02504788, NCT03223675.

Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease

PURPOSE Graft-versus-host disease (GVHD) causes morbidity and mortality following allogeneic hematopoietic cell transplantation. Naive T cells (TN) cause severe GVHD in murine models. We evaluated chronic GVHD (cGVHD) and other outcomes in three phase II clinical trials of TN-depletion of peripheral blood stem-cell (PBSC) grafts. METHODS One hundred thirty-eight patients with acute leukemia received TN-depleted PBSC from HLA-matched related or unrelated donors following conditioning with high- or intermediate-dose total-body irradiation and chemotherapy. GVHD prophylaxis was with tacrolimus, with or without methotrexate or mycophenolate mofetil. Subjects received CD34-selected PBSC and a defined dose of memory T cells depleted of TN. Median follow-up was 4 years. The primary outcome of the analysis of cumulative data from the three trials was cGVHD. RESULTS cGVHD was very infrequent and mild (3-year cumulative incidence total, 7% [95% CI, 2 to 11]; moderate, 1% [95% CI, 0 to 2]; severe, 0%). Grade III and IV acute GVHD (aGVHD) occurred in 4% (95% CI, 1 to 8) and 0%, respectively. The cumulative incidence of grade II aGVHD, which was mostly stage 1 upper gastrointestinal GVHD, was 71% (95% CI, 64 to 79). Recipients of matched related donor and matched unrelated donor grafts had similar rates of grade III aGVHD (5% [95% CI, 0 to 9] and 4% [95% CI, 0 to 9]) and cGVHD (7% [95% CI, 2 to 13] and 6% [95% CI, 0 to 12]). Overall survival, cGVHD-free, relapse-free survival, relapse, and nonrelapse mortality were, respectively, 77% (95% CI, 71 to 85), 68% (95% CI, 61 to 76), 23% (95% CI, 16 to 30), and 8% (95% CI, 3 to 13) at 3 years. CONCLUSION Depletion of TN from PBSC allografts results in very low incidences of severe acute and any cGVHD, without apparent excess risks of relapse or nonrelapse mortality, distinguishing this novel graft engineering strategy from other hematopoietic cell transplantation approaches.

Relationship between platelet aggregation and stroke risk after percutaneous coronary intervention: a PENDULUM analysis

In patients undergoing percutaneous coronary intervention (PCI) with a stent, high on-treatment platelet reactivity may be associated with an increased risk of stroke. This post hoc analysis of the PENDULUM registry compared the risk of post-PCI stroke according to on-treatment P2Y12 reaction unit (PRU) values. Patients aged ≥ 20 years who underwent PCI were stratified by baseline PRU (at 12 and 48 h post-PCI) as either high (HPR, > 208), optimal (OPR, > 85 to ≤ 208), or low on-treatment platelet reactivity (LPR, ≤ 85). The incidences of non-fatal ischemic and non-ischemic stroke through to 12 months post-PCI were recorded. Almost all enrolled patients (6102/6267 [97.4%]) had a risk factor for ischemic stroke, and most were receiving dual antiplatelet therapy. Of the 5906 patients with PRU data (HPR, n = 2227; OPR, n = 3002; LPR, n = 677), 47 had a non-fatal stroke post-PCI (cumulative incidence: 0.68%, ischemic; 0.18%, non-ischemic stroke). Patients with a non-fatal ischemic stroke event had statistically significantly higher post-PCI PRU values versus those without an event (P = 0.037). The incidence of non-fatal non-ischemic stroke was not related to PRU value. When the patients were stratified by PRU ≤ 153 versus > 153 at 12–48 h post-PCI, a significant difference was observed in the cumulative incidence of non-fatal stroke at 12 months (P = 0.044). We found that patients with ischemic stroke tended to have higher PRU values at 12–48 h after PCI versus those without ischemic stroke.Clinical trial registration: UMIN000020332.

Aspirin Use Is Not Associated with the Risk of Metachronous Gastric Cancer in Patients without Helicobacter pylori Infection

Introduction: Helicobacter pylori (H. pylori) eradication can prevent metachronous gastric cancer (MGC) after the performance of an endoscopic resection for early gastric cancer (EGC). However, 50% of infections persist after eradication, and the identification of MGC protective factors is important. The anti-tumor activity of aspirin has been demonstrated, but its efficacy in preventing MGC remains controversial. We evaluated the effect of aspirin on metachronous recurrence in H. pylori-negative patients. Methods: A total of 4351 patients were evaluated between January 2007 and December 2016, and 2151 patients who met the inclusion criteria were analyzed. The primary outcome was the cumulative incidence of MGC after an endoscopic resection for EGC. Results: During a 5-year median follow-up (interquartile range, 3.5–6.2), MGC developed in 176 (7.7%) patients, with a cumulative incidence of 89.4% in aspirin users and 92.7% in non-users; this difference was not statistically significant (p = 0.64). The duration of aspirin uses and the occurrence of MGC in both groups were not significantly different. There was no significant difference between groups when the duration of aspirin use was categorized into ≤1 year (hazard ratio (HR), 0.64; 0.20–2.01, p = 0.45), 1–4 years (HR, 1.35; 0.66–2.76, p = 0.41), and >4 years (HR, 1.17; 0.67–2.03, p = 0.58). Conclusions: Aspirin use was not associated with a lower risk of MGC in H. pylori-negative patients. Further prospective studies are needed.

Role of social benefits for future long-term sickness absence, disability pension and unemployment among individuals on sickness absence due to mental diagnoses: a competing risk approach

Purpose To investigate associations between social benefits and disability pension (DP), long-term sickness absence (LTSA, ≥ 90 days), or unemployment among Swedish twins with sickness absence (SA) due to mental diagnoses. Methods This population-based prospective twin study included register data on first incident SA spell (< 90 days) due to mental diagnoses (ICD 10 codes F00-F99) during the follow-up 2005–2016. SA < 90 days due to other diagnoses than mental diagnoses or any other social insurance benefit was identified for the preceding year of the first incident SA spell due to mental diagnoses (coded yes/no). Comparing those with any previous social benefits vs without, cumulative incidence curve to compare time to an event, and Cox proportional hazards models for cause-specific hazard ratios (HR, 95% confidence intervals, CI) treating first incident DP, LTSA and unemployment as competing risks were modeled. Results During follow-up, 21 DP, 1619 LTSA, and 808 unemployment events took place. Compared to those without, those with at least one benefit had a higher risk for DP (HR 5.03; 95%CI 1.80, 14.01), LTSA (1.67; 1.50, 1.84) and unemployment (1.24; 1.03, 1.50). The cumulative incidence for DP was very low, < 1%, for LTSA 80% with any previous social benefits vs. 60% without, and for unemployment ≤ 5%. Conclusion Social benefits received during the preceding year of SA due to mental diagnoses (< 90 days) predict DP, LTSA, and unemployment. Hence, previous social benefits may provide means for early identification of persons at risk for exit from labor market.

Association between SARS-CoV-2 Seroprevalence in Nursing Home Staff and Resident COVID-19 Cases and Mortality: A Cross-Sectional Study

The burden of COVID-19 has disproportionately impacted the elderly, who are at increased risk of severe disease, hospitalization, and death. This cross-sectional study aimed to assess the association between SARS-CoV-2 seroprevalence among nursing home staff, and cumulative incidence rates of COVID-19 cases, hospitalizations, and deaths among residents. Staff seroprevalence was estimated within the SEROCoV-WORK+ study between May and September 2020 across 29 nursing homes in Geneva, Switzerland. Data on nursing home residents were obtained from the canton of Geneva for the period between March and August 2020. Associations were assessed using Spearman’s correlation coefficient and quasi-Poisson regression models. Overall, seroprevalence among staff ranged between 0 and 31.4%, with a median of 8.3%. A positive association was found between staff seroprevalence and resident cumulative incidence of COVID-19 cases (correlation coefficient R = 0.72, 95%CI 0.45–0.87; incidence rate ratio [IRR] = 1.10, 95%CI 1.07–1.17), hospitalizations (R = 0.59, 95%CI 0.25–0.80; IRR = 1.09, 95%CI 1.05–1.13), and deaths (R = 0.71, 95%CI 0.44–0.86; IRR = 1.12, 95%CI 1.07–1.18). Our results suggest that SARS-CoV-2 transmission between staff and residents may contribute to the spread of the virus within nursing homes. Awareness among nursing home professionals of their likely role in the spread of SARS-CoV-2 has the potential to increase vaccination coverage and prevent unnecessary deaths due to COVID-19.

Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies

Background. Patients with Multiple Sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to mRNA-based SARS-CoV-2 vaccines, while the degree of such responses is unimpaired and similar in pwMS treated with other disease modifying therapies (DMTs), or untreated. However, the nature of the SARS-CoV-2 vaccine-induced immune response is based also on cellular immunity and there is emerging evidence that anti-SARS-CoV-2 specific CD4 and CD8 T cell responses can be detected after vaccination also in patients with low antibody levels. In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection and to identify correlates of reduced protection in frail vaccinated pwMS on different DMTs. Methods. We designed a long term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) , a prospective multicenter cohort study enrolling pwMS scheduled for SARS-CoV-2 vaccination with mRNA vaccines and tested for SARS-CoV-2 antibodies before and after the second vaccine dose. These patients were followed with periodic phone calls up to a mean time of 6 months, and all the SARS-CoV-2 breakthrough infections were registered. The impact of DMTs on cumulative incidence of breakthrough Covid-19 cases was presented by Kaplan-Meier curves. A multivariable logistic model was run to assess factors associated to a higher risk of breakthrough infections. Findings. 1705 pwMS (81.6% BNT162b2 and 18.4% mRNA-1273) had a full vaccination cycle (2 vaccine doses, 21/28 days apart). Of them, 1509 (88.5%) had blood assessment 4 weeks after the second vaccine dose. During follow-up, 23 breakthrough Covid-19 infections (cumulative incidence: 1.5%, SE=0.3%) were detected after a mean of 108 days after the second dose (range, 18-230). Of them, 9 were on ocrelizumab, one on rituximab, 4 on fingolimod, 6 on dimethyl-fumarate, one on teriflunomide, and 2 were untreated. Just two cases (a woman on ocrelizumab and a man on teriflunomide) required hospitalization. The probability to be infected was associated only with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.63, p=0.007); an antibody level of 660 U/mL was calculated as the cut-off for higher risk of infection. Interpretation. Our data show that the risk of breakthrough SARS-CoV-2 infections is mainly associated with reduced levels of the virus-specific humoral immune response. Funding. FISM [2021/Special-Multi/001]; the Italian Ministry of Health grant Progetto Z844A 5x1000. Italian Ministry of Health: Ricerca Corrente to IRCCS Ospedale Policlinico San Martino.