Exposure misclassification is a common challenge in shift-work epidemiology. This study used a large national survey of Canadian nurses to examine shift-work's effects on depression; multiple exposure definitions with varying levels of specificity were applied to illustrate the impacts of exposure assessment.
Methods
The analytic sample (n=11,450) was obtained from the 2005 National Survey of the Work and Health of Nurses. Logistic regression was used to assess relationships between shift-work and depression for high, moderate, and low specificity definitions of shift-work exposure. The low and moderate specificity definitions described shift timing (day/shift and day/evening/night/rotating, respectively); the high specificity definition described both shift timing (day/evening/night/rotating) and frequency of rotation (slow/medium/rapid/undefined). All model estimates were bootstrapped and adjusted for the potential confounding effects of sociodemographic, health, and work variables.
Results
The high specificity shift-work definition model showed the strongest relationships, with increased odds of depression in the rapid rotating shift group (OR=1.51, 95% CI=0.91–2.51) and in the undefined rotating group (OR=1.67, CI=0.92–3.02), relative to the regular day group. Odds of depression were decreased in the slow rotating group (OR=0.79, 95% CI=0.57–1.08). For the low and moderate specificity exposure definition models, weak relationships were observed for all shift categories (OR range 0.95 to 0.99).
Conclusions
This study's findings support associations between shift-work and depression, and the need for specific and hypothesis-driven exposure assessment in future studies to correctly identify exposure-response relationships and to appropriately target health interventions.
Coarse exposure assessment and assignment is a common issue facing epidemiological studies of shift work. Such measures ignore a number of exposure characteristics that may impact on health, increasing the likelihood of biased effect estimates and masked exposure-response relationships. To demonstrate the impacts of exposure assessment precision in shift work research, this study investigated relationships between work schedule and depression in a large survey of Canadian nurses.
Antineoplastic drugs are widely used in the treatment of cancer. However, some are known carcinogens and reproductive toxins, and incidental low-level exposure to workers is a health concern. CAREX Canada estimated that approximately 75,000 Canadians are exposed to antineoplastic drugs in workplace settings. While policies and guidelines on safe handling of antineoplastic drugs are available, evidence suggests that compliance is low. In this paper, we identify barriers and facilitators for safe handling of antineoplastic drugs in workplace settings.We utilized a unique method to study public policy which involved compiling policy levers, developing a logic model, conducting a literature review, and contextualizing data through a deliberative process with stakeholders to explore in-depth contextual factors and experiences for the safe handling of antineoplastic drugs.The most common barriers identified in the literature were: poor training (46%), poor safety culture (41%), and inconsistent policies (36%). The most common facilitators were: adequate safety training (41%), leadership support (23%), and consistent policies (21%). Several of these factors are intertwined and while this means one barrier can cause other barriers, it also allows healthcare employers to mitigate these barriers by implementing small but meaningful changes in the workplace.The combination of barriers and facilitators identified in our review highlight the importance of creating work environments where safety is a priority for the safe handling of antineoplastic drugs. The results of this study will assist policy makers and managers in identifying gaps and enhancing strategies that reduce occupational exposure to antineoplastic drugs.
Objective To assess survival outcomes with the intervention of an interprofessional mobilization program for patients with COVID-19 who were receiving venovenous extracorporeal membrane oxygenation (VV-ECMO). Design Preintervention and postintervention retrospective cohort study. Methods Survival outcomes of nonmobilized, adult patients (n = 16) with COVID-19 who were receiving VV-ECMO (May 2020 through December 2020) were compared with those of 26 patients who received a mobility care plan (January 2021 through November 2021). In the preintervention group, full sedation and paralysis were used. In the postintervention group, an early mobilization strategy involving interprofessional collaboration was introduced. Results The postintervention group had improved survival (73.1% vs 43.8%; P < .04); fewer days of receiving paralytics, fentanyl, and midazolam (P < .01 for all); but more days of dexmedetomidine, morphine, and ketamine administration (P < .01 for all). Concomitantly, more patients in the postintervention cohort received oral or transdermal analgesics, oral anxiolytics, and oral antipsychotics (P < .01 for all), and also required more VV-ECMO cannula adjustments (P = .03). Conclusion Early mobilization of patients with COVID-19 who were receiving VV-ECMO improved survival rates but led to more cannula adjustments.
Reading Fear and Trembling with Works of Love heightens Kierkegaard's summons to acknowledge the ambiguity of our aims and the treachery of our love. Works of Love underscores that there is a“neighbor” in Fear and Trembling whose justified or damnable banishment occasions Kierkegaard's attempt to “track down” the “illusions” of love. Through de Silentio, Kierkegaard prompts the reader to consider whether the promise has been broken due to radical obedience, lack of faith, dearth of imagination, or a gnarled combination of motives. We are to recognize our kinship with the duplicitous merman and discover that we must, like Tobit's Sarah, receive an extravagant gift. Fear and Trembling is thus a text with soteriological import, but with ethical import as well. Convicted by and indebted to God, we are to find in Abraham's act a premonitory paradigm for every engagement.
Introduction Depression-related mood disorders affect millions of people worldwide and contribute to substantial morbidity and disability, yet little is known about the effects of work scheduling on depression. This study used a large Swedish survey to prospectively examine the effects of work schedule on registry-based antidepressant prescriptions in females and males over a 2-year period. Methods The study was based on an approximately representative sample (n=3980 males, 4663 females) of gainfully employed participants in the Swedish Longitudinal Occupational Survey of Health. Sex-stratified analyses were conducted using logistic regression. For exposure, eight categories described work schedule in 2008: ‘regular days’ (three categories of night work history: none, ≤3 years, 4+ years), ‘night shift work’, ‘regular shift work (no nights)’, ‘rostered work (no nights)’, ‘flexible/non-regulated hours’ and ‘other’. For the primary outcome measure, all prescriptions coded N06A according to the Anatomical Therapeutic Chemical System were obtained from the Swedish National Prescribed Drug Register and dichotomised into ‘any’ or ‘no’ prescriptions between 2008 and 2010. Estimates were adjusted for potential sociodemographic, health and work confounders, and for prior depressive symptoms. Results In 2008, 22% of females versus 19% of males worked outside of regular daytime schedule. Registered antidepressant prescription rates in the postsurvey period were 11.4% for females versus 5.8% for males. In fully adjusted models, females in ‘flexible/non-regulated’ schedules showed an increased OR for prospective antidepressant prescriptions (OR=2.01, 95% CI=1.08 to 3.76). In males, odds ratios were most increased in those working ‘other’ schedules (OR=1.72, 95% CI=0.75 to 3.94) and ‘Regular days with four or more years’ history of night work’ (OR=1.54, 95% CI=0.93 to 2.56). Conclusions This study’s findings support a relationship between work schedule and prospective antidepressant prescriptions in the Swedish workforce. Future research should continue to assess sex-stratified relationships, using detailed shift work exposure categories and objective registry data where possible.
MDSCs are a significant barrier to adoptive cell therapy (ACT) due to their suppressive effects on T-cells. We predict that there is an enrichment of MDSCs within bladder tumors and depletion of MDSCs may augment anti-tumor responses after intravesical ACT with tumor reactive T-cells.
Methods
For murine studies, orthotopic MB49-OVA bladder tumors were collected, stained for MDSCs, and analyzed by flow cytometry. Urine samples from bladder cancer patients were also collected and stained for MDSCs. From mice, purified MDSCs and OT-I T-cells were cocultured and from bladder cancer patients, purified urine MDSCs and CD3-stimulated peripheral blood T-cells were cocultured to assess suppression of T-cell proliferation or IFN-gamma secretion. Mice bearing MB49-OVA tumors were treated with intravesical instillation of gemcitabine and/or OT-I T-cells and tumor growth was monitored via ultrasound.
Results
In mice bearing MB49-OVA tumors, the levels of polymorphonuclear (PMN)-MDSCs averaged between 11.1–23.5% of live cells and monocytic (M)-MDSCs averaged 7.6% of live cells, demonstrating that nearly 20–30% of live cells within murine bladder tumors are MDSCs. In the urine of bladder cancer patients, PMN-MDSCs predominantly make up the live cell population, averaging 71.7%, demonstrating an enrichment for MDSCs within the microenvironment of human bladder cancer. In murine coculture assays, MDSCs reduced the proliferation of OT-I T-cells and in human cocultures, MDSCs reduced T-cell IFN-gamma production to a fourth of control levels. Therefore, MDSCs from bladder tumors suppress anti-tumor T-cells by inhibiting proliferation and reactivity. In mice bearing large MB49-OVA tumors (>50mm3), pretreatment with gemcitabine improved anti-tumor response in combination with intravesical ACT with OT-I T cells in comparison to treatment with gemcitabine only (p=0.0387), OT-I only (p=0.0148), and untreated (p=.0039). In smaller MB49-OVA tumors (<50mm3), gemcitabine pretreatment provided little added benefit to ACT in comparison to treatment with gemcitabine only (p>0.05) and OT-I only (p>0.05). All p-values generated by performing Mann-Whitney tests on tumor volumes at final time points.
Conclusions
MDSCs make up a significant proportion of the immune population within bladder tumors and exert suppressive effects on T-cells. Our studies support the selective targeting of MDSCs via gemcitabine to improve the anti-tumor effects of ACT. While we show that a single instillation of gemcitabine and ACT improves anti-tumor responses, we predict that this effect will be further enhanced with multiple instillations of T-cells.
Acknowledgements
This study was supported by funds from the NIH/NCI R01CA259387. This work was supported in part by the Tissue Core Facility at the Moffitt Cancer Center, and in part by the Cancer Center Support Grant P30 CA076292 from the National Cancer Institute.
Ethics Approval
This study was approved by the Advarra IRB; approval number IRB# 00000971 and the University of South Florida IACUC, approval number R IS00007685.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
