Healthcare workers in intensive care units often experience moral distress, depression, and stress-related symptoms. These conditions can lower staff retention and influence the quality of patient ...care. This study aimed to evaluate the prevalence of moral distress and psychological status among healthcare workers in a newly established paediatric intensive care unit (PICU) in Hong Kong.
A cross-sectional questionnaire survey was conducted in the PICU of the Hong Kong Children's Hospital; healthcare workers (doctors, nurses and allied health professionals) were invited to participate. The Revised Moral Distress Scale (MDS-R) Paediatric Version and Depression Anxiety and Stress Scale-21 items were used to assess moral distress and psychological status, respectively. Demographic characteristics were examined in relation to moral distress, depression, anxiety, and stress scores to identify risk factors for poor psychological outcomes. Correlations of moral distress with depression, anxiety, and stress were examined.
Forty-six healthcare workers completed the survey. The overall median MDS-R moral distress score was 71. Nurses had a significantly higher median moral distress score, compared with doctors and allied health professionals (102 vs 47 vs 20). Nurses also had the highest median anxiety and stress scores (11 and 20, respectively). Moral distress scores were correlated with depression (r=0.445; P=0.002) and anxiety scores (r=0.417; P<0.05). Healthcare workers intending to quit their jobs had significantly higher moral distress scores (P<0.05).
Among PICU healthcare workers, nurses had the highest level of moral distress. Moral distress was associated with greater depression, anxiety, and intention to quit. Healthcare workers need support and a sustainable working environment to cope with moral distress.
Summary
Vitamin D deficiency and insufficiency are highly prevalent among adolescents in Hong Kong, which is a sub-tropical city with ample sunshine. Vitamin D level is significantly correlated with ...key bone density and bone quality parameters. Further interventional studies are warranted to define the role of vitamin D supplementation for improvement of bone health among adolescents.
Introduction
The relationship between bone quality parameters and vitamin D (Vit-D) status remains undefined among adolescents. The aims of this study were to evaluate Vit-D status and its association with both bone density and bone quality parameters among adolescents.
Methods
Three hundred thirty-three girls and 230 boys (12–16 years old) with normal health were recruited in summer and winter separately from local schools. Serum 25(OH) Vit-D level, bone density and quality parameters by Dual Energy X-ray Absorptiometry (DXA) and High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), dietary calcium intake, and physical activity level were assessed.
Results
Sixty-four point seven percent and 11.4 % of subjects were insufficient 25 ≤ 25(OH)Vit-D ≤ 50 nmol/L and deficient 25(OH)Vit-D < 25 nmol/L in Vit-D, respectively. The mean level of serum 25(OH)Vit-D in summer was significantly higher than that in winter (44.7 ± 13.6 and 35.9 ± 12.6 nmol/L, respectively) without obvious gender difference. In girls, areal bone mineral density (aBMD) and bone mineral content (BMC) of bilateral femoral necks, cortical area, cortical thickness, total volumetric bone mineral density (vBMD), and trabecular thickness were significantly correlated with 25(OH)Vit-D levels. In boys, aBMD of bilateral femoral necks, BMC of the dominant femoral neck, cortical area, cortical thickness, total vBMD, trabecular vBMD, BV/TV, and trabecular separation were significantly correlated with 25(OH)Vit-D levels.
Conclusion
Vit-D insufficiency was highly prevalent among adolescents in Hong Kong with significant correlation between Vit-D levels and key bone density and bone quality parameters being detected in this study. Given that this is a cross-sectional study and causality relationship cannot be inferred, further interventional studies investigating the role of Vit-D supplementation on improving bone health among adolescents are warranted.
To examine the real-world safety of adding bevacizumab to first-line irinotecan-based chemotherapy for patients with metastatic colorectal cancer (mCRC).
Patients diagnosed with CRC in three Canadian ...provinces (Ontario, Saskatchewan and British Columbia) who received publicly funded bevacizumab and/or irinotecan from 2000 to 2016 were identified from cancer registries. Propensity score 1:1 matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to contemporaneous and historical controls, adjusting for baseline demographic and clinical characteristics. Safety end points evaluated during first-line treatment plus 30 days included mortality within 30 days and all-cause-, chemotherapy- and bevacizumab-related hospitalisations. Chemotherapy- and bevacizumab-related visits were defined as hospitalisations for specific conditions commonly associated with chemotherapy (e.g. infections) or bevacizumab (e.g. arteriovenous thromboembolism) using most responsible diagnosis codes. In PSM and IPTW-weighted cohorts, we assessed event frequencies using odds ratios from logistic regressions and event rate ratios using negative binomial regression models. The results from each province and comparison were pooled using random-effects meta-analysis.
We identified 16 250 mCRC patients who received first-line irinotecan-based treatment. In PSM cohorts, bevacizumab was associated with fewer deaths within 30 days of treatment compared with contemporaneous (pooled odds ratio = 0.62; 95% confidence interval 0.50–0.75) and historical controls (pooled odds ratio = 0.73; 95% confidence interval 0.58–0.93). Hospitalisations were more frequent among patients treated with bevacizumab compared with historical controls but similar to contemporaneous controls. As patients receiving bevacizumab were exposed to a longer average treatment duration, across their full treatment duration, patients receiving bevacizumab had significantly lower rates of hospitalisations (contemporaneous pooled rate ratio = 0.56; 95% confidence interval 0.47–0.67; historical pooled rate ratio = 0.73; 95% confidence interval 0.56–0.95). Similar trends were observed for chemotherapy- and bevacizumab-related hospitalisations and in IPTW-weighted cohorts.
We did not observe any increase in rates of hospitalisation or death within 30 days of treatment among mCRC patients treated with bevacizumab plus chemotherapy versus chemotherapy alone; these findings should be interpreted with caution due to the risk of residual confounding.
•Bevacizumab with chemotherapy to treat metastatic colorectal cancer increased hospital visits during treatment compared with chemotherapy alone.•Patients receiving bevacizumab experienced lower rate of hospitalisation over longer treatment duration than chemotherapy alone.•No observed increase in deaths within 30 days of treatment suggests bevacizumab toxicity to be manageable in the real world.•Comparative real-world safety evaluation with population-based administrative data enables valuable ongoing pharmacovigilance.
The PI3K-Akt signal pathway plays a key role in tumorigenesis and the development of drug-resistance. Cytotoxic chemotherapy resistance is linked to limited therapeutic options and poor prognosis.
...Examination of FOXO3a and phosphorylated-Akt (P-Akt) expression in breast cancer tissue microarrays showed nuclear FOXO3a was associated with lymph node positivity (p = 0.052), poor prognosis (p = 0.014), and P-Akt expression in invasive ductal carcinoma. Using tamoxifen and doxorubicin-sensitive and -resistant breast cancer cell lines as models, we found that doxorubicin- but not tamoxifen-resistance is associated with nuclear accumulation of FOXO3a, consistent with the finding that sustained nuclear FOXO3a is associated with poor prognosis. We also established that doxorubicin treatment induces proliferation arrest and FOXO3a nuclear relocation in sensitive breast cancer cells. Induction of FOXO3a activity in doxorubicin-sensitive MCF-7 cells was sufficient to promote Akt phosphorylation and arrest cell proliferation. Conversely, knockdown of endogenous FOXO3a expression reduced PI3K/Akt activity. Using MDA-MB-231 cells, in which FOXO3a activity can be induced by 4-hydroxytamoxifen, we showed that FOXO3a induction up-regulates PI3K-Akt activity and enhanced doxorubicin resistance. However FOXO3a induction has little effect on cell proliferation, indicating that FOXO3a or its downstream activity is deregulated in the cytotoxic drug resistant breast cancer cells. Thus, our results suggest that sustained FOXO3a activation can enhance hyperactivation of the PI3K/Akt pathway.
Together these data suggest that lymph node metastasis and poor survival in invasive ductal breast carcinoma are linked to an uncoupling of the Akt-FOXO3a signaling axis. In these breast cancers activated Akt fails to inactivate and re-localize FOXO3a to the cytoplasm, and nuclear-targeted FOXO3a does not induce cell death or cell cycle arrest. As such, sustained nuclear FOXO3a expression in breast cancer may culminate in cancer progression and the development of an aggressive phenotype similar to that observed in cytotoxic chemotherapy resistant breast cancer cell models.
Importance Acupuncture has been used to treat neurological and neuropsychiatric symptoms in China and other parts of the world. These symptoms, such as fatigue, headache, cognitive impairment, ...anxiety, depression, and insomnia, are common in people experiencing long COVID. Objective This study aims to explore the feasibility of acupuncture in the treatment of neurological and neuropsychiatric symptoms in long COVID patients. Data Sources A systematic search was conducted in four English and four Chinese databases from inception to 23 June 2023. Literature selection and data extraction were conducted by two pairs of independent reviewers. Study Selection Randomized controlled trials (RCTs) that explored the effect of acupuncture on fatigue, depression, anxiety, cognitive abnormalities, headache, and insomnia were included. Data Extraction and Synthesis RCTs that explored the effect of acupuncture on fatigue, depression, anxiety, cognitive abnormalities, headache, and insomnia were included. A meta-analysis was performed using R software. Heterogeneity was measured using I 2 . Subgroup analyses were performed focusing on the duration of treatment and acupuncture modalities. The systematic review protocol was registered on PROSPERO (registration number: CRD42022354940). Main outcomes and measures Widely adopted clinical outcome scales included the Fatigue Scale for assessing fatigue, the Hamilton Depression Rating Scale for evaluating depression, the Mini-Mental State Examination for assessing cognitive impairment, the Visual Analog Scale for headache severity, and the Pittsburgh Sleep Quality Index for measuring insomnia. Results A total of 110 RCTs were included in the systematic review and meta–analysis. Overall, acupuncture was found to improve the scores of the Fatigue Scale (vs. medication: mean differences (MD): −2.27, P < 0.01; vs. sham acupuncture: MD: −3.36, P < 0.01), the Hamilton Depression Rating Scale (vs. medication: MD: −1.62, 95%, P < 0.01; vs. sham acupuncture: MD: −9.47, P < 0.01), the Mini–Mental State Examination (vs. medication: MD: 1.15, P < 0.01; vs. sham acupuncture: MD: 1.20, P < 0.01), the Visual Analog Scale (vs. medication: MD: −1.05, P < 0.01; vs. waitlist: MD: −0.48, P=0.04), and the Pittsburgh Sleep Quality Index (vs. medication: MD: −2.33, P < 0.01; vs. sham acupuncture: MD: −4.19, P < 0.01). Conclusion and relevance This systematic review suggested acupuncture as a potentially beneficial approach for the treatment of neurological and neuropsychiatric symptoms, as assessed using clinical scales, and it may have applicability in long COVID patients. Further well-designed clinical studies specifically targeting long COVID patients are needed to validate the role of acupuncture in alleviating long COVID symptoms. Systematic Review Registration PROSPERO, identifier CRD42022354940.
In this article, we study two broad classes of convex order related optimal insurance decision problems, in which the objective function or the premium valuation is a general functional of the ...expectation, Value-at-Risk and Average Value-at-Risk of the loss variables. These two classes of problems include many existing and contemporary optimal insurance problems as interesting examples being prevalent in the literature. To solve these problems, we apply the Karlin–Novikoff–Stoyan–Taylor multiple-crossing conditions, which is a useful sufficient criterion in the theory of convex ordering, to replace an arbitrary insurance indemnity by a more favorable one in convex order sense. The convex ordering established provides a unifying approach to solve the special cases of the problem classes. We show that the optimal indemnities for these problems in general take the double layer form.
Eukaryotic translation initiation factor 4E (eIF4E) selectively promotes translation of mRNAs with atypically long and structured 5'-UTRs and has been implicated in drug resistance. Through ...genome-wide transcriptome and translatome analysis we revealed eIF4E overexpression could promote cellular activities mediated by ERα and FOXM1 signalling pathways. Whilst eIF4E overexpression could enhance the translation of both ERα and FOXM1, it also led to enhanced transcription of FOXM1. Polysome fractionation experiments confirmed eIF4E could modulate the translation of ERα and FOXM1 mRNA. The enhancement of FOXM1 transcription was contingent upon the presence of ERα, and it was the high levels of FOXM1 that conferred Tamoxifen resistance. Furthermore, tamoxifen resistance was conferred by phosphorylation independent eIF4E overexpression. Immunohistochemistry on 134 estrogen receptor (ER
) primary breast cancer samples confirmed that high eIF4E expression was significantly associated with increased ERα and FOXM1, and significantly associated with tamoxifen resistance. Our study uncovers a novel mechanism whereby phosphorylation independent eIF4E translational reprogramming in governing the protein synthesis of ERα and FOXM1 contributes to anti-estrogen insensitivity in ER
breast cancer. In eIF4E overexpressing breast cancer, the increased ERα protein expression in turn enhances FOXM1 transcription, which together with its increased translation regulated by eIF4E, contributes to tamoxifen resistance. Coupled with eIF4E translational regulation, our study highlights an important mechanism conferring tamoxifen resistance via both ERα dependent and independent pathways.
Immunomodulators have been shown to improve the outcome of severe pneumonia. We have previously shown that mycophenolic acid (MPA), an immunomodulator, has antiviral activity against influenza ...A/WSN/1933(H1N1) using a high-throughput chemical screening assay. This study further investigated the antiviral activity and mechanism of action of MPA against contemporary clinical isolates of influenza A and B viruses. The 50 % cellular cytotoxicity (CC50) of MPA in Madin Darby canine kidney cell line was over 50 µM. MPA prevented influenza virus-induced cell death in the cell-protection assay, with significantly lower IC50 for influenza B virus B/411 than that of influenza A(H1N1)pdm09 virus H1/415 (0.208 vs 1.510 µM, P=0.0001). For H1/415, MPA interfered with the early stage of viral replication before protein synthesis. For B/411, MPA may also act at a later stage since MPA was active against B/411 even when added 12 h post-infection. Virus-yield reduction assay showed that the replication of B/411 was completely inhibited by MPA at concentrations ≥0.78 µM, while there was a dose-dependent reduction of viral titer for H1/415. The antiviral effect of MPA was completely reverted by guanosine supplementation. Plaque reduction assay showed that MPA had antiviral activity against eight different clinical isolates of A(H1N1), A(H3N2), A(H7N9) and influenza B viruses (IC50 <1 µM). In summary, MPA has broad-spectrum antiviral activity against human and avian-origin influenza viruses, in addition to its immunomodulatory activity. Together with a high chemotherapeutic index, the use of MPA as an antiviral agent should be further investigated in vivo.
The configuration and performance of a new global atmosphere and land model for climate research developed at the Geophysical Fluid Dynamics Laboratory (GFDL) are presented. The atmosphere model, ...known as AM2, includes a new gridpoint dynamical core, a prognostic cloud scheme, and a multispecies aerosol climatology, as well as components from previous models used at GFDL. The land model, known as LM2, includes soil sensible and latent heat storage, groundwater storage, and stomatal resistance. The performance of the coupled model AM2–LM2 is evaluated with a series of prescribed sea surface temperature (SST) simulations. Particular focus is given to the model’s climatology and the characteristics of interannual variability related to El Niño–Southern Oscillation (ENSO).
One AM2–LM2 integration was performed according to the prescriptions of the second Atmospheric Model Intercomparison Project (AMIP II) and data were submitted to the Program for Climate Model Diagnosis and Intercomparison (PCMDI). Particular strengths of AM2–LM2, as judged by comparison to other models participating in AMIP II, include its circulation and distributions of precipitation. Prominent problems of AM2–LM2 include a cold bias to surface and tropospheric temperatures, weak tropical cyclone activity, and weak tropical intraseasonal activity associated with the Madden–Julian oscillation.
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