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The association of QTc prolongation with cardiovascular events in cancer patients taking tyrosine kinase inhibitors (TKIs)

Cardiooncology. 2023 May 19;9(1):25. doi: 10.1186/s40959-023-00178-x.

ABSTRACT

OBJECTIVE: To investigate the association between stages of QTc prolongation and the risk of cardiac events among patients on TKIs.

METHODS: This was a retrospective cohort study performed at an academic tertiary care center of cancer patients who were taking TKIs or not taking TKIs. Patients with two recorded ECGs between January 1, 2009, and December 31, 2019, were selected from an electronic database. The QTc duration > 450ms was determined as prolonged. The association between QTc prolongation progression and events of cardiovascular disease were compared.

RESULTS: This study included a total of 451 patients with 41.2% of patients taking TKIs. During a median follow up period of 3.1 years, 49.5% subjects developed CVD and 5.4% subjects suffered cardiac death in patient using TKIs (n = 186); the corresponding rates are 64.2% and 1.2% for patients not on TKIs (n = 265), respectively. Among patient on TKIs, 4.8% of subjects developed stroke, 20.4% of subjects suffered from heart failure (HF) and 24.2% of subjects had myocardial infarction (MI); corresponding incidence are 6.8%, 26.8% and 30.6% in non-TKIs. When patients were regrouped to TKIs versus non-TKIs with and without diabetes, there was no significant difference in the incidence of cardiac events among all groups. Adjusted Cox proportional hazards models were applied to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). There is a significant increased risk of HF events (HR, 95% CI: 2.12, 1.36-3.32) and MI events (HR, 95% CI: 1.78, 1.16-2.73) during the 1st visit. There are also trends for an increased incidence of cardiac adverse events associated with QTc prolongation among patient with QTc > 450ms, however the difference is not statistically significant. Increased cardiac adverse events in patients with QTc prolongation were reproduced during the 2nd visit and the incidence of heart failure was significantly associated with QTc prolongation(HR, 95% CI: 2.94, 1.73-5.0).

CONCLUSION: There is a significant increased QTc prolongation in patients taking TKIs. QTc prolongation caused by TKIs is associated with an increased risk of cardiac events.

PMID:37208762 | DOI:10.1186/s40959-023-00178-x

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A short-term bioreactor assay to assess the effect of essential oils on a microbiota derived from piglet’s intestinal content

Acta Vet Scand. 2023 May 19;65(1):17. doi: 10.1186/s13028-023-00679-w.

ABSTRACT

BACKGROUND: Modulating the microbiota is an emerging way to improve pig health. In-vitro bioreactor systems can be used to reproduce intestinal microbiota to study modulating avenues. In this study, a continuous feeding system to support a microbiota derived from piglet colonic contents, over 72 h, was developed. The microbiota from piglets was collected and used as inoculum. The culture media was derived from an artificial digestion of piglet feed. The microbiota diversity in time, the reproducibility between replicates and the diversity of the bioreactor microbiota compared to the inoculum was assessed. Essential oils were used as a proof of concept to assess the in vitro microbiota modulation. The microbiota diversity was assessed by 16S rRNA amplicon sequencing. Quantitative PCR was also used for total bacteria, lactobacilli and Enterobacteria.

RESULTS: At the start of the assay, the bioreactor microbiota diversity was similar to the inoculum. Time and replication affected the bioreactor microbiota diversity. Between 48 and 72 h, no statistical variation of the microbiota diversity was observable. After a 48 h running period, thymol and carvacrol were added at 200 ppm or 1000 ppm for 24 h. No microbiota modification was observed by sequencing. Quantitative PCR results showed a significant growth of lactobacilli when thymol was used at 1000 ppm, where only a trend was observed with the 16S analysis.

CONCLUSIONS: This study presents a bioreactor assay that can be used as a tool for rapid screening of additives and suggests that the effects of essential oils on the microbiota are subtle, acting against a few bacterial genera.

PMID:37208761 | DOI:10.1186/s13028-023-00679-w

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Assessing the role of Piscine orthoreovirus in disease and the associated risk for wild Pacific salmon

BMC Biol. 2023 May 19;21(1):114. doi: 10.1186/s12915-023-01548-8.

ABSTRACT

This paper is a response to Polinski, M. P. et al. Innate antiviral defense demonstrates high energetic efficiency in a bony fish. BMC Biology 19, 138 (2021). https://doi.org/10.1186/s12915-021-01069-2.

PMID:37208758 | DOI:10.1186/s12915-023-01548-8

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Identifying facilitators and barriers to integrated and equitable care for community-dwelling older adults with high emergency department use from historically marginalized groups

Int J Equity Health. 2023 May 19;22(1):97. doi: 10.1186/s12939-023-01900-y.

ABSTRACT

BACKGROUND: High rates of emergency department (ED) use by older adults persist despite attempts to improve accessibility of appropriate and comprehensive care. Understanding the drivers of ED visits from the perspective of older adults from historically marginalized groups could help reduce ED use by patients with needs that are preventable or could have been treated in a more appropriate setting. This interpretivist, feminist study aims to explore the unmet care needs of older adults (age 65 +) with high ED use and belonging to historically marginalized groups to better understand how social and structural inequities reinforced by neoliberalism; federal and provincial governance structures and policy frameworks; and regional processes and local institutional practices, shape the experiences of these older adults, particularly those at risk of poor health outcomes based on the social determinants of health (SDH).

METHODS/DESIGN: This mixed methods study will employ an integrated knowledge translation (iKT) approach, starting with a quantitative phase followed by a qualitative phase. Older adults self-identifying as belonging to a historically marginalized group, having visited an ED three or more times in the past 12 months, and living in a private dwelling, will be recruited using flyers posted at two emergency care sites and by an on-site research assistant. Data obtained through surveys, short answer questions, and chart review will be used to compile case profiles of patients from historically marginalized groups with potentially avoidable ED visits. Descriptive and inferential statistical analyses and inductive thematic analysis will be conducted. Findings will be interpreted using the Intersectionality-Based Policy Analysis Framework to identify the interconnections between unmet care needs, potentially avoidable ED admissions, structural inequalities, and the SDH. Semi-structured interviews will be conducted with a subset of older adults at risk of poor health outcomes based on SDH, family care partners, and health care professionals to validate preliminary findings and collect additional data on perceived facilitators and barriers to integrated and accessible care.

DISCUSSION: Exploring the linkages between potentially avoidable ED visits by older adults from marginalized groups and how their care experiences have been shaped by inequities in the systems, policies, and institutions that structure health and social care provision will enable researchers to offer recommendations for equity-focused policy and clinical practice reforms to improve patient outcomes and system integration.

PMID:37208757 | DOI:10.1186/s12939-023-01900-y

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“In some clinics, they said it’s elective, and then they would refuse”: A Mixed-Methods Study on the impact of the COVID-19 pandemic on access to abortion services in Germany

Sex Reprod Healthc. 2023 May 5;36:100854. doi: 10.1016/j.srhc.2023.100854. Online ahead of print.

ABSTRACT

OBJECTIVE: The World Health Organization recognizes abortion as essential health care and has encouraged governments to ensure access to abortion services throughout the COVID-19 pandemic. However, the threat of infection combined with government responses to COVID-19 have impacted access to abortion services globally. This study explores access to abortion in Germany during the pandemic.

METHODS: This study used a mixed-methods design. An analysis of data collected by Women on Web (WoW) was carried out to assess women’s reasons for choosing telemedicine abortion outside the formal health system in Germany during the pandemic. Descriptive statistics were generated for 2057 requests for telemedicine abortion received by WoW between March 2020-March 2021. Semi-structured interviews were conducted with eight healthcare professionals involved in the provision of abortion services to explore how they perceive of women’s access to abortion services in Germany during the pandemic.

RESULTS: The quantitative analysis found that preferences and needs for privacy (47.3%), secrecy (44.4%) and comfort (43.9%) were the most common reasons for choosing telemedicine abortion. COVID-19 was another important reason (38.8%). The thematic analysis of the interviews was organized into two overarching themes: service provision, and axes of difference.

CONCLUSIONS: The pandemic affected the provision of abortion services as well as the circumstances of women seeking abortion. The main barriers to access were financial constraints, privacy issues, and lack of abortion providers. Throughout the pandemic, accessing abortion services was more difficult for many women in Germany, especially women experiencing multiple and overlapping forms of discrimination.

PMID:37207395 | DOI:10.1016/j.srhc.2023.100854

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Ask questions (ASQ): Implementation of a question prompt list communication intervention in a network of outpatient medical oncology clinics

Patient Educ Couns. 2023 May 12;113:107793. doi: 10.1016/j.pec.2023.107793. Online ahead of print.

ABSTRACT

OBJECTIVE: This descriptive, single-arm study assessed the implementation and patient perceptions of an evidence-based Question Prompt List (QPL), the ASQ brochure, across a network of oncology clinics in a diverse patient population.

METHOD: The QPL was revised in collaboration with stakeholders. Implementation was assessed using the RE-AIM framework. Eligible patients were scheduled for a first appointment with an oncologist at any of eight participating clinics. All participants received the ASQ brochure and completed three surveys: one at baseline, one immediately before, and one following their appointment. Surveys assessed sociodemographic characteristics; communication-related outcomes (perceived knowledge, self-efficacy in interacting with physicians, trust in physicians, distress); and perceptions of the ASQ brochure. Analyses included descriptive statistics and linear mixed-effects models.

RESULTS: Reach: Participants (n = 81) represented the diverse population served by the clinic network.

EFFICACY: All outcomes improved significantly, with no significant differences by clinic site or patient race. Adoption: All eight invited clinics participated and recruited patients. Patient perceptions of the ASQ brochure were overwhelmingly positive.

CONCLUSION: Implementation of the ASQ brochure was successful in this oncology clinic network providing care to a diverse patient population.

PRACTICAL IMPLICATIONS: This evidence-based communication intervention can be implemented widely in similar medical contexts and populations.

PMID:37207383 | DOI:10.1016/j.pec.2023.107793

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Analysis of rebound intracranial pressure occurring during rewarming after therapeutic hypothermia in traumatic brain injury patients

Clin Neurol Neurosurg. 2023 May 5;230:107755. doi: 10.1016/j.clineuro.2023.107755. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the risk factors associated with rebound intracranial pressure (ICP), a phenomenon that occurs when brain swelling reprogresses rapidly during rewarming in patients who have undergone therapeutic hypothermia for traumatic brain injury (TBI).

METHODS: This study analyzed 42 patients who underwent therapeutic hypothermia among 172 patients with severe TBI admitted to a single regional trauma center between January 2017 and December 2020. Forty-two patients were classified into 34.5 °C (mild) and 33 °C (moderate) hypothermia groups according to the therapeutic hypothermia protocol for TBI. Rewarming was initiated post-hypothermia, wherein ICP was maintained at ≤ 20 mmHg and cerebral perfusion pressure was maintained at ≥ 50 mmHg for ≥ 24 h. In the rewarming protocol, the target core temperature was increased to 36.5 °C at 0.1 °C/h.

RESULTS: Of the 42 patients who underwent therapeutic hypothermia, 27 did not survive: 9 in the mild and 18 in the moderate hypothermia groups. The moderate hypothermia group had a significantly higher mortality rate than the mild hypothermia group (p = 0.013). Rebound ICP occurred in 9 of 25 patients: 2 in the mild and 7 in the moderate hypothermia groups. In the risk factor analysis of rebound ICP, only the degree of hypothermia was statistically significant, and rebound ICP was observed more frequently in the moderate than in the mild hypothermia group (p = 0.025).

CONCLUSIONS: In patients who underwent rewarming after therapeutic hypothermia, rebound ICP presented a higher risk at 33 °C than at 34.5 °C. Therefore, more careful rewarming is needed in patients receiving therapeutic hypothermia at 33 °C.

PMID:37207371 | DOI:10.1016/j.clineuro.2023.107755

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The effect of subacute co-exposure to carbon tetrachloride and diclofenac on the liver of male wistar rats

Toxicol Ind Health. 2023 May 19:7482337231174994. doi: 10.1177/07482337231174994. Online ahead of print.

ABSTRACT

Carbon tetrachloride (CCl4) is a potent liver toxin. Diclofenac (Dic), leading adverse effects on the liver, is used among the employees of the industries that use CCl4. The increased use of CCl4 and Dic in industrial workers has prompted us to investigate their synergistic effect on the liver using male Wistar rats as a model. Male Wistar rats were divided into seven groups (n = 6), and the exposure was by intraperitoneal injection for 14 days as follows. Group 1: Control, 2: Olive oil, 3: CCl4 (0.8 mL/kg/day (3 times per week)), 4: Normal saline, 5: Dic (1.5 mg/kg/day per day), 6: Olive oil with normal saline, 7: CCl4 (0.8 mL/kg/day (3 times per week)) and Dic (1.5 mg/kg/day daily). At the end of day 14, the heart blood was collected to measure the liver enzymes, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), blood alkaline phosphatase (ALP), albumin (ALB), direct bilirubin, and total bilirubin. A pathologist examined the liver tissue. Prism software was used to analyze data using ANOVA and Tukey statistical tests. ALT, AST, ALP, and Total Bilirubin enzymes were increased significantly in the co-administered CCl4 and Dic group, while the ALB levels decreased (p < 0.05). The histological findings reported liver necrosis, focal hemorrhage, adipose tissue change, and lymphocytic portal hepatitis. In conclusion, using Dic while exposed to CCl4 may exacerbate hepatotoxicity in rats. Therefore, it is suggested that more severe restrictions and safety regulations be placed on using CCl4 in the industry, and caution is advised to these industry workers to use Diclofenac.

PMID:37207345 | DOI:10.1177/07482337231174994

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Single-Molecule Ultrafast Fluorescence-Detected Pump-Probe Microscopy

J Phys Chem Lett. 2023 May 19:4923-4932. doi: 10.1021/acs.jpclett.3c00839. Online ahead of print.

ABSTRACT

We introduce fluorescence-detected pump-probe microscopy by combining a wavelength-tunable ultrafast laser with a confocal scanning fluorescence microscope, enabling access to the femtosecond time scale on the micrometer spatial scale. In addition, we obtain spectral information from Fourier transformation over excitation pulse-pair time delays. We demonstrate this new approach on a model system of a terrylene bisimide (TBI) dye embedded in a PMMA matrix and acquire the linear excitation spectrum as well as time-dependent pump-probe spectra simultaneously. We then push the technique toward single TBI molecules and analyze the statistical distribution of their excitation spectra. Furthermore, we demonstrate the ultrafast transient evolution of several individual molecules, highlighting their different behavior in contrast to the ensemble due to their individual local environment. By correlating the linear and nonlinear spectra, we assess the effect of the molecular environment on the excited-state energy.

PMID:37207316 | DOI:10.1021/acs.jpclett.3c00839

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Randomized Phase II Trial of Endocrine Therapy With or Without Ribociclib After Progression on Cyclin-Dependent Kinase 4/6 Inhibition in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: MAINTAIN Trial

J Clin Oncol. 2023 May 19:JCO2202392. doi: 10.1200/JCO.22.02392. Online ahead of print.

ABSTRACT

PURPOSE: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with endocrine therapy (ET) improves progression-free survival (PFS) and overall survival (OS) in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Although preclinical and clinical data demonstrate a benefit in changing ET and continuing a CDK4/6i at progression, no randomized prospective trials have evaluated this approach.

METHODS: In this investigator-initiated, phase II, double-blind placebo-controlled trial in patients with HR+/HER2- MBC whose cancer progressed during ET and CDK4/6i, participants switched ET (fulvestrant or exemestane) from ET used pre-random assignment and randomly assigned 1:1 to the CDK4/6i ribociclib versus placebo. PFS was the primary end point, defined as time from random assignment to disease progression or death. Assuming a median PFS of 3.8 months with placebo, we had 80% power to detect a hazard ratio (HR) of 0.58 (corresponding to a median PFS of at least 6.5 months with ribociclib) with 120 patients randomly assigned using a one-sided log-rank test and significance level set at 2.5%.

RESULTS: Of the 119 randomly assigned participants, 103 (86.5%) previously received palbociclib and 14 participants received ribociclib (11.7%). There was a statistically significant PFS improvement for patients randomly assigned to switched ET plus ribociclib (median, 5.29 months; 95% CI, 3.02 to 8.12 months) versus switched ET plus placebo (median, 2.76 months; 95% CI, 2.66 to 3.25 months) HR, 0.57 (95% CI, 0.39 to 0.85); P = .006. At 6 and 12 months, the PFS rate was 41.2% and 24.6% with ribociclib, respectively, compared with 23.9% and 7.4% with placebo.

CONCLUSION: In this randomized trial, there was a significant PFS benefit for patients with HR+/HER2- MBC who switched ET and received ribociclib compared with placebo after previous CDK4/6i and different ET.

PMID:37207300 | DOI:10.1200/JCO.22.02392