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The Healthy Eating Index-2015 and All-Cause/Cause-Specific Mortality: A Systematic Review and Dose-Response Meta-Analysis

Adv Nutr. 2024 Feb 23:100166. doi: 10.1016/j.advnut.2023.100166. Online ahead of print.

ABSTRACT

This meta-analysis was undertaken to determine the predictive value of Healthy Eating Index (HEI)-2015 in all-cause, cancer-cause, and cardiovascular disease (CVD)-cause mortality. This review was registered with PROSPERO as CRD42023421585. PubMed and Web of Science were searched for articles published by September 15, 2023. The hazard ratio (HR) was calculated with exact confidence intervals (CIs) of 95%. Statistical heterogeneity among studies was measured by Cochran’s Q test (χ2) and the I2 statistic. Eighteen published studies were finally identified in this meta-analysis. The results showed that the HEI-2015 was associated with all-cause mortality either as a categorical variable (HR: 0.80; 95% CI: 0.79, 0.82) or continuous variable (HR: 0.90; 95% CI: 0.88, 0.92). The HEI-2015 was also associated with cancer-cause mortality as categorical variable (HR: 0.81; 95% CI: 0.78, 0.83) or continuous variable (HR: 0.90; 95% CI: 0.81, 0.99). The categorical HEI-2015 was also independently correlated with decreasing CVD-cause mortality (HR: 0.81; 95% CI: 0.75, 0.87). A nonlinear dose-response relation between the HEI-2015 and all-cause mortality was found. In the linear dose-response analysis, the risk of mortality from cancer decreased by 0.42% per 1 score increment of the HEI-2015 and the risk of CVD-cause mortality decreased by 0.51% with the increment of the HEI-2015 per 1 score. Our analysis indicated a significant relationship between the HEI-2015 and all-cause, cancer-cause, and CVD-cause mortality.

PMID:38461130 | DOI:10.1016/j.advnut.2023.100166

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Analysis of retreatment with monoclonal antibodies in chronic/episodic migraine: Real world data

Farm Hosp. 2024 Mar 8:S1130-6343(24)00023-0. doi: 10.1016/j.farma.2024.02.003. Online ahead of print.

ABSTRACT

OBJECTIVE: To analyze the response to retreatment in patients with chronic/episodic migraine who discontinued therapy with erenumab/fremanezumab after 1 year of treatment.

METHODS: Observational, retrospective, single-center, multidisciplinary study in patients with chronic/episodic migraine who received therapy with erenumab/fremanezumab for at least 1 year and discontinued it after achieving an adequate response (optimization). The evaluation of the response after retreatment included the following variables: DMM, MIDAS, and HIT-6 scales at the beginning of retreatment and 3 months later. The response was evaluated in different subgroups (episodic/chronic, erenumab/fremanezumab, and time until retreatment).

RESULTS: 48 patients were included. 70.8% (n=34) required retreatment with mAb, with a median of 3.9 (2.9-6.4) months until reintroduction. Clinical response after retreatment was achieved in 67.6% (n=23) of patients. No statistically significant differences were found in the analyzed subgroups.

CONCLUSION: Interruption of treatment with erenumab/fremanezumab for chronic/episodic migraine produces a clinical worsening of the disease requiring retreatment in most cases, approximately after 4 months. Two out of three patients respond positively after restarting monoclonal therapy. This response does not appear to be related to the type of migraine, the specific monoclonal antibody prescribed, or the time to retreatment.

PMID:38461112 | DOI:10.1016/j.farma.2024.02.003

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The IRELAnD study-investigating the role of early low-dose aspirin in diabetes mellitus: a double-blinded, placebo-controlled, randomized trial

Am J Obstet Gynecol MFM. 2024 Mar 8:101297. doi: 10.1016/j.ajogmf.2024.101297. Online ahead of print.

ABSTRACT

BACKGROUND: Although aspirin therapy is being increasingly advocated with the intention of risk modification for a wide range of pregnancy complications, women with prepregnancy diabetes mellitus are commonly excluded from clinical trials.

OBJECTIVE: The primary aim of this study was to examine the effect of aspirin therapy on a composite measure of adverse perinatal outcome in pregnancies complicated by pregestational diabetes mellitus.

STUDY DESIGN: A double-blinded, placebo-controlled randomized trial was conducted at 6 university-affiliated perinatology centers. Women with type 1 diabetes mellitus or type 2 diabetes mellitus of at least 6 months’ duration were randomly allocated to 150-mg daily aspirin or placebo from 11 to 14 weeks’ gestation until 36 weeks. Established vascular complications of diabetes mellitus, including chronic hypertension or nephropathy, led to exclusion from the trial. The primary outcome was a composite measure of placental dysfunction (preeclampsia, fetal growth restriction, preterm birth <34 weeks’ gestation, or perinatal mortality). The planned sample size was 566 participants to achieve a 35% reduction in the primary outcome, assuming 80% statistical power. Secondary end points included maternal and neonatal outcomes and determination of insulin requirements across gestation. Data were centrally managed using ClinInfo and analyzed using SAS 9.4. The 2 treatment groups were compared using t tests or chi-square tests, as required, and longitudinal data were compared using a repeated-measures analysis.

RESULTS: From February 2020 to September 2022, 191 patients were deemed eligible, 134 of whom were enrolled (67 randomized to aspirin and 67 to placebo) with a retrospective power of 64%. A total of 101 (80%) women had type 1 diabetes mellitus and 25 (20%) had type 2 diabetes mellitus. Reaching the target sample size was limited by the impact of the COVID-19 pandemic. Baseline characteristics were similar between the aspirin and placebo groups. Treatment compliance was very high and similar between groups (97% for aspirin, 94% for placebo). The risk of the composite measure of placental dysfunction did not differ between groups (25% aspirin vs 21% placebo; P=.796). Women in the aspirin group had significantly lower insulin requirements throughout pregnancy compared with the placebo group. Insulin requirements in the aspirin group increased on average from 0.7 units/kg at baseline to 1.1 units/kg by 36 weeks’ gestation (an average 83% within-patient increase), and increased from 0.7 units/kg to 1.3 units/kg (a 181% within-patient increase) in the placebo group, over the same gestational period (P=.002). Serial hemoglobin A1c levels were lower in the aspirin group than in the placebo group, although this trend did not reach statistical significance.

CONCLUSION: In this multicenter, double-blinded, placebo-controlled randomized trial, aspirin did not reduce the risk of adverse perinatal outcome in pregnancies complicated by prepregnancy diabetes mellitus. Compared with the placebo group, aspirin-treated patients required significantly less insulin throughout pregnancy, indicating a beneficial effect of aspirin on glycemic control. Aspirin may exert a plausible placenta-mediated effect on pregestational diabetes mellitus that is not limited to its antithrombotic properties.

PMID:38461094 | DOI:10.1016/j.ajogmf.2024.101297

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What do parents of nonverbal and minimally verbal autistic children think about genomic autism research?

Autism. 2024 Mar 9:13623613231213431. doi: 10.1177/13623613231213431. Online ahead of print.

ABSTRACT

In Summer 2021, a genomic study of autism, Spectrum 10 K, was paused due to backlash from the autistic and autism communities. This raised important questions about how these communities perceive genomic research. The Personal Experiences of Autism and Perceptions of DNA-based research study was established to address this issue among a range of sub-groups within these communities. Twenty parents of nonverbal or minimally verbal autistic children took part in the current study. Data were provided in diverse formats including online interviews, telephone interviews, and writing. This approach was co-produced with autistic experts by experience and involved a parent of a minimally verbal autistic child. Data were analysed using reflexive Thematic Analysis. We found that participants were supportive of autism research, including some genomic research, as long as it is designed to support autistic people and is ethical and transparent. However, while some believed that polygenic scores, genomic predictors of the statistical probability of being autistic, would be helpful, others argued that this would only be true in an ideal world and that the world is too far from ideal. Participants felt excluded from the autistic and autism communities and that the dominant voices in those communities do not represent them or their children. We concluded that genomic researchers need to work with the autistic and autism communities to design future work, and that it is important to ensure a representative range of voices are heard.

PMID:38459822 | DOI:10.1177/13623613231213431

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Canadian intensive care unit nurses’ responses to moral distress during the COVID-19 pandemic, and their recommendations for mitigative interventions

J Adv Nurs. 2024 Mar 9. doi: 10.1111/jan.16135. Online ahead of print.

ABSTRACT

AIMS: To describe intensive care unit nurses’ experiences of moral distress during the COVID-19 pandemic, and their recommendations for mitigative interventions.

DESIGN: Interpretive description.

METHODS: Data were collected with a purposeful sample of 40 Canadian intensive care unit nurses between May and September 2021. Nurses completed a demographic questionnaire, the Measure of Moral Distress-Healthcare Professionals survey and in-depth interviews. Quantitative data were analysed using descriptive statistics. Qualitative data were categorized and synthesized using reflexive thematic analysis and rapid qualitative analysis.

RESULTS: Half of the nurses in this sample reported moderate levels of moral distress. In response to moral distress, nurses experienced immediate and long-term effects across multiple health domains. To cope, nurses discussed varied reactions, including action, avoidance and acquiescence. Nurses provided recommendations for interventions across multiple organizations to mitigate moral distress and negative health outcomes.

CONCLUSION: Nurses reported that moral distress drove negative health outcomes and attrition in response to moral events in practice. To change these conditions of moral distress, nurses require organizational investments in interventions and cultures that prioritize the inclusion of nursing perspectives and voices.

IMPLICATIONS FOR THE PROFESSION: Nurses engage in a variety of responses to cope with moral distress. They possess valuable insights into the practice issues central to moral distress that have significant implications for all members of the healthcare teams, patients and systems. It is essential that nurses’ voices be included in the development of future interventions central to the responses to moral distress.

REPORTING METHOD: This study adheres to COREQ guidelines.

IMPACT: What Problem did the Study Address? Given the known structural, systemic and environmental factors that contribute to intensive care unit nurses’ experiences of moral distress, and ultimately burnout and attrition, it was important to learn about their experiences of moral distress and their recommendations for organizational mitigative interventions. Documentation of these experiences and recommendations took on a greater urgency during the context of a global health emergency, the COVID-19 pandemic, where such contextual influences on moral distress were less understood. What Were the Main Findings? Over half of the nurses reported a moderate level of moral distress. Nurses who were considering leaving nursing practice reported higher moral distress scores than those who were not considering leaving. In response to moral distress, nurses experienced a variety of outcomes across several health domains. To cope with moral distress, nurses engaged in patterns of action, avoidance and acquiescence. To change the conditions of moral distress, nurses desire organizational interventions, practices and culture changes situated in the amplification of their voices. Where and on Whom Will the Research Have an Impact on? These findings will be of interest to: (1) researchers developing and evaluating interventions that address the complex phenomenon of moral distress, (2) leaders and administrators in hospitals, and relevant healthcare and nursing organizations, and (3) nurses interested in leveraging evidence-informed recommendations to advocate for interventions to address moral distress. What Does this Paper Contribute to the Wider Global Community? This paper advances the body of scientific work on nurses’ experiences of moral distress, capturing this phenomenon within the unique context of a global health emergency. Nurses’ levels of moral distress using Measure of Moral Distress-Healthcare Professional survey were reported, serving as a comparator for future studies seeking to measure and evaluate intensive care unit nurses’ levels of moral distress. Nurses’ recommendations for mitigative interventions for moral distress have been reported, which can help inform future interventional studies.

PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

PMID:38459779 | DOI:10.1111/jan.16135

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Use of FreeStyle Libre for continuous glucose monitoring in adult horses

J Vet Emerg Crit Care (San Antonio). 2024 Mar 8. doi: 10.1111/vec.13367. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the feasibility of using the FreeStyle Libre (a continuous glucose monitoring system [CGMS]) for instantaneous continuous monitoring of interstitial glucose in adult horses and examine the applicability and accuracy of this system in horses submitted to combined glucose-insulin test (CGIT).

DESIGN: Laboratory measurements and continuous glucose monitoring system (CGMS) readings were analyzed using a 2 × 2 factorial statistical model with repeated measures over time. This analysis assessed the effects of the test (factor 1), group (factor 2), and their interactions (test × group, test × time, and group × time). Pearson’s correlation analysis was applied to blood glucose values. Mean comparisons were conducted using the t-test, and agreement between techniques was assessed via the Bland-Altman method, with a 95% confidence interval.

SETTING: Field study on private horse farms in association with a veterinary school.

ANIMALS: Ten healthy stallions were assigned to one of two groups based on their body condition scores (BCS). Group 1 (G1, n = 5) consisted of nonobese horses with a BCS of 5 or 6, while Group 2 (G2, n = 5) consisted of obese horses with a BCS of 7 or higher.

INTERVENTIONS: A CGMS sensor was attached to the dorsolateral aspect of the proximal one third of each horse’s neck. Laboratory blood glucose measurements and CGMS interstitial glucose readings were compared at different time points for up to 7 days after sensor fixation. Obese horses were also submitted to CGIT on Day 4.

MEASUREMENTS AND MAIN RESULTS: A comparative analysis of glucose measurements obtained in G1 and G2 horses using the CGMS and enzymatic methods revealed significant group × time interactions (P < 0.001) and time effects (P < 0.001). No interactions were detected between group (P = 0.45), test (P = 0.62), group and test (P = 0.28), or time and test (P = 0.92). In G1 and G2, tests were significantly correlated (r = 0.84 and P = 0.00) at all time points (T0-T5). Agreement between the glucose values obtained using different methods was excellent despite a small time delay in CGMS detection of rapid changes in blood glucose.

CONCLUSIONS: It was concluded that the CGMS can be used for indirect assessment of glycemic status (ie, based on interstitial glucose measurements) in nonobese and obese adult horses submitted to CGIT.

PMID:38459745 | DOI:10.1111/vec.13367

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CTLA-4 Blockade of Natural Killer Cells Increases Cytotoxicity against Acute Lymphoid Leukaemia Cells Neda

Cell J. 2024 Feb 1;26(2):150-157. doi: 10.22074/cellj.2024.2015187.1444.

ABSTRACT

OBJECTIVE: There is interest in using cytotoxic T lymphocyte antigen-4 (CTLA-4) immunotherapy to treat blood cancers. Unfortunately, patients with acute lymphoblastic leukaemia (ALL) frequently exhibit resistance to treatment and natural killer (NK) cell exhaustion. This study aims to increase the cytotoxic potency of natural killer cells by using CTLA-4 to block the Nalm-6 leukaemia cell line.

MATERIALS AND METHODS: In this experimental study, NK cells were purified from the peripheral blood mononuclear cells (PBMCs) of 10 healthy people and assessed by flow cytometry for purity and viability. The purified cells were activated overnight at 37°C and 5% CO2 with interleukin-15 (IL-15, 10 ng/ml) followed by evaluation of expressions of CTLA-4, activating and inhibitory receptors, and the release of interferon gamma (IFN-γ) and granzyme B (GZM B). CTLA-4 expression on NK cells from recurrent ALL patients was also evaluated. Finally, the cytotoxic activity of NK cells was assessed after the CTLA-4 blockade.

RESULTS: The purity of the isolated cells was 96.58 ± 2.57%. Isolated NK cells activated with IL-15 resulted in significantly higher CTLA-4 expression (8.75%, P<0.05). Similarly, CTLA-4 expression on the surface of NK cells from patients with ALL was higher (7.46%) compared to healthy individuals (1.46%, P<0.05). IL-15 reduced NKG2A expression (P<0.01), and increased expressions of NKP30 (P<0.05) and NKP46 (P<0.01). The activated NK cells released more IFN-γ (P<0.5) and GZM B (P<0.01) compared to unactivated NK cells. Blockade of CTLA-4 enhanced the NK cell killing potential against Nalm-6 cells (56.3%, P<0.05); however, IFN-γ and GZM B levels were not statistically different between the blocked and non-blocked groups.

CONCLUSION: Our findings suggest that CTLA-4 blockage of Nalm-6 cells causes an increase in antitumour activity of NK cells against these cells. Our study also provides evidence for the potential of cancer immunotherapy treatment using blocking anti-CTLA-4 mAbs.

PMID:38459732 | DOI:10.22074/cellj.2024.2015187.1444

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Mendelian randomization analysis using multiple biomarkers of an underlying common exposure

Biostatistics. 2024 Mar 8:kxae006. doi: 10.1093/biostatistics/kxae006. Online ahead of print.

ABSTRACT

Mendelian randomization (MR) analysis is increasingly popular for testing the causal effect of exposures on disease outcomes using data from genome-wide association studies. In some settings, the underlying exposure, such as systematic inflammation, may not be directly observable, but measurements can be available on multiple biomarkers or other types of traits that are co-regulated by the exposure. We propose a method for MR analysis on latent exposures (MRLE), which tests the significance for, and the direction of, the effect of a latent exposure by leveraging information from multiple related traits. The method is developed by constructing a set of estimating functions based on the second-order moments of GWAS summary association statistics for the observable traits, under a structural equation model where genetic variants are assumed to have indirect effects through the latent exposure and potentially direct effects on the traits. Simulation studies show that MRLE has well-controlled type I error rates and enhanced power compared to single-trait MR tests under various types of pleiotropy. Applications of MRLE using genetic association statistics across five inflammatory biomarkers (CRP, IL-6, IL-8, TNF-α, and MCP-1) provide evidence for potential causal effects of inflammation on increasing the risk of coronary artery disease, colorectal cancer, and rheumatoid arthritis, while standard MR analysis for individual biomarkers fails to detect consistent evidence for such effects.

PMID:38459704 | DOI:10.1093/biostatistics/kxae006

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The utility of the surprise question by nurses to identify hospitalised older patients nearing the end-of-life and promotion of advance care planning: An interventional study

J Clin Nurs. 2024 Mar 8. doi: 10.1111/jocn.17096. Online ahead of print.

ABSTRACT

AIMS AND OBJECTIVES: To assess the prognostic accuracy of the surprise question (SQ) when used by nurses working in hospital wards to determine 1-year mortality in acutely hospitalised older patients.

BACKGROUND: The predictive accuracy of the SQ, when used by general nurses caring for older hospitalised patients, has not been comprehensively studied.

DESIGN: A prospective cohort study.

METHODS: This cohort study recruited consecutive 10,139 older patients (aged ≥65 years) who were admitted to Taipei City Hospital and were evaluated for the needs of palliative care in 2015. All patients were followed up for 12 months or until their death. The c-statistic value was calculated to indicate the predictive accuracy of the SQ and Palliative Care Screening Tool (PCST).

RESULTS: Of all participants, 18.8% and 18.6% had a SQ response of ‘no’ and a PCST score ≥4, respectively. After controlling for other covariates, an SQ response of ‘no’ (adjusted hazard ratio [aHR], 2.05; 95% confidence interval [CI], 1.83-2.31) and a PCST score ≥4 (AHR = 1.50; 95% CI: 1.29-1.75) were found to be the independent predictors for patients’ 12-month mortality. The C-statistic values of the SQ and the PCST at recognising patients in their last year of life were .663 and .670, respectively. Moreover, there was moderate concordance (k = .44) between the SQ and the PCST in predicting 12-month mortality.

CONCLUSIONS: SQ response of ‘no’ and a PCST score ≥4 were independent predictors of 12-month mortality in older patients.

RELEVANCE TO CLINICAL PRACTICE: The SQ, when used by nurses working in hospital wards, is effective in identifying older patients nearing the end of life, as well as in providing advance care planning for patients.

PATIENT OR PUBLIC CONTRIBUTION: Patients’ palliative care needs at admission were assessed by general nurses using the SQ and PCST.

PMID:38459702 | DOI:10.1111/jocn.17096

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Comparison of Dry Needling and Cold-Spray-Stretching Treatments by Ultrasonography and Electrophysiology: Prospective, Randomized Controlled Trial

J Ultrasound Med. 2024 Mar 8. doi: 10.1002/jum.16445. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare the efficacy of dry needling (DN) and cold-spray-stretching treatments using surface electromyography (sEMG) and ultrasound (US) in the treatment of patients with myofascial pain syndrome (MPS) with active trigger point (ATrP) in the upper trapezius muscle.

METHODS: This prospective randomized single-blind study included 60 MPS patients aged 18-65 years who have ATrP in the upper trapezius muscle. Patients were randomized into two treatment groups as DN and cold spray stretching. Both treatment groups received 1 treatment per week and totally 3 sessions. Evaluation parameters were pain level assessed by Numeric Rating Scale and algometer, neck range of motion angles, neck disability index (NDI). The effects of the treatments on ATrP were evaluated by sEMG and US histogram. All parameters were evaluated at the beginning of the treatment and at the end. Algometer and sEMG were performed also before and after the first and third sessions.

RESULTS: There was no significant difference between the two groups regarding demographic data. The mean age of the participants was 39.7 ± 11.6 years. Fifty-one patients were female. Significant improvement in terms of pain level, functionality, sEMG, and US histogram were achieved in both groups (P < .05). When comparing the two groups, algometer scores and the NDI score were statistically higher in the cold-spray-stretching group than in the DN group (P < .008 and P < .028, respectively).

CONCLUSION: Both treatment options should be preferred. The efficacy of both treatments was observed via sEMG and US histograms.

PMID:38459670 | DOI:10.1002/jum.16445