Investigating Mortality Disparities Among Insured Patients With Colon Cancer Treated in an Integrated Health care System and Other Private Settings.

BACKGROUND: Lower socioeconomic status (SES) affects health care delivery and is associated with worse outcomes. Integrated healthcare systems (IHS) may help reduce barriers to health care and affect outcomes. Our aim was to compare outcomes of colon cancer cases diagnosed at the largest IHS in California, Kaiser Permanente Southern California (KPSC), to other insured patients (OI) to determine how SES influences mortality. METHODS: This retrospective cohort study included insured adults in southern California diagnosed with colon cancer between 2009 and 2014, using data from the California Cancer Registry, and followed through 2017. Main outcome was all-cause mortality. Person-year mortality rates were calculated for two groups, KPSC and OI. Multivariable hazard ratios were calculated for association between SES quintiles and mortality. RESULTS: Total of 15 923 patients were diagnosed with colon cancer, 4195 patients (26.3%) within KPSC and 11 728 patients (73.7%) in OI. The overall mortality rate per 1000 person-years (PY) was lower in KPSC [103.8/1000 PY (95% CI:98.5-109.3)] compared to OI [139.3/1000 PY (95% CI:135.2-143.4)]. Compared to the highest SES group, the lowest SES group did not experience higher mortality risk in the KPSC population, after adjusting for race/ethnicity and other factors (HR, 95% CI = 1.13, .93-1.38). However, in OI patients, lowest and lower-middle SES groups had higher mortality risk compared to the highest SES group (HR, 95% CI = 1.26, 1.13-1.40 and 1.28, 1.16-1.41, respectively). DISCUSSION: Lower SES was associated with higher mortality risk within the OI group; however, within KPSC no such association was observed. Care coordination in IHS settings mitigate SES-related mortality differences.

Coping with Workplace Incivility in Hospital Teams: How Does Team Mindfulness Influence Prevention- and Promotion-Focused Emotional Coping?

Incivility is a growing concern for researchers and practitioners alike, yet we know little about how the team context is related to the way that employees respond to it. In this study, we examined the role of team mindfulness and its direct and buffering effects on individual-level promotion- and prevention-focused emotional coping. We also examined how these forms of coping were related to individual work engagement. In a temporally lagged study of 73 hospital teams (involving 440 team members), multi-level analyses showed that team mindfulness was directly negatively associated with individual-level prevention-focused emotional coping (behavioral disengagement, denial, and venting); however, it was not positively related to individual-level promotion-focused forms of coping (positive reframing and acceptance). In addition, a cross-level interaction effect was identified whereby team mindfulness reduced the positive relationship between incivility and venting, meaning there was less individual-level venting following incivility in the context of higher team mindfulness. These findings may have implications for work engagement, which was shown to be negatively related to venting and behavioral disengagement. Our findings are useful for managers of teams that regularly experience customer incivility as it uncovers how they can develop a team context that discourages ineffective coping responses.

Effectiveness and safety profiling of zolpidem and acupressure in CKD associated pruritus: An interventional study.

BACKGROUND: Chronic kidney disease (CKD)-associated pruritus (CKD-aP) contributes to poor quality of life, including reduced sleep quality and poor sleep quality is a source of patient stress and is linked to lower health-related quality of life. This study aimed to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-aP. METHOD: A multicenter, prospective, randomized, parallel-design, open label interventional study to estimate the effectiveness of zolpidem (10 mg) oral tablets versus acupressure on sleep quality and quality of life in patients with CKD-aP on hemodialysis. A total of 58 hemodialysis patients having sleep disturbance due to CKD-aP completed the entire 8-week follow-up. The patients were divided into a control (acupressure) group of 28 patients and an intervention (zolpidem) group of 30 patients. RESULTS: A total of 58 patients having CKD-aP and sleep disturbance were recruited. In the control group there was a reduction in the PSQI score with a mean ±â€ŠSD from 12.28 ±â€Š3.59 to 9.25 ±â€Š3.99, while in the intervention group the reduction in PSQI score with a mean ±â€ŠSD was from 14.73 ±â€Š4.14 to 10.03 ±â€Š4.04 from baseline to endpoint. However, the EQ5D index score and EQ-visual analogue scale (VAS) at baseline for the control group with a mean ±â€ŠSD was 0.49 ±â€Š0.30 and 50.17 ±â€Š8.65, respectively, while for the intervention group the values were 0.62 ±â€Š0.26 and 47.17 ±â€Š5.82, respectively. The mean EQ5D index score in the control group improved from 0.49 ±â€Š0.30 to 0.53 ±â€Š0.30, but in the intervention group there was no statistical improvement in mean EQ5D index score from 0.62 ±â€Š0.26 to 0.62 ±â€Š0.27 from baseline to week 8. The EQ 5D improved in both groups and the EQ-VAS score was 2.67 points higher at week 8 as compared to baseline in the control group, while in the intervention group the score was 3.33 points higher at week 8 as compared to baseline. Comparing with baseline, the PSQI scores were significantly reduced after week 4 and week 8 (P =  < .001). Furthermore, at the end of the study, the PSQI scores were significantly higher in the control as compared to the intervention group (P = .012). CONCLUSION: An improvement in sleep quality and quality of life among CKD-aP patients on hemodialysis has been observed in both the control and intervention groups. Zolpidem and acupressure safety profiling showed no severe adverse effect other that drowsiness, nausea and daytime sleeping already reported in literature of zolpidem.

A Call to Action to Address Disparities in Palliative Care Access: A Conceptual Framework for Individualizing Care Needs.

Palliative care is a values-driven approach for providing holistic care for individuals and their families enduring serious life-limiting illness. Despite its proven benefits, access and acceptance is not uniform across society. The genesis of palliative care was developed through a traditional Western lens, which dictated models of interaction and communication. As the importance of palliative care is increasingly recognized, barriers to accessing services and perceptions of relevance and appropriateness are being given greater consideration. The COVID-19 pandemic and recent social justice movements in the United States, and around the world, have led to an important moment in time for the palliative care community to step back and consider opportunities for expansion and growth. This article reviews traditional models of palliative care delivery and outlines a modified conceptual framework to support researchers, clinicians, and staff in evaluating priorities for ensuring individualized patient needs are addressed from a position of equity, to create an actionable path forward.

Coffee Consumption and Risk of Stroke: A Mendelian Randomization Study.

OBJECTIVE: Observational epidemiological studies have reported a relationship between coffee intake and risk of stroke. However, evidence for this association is inconsistent, and it remains uncertain whether the association is causal or due to confounding or reverse causality. To clarify this relationship, we adopted a Mendelian randomization (MR) approach to evaluate the effects of coffee consumption on the risk of stroke and its subtypes. METHODS: A meta-analysis of genome-wide association studies (GWASs) including 91,462 coffee consumers was used to identify instruments for coffee consumption. Summary-level data for stroke, intracerebral hemorrhage, ischemic stroke (IS), and IS subtypes were obtained from GWAS meta-analyses conducted by the MEGASTROKE consortium. MR analyses were performed using the inverse-variance-weighted, weighted-median, MR-PRESSO (Pleiotropy RESidual Sum and Outlier) test and MR-Egger regression. Sensitivity analyses were further performed using alternative instruments to test the robustness of our findings. RESULTS: Genetically predicted coffee consumption (high vs infrequent/no) was not associated with risk of stroke. Similarly, among coffee consumers, MR analysis did not indicate causal associations between coffee consumption (cups/day) and risk of stroke. However, in the subgroup analysis, we found weak suggestive evidence for a potential protective effect of coffee consumption on risk of small vessel (SV)-IS, although the association did not reach statistical significance after correction for multiple comparisons. INTERPRETATION: This study suggests that coffee consumption is not causally associated with risk of stroke or its subtypes. Further studies are warranted to elucidate the possible association between coffee intake and risk of SV-IS, as well as its potential underlying mechanisms. ANN NEUROL 2020;87:525-532.

Bone morphogenetic protein signaling in inflammation.

IMPACT STATEMENT: By compiling findings from recent studies, this review will garner novel insight on the dynamic and complex role of BMP signaling in diseases of inflammation, highlighting the specific roles played by both individual ligands and endogenous antagonists. Ultimately, this summary will help inform the high therapeutic value of targeting this pathway for modulating diseases of inflammation.

A randomized controlled trial for effectiveness of zolpidem versus acupressure on sleep in hemodialysis patients having chronic kidney disease-associated pruritus.

BACKGROUND: Pruritus adds to the complications of chronic kidney disease (CKD) patient and a well-recognized complication among the CKD patients. Majority of the patients on hemodialysis experience a generalized pruritus and patients reported being moderately to extremely disturbed by at least one of the sleep-related condition. This study aim to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-associated pruritus. METHODS: A multicentered, open-label, parallel group, prospective randomized controlled trial among patients suffering from CKD-associated pruritus with sleep disturbance, after randomization into control, and intervention group to be held at North West General Hospital and Research Center Peshawar, Pakistan and Institute of Kidney Diseases Peshawar, Pakistan. RESULTS: The primary outcome is to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-associated pruritus. After baseline assessment by Urdu version of 5D itch scale and Urdu version of Pittsburgh Sleep Quality Index (PSQI) and Urdu EQ-5D 3L, the intervention group will be given zolpidem 10 mg oral tablets and control group with acupressure on both foots on KI-1 acupoints for total of 6 minutes. Assessment will be done at weeks 4 and 8 from baseline by using Urdu version of 5D itch scale and Urdu version of PSQI and Urdu EQ-5D 3L, whereas safety profiling of zolpidem 10 mg tablet at week 6 from baseline and acupressure acceptability at week 6 from baseline. Analysis of covariance will be used to examine the differences in treatment effects between the intervention and control groups. CONCLUSION: Improvement of sleep quality and quality of life among patients with CKD-associated pruritus requires great importance. This study aims to improve the quality of sleep and quality of life among patients with hemodialysis suffering from CKD-associated pruritus.

Fenofibrate prevents skeletal muscle loss in mice with lung cancer.

The cancer anorexia cachexia syndrome is a systemic metabolic disorder characterized by the catabolism of stored nutrients in skeletal muscle and adipose tissue that is particularly prevalent in nonsmall cell lung cancer (NSCLC). Loss of skeletal muscle results in functional impairments and increased mortality. The aim of the present study was to characterize the changes in systemic metabolism in a genetically engineered mouse model of NSCLC. We show that a portion of these animals develop loss of skeletal muscle, loss of adipose tissue, and increased inflammatory markers mirroring the human cachexia syndrome. Using noncachexic and fasted animals as controls, we report a unique cachexia metabolite phenotype that includes the loss of peroxisome proliferator-activated receptor-α (PPARα) -dependent ketone production by the liver. In this setting, glucocorticoid levels rise and correlate with skeletal muscle degradation and hepatic markers of gluconeogenesis. Restoring ketone production using the PPARα agonist, fenofibrate, prevents the loss of skeletal muscle mass and body weight. These results demonstrate how targeting hepatic metabolism can prevent muscle wasting in lung cancer, and provide evidence for a therapeutic strategy.

Effectiveness of fenugreek as a galactagogue: A network meta-analysis.

A systematic review and network-meta analysis (NMA) were performed to test significance of the galactagogue effect of fenugreek administrated to lactating women versus other comparators (i.e., placebo/control/other galactagogues). A pairwise comparison for the treatment effect was carried out to generate the forest plot for the NMA. League tables were generated using treatment effect, weighted mean difference (WMD; 95% confidence interval, CI) for all pairwise comparisons, where WMD > 0 favors the column-defining treatment. Five studies were identified with 122 participants receiving treatment with fenugreek. The NMA results of 4 studies indicated that consumption of fenugreek significantly increased amount of the produced breast milk [11.11, CI 95% 6.77, 15.46] versus placebo. The pairwise comparison revealed that fenugreek was effective as a galactagogue compared to placebo, control, and reference groups WMD 17.79 [CI 11.71, 23.88]. However, the effect of fenugreek was substantially inferior to Coleus amboinicus Lour and palm date. The NMA using pairwise comparison demonstrated the effect of C. amboinicus and palm date in the stimulation of the breast milk production was comparable and superior to all comparators.

HIF-1α is required for disturbed flow-induced metabolic reprogramming in human and porcine vascular endothelium.

Hemodynamic forces regulate vascular functions. Disturbed flow (DF) occurs in arterial bifurcations and curvatures, activates endothelial cells (ECs), and results in vascular inflammation and ultimately atherosclerosis. However, how DF alters EC metabolism, and whether resulting metabolic changes induce EC activation, is unknown. Using transcriptomics and bioenergetic analysis, we discovered that DF induces glycolysis and reduces mitochondrial respiratory capacity in human aortic ECs. DF-induced metabolic reprogramming required hypoxia inducible factor-1α (HIF-1α), downstream of NAD(P)H oxidase-4 (NOX4)-derived reactive oxygen species (ROS). HIF-1α increased glycolytic enzymes and pyruvate dehydrogenase kinase-1 (PDK-1), which reduces mitochondrial respiratory capacity. Swine aortic arch endothelia exhibited elevated ROS, NOX4, HIF-1α, and glycolytic enzyme and PDK1 expression, suggesting that DF leads to metabolic reprogramming in vivo. Inhibition of glycolysis reduced inflammation suggesting a causal relationship between flow-induced metabolic changes and EC activation. These findings highlight a previously uncharacterized role for flow-induced metabolic reprogramming and inflammation in ECs.

The Effects of Mindfulness on Older Adults with Mild Cognitive Impairment.

BACKGROUND: The current lack of an effective cure for dementia would exacerbate its prevalence and incidence globally. Growing evidence has linked mindfulness to cognitive and psychological improvements that could be relevant for mild cognitive impairment (MCI). OBJECTIVE: To investigate whether mindfulness practice can improve health outcomes of MCI. METHODS: The study is the first longitudinal mixed-methods observational study with a one-year follow-up period, that customized an eight-week group-based mindfulness training program for older adults with MCI (n = 14). Measures included cognitive function, psychological health, trait mindfulness, adherence to mindfulness practice, and everyday activities functioning as assessed at pre-intervention, post-intervention, and one-year follow-up. Repeated measures ANOVAs, Pearson's correlation analyses, and Mann-Whitney U tests were performed. RESULTS: The MCI participants showed significant improvements in cognitive function (p < 0.05) and trait mindfulness (p < 0.05) after completing the intervention. Between program intervention and one-year follow-up (59 weeks), positive correlations were found between their cognitive function (p < 0.05) and everyday activities functioning (p < 0.05) with the duration of mindfulness meditation; and between trait mindfulness and the level of informal mindfulness practice (p < 0.05). Those who meditated more during these 59 weeks, showed greater improvements in cognitive function (p < 0.05) and everyday activities functioning (p < 0.05), with large effect sizes at the one-year follow-up. Qualitative findings will be reported separately. CONCLUSION: Long-term mindfulness practice may be associated with cognitive and functional improvements for older adults with MCI. Mindfulness training could be a potential efficacious non-pharmacological therapeutic intervention for MCI.

A phase I dose-finding study of silybin phosphatidylcholine (milk thistle) in patients with advanced hepatocellular carcinoma.

PURPOSE: To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. EXPERIMENTAL DESIGN: Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. RESULTS: Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. CONCLUSION: Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests.

Alanyl-glutamine promotes intestinal epithelial cell homeostasis in vitro and in a murine model of weanling undernutrition.

Alanyl-glutamine (Ala-Gln) has recently been shown to enhance catch-up growth and gut integrity in undernourished children from Northeast Brazil. We hypothesized that the intestinal epithelial effects of Ala-Gln in malnourished weanling mice and mouse small intestinal epithelial (MSIE) cells would include modulation of barrier function, proliferation, and apoptosis. Dams of 10-day-old suckling C57BL/6 pups were randomized to a standard diet or an isocaloric Northeast Brazil "regional basic diet," moderately deficient in protein, fat, and minerals. Upon weaning to their dam's diet on day of life 21, pups were randomized to Ala-Gln solution or water. At 6 wk of age, mice were killed, and jejunal tissue was collected for morphology, immunohistochemistry, and Ussing chamber analysis of transmucosal resistance and permeability. Proliferation of MSIE cells in the presence or absence of Ala-Gln was measured by MTS and bromodeoxyuridine assays. MSIE apoptosis was assessed by annexin and 7-amino-actinomycin D staining. Pups of regional basic diet-fed dams exhibited failure to thrive. Jejunal specimens from undernourished weanlings showed decreased villous height and crypt depth, decreased transmucosal resistance, increased permeability to FITC-dextran, increased claudin-3 expression, and decreased epithelial proliferation and increased epithelial apoptosis (as measured by bromodeoxyuridine and cleaved caspase-3 staining, respectively). Undernourished weanlings supplemented with Ala-Gln showed improvements in weight velocity, villous height, crypt depth, transmucosal resistance, and epithelial proliferation/apoptosis compared with unsupplemented controls. Similarly, Ala-Gln increased proliferation and reduced apoptosis in MSIE cells. In summary, Ala-Gln promotes intestinal epithelial homeostasis in a mouse model of malnutrition-associated enteropathy, mimicking key features of the human disease.

Disclosure to physicians of CAM use by breast cancer patients: findings from the Women's Healthy Eating and Living Study.

BACKGROUND: Physician awareness of their patients' use of complementary and alternative medicine (CAM) is crucial, particularly in the setting of a potentially life-threatening disease such as cancer. The potential for harmful treatment interactions may be greatest when a patient sees a CAM practitioner--perceived as a physician-like authority figure--but does not disclose this to their physician. Therefore, this study investigated the extent of nondisclosure in a large cohort of cancer patients. METHODS: CAM use in participants of the UCSD Women's Healthy Eating and Living (WHEL) Study, a multicenter study of the effect of diet and lifestyle on disease-free and overall survival in women aged 18-70 years who had completed treatment for invasive breast cancer between 1995 and 2000, is investigated. Data regarding CAM use and disclosure were collected via a telephone-administered questionnaire in 2003-2004. This questionnaire asked about different CAM modalities, including those requiring a "skilled CAM practitioner" (acupuncturist, chiropractor, homeopath, or naturopath) for administration. Demographic data were obtained at the WHEL baseline clinic interview. Modality-specific disclosure rates were determined and a comparison of demographic variables of disclosers versus nondisclosers was conducted using 2 tests for categorical variables, and t tests for continuous variables. RESULTS: Of 3088 total WHEL participants, 2527 completed the CAM questionnaire. Of these, 2017 reported using some form of CAM. Of these, 300 received treatment from an acupuncturist, chiropractor, homeopath, or naturopath and also provided information on whether or not they disclosed this care to their conventional physician. The highest disclosure rate was for naturopathy (85%), followed by homeopathy (74%), acupuncture (71%), and chiropractic (47%). Among demographic characteristics, only education (P=.047) and study site (P=.039) were associated with disclosure. College graduates and postgraduates, in particular, were more likely to disclose CAM use to their physicians than those with lesser education. CONCLUSION: Overall, moderately high rates of physician disclosure of CAM use for all modalities except chiropractic were observed. Education and study site associations suggest that disclosure may be greater when CAM use is more prevalent and possibly more socially accepted. These findings underscore the importance of open, destigmatized patient--physician communication regarding CAM use.