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Feasibility of a Palliative Care Intervention within Routine Care of Hepatocellular Carcinoma: A Pilot Randomized Controlled Trial

J Palliat Med. 2022 Sep 23. doi: 10.1089/jpm.2022.0338. Online ahead of print.

ABSTRACT

Background: Patients with hepatocellular cancer (HCC) are at risk for poor quality of life (QoL) and high symptom burden, coupled with limited treatment options. Palliative care (PC) can play an important role in reducing the suffering of this population, but remains underutilized. Aim: To demonstrate feasibility of an outpatient PC intervention within HCC care. Methods: This is a pilot randomized controlled trial conducted at an academic center. All stages of HCC patients (except Barcelona Clinic Liver Cancer stage D) with a scheduled hepatology appointment were eligible. Patients were randomized to receive PC intervention or usual care (control arm). In the PC arm, patients received PC from a PC provider at enrollment and at three months from the baseline visit, in addition to continued standard of care. Control arm received only standard care. All patients completed FACT-Hep (Functional Assessment of Cancer Therapy-Hepatobiliary Cancer) and modified Edmonton Symptom Assessment Scale at baseline and at three-month visit. Descriptive statistics were utilized to summarize questionnaires, and change in QoL and symptoms from baseline to three months were compared between the two study groups. Results: Of the 109 approached, 57 patients (52.3%) consented to enroll, and 52 (91%) completed the study. QoL and symptom burden assessments demonstrated impaired QoL and high symptom burden in both arms of the study. At least 50% of enrolled patients in each arm had some degree of fatigue, pain, sleep disturbance, and appetite loss, at baseline. Post-intervention, symptom burden and QoL improved in the intervention arm and remained same or worsened in the control group. All FACT-Hep scores decreased numerically among controls and increased numerically among patients in the PC intervention group. Conclusion: Outpatient PC intervention within routine HCC care is feasible, and can potentially improve QoL and symptoms.

PMID:36149682 | DOI:10.1089/jpm.2022.0338

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Association of Exposure to Phthalate Metabolites With Sex Hormones, Obesity, and Metabolic Syndrome in US Women

JAMA Netw Open. 2022 Sep 1;5(9):e2233088. doi: 10.1001/jamanetworkopen.2022.33088.

ABSTRACT

IMPORTANCE: Obesity and metabolic syndrome are highly prevalent among the US population and are associated with the dysregulation of sex hormones. An increase in obesity and metabolic syndrome may also be associated with exposure to phthalates. The association of exposure to phthalate metabolites with sex hormones and metabolic health has been understudied in the female population.

OBJECTIVE: To evaluate the association between exposure to common phthalate metabolites with total testosterone (TT) levels, sex hormone-binding globulin (SHBG) levels, obesity, and metabolic syndrome among women.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data collected from the National Health and Nutrition Examination Survey during 2013 to 2016. Female participants aged 15 years or older with urinary profiles containing common phthalate metabolites were included in this study. Statistical analyses were performed from March 15, 2021, to April 30, 2022.

EXPOSURES: Urinary concentrations of phthalate metabolites were classified into tertiles, and the lowest tertile was used as a reference category. The concentrations of phthalate metabolites and their composite scores based on clustering were also used in the analysis.

MAIN OUTCOMES AND MEASURES: Serum concentrations of TT and SHBG were dichotomized into high TT levels (>46 ng/dL [to convert to nanomoles per liter, multiply by 0.0347] for age <50 years and >32 ng/dL for age ≥50 years) and low SHBG levels (<2.85 μg/mL [to convert to nanomoles per liter, multiply by 10.53]) as established for the female population. Obesity was defined as a body mass index of 30 or more (calculated as weight in kilograms divided by height in meters squared), and metabolic syndrome was defined using the National Cholesterol Education Program criteria. The serum concentrations of TT and SHBG were also included in the validation analyses. Modified Poisson models were used to estimate the adjusted relative risk (RR) with 95% CIs for the associations.

RESULTS: Among the 2004 women included in this study, the mean (SD) age was 46.6 (18.5) years (14.7% Hispanic participants, 62.7% non-Hispanic White participants, and 13.2% non-Hispanic Black participants; 17.4% of participants were born outside the US [weighted percentages]; 230 (11.8%) had high TT levels, 210 (10.4%) had low SHBG levels, 825 (39.8%) had obesity, and 965 (45.5%) had metabolic syndrome (weighted percentages). Of the 13 phthalate metabolites, 8 had the highest tertile level greater than 6.2 ng/mL (range, 0.5-75.2 ng/mL). High levels of exposure to mono(2-ethyl-5-carboxypentyl) phthalate (RR, 1.84 [95% CI, 1.33-2.54]), mono(2-ethyl-5-oxohexyl) phthalate (RR, 1.77 [95% CI, 1.21-2.59]), mono(2-ethyl-5-hydroxyhexyl) phthalate (RR, 1.94 [95% CI, 1.34-2.81]), and monobenzyl phthalate (RR, 1.75 [95% CI, 1.21-2.54]) were associated with low SHBG levels but not with high TT levels. High levels of exposure to some of these metabolites were also associated with obesity and metabolic syndrome. Most associations were specific to premenopausal or postmenopausal women.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, exposure to certain phthalate metabolites could be associated with low SHBG levels, obesity, and metabolic syndrome depending on menopausal status.

PMID:36149653 | DOI:10.1001/jamanetworkopen.2022.33088

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Multifaceted Assessment of Functional Outcomes in Survivors of First-time Stroke

JAMA Netw Open. 2022 Sep 1;5(9):e2233094. doi: 10.1001/jamanetworkopen.2022.33094.

ABSTRACT

IMPORTANCE: Because stroke causes diverse functional deficits, understanding the long-term recovery pattern of each functional domain may inform prognosis and therapeutic strategies.

OBJECTIVE: To observe long-term changes in functional status and residual disability in survivors of first-time stroke.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. Between August 2012 and May 2015, 7858 of 10 636 screened patients with first-time strokes from 9 district hospitals in Korea provided informed consent to participate. Data were analyzed from September 2021 through February 2022.

EXPOSURE: First-time stroke.

MAIN OUTCOMES AND MEASURES: Study data include multifaceted face-to-face functional assessments obtained at 8 to 9 points until 60 months after stroke onset. The Korean Mini-Mental State Examination (K-MMSE), Fugl-Meyer Assessment, Functional Ambulatory Category, American Speech-Language-Hearing Association National Outcome Measurement System Swallowing Scale, and Short Korean version of the Frenchay Aphasia Screening Test were performed from 7 days to 60 months after stroke. The Korean Modified Barthel Index was measured from 3 months to 60 months after stroke.

RESULTS: A total of 4443 patients (2649 men [59.62%]; mean [SD] age 62.13 [12.43] years) who underwent repeated functional assessments for 60 months after stroke (3508 patients with ischemic and 935 patients with hemorrhagic stroke) were included. Overall, functions plateaued between 12 and 18 months after stroke and declined after 30 months; for example, mean (SD) K-MMSE improved from 7 days (22.89 [7.89]) to 12 months (26.03 [5.48]) (P < .001), plateaued until 36 months (26.03 [5.84]), and decreased to 48 months (26.02 [5.82]) (P < .001). Interaction associations were found between time after stroke and age, stroke severity, and stroke type in functional assessment outcomes. For example, mean (SE) FMA for ages 65 years or younger vs older than 65 years was 81.64 (0.63) vs 80.69 (0.68) at 7 days and 91.28 (0.47) vs 88.46 (0.58) at 6 months (P for interaction < .001), and for IS vs HS, it was 84.46 (0.47) vs 69.02 (1.24) at 7 days and 91.20 (0.38) vs 85.51 (0.98) at 6 months (P for interaction < .001). Mean (SE) FMA was 94.39 (0.21) at 7 days and 97.57 (0.14) at 6 months for mild stroke, 44.69 (1.18) at 7 days and 70.43 (1.21) at 6 months for moderate stroke, and 13.22 (0.99) at 7 days and 48.07 (2.62) at 6 months for severe stroke (P for interaction < .001). Factors associated with activities of daily living independence at 60 months included older age (β per 1-year increase = -0.35; standard error [SE], 0.03; P < .001), male sex (β = 2.12; SE, 0.73; P = .004), and hemorrhagic stroke type (β vs ischemic stroke = 2.35; SE, 0.81; P = .004).

CONCLUSIONS AND RELEVANCE: This study found that long-term recovery patterns in multifaceted functional domains differed from one another and varied by patient age, stroke severity, and stroke type. Understanding the diversity of long-term functional recovery patterns and factors associated with these outcomes in survivors of stroke may help clinicians develop strategies for effective stroke care and rehabilitation.

PMID:36149652 | DOI:10.1001/jamanetworkopen.2022.33094

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Influence of implementation strategies on implementation outcomes in a statewide dissemination of Faith, Activity, and Nutrition (FAN)

Health Educ Res. 2022 Sep 23:cyac025. doi: 10.1093/her/cyac025. Online ahead of print.

ABSTRACT

Faith-based organizations are promising settings for implementation science because they can reach populations bearing a disproportionate burden of chronic disease. This study examined how implementation strategies influenced implementation outcomes in Faith, Activity, and Nutrition (FAN) statewide dissemination. Ninety-three (9%) of 985 invited churches enrolled; 91 (98%) and 83 (89%) completed baseline and 12-month assessments. Community Health Advisors trained and provided phone technical assistance to church committees, led by a FAN coordinator. Church committees were charged with developing plans and installing healthy eating (HE) and physical activity (PA) policies, opportunities, messages and pastor support (implementation outcomes). Structural equation modeling examined how implementation strategies influenced implementation outcomes. Nearly all (99%) FAN coordinators and 60% of pastors attended training, 57% of committees submitted program plans and 51%/54% (HE/PA) of committees met ‘every few months’. Statistically significant (P < 0.05) model paths showed positive influences of strategies on implementation outcomes: pastor training on HE and PA pastor support; plan completion on HE and PA messages, PA policies and opportunities as well as FAN committee meetings and committee meetings on HE pastor support, HE policies, PA opportunities and HE and PA messages. This study advances implementation science and provides a model applicable to organizations such as worksites and schools.

PMID:36149635 | DOI:10.1093/her/cyac025

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Use of oral fluid samples for the investigation of outbreaks of human parvovirus B19 infection

Braz J Microbiol. 2022 Sep 23. doi: 10.1007/s42770-022-00828-9. Online ahead of print.

ABSTRACT

The use of oral fluid (OF) samples for serological diagnosis of parvovirus B19 infection during outbreaks of erythema infectiosum had already been demonstrated, but the feasibility of using OF for the characterization of B19 genotypes circulating during outbreaks has not been described. The aim of this study was to assess the use of “in-house” PCR-based assays as a powerful tool for a rapid diagnosis and molecular characterization of B19 strains in OF samples during outbreaks. Paired serum and OF samples collected from anti-B19 IgM-positive patients, during two outbreaks of ertythema infectiosum (1999-2000 and 2004-2005), were tested by conventional (cPCR) and quantitative PCR (qPCR). qPCR was more sensitive than cPCR for detecting B19-DNA in both OF and serum. Overall, OF presented lower viral load (9.97 × 106 UI/mL) than serum (2.42 × 1010 UI/mL) and this difference was statistically significant. All OF samples obtained from patients in the age group < 14 years presented low viral load (< 104 IU/mL). No correlation was found between viral load and the number of days of onset of rash. Sequence analysis from PCR positive OF samples confirmed the circulation of subgenotype 1a (G1a) during these outbreaks. Our findings indicate that PCR-based assays may fail to detect B19-DNA in approximately 50% of OF compared to serum samples. Nevertheless, our study has shown for the first time that the genome sequence of the amplicon from non-invasive clinical sample is useful for molecular genotyping and may be a tool to clarify the genetic diversity of B19 strains circulating in distinct outbreaks.

PMID:36149627 | DOI:10.1007/s42770-022-00828-9

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Diagnostic value of corneal higher-order aberrations in keratoconic eyes

Int Ophthalmol. 2022 Sep 23. doi: 10.1007/s10792-022-02518-9. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to investigate the diagnostic value of corneal anterior, posterior, and total higher-order aberrations in keratoconic eyes.

METHODS: We enrolled 94 patients (152 eyes) with mild keratoconus (Group 1), 64 patients (101 eyes) with moderate keratoconus (Group 2), and 32 patients (52 eyes) with advanced keratoconus (Group 3) according to the Amsler-Krumeich classification system; 99 healthy controls (197 normal eyes) were likewise enrolled. Anterior, posterior, and total corneal higher-order aberrations were assessed using a rotating Scheimpflug camera. The 3rd-order and 4th-order root-mean-square values were calculated for higher-order aberrations, including coma, spherical, and trefoil aberrations. Differences between keratoconic and normal eyes were analyzed using Kruskal-Wallis tests. Receiver operating characteristic curves were evaluated for the keratoconus and control groups.

RESULTS: The differences in coma 90, coma, trefoil, and spherical aberrations, as well as 3rd-order and 4th-order root-mean-square values, were statistically significant between the keratoconus and control groups for all anterior, posterior, and corneal aberrations. The absolute values of these higher-order aberrations were higher in the keratoconus groups than in the control group and increased with keratoconus severity in Groups 1-3. Coma and 3rd-order RMS values showed excellent sensitivity and specificity for discriminating between normal and keratoconus eyes for all anterior, posterior, and corneal aberrations.

CONCLUSION: Coma aberrations and 3rd-order root-mean-square values may be valuable for diagnosing keratoconus. Combining these data with topography information may enable the effective and efficient detection of keratoconus in the future.

PMID:36149622 | DOI:10.1007/s10792-022-02518-9

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ABCA6 affects the malignancy of Ewing sarcoma cells via cholesterol-guided inhibition of the IGF1R/AKT/MDM2 axis

Cell Oncol (Dordr). 2022 Sep 23. doi: 10.1007/s13402-022-00713-5. Online ahead of print.

ABSTRACT

PURPOSE: The relevance of the subfamily A members of ATP-binding cassette (ABCA) transporters as biomarkers of risk and response is emerging in different tumors, but their mechanisms of action have only been partially defined. In this work, we investigated their role in Ewing sarcoma (EWS), a pediatric cancer with unmet clinical issues.

METHODS: The expression of ABC members was evaluated by RT-qPCR in patients with localized EWS. The correlation with clinical outcome was established in different datasets using univariate and multivariate statistical methods. Functional studies were conducted in cell lines from patient-derived xenografts (PDXs) using gain- or loss-of-function approaches. The impact of intracellular cholesterol levels and cholesterol lowering drugs on malignant parameters was considered.

RESULTS: We found that ABCA6, which is usually poorly expressed in EWS, when upregulated became a prognostic factor of a favorable outcome in patients. Mechanistically, high expression of ABCA6 impaired cell migration and increased cell chemosensitivity by diminishing the intracellular levels of cholesterol and by constitutive IGF1R/AKT/mTOR expression/activation. Accordingly, while exposure of cells to exogenous cholesterol increased AKT/mTOR activation, the cholesterol lowering drug simvastatin inhibited IGF1R/AKT/mTOR signaling and prevented Ser166 phosphorylation of MDM2. This, in turn, favored p53 activation and enhanced pro-apoptotic effects of doxorubicin.

CONCLUSIONS: Our study reveals that ABCA6 acts as tumor suppressor in EWS cells via cholesterol-mediated inhibition of IGF1R/AKT/MDM2 signaling, which promotes the pro-apoptotic effects of doxorubicin and reduces cell migration. Our findings also support a role of ABCA6 as biomarker of EWS progression and sustains its assessment for a more rational use of statins as adjuvant drugs.

PMID:36149602 | DOI:10.1007/s13402-022-00713-5

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Contrast-Enhanced Spectral Mammography and tumor size assessment: a valuable tool for appropriate surgical management of breast lesions

Radiol Med. 2022 Sep 23. doi: 10.1007/s11547-022-01561-x. Online ahead of print.

ABSTRACT

PURPOSE: To compare the accuracy of Contrast-Enhanced Spectral Mammography (CESM), MG, US, and breast MRI in estimating the size of breast lesions requiring surgery. The postoperative histology size of the lesion was used as the gold standard.

MATERIAL AND METHODS: Two hundred thirty-three non-benign lesions in 189 patients were included in the analyses. All the selected patients underwent CESM and at least one other conventional diagnostic exam (US, MG, or MRI). Subsequently, all the patients underwent surgery preceded by cytological/histological examination. The largest diameter of the lesion at imaging was measured by a radiologist with more than 10 years’ experience and then compared with the size of the lesion in the histological sample at the surgery (gold standard).

RESULTS: Among the 233 breast lesions, 196 were evaluated with US, 206 with MG and 160 with MRI. We found no statistically significant differences between size measurements using CESM and MRI compared with the measurements at the surgery (p value 0.63 and 0.51), whereas a significant difference was found for MG and US (p < 0.001).

CONCLUSION: CESM is a reliable method for estimating the size of breast lesions: its performance seems superior to US and MG and comparable to MRI.

PMID:36149581 | DOI:10.1007/s11547-022-01561-x

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Racial and Ethnic Variation in COVID-19 Vaccination Uptake Among Medicare Beneficiaries with Cancer History

J Racial Ethn Health Disparities. 2022 Sep 23. doi: 10.1007/s40615-022-01415-2. Online ahead of print.

ABSTRACT

BACKGROUND: The purpose of this study was to estimate COVID-19 vaccination rate among Medicare beneficiaries with cancer history and determine whether COVID-19 vaccine uptake is higher among non-Hispanic White beneficiaries compared with racially and ethnically minoritized beneficiaries.

METHODS: We used US representative, cross-sectional data from the Medicare Current Beneficiary Survey COVID-19 Winter 2021 Rapid Response Community Supplement Survey. A total of 1,863 respondents with self-reported cancer history (other than skin cancer) were included. The outcome was self-reported receipt of at least one coronavirus vaccine dose since vaccines became available. The key independent variable of interest was self-reported race and ethnicity. We applied sample weights to account for the survey design and provide population estimates to 9.6 million beneficiaries with cancer history. Weighted descriptive statistics and multivariable logistic regression analyses were conducted.

RESULTS: During the first 4 months of vaccine availability, 69.6% of beneficiaries received at least one vaccine dose of which 65.4% had two vaccine doses. A larger proportion of non-Hispanic White beneficiaries (71.9%) had at least one vaccine dose compared with non-Hispanic Black (60.4%) and Hispanic (57.4%) beneficiaries. An estimated 30.4% of beneficiaries were still unvaccinated, that represents approximately 2.9 million unvaccinated beneficiaries with cancer history. Hispanic beneficiaries were 42% (OR: 0.58; 95% CI: 0.33-0.99; p = .048) less likely to be vaccinated compared with non-Hispanic White beneficiaries.

CONCLUSIONS: Results indicate racial and ethnic differences in vaccine uptake among Medicare beneficiaries with cancer history. Effective strategies are needed to help increase vaccine confidence and uptake among adults with cancer history.

PMID:36149576 | DOI:10.1007/s40615-022-01415-2

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Pre-pregnancy Diabetes, Pre-pregnancy Hypertension and Prenatal Care Timing among Women in the United States, 2018

Matern Child Health J. 2022 Sep 23. doi: 10.1007/s10995-022-03531-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Women with pre-pregnancy diabetes or pre-pregnancy hypertension have increased risks of complications during pregnancy. Women who obtain prenatal care in the first trimester receive necessary routine testing and disease management tools that aid in controlling such conditions. However, research on the association between pre-pregnancy hypertension and pre-pregnancy diabetes and prenatal care timing among US women is limited.

METHODS: This study used data from the 2018 National Vital Statistic System (n = 3,618,853). Trained personnel collected information on prenatal care timing, maternal conditions, and demographics. Multivariate logistic regression models evaluated the association between pre-pregnancy hypertension, pre-pregnancy diabetes and prenatal care timing. A stratified analysis was conducted to determine if race/ethnicity modified the associations.

RESULTS: After adjustment, women with pre-pregnancy hypertension or pre-pregnancy diabetes had statistically significant increased odds of receiving early prenatal care compared to women without these conditions (OR 1.23; 95% CI: 1.21-1.26 and OR 1.27; 95% CI: 1.24-1.31, respectively). Among non-Hispanic White, non-Hispanic Black, and Hispanic women, those with pre-pregnancy hypertension or pre-pregnancy diabetes had statistically significantly increased odds of receiving early prenatal care compared to women without those pre-existing conditions (P < .001).

DISCUSSION: Further research is needed on the transition from preconception care to obstetric care for women with pre-existing diabetes or hypertension. However, these findings suggest that women who have conditions that could cause pregnancy complications are pursuing early prenatal care services to mitigate the development of adverse maternal and infant health conditions.

PMID:36149535 | DOI:10.1007/s10995-022-03531-1