57 results on '"Williams CP"'
Search Results
2. Abstract PD7-01: Impact of guideline concordant treatment on cost and health care utilization in early stage breast cancer patients
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Williams, CP, primary, Azuero, A, additional, Pisu, M, additional, Halilova, KI, additional, Adewakun, S, additional, Yagnik, SK, additional, Goertz, H-P, additional, and Rocque, GB, additional
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- 2018
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3. Abstract P6-11-12: Health-related quality of life, symptom burden and management in older women with breast cancer across the illness trajectory
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Halilova, KI, primary, Williams, CP, additional, Azuero, A, additional, Kvale, EA, additional, Yagnik, SK, additional, Goertz, H-P, additional, Pizu, M, additional, and Rocque, GB, additional
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- 2018
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4. Abstract P3-10-10: Withdrawn
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Kandhare, PG, primary, Williams, CP, additional, Nakhmani, A, additional, Burkard, ME, additional, Azuero, A, additional, Halilova, KL, additional, Pisu, M, additional, Bhatia, S, additional, Forero, A, additional, and Rocque, GB, additional
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- 2018
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5. Abstract P2-07-02: Concordance with National comprehensive cancer network (NCCN) metastatic breast cancer guidelines and impact on overall survival
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Rocque, GB, primary, Williams, CP, additional, Jackson, BE, additional, Halilova, KI, additional, Pisu, M, additional, Andres, F, additional, and Smita, B, additional
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- 2017
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6. Why location matters: associations between county-level characteristics and availability of National Cancer Oncology Research Program and National Cancer Institute sites.
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Caston NE, Williams CP, Levitan EB, Griffin R, Azuero A, Wheeler SB, and Rocque GB
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- Humans, United States, Cross-Sectional Studies, Health Services Accessibility statistics & numerical data, Clinical Trials as Topic statistics & numerical data, Racial Groups statistics & numerical data, Vulnerable Populations statistics & numerical data, Cancer Care Facilities statistics & numerical data, Cancer Care Facilities supply & distribution, Medical Oncology, Ethnicity statistics & numerical data, Socioeconomic Factors, National Cancer Institute (U.S.), Neoplasms
- Abstract
Background: The majority of patients with cancer seek care at community oncology sites; however, most clinical trials are available at National Cancer Institute (NCI)-designated sites. Although the NCI National Cancer Oncology Research Program (NCORP) was designed to address this problem, little is known about the county-level characteristics of NCORP site locations., Methods: This cross-sectional analysis determined the association between availability of NCORP or NCI sites and county-level characteristic theme percentile scores from the Center for Disease Control and Prevention's Social Vulnerability Index themes. Health Resources and Services Administration's Area Health Resource Files were used to determine contiguous counties. We estimated risk ratios and 95% confidence intervals (CIs) using modified Poisson regression models to evaluate the association between county-level characteristics and site availability within singular and singular and contiguous counties., Results: Of 3141 included counties, 14% had an NCORP, 2% had an NCI, and 1% had both sites. Among singular counties, for a standard deviation increase in the racial and ethnic theme score, there was a 22% higher likelihood of NCORP site availability (95% CI = 1.10 to 1.36); for a standard deviation increase in the socioeconomic status theme score, there was a 24% lower likelihood of NCORP site availability (95% CI = 0.67 to 0.87). Associations were of smaller magnitude when including contiguous counties. NCI sites were located in more vulnerable counties., Conclusions: NCORP sites were more often in racially diverse counties and less often in socioeconomically vulnerable counties. Research is needed to understand how clinical trial representation will increase if NCORP sites strategically increase their locations in more vulnerable counties., (© The Author(s) 2024. Published by Oxford University Press.)
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- 2024
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7. Understanding the financial cost of cancer clinical trial participation.
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Williams CP, Deng L, Caston NE, Gallagher K, Angove R, Pisu M, Azuero A, Arend R, and Rocque GB
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- Adult, Aged, Humans, Cost of Illness, Cross-Sectional Studies, Health Expenditures, Income, Medicare, Surveys and Questionnaires, United States, Neoplasms therapy, Clinical Trials as Topic
- Abstract
Background: Though financial hardship is a well-documented adverse effect of standard-of-care cancer treatment, little is known about out-of-pocket costs and their impact on patients participating in cancer clinical trials. This study explored the financial effects of cancer clinical trial participation., Methods: This cross-sectional analysis used survey data collected in December 2022 and May 2023 from individuals with cancer previously served by Patient Advocate Foundation, a nonprofit organization providing social needs navigation and financial assistance to US adults with a chronic illness. Surveys included questions on cancer clinical trial participation, trial-related financial hardship, and sociodemographic data. Descriptive and bivariate analyses were conducted using Cramer's V to estimate the in-sample magnitude of association. Associations between trial-related financial hardship and sociodemographics were estimated using adjusted relative risks (aRR) and corresponding 95% confidence intervals (CI) from modified Poisson regression models with robust standard errors., Results: Of 650 survey respondents, 18% (N = 118) reported ever participating in a cancer clinical trial. Of those, 47% (n = 55) reported financial hardship as a result of their trial participation. Respondents reporting trial-related financial hardship were more often unemployed or disabled (58% vs. 43%; V = 0.15), Medicare enrolled (53% vs. 40%; V = 0.15), and traveled >1 h to their cancer provider (45% vs. 17%; V = 0.33) compared to respondents reporting no hardship. Respondents who experienced trial-related financial hardship most often reported expenses from travel (reported by 71% of respondents), medical bills (58%), dining out (40%), or housing needs (40%). Modeling results indicated that respondents traveling >1 h vs. ≤30 min to their cancer provider had a 2.2× higher risk of financial hardship, even after adjusting for respondent race, income, employment, and insurance status (aRR = 2.2, 95% CI 1.3-3.8). Most respondents (53%) reported needing $200-$1000 per month to compensate for trial-related expenses. Over half (51%) of respondents reported less willingness to participate in future clinical trials due to incurred financial hardship. Notably, of patients who did not participate in a cancer clinical trial (n = 532), 13% declined participation due to cost., Conclusion: Cancer clinical trial-related financial hardship, most often stemming from travel expenses, affected almost half of trial-enrolled patients. Interventions are needed to reduce adverse financial participation effects and potentially improve cancer clinical trial participation., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2024
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8. Associations between health insurance status, neighborhood deprivation, and treatment delays in women with breast cancer living in Georgia.
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Awan S, Saini G, Gogineni K, Luningham JM, Collin LJ, Bhattarai S, Aneja R, and Williams CP
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- Humans, Female, Aged, United States epidemiology, Medicare, Time-to-Treatment, Georgia epidemiology, Cohort Studies, Medicaid, Insurance Coverage, Insurance, Health, Breast Neoplasms epidemiology, Breast Neoplasms therapy, Breast Neoplasms diagnosis
- Abstract
Background: Little is known regarding the association between insurance status and treatment delays in women with breast cancer and whether this association varies by neighborhood socioeconomic deprivation status., Methods: In this cohort study, we used medical record data of women diagnosed with breast cancer between 2004 and 2022 at two Georgia-based healthcare systems. Treatment delay was defined as >90 days to surgery or >120 days to systemic treatment. Insurance coverage was categorized as private, Medicaid, Medicare, other public, or uninsured. Area deprivation index (ADI) was used as a proxy for neighborhood-level socioeconomic status. Associations between delayed treatment and insurance status were analyzed using logistic regression, with an interaction term assessing effect modification by ADI., Results: Of the 14,195 women with breast cancer, 54% were non-Hispanic Black and 52% were privately insured. Compared with privately insured patients, those who were uninsured, Medicaid enrollees, and Medicare enrollees had 79%, 75%, and 27% higher odds of delayed treatment, respectively (odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.32-2.43; OR: 1.75, 95% CI: 1.43-2.13; OR: 1.27, 95% CI: 1.06-1.51). Among patients living in low-deprivation areas, those who were uninsured, Medicaid enrollees, and Medicare enrollees had 100%, 84%, and 26% higher odds of delayed treatment than privately insured patients (OR: 2.00, 95% CI: 1.44-2.78; OR: 1.84, 95% CI: 1.48-2.30; OR: 1.26, 95% CI: 1.05-1.53). No differences in the odds of delayed treatment by insurance status were observed in patients living in high-deprivation areas., Discussion/conclusion: Insurance status was associated with treatment delays for women living in low-deprivation neighborhoods. However, for women living in neighborhoods with high deprivation, treatment delays were observed regardless of insurance status., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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9. Expanding research on the impact of financial hardship on emotional well-being: guidance of diverse stakeholders to the Emotional Well-Being and Economic Burden of Disease (EMOT-ECON) Research Network.
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Pisu M, Liang MI, Pressman SD, Ryff CD, Patel MR, Hussein M, Williams CP, Henrikson NB, Schoenberger YM, Pracht LJ, Bradshaw E, Carpenter TT, Matthis A, Schwartz DL, and Martin MY
- Abstract
The Emotional Well-Being and Economic Burden (EMOT-ECON) Research Network is one of six research networks funded by the National Institutes of Health (NIH) to advance research about emotional well-being (EWB), and the only one that focuses on addressing how economic burden due to disease or illness affects EWB. The network convened researchers, patients, patient advocates, health care providers and other stakeholders from across the US to discuss the significance of addressing the impact of the economic burden of disease on EWB, the complexity of this prevalent problem for patients and families, and the research gaps that still need to be studied to ultimately develop strategies to reduce the impact of economic burden of disease on EWB and health. Participants identified some important future areas of research as those investigating: (i) prevalent and relevant emotions for patients experiencing economic burden of disease and financial hardship, and how their broader outlook on life is impacted; (ii) constructs and contexts that influence whether the economic burden is stressful; (iii) strategies to deal and cope and their positive or negative effects on EWB and health; and (iv) multi-level and multi-stakeholder interventions to address economic factors (e.g., costs, ability to pay), administrative burdens, education and training, and especially patients' emotional as well as financial status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pisu, Liang, Pressman, Ryff, Patel, Hussein, Williams, Henrikson, Schoenberger, Pracht, Bradshaw, Carpenter, Matthis, Schwartz and Martin.)
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- 2023
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10. "It's just not easy to understand": A mixed methods study of health insurance literacy and insurance plan decision-making in cancer survivors.
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Williams CP, Platter HN, Davidoff AJ, Vanderpool RC, Pisu M, and de Moor JS
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- Humans, Health Expenditures, Insurance, Health, Costs and Cost Analysis, Cancer Survivors, Health Literacy, Neoplasms therapy
- Abstract
Background: Understanding cancer survivors' health insurance decision-making is needed to improve insurance choice, potentially resulting in reduced financial hardship., Methods: This explanatory mixed methods study assessed health insurance decision-making in cancer survivors. Health Insurance Literacy Measure (HILM) captured HIL. Quantitative eye-tracking data collected from two simulated health insurance plan choice sets gauged dwell time (seconds), or interest, in benefits. Dwell time differences by HIL were estimated using adjusted linear models. Qualitative interviews explored survivors' insurance decision-making choices., Results: Cancer survivors (N = 80; 38% breast cancer) had a median age of 43 at diagnosis (IQR 34-52). When comparing traditional and high-deductible health plans, survivors were most interested in drug costs (median dwell time 58 s, IQR 34-109). When comparing health maintenance organization and preferred provider organization plans, survivors were most interested in test/imaging costs (40s, IQR 14-67). Survivors with low versus high HIL had more interest in deductible (β = 19 s, 95% CI 2-38) and hospitalization costs (β = 14 s, 95% CI 1-27) in adjusted models. Survivors with low versus high HIL more often ranked out-of-pocket (OOP) maximums and coinsurance as the most important and confusing benefits, respectively. Interviews (n = 20) revealed survivors felt alone "to do their own research" about insurance choices. OOP maximums were cited as the deciding factor since it is "how much money is going to be taken out of my pocket." Coinsurance was considered "rather than a benefit, it's a hindrance.", Conclusion: Interventions to aid in health insurance understanding and choice are needed to optimize plan choice and potentially reduce cancer-related financial hardship., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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11. A nationwide cross-sectional study on the association of patient-level factors with financial anxiety in the context of chronic medical conditions.
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Hassan AM, Chu CK, Liu J, Angove R, Rocque G, Gallagher KD, Momoh AO, Caston NE, Williams CP, Wheeler S, and Offodile AC 2nd
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- Humans, Male, Female, Cross-Sectional Studies, Chronic Disease, Marital Status, Ethnicity, Anxiety epidemiology
- Abstract
Patient-level characteristics associated with the prevalence and severity of financial anxiety have yet to be described. We conducted a cross-sectional analysis of survey data assessing financial anxiety in patients with chronic medical conditions in December 2020. 1771 patients (42.6% response rate) participated in the survey. Younger age (19-35 age compared to ≥ 75 age) (β, 5.86; 95% CI 2.10-9.63), male sex (β, - 1.9; 95% CI - 3.1 to - 0.73), Hispanic/Latino race/ethnicity (compared with White patients) (β, 2.55; 95% CI 0.39-4.71), household size ≥ 4 (compare with single household) (β, 4.54; 95% CI 2.44-6.64), household income of ≥ $96,000-$119,999 (compared with ≤ $23,999) (β, - 3.2; 95% CI - 6.3 to 0.04), single marital status (compared with married) (β, 2.18; 95% CI 0.65-3.71), unemployment (β, 2.07; 95% CI 0.39-3.74), high-school education (compared with advanced degrees) (β, 3.10; 95% CI 1.32-4.89), lack of insurance coverage (compared with private insurance) (β, 6.05; 95% CI 2.66-9.45), more comorbidities (≥ 3 comorbidities compared to none) (β, 2.95; 95% CI 1.00-4.90) were all independently associated with financial anxiety. Patients who are young, female, unmarried, and representing vulnerable sub-populations are at elevated risk for financial anxiety., (© 2023. The Author(s).)
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- 2023
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12. Influence of Cost-Related Considerations on Clinical Trial Participation: Results from the 2020 Health Information National Trends Survey (HINTS).
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Williams CP, Geiger AM, Norton WE, de Moor JS, and Everson NS
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- Adult, Humans, Middle Aged, Cross-Sectional Studies, Surveys and Questionnaires, Income
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Background: People experiencing financial burden are underrepresented in clinical trials., Objective: Describe the prevalence of cost-related considerations influential to trial participation and their associations with person-level characteristics., Design: This cross-sectional study used and assessed how three cost-related considerations would influence the decision to participate in a hypothetical clinical trial., Participants: A total of 3682 US adult respondents to the Health Information National Trends Survey MAIN MEASURES: Survey-weighted multivariable logistic regression estimated associations between respondent characteristics and odds of reporting cost-related considerations as very influential to participation., Key Results: Among 3682 respondents, median age was 48 (IQR 33-61). Most were non-Hispanic White (60%), living comfortably or getting by on their income (74%), with ≥ 1 medical condition (61%). Over half (55%) of respondents reported at least one cost-related consideration as very influential to trial participation, including if usual care was not covered by insurance (reported by 42%), payment for participation (24%), or support for participation (24%). Respondents who were younger (18-34 vs. ≥ 75, adjusted odds ratio [aOR] 4.3, 95% CI 2.3-8.1), more educated (high school vs.
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- 2023
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13. Health insurance and financial hardship in cancer survivors during the COVID-19 pandemic.
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Williams CP, Rocque GB, Caston NE, Gallagher KD, Angove RSM, Anderson E, de Moor JS, Halpern MT, Offodile AC 2nd, and Gidwani R
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- Aged, Cross-Sectional Studies, Financial Stress epidemiology, Humans, Insurance Coverage, Insurance, Health, Medically Uninsured, Medicare, Pandemics, Patient Protection and Affordable Care Act, United States epidemiology, COVID-19 epidemiology, Cancer Survivors, Neoplasms epidemiology
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Uninsured or underinsured individuals with cancer are likely to experience financial hardship, including forgoing healthcare or non-healthcare needs such as food, housing, or utilities. This study evaluates the association between health insurance coverage and financial hardship among cancer survivors during the COVID-19 pandemic. This cross-sectional analysis used Patient Advocate Foundation (PAF) survey data from May to July 2020. Cancer survivors who previously received case management or financial aid from PAF self-reported challenges paying for healthcare and non-healthcare needs during the COVID-19 pandemic. Associations between insurance coverage and payment challenges were estimated using Poisson regression with robust standard errors, which allowed for estimation of adjusted relative risks (aRR). Of 1,437 respondents, 74% had annual household incomes <$48,000. Most respondents were enrolled in Medicare (48%), 22% in employer-sponsored insurance, 13% in Medicaid, 6% in an Affordable Care Act (ACA) plan, and 3% were uninsured. Approximately 31% of respondents reported trouble paying for healthcare during the COVID-19 pandemic. Respondents who were uninsured (aRR 2.58, 95% confidence interval [CI] 1.83-3.64), enrolled in an ACA plan (aRR 1.86, 95% CI 1.28-2.72), employer-sponsored insurance (aRR 1.70, 95% CI 1.23-2.34), or Medicare (aRR 1.49, 95% CI 1.09-2.03) had higher risk of trouble paying for healthcare compared to Medicaid enrollees. Challenges paying for non-healthcare needs were reported by 57% of respondents, with 40% reporting trouble paying for food, 31% housing, 28% transportation, and 20% internet. In adjusted models, Medicare and employer-sponsored insurance enrollees were less likely to have difficulties paying for non-healthcare needs compared to Medicaid beneficiaries. Despite 97% of our cancer survivor sample being insured, 31% and 57% reported trouble paying for healthcare and non-healthcare needs during the COVID-19 pandemic, respectively. Greater attention to both medical and non-medical financial burden is needed given the economic pressures of the COVID-19 pandemic., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Rocque is supported by an American Cancer Society Mentored Research Scholar Grant (MRSG-17-051-01-PCSM) and has received research funding from Genentech, Pfizer, and Carevive and consulting fees for Genentech and Pfizer for work unrelated to the current study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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- 2022
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14. Cancer-Related Care Costs and Employment Disruption: Recommendations to Reduce Patient Economic Burden as Part of Cancer Care Delivery.
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de Moor JS, Williams CP, and Blinder VS
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- Employment, Financial Stress, Humans, Prospective Studies, Cancer Survivors, Neoplasms diagnosis, Neoplasms therapy
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Cancer survivors are frequently unprepared to manage the out-of-pocket (OOP) costs associated with undergoing cancer treatment and the potential for employment disruption. This commentary outlines a set of research recommendations stemming from the National Cancer Institute's Future of Health Economics Research Conference to better understand and reduce patient economic burden as part of cancer care delivery. Currently, there are a lack of detailed metrics and measures of survivors' OOP costs and employment disruption, and data on these costs are rarely available at the point of care to guide patient-centered treatment and survivorship care planning. Future research should improve the collection of data about survivors' OOP costs for medical care, other cancer-related expenses, and experiences of employment disruption. Methods such as microcosting and the prospective collection of patient-reported outcomes in cancer care are needed to understand the true sum of cancer-related costs taken on by survivors and caregivers. Better metrics and measures of survivors' costs must be coupled with interventions to incorporate that information into cancer care delivery and inform meaningful communication about OOP costs and employment disruption that is tailored to different clinical situations. Informing survivors about the anticipated costs of their cancer care supports informed decision making and proactive planning to mitigate financial hardship. Additionally, system-level infrastructure should be developed and tested to facilitate screening to identify survivors at risk for financial hardship, improve communication about OOP costs and employment disruption between survivors and their health-care providers, and support the delivery of appropriate financial navigation services., (Published by Oxford University Press 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)
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- 2022
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15. Demographic and Health Behavior Factors Associated With Clinical Trial Invitation and Participation in the United States.
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Williams CP, Senft Everson N, Shelburne N, and Norton WE
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- Adult, Aged, Cross-Sectional Studies, Female, Health Behavior, Health Surveys, Humans, Male, Middle Aged, Research Subjects psychology, United States, Clinical Trials as Topic, Demography statistics & numerical data, Ethnicity statistics & numerical data, Research Subjects statistics & numerical data
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Importance: Representative enrollment in clinical trials is critical to ensure equitable and effective translation of research to practice, yet disparities in clinical trial enrollment persist., Objective: To examine person-level factors associated with invitation to and participation in clinical trials., Design, Setting, and Participants: This cross-sectional study analyzed responses from 3689 US adults who participated in the nationally representative Health Information National Trends Survey, collected February through June 2020 via mailed questionnaires., Exposures: Demographic, clinical, and health behavior-related characteristics., Main Outcomes and Measures: History of invitation to and participation in a clinical trial, primary information sources, trust in information sources, and motives for participation in clinical trials were described. Respondent characteristics are presented as absolute numbers and weighted percentages. Associations between respondent demographic, clinical, and health behavior-related characteristics and clinical trial invitation and participation were estimated using survey-weighted logistic regression models., Results: The median (IQR) age of the 3689 respondents was 48 (33-61) years, and most were non-Hispanic White individuals (2063 [59%]; non-Hispanic Black, 452 [10%]; Hispanic, 521 [14%]), had more than a high school degree (2656 [68%]), were employed (1809 [58%]), and had at least 1 medical condition (2535 [61%]). Overall, 439 respondents (9%) had been invited to participate in any clinical trial. Respondents with increased odds of invitation were non-Hispanic Black compared with non-Hispanic White (adjusted odds ratio [aOR], 1.85; 95% CI, 1.13-3.02), had greater than a high school education compared with less than high school education (eg, ≥college degree: aOR, 4.84; 95% CI, 1.89-12.39), were single compared with married or living as married (aOR, 1.68; 95% CI, 1.04-2.73), and had at least 1 medical condition compared to none (eg, 1 medical condition: aOR, 2.25; 95% CI, 1.32-3.82). Respondents residing in rural vs urban areas had 77% decreased odds of invitation to a clinical trial (aOR 0.33; 95% CI 0.17-0.65). Of invited respondents, 199 (47%) participated. Compared with non-Hispanic White respondents, non-Hispanic Black respondents had 72% decreased odds of clinical trial participation (aOR, 0.28; 95% CI, 0.09-0.87). Respondents most frequently reported "health care providers" as the first and most trusted source of clinical trial information (first source: 2297 [59%]; most trusted source: 2597 [70%]). The most frequently reported motives for clinical trials participation were "wanting to get better" (2294 [66%]) and the standard of care not being covered by insurance (1448 [41%])., Conclusions and Relevance: The findings of this study suggest that invitation to and participation in clinical trials may differ by person-level demographic and clinical characteristics. Strategies toward increasing trial invitation and participation rates across diverse patient populations warrant further research to ensure equitable translation of clinical benefits from research to practice.
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- 2021
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16. Patient perspectives on chemotherapy de-escalation in breast cancer.
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Rocque GB, Williams CP, Andrews C, Childers TC, Wiseman KD, Gallagher K, Tung N, Balch A, Lawhon VM, Ingram SA, Brown T, Kaufmann T, Smith ML, DeMichele A, Wolff AC, and Wagner L
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- Adult, Aged, Anxiety psychology, Breast Neoplasms psychology, COVID-19 epidemiology, COVID-19 virology, Cross-Sectional Studies, Fear psychology, Female, Humans, Middle Aged, Pandemics, Qualitative Research, SARS-CoV-2 physiology, Breast Neoplasms drug therapy, COVID-19 prevention & control, SARS-CoV-2 isolation & purification, Surveys and Questionnaires
- Abstract
Background: Given excellent survival outcomes in breast cancer, there is interest in de-escalating the amount of chemotherapy delivered to patients. This approach may be of even greater importance in the setting of the COVID-19 pandemic., Methods: This concurrent mixed methods study included (1) interviews with patients and patient advocates and (2) a cross-sectional survey of women with breast cancer served by a charitable nonprofit organization. Questions evaluated interest in de-escalation trial participation, perceived barriers/facilitators to participation, and language describing de-escalation., Results: Sixteen patient advocates and 24 patients were interviewed. Key barriers to de-escalation included fear of recurrence, worry about decision regret, lack of clinical trial interest, and dislike for focus on less treatment. Facilitators included trust in physician recommendation, toxicity avoidance, monitoring for progression, perception of good prognosis, and impact on daily life. Participants reported that the COVID-19 pandemic made them more likely to avoid chemotherapy if possible. Of 91 survey respondents, many (43%) patients would have been unwilling to participation in a de-escalation clinical trial. The most commonly reported barrier to participation was fear of recurrence (85%). Few patients (19%) considered clinical trials themselves as a barrier to de-escalation trial participation. The most popular terminology describing chemotherapy de-escalation was "lowest effective chemotherapy dose" (53%); no patients preferred the term "de-escalation.", Conclusions: Fear of recurrence is a common concern among breast cancer survivors and patient advocates, contributing to resistance to de-escalation clinical trial participation. Additional research is needed to understand how to engage patients in de-escalation trials., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2021
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17. Health care-related time costs in patients with metastatic breast cancer.
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Rocque GB, Williams CP, Ingram SA, Azuero A, Mennemeyer ST, Young Pierce J, Nipp RD, Reeder-Hayes KE, and Kenzik KM
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- Aged, Antineoplastic Agents adverse effects, Breast Neoplasms pathology, Cross-Sectional Studies, Databases, Factual, Female, Financial Stress economics, Health Expenditures, Hospital Costs, Humans, Inpatients, Middle Aged, Neoplasm Metastasis, Oncology Service, Hospital economics, Prospective Studies, Quality of Life, SEER Program, Time Factors, Transportation of Patients economics, Antineoplastic Agents administration & dosage, Breast Neoplasms drug therapy, Breast Neoplasms economics, Cost of Illness, Health Care Costs
- Abstract
Background: Burdens related to time spent receiving cancer care may be substantial for patients with incurable, life-limiting cancers such as metastatic breast cancer (MBC). Estimates of time spent on health care are needed to inform treatment-related decision-making., Methods: Estimates of time spent receiving cancer-related health care in the initial 3 months of treatment for patients with MBC were calculated using the following data sources: (a) direct observations from a time-in-motion quality improvement evaluation (process mapping); (b) cross-sectional patient surveys; and (c) administrative claims. Average ambulatory, inpatient, and total health care time were calculated for specific treatments which differed by antineoplastic type and administration method, including fulvestrant (injection, hormonal), letrozole (oral, hormonal), capecitabine (oral, chemotherapy), and paclitaxel (infusion, chemotherapy)., Results: Average total time spent on health care ranged from 7% to 10% of all days included within the initial 3 months of treatment, depending on treatment. The greatest time contributions were time spent traveling for care and on inpatient services. Time with providers contributed modestly to total care time. Patients receiving infusion/injection treatments, compared with those receiving oral therapy, spent more time in ambulatory care. Health care time was higher for patients receiving chemotherapeutic agents compared to those receiving hormonal agents., Conclusion: Time spent traveling and receiving inpatient care represented a substantial burden to patients with MBC, with variation in time by treatment type and administration method., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2020
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18. Healthy lifestyle discussions between healthcare providers and older cancer survivors: Data from 12 cancer centers in the Southeastern United States.
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Halilova KI, Pisu M, Azuero A, Williams CP, Kenzik KM, Williams GR, Rocque GB, Martin MY, Kvale EA, and Demark-Wahnefried W
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- Aged, Aged, 80 and over, Cancer Care Facilities, Exercise, Female, Health Behavior, Health Personnel, Humans, Male, Patient Education as Topic, Smoking Cessation, Southeastern United States, Surveys and Questionnaires, Weight Loss, Cancer Survivors, Healthy Lifestyle
- Abstract
Background: Little is known about the prevalence of healthy lifestyle (HLS) discussions between providers and older cancer survivors., Methods: We utilized cross-sectional data from older cancer survivors (≥65 years) seen at 12 southeastern cancer centers during 2013-2015. Data on demographics, time since diagnosis, weight, height, and healthy behaviors were collected. Respondents were asked if providers (oncologists, other physicians, and/or nurses) discussed exercise, healthy diet, weight management, and/or smoking cessation during clinical encounters. Descriptive statistics and bivariate associations between HLS topics and survivor characteristics were calculated., Results: Among 1460 cancer survivors, mean age was 74 years (SD 6), most were white (81%), and >1 year postdiagnosis (84%). The majority (71%) reported discussing at least one of three HLS topics (exercise 49%, healthy diet 53%, vegetable consumption 28%); 17% received counseling on all three. Weight loss was recommended to 33% of overweight/obese survivors and smoking cessation to 85% of current smokers. Oncologists and nurses discussed HLS less frequently compared to other physicians. Younger survivors (65-74 years) received recommendations for exercise, weight loss, and tobacco cessation more often than older survivors (≥75 years). Compared to white respondents, minorities reported discussions on all topics more often except for tobacco cessation. Excluding tobacco cessation, survivors with recent cancer diagnoses (<1 year) reported HLS discussions more often than survivors >1 year postdiagnosis., Conclusion: Despite the American Cancer Society's recommendations, older survivors reported a low prevalence of HLS discussions with their providers, with some variation by demographic groups. Strategies are needed to promote these important discussions in this population., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2019
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19. What Is Important When Making Treatment Decisions in Metastatic Breast Cancer? A Qualitative Analysis of Decision-Making in Patients and Oncologists.
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Rocque GB, Rasool A, Williams BR, Wallace AS, Niranjan SJ, Halilova KI, Turkman YE, Ingram SA, Williams CP, Forero-Torres A, Smith T, Bhatia S, and Knight SJ
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- Adult, Aged, Decision Making, Female, Humans, Middle Aged, Neoplasm Metastasis, Breast Neoplasms complications, Oncologists standards
- Abstract
Background: Metastatic breast cancer (MBC) is an ideal environment for shared decision-making because of the large number of guideline-based treatment options with similar efficacy but different toxicity profiles. This qualitative analysis describes patient and provider factors that influence decision-making in treatment of MBC., Materials and Methods: Patients and community oncologists completed in-person interviews. Academic medical oncologists participated in focus groups. Interviews and focus groups were audio-recorded, transcribed, and analyzed using NVivo. Using an a priori model based on the Ottawa Framework, two independent coders analyzed transcripts using a constant comparative method. Major themes and exemplary quotes were extracted., Results: Participants included 20 patients with MBC, 6 community oncologists, and 5 academic oncologists. Analysis of patient interviews revealed a decision-making process characterized by the following themes: decision-making style, contextual factors, and preferences. Patient preference subthemes include treatment efficacy, physical side effects of treatment, emotional side effects of treatment, cognitive side effects of treatment, cost and financial toxicity, salience of cutting-edge treatment options (clinical trial or newly approved medication), treatment logistics and convenience, personal and family responsibilities, treatment impact on daily activities, participation in self-defining endeavors, attending important events, and pursuing important goals. Physician decisions emphasized drug-specific characteristics (treatment efficacy, side effects, cost) rather than patient preferences, which might impact treatment choice., Conclusion: Although both patients with MBC and oncologists considered treatment characteristics when making decisions, patients' considerations were broader than oncologists', incorporating contextual factors such as the innovative value of the treatment and life responsibilities. Differences in perspectives between patients and oncologists suggests the value of tools to facilitate systematic communication of preferences in the setting of MBC., Implications for Practice: Both patients with metastatic breast cancer (MBC) and oncologists emphasized importance of efficacy and physical side effects when making treatment decisions. However, other patient considerations for making treatment decisions were broader, incorporating contextual factors such as the logistics of treatments, personal and family responsibilities, and ability to attend important events. Furthermore, individual patients varied substantially in priorities that they want considered in treatment decisions. Differences in perspectives between patients and oncologists suggest the value of tools to facilitate systematic elicitation of preferences and communication of those preferences to oncologists for integration into decision-making in MBC., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)
- Published
- 2019
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20. Disparities in Hospice Utilization for Older Cancer Patients Living in the Deep South.
- Author
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Turkman YE, Williams CP, Jackson BE, Dionne-Odom JN, Taylor R, Ejem D, Kvale E, Pisu M, Bakitas M, and Rocque GB
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Inpatients, Length of Stay, Male, Medicare, Palliative Care, Retrospective Studies, United States, Hospice Care statistics & numerical data, Hospices statistics & numerical data, Patient Acceptance of Health Care
- Abstract
Context: Hospice utilization is an end-of-life quality indicator. The Deep South has known disparities in palliative care that may affect hospice utilization., Objectives: The objective of this study was to evaluate the association among Deep South patient and hospital characteristics and hospice utilization., Methods: This retrospective cohort study evaluated patient and hospital characteristics associated with hospice among Medicare cancer decedents aged ≥65 years in 12 southeastern cancer centers between 2012 and 2015. We examined patient-level characteristics (age, race, gender, cancer type, and received patient navigation) and hospital-level characteristics (board-certified palliative physician, inpatient palliative care beds, and hospice ownership). Outcomes included hospice (within 90 vs. three days of death). Relative risks (RRs) and 95% CIs evaluated the association between patient- and hospital-level characteristics and hospice outcomes using generalized log-linear models with Poisson distribution and robust variance estimates., Results: Of 12,725 cancer decedents, 4142 (33%) did not utilize hospice. "No hospice" was associated with nonwhite (RR 1.24, 95% CI 1.17-1.32) and nonnavigated patients (RR 1.17, 95% CI 1.10-1.25), and those at a hospital with inpatient palliative care beds (RR 1.15, 95% CI 1.10-1.21). "Late hospice" (20%; n = 1458) was associated with being male (RR 1.31, 95% CI 1.19-1.44) and seen at a hospital without inpatient palliative care beds (RR 0.82, 95% CI 0.75-0.90)., Conclusions: Hospice utilization differed by patient and hospital characteristics. Patients who were nonwhite, and nonnavigated, and hospitals with inpatient palliative care beds, were associated with no hospice. Research should focus on ways to improve hospice utilization in Deep South older cancer patients., (Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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21. Impact of Guideline-Discordant Treatment on Cost and Health Care Utilization in Older Adults with Early-Stage Breast Cancer.
- Author
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Williams CP, Kenzik KM, Azuero A, Williams GR, Pisu M, Halilova KI, Ingram SA, Yagnik SK, Forero A, Bhatia S, and Rocque GB
- Subjects
- Aged, Cohort Studies, Female, Humans, Neoplasm Staging, Retrospective Studies, Breast Neoplasms economics, Patient Acceptance of Health Care statistics & numerical data
- Abstract
Background: National Comprehensive Cancer Network (NCCN) guideline-based treatment is a marker of high-quality care. The impact of guideline discordance on cost and health care utilization is unclear., Materials and Methods: This retrospective cohort study of Medicare claims data from 2012 to 2015 included women age ≥65 with stage I-III breast cancer receiving care within the University of Alabama at Birmingham Cancer Community Network. Concordance with NCCN guidelines was assessed for treatment regimens. Costs to Medicare and health care utilization were identified from start of cancer treatment until death or available follow-up. Adjusted monthly cost and utilization rates were estimated using linear mixed effect and generalized linear models., Results: Of 1,177 patients, 16% received guideline-discordant treatment, which was associated with nonwhite race, estrogen receptor/progesterone receptor negative, human epidermal growth receptor 2 (HER2) positive, and later-stage cancer. Discordant therapy was primarily related to reduced-intensity treatments (single-agent chemotherapy, HER2-targeted therapy without chemotherapy, bevacizumab without chemotherapy, platinum combinations without anthracyclines). In adjusted models, average monthly costs for guideline-discordant patients were $936 higher compared with concordant (95% confidence limits $611, $1,260). For guideline-discordant patients, adjusted rates of emergency department visits and hospitalizations per thousand observations were 25% higher (49.9 vs. 39.9) and 19% higher (24.0 vs. 20.1) per month than concordant patients, respectively., Conclusion: One in six patients with early-stage breast cancer received guideline-discordant care, predominantly related to undertreatment, which was associated with higher costs and rates of health care utilization. Additional randomized trials are needed to test lower-toxicity regimens and guide clinicians in treatment for older breast cancer patients., Implications for Practice: Previous studies lack details about types of deviations from chemotherapy guidelines that occur in older early-stage breast cancer patients. Understanding the patterns of guideline discordance and its impact on patient outcomes will be particularly important for these patients. This study found 16% received guideline-discordant care, predominantly related to reduced intensity treatment and associated with higher costs and rates of health care utilization. Increasing older adult participation in clinical trials should be a priority in order to fill the knowledge gap about how to treat older, less fit patients with breast cancer., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)
- Published
- 2019
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22. Hospice care, cancer-directed therapy, and Medicare expenditures among older patients dying with malignant brain tumors.
- Author
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Dover LL, Dulaney CR, Williams CP, Fiveash JB, Jackson BE, Warren PP, Kvale EA, Boggs DH, and Rocque GB
- Subjects
- Aged, Combined Modality Therapy, Female, Follow-Up Studies, Hospitalization economics, Hospitalization statistics & numerical data, Humans, Male, Medicare economics, Outcome Assessment, Health Care, Prognosis, Retrospective Studies, Survival Rate, United States, Brain Neoplasms economics, Brain Neoplasms therapy, Health Expenditures statistics & numerical data, Hospice Care economics, Hospice Care statistics & numerical data, Medicare statistics & numerical data, Terminal Care economics
- Abstract
Background: End-of-life care for older adults with malignant brain tumors is poorly understood. The purpose of this study is to quantify end-of-life utilization of hospice care, cancer-directed therapy, and associated Medicare expenditures among older adults with malignant brain tumors., Methods: This retrospective cohort study included deceased Medicare beneficiaries age ≥65 with primary malignant brain tumor (PMBT) or secondary MBT (SMBT) receiving care within a southeastern cancer community network including academic and community hospitals from 2012-2015. Utilization of hospice and cancer-directed therapy and total Medicare expenditures in the last 30 days of life were calculated using generalized linear and mixed effect models, respectively., Results: Late (1-3 days prior to death) or no hospice care was received by 24% of PMBT (n = 383) and 32% of SMBT (n = 940) patients. SMBT patients received late hospice care more frequently than PMBT patients (10% vs 5%, P = 0.002). Cancer-directed therapy was administered to 18% of patients with PMBT versus 25% with SMBT (P = 0.003). Nonwhite race, male sex, and receipt of any hospital-based care in the final 30 days of life were associated with increased risk of late or no hospice care. The average decrease in Medicare expenditures associated with hospice utilization for patients with PMBT was $-12,138 (95% CI: $-18,065 to $-6210) and with SMBT was $-1,508 (95% CI: $-3,613 to $598)., Conclusions: Receiving late or no hospice care was common among older patients with malignant brain tumors and was significantly associated with increased total Medicare expenditures for patients with PMBT.
- Published
- 2018
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23. Feasibility of a Telehealth Educational Program on Self-Management of Pain and Fatigue in Adult Cancer Patients.
- Author
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Rocque GB, Halilova KI, Varley AL, Williams CP, Taylor RA, Masom DG, Wright WJ, Partridge EE, and Kvale EA
- Subjects
- Aged, Cancer Pain diagnosis, Cancer Pain physiopathology, Fatigue diagnosis, Fatigue physiopathology, Feasibility Studies, Female, Humans, Male, Middle Aged, Neoplasms physiopathology, Patient Compliance, Patient Selection, Prospective Studies, Treatment Outcome, Cancer Pain therapy, Fatigue therapy, Neoplasms therapy, Patient Education as Topic methods, Self-Management education, Telemedicine methods
- Abstract
Context: Pain and fatigue are common symptoms among cancer patients and often lead to substantial distress. Innovative self-management programs for pain and fatigue are needed., Objectives: The primary objective was to assess the feasibility of a telehealth pain and fatigue self-management program among adult cancer patients. Secondary objectives included assessment of differences in patient characteristics, recruitment, and retention of patients based on two screening strategies: 1) navigator-collected, patient-reported pain or fatigue and 2) in-clinic, physician-identified pain or fatigue., Methods: This prospective, nonrandomized, pre-post evaluation assessed feasibility, which was defined as 50% of eligible patients choosing to participate and completing the intervention. Patient demographics and patient-reported outcomes (patient activation, distress, symptoms, and quality of life) were collected at baseline and study completion. Differences in baseline characteristics were compared between cohorts and for patients who did vs. did not graduate from the program., Results: The program did not meet feasibility requirements because of only 34% of eligible patients choosing to participate. However, 50% of patients starting the program graduated. Differences in baseline characteristics and retention rates were noted by recruitment strategy. At baseline, 27.3% of navigated patients were at the highest activation level compared with 7.1% in the physician-referred, non-navigated patients (P = 0.17); more than 15% of non-completers were at the lowest activation level compared with 9% of completers (P = 0.85)., Conclusion: Telehealth self-management program for pain and fatigue may be better accepted among selected segments of cancer patients. Larger scale studies are needed to assess the efficacy of this program in a more selective activated population., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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24. Implementation and Impact of Patient Lay Navigator-Led Advance Care Planning Conversations.
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Rocque GB, Dionne-Odom JN, Sylvia Huang CH, Niranjan SJ, Williams CP, Jackson BE, Halilova KI, Kenzik KM, Bevis KS, Wallace AS, Lisovicz N, Taylor RA, Pisu M, Partridge EE, Butler TW, Briggs LA, and Kvale EA
- Subjects
- Aged, Antineoplastic Agents therapeutic use, Education, Medical, Feasibility Studies, Female, Follow-Up Studies, Humans, Interviews as Topic, Male, Neoplasms epidemiology, Neoplasms therapy, Patient Preference, Qualitative Research, Self Efficacy, Surveys and Questionnaires, Terminal Care statistics & numerical data, Advance Care Planning, Communication, Health Personnel education, Health Personnel psychology, Patient Navigation
- Abstract
Context: Advance care planning (ACP) improves alignment between patient preferences for life-sustaining treatment and care received at end of life (EOL)., Objectives: To evaluate implementation of lay navigator-led ACP., Methods: A convergent, parallel mixed-methods design was used to evaluate implementation of navigator-led ACP across 12 cancer centers. Data collection included 1) electronic navigation records, 2) navigator surveys (n = 45), 3) claims-based patient outcomes (n = 820), and 4) semistructured navigator interviews (n = 26). Outcomes of interest included 1) the number of ACP conversations completed, 2) navigator self-efficacy, 3) patient resource utilization, hospice use, and chemotherapy at EOL, and 4) navigator-perceived barriers and facilitators to ACP., Results: From June 1, 2014 to December 31, 2015, 50 navigators completed Respecting Choices
® First Steps ACP Facilitator training. Navigators approached 18% of patients (1319/8704); 481 completed; 472 in process; 366 declined. Navigators were more likely to approach African American patients than Caucasian patients (20% vs. 14%, P < 0.001). Significant increases in ACP self-efficacy were observed after training. The mean score for feeling prepared to conduct ACP conversations increased from 5.6/10 to 7.5/10 (P < 0.001). In comparison with patients declining ACP participation (n = 171), decedents in their final 30 days of life who engaged in ACP (n = 437) had fewer hospitalizations (46% vs. 56%, P = 0.02). Key facilitators of successful implementation included physician buy-in, patient readiness, and prior ACP experience; barriers included space limitations, identifying the "right" time to start conversations, and personal discomfort discussing EOL., Conclusion: A navigator-led ACP program was feasible and may be associated with lower rates of resource utilization near EOL., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. All rights reserved.)- Published
- 2017
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25. The Impact of Veteran Status on Life-Space Mobility among Older Black and White Men in the Deep South.
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McCaskill GM, Sawyer P, Burgio KL, Kennedy R, Williams CP, Clay OJ, Brown CJ, and Allman RM
- Subjects
- Aged, Follow-Up Studies, Humans, Male, Prospective Studies, Activities of Daily Living, Black or African American, Aging ethnology, Mobility Limitation, Veterans statistics & numerical data, White People
- Abstract
Objective: To examine life-space mobility over 8.5 years among older Black and White male veterans and non-veterans in the Deep South., Design: A prospective longitudinal study of community-dwelling Black and White male adults aged >65 years (N=501; mean age=74.9; 50% Black and 50% White) enrolled in the University of Alabama at Birmingham (UAB) Study of Aging. Data from baseline in-home assessments with follow-up telephone assessments of life-space mobility completed every 6 months were used in linear mixed-effects modeling analyses to examine life-space mobility trajectories., Main Outcome Measures: Life-space mobility., Results: In comparison to veterans, non-veterans were more likely to be Black, single, and live in rural areas. They also reported lower income and education. Veterans had higher baseline life-space (73.7 vs 64.9 for non-veterans; P<.001). Race-veteran subgroup analyses revealed significant differences in demographics, comorbidity, cognition, and physical function. Relative to Black veterans, there were significantly greater declines in life-space trajectories for White non-veterans (P=.009), but not for White veterans (P=.807) nor Black non-veterans (P=.633). Mortality at 8.5 years was 43.5% for veterans and 49.5% for non-veterans (P=.190) with no significant differences by race-veteran status., Conclusions: Veterans had significantly higher baseline life-space mobility. There were significantly greater declines in life-space trajectories for White non-veterans in comparison to other race-veteran subgroups. Black veterans and non-veterans did not have significantly different trajectories.
- Published
- 2015
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26. Phosphorylation of Pex11p does not regulate peroxisomal fission in the yeast Hansenula polymorpha.
- Author
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Thomas AS, Krikken AM, van der Klei IJ, and Williams CP
- Subjects
- Mutation genetics, Phosphorylation, Phosphoserine metabolism, Protein Transport, Saccharomyces cerevisiae metabolism, Fungal Proteins metabolism, Peroxisomes metabolism, Pichia metabolism
- Abstract
Pex11p plays a crucial role in peroxisomal fission. Studies in Saccharomyces cerevisiae and Pichia pastoris indicated that Pex11p is activated by phosphorylation, which results in enhanced peroxisome proliferation. In S. cerevisiae but not in P. pastoris, Pex11p phosphorylation was shown to regulate the protein's trafficking to peroxisomes. However, phosphorylation of PpPex11p was proposed to influence its interaction with Fis1p, another component of the organellar fission machinery. Here, we have examined the role of Pex11p phosphorylation in the yeast Hansenula polymorpha. Employing mass spectrometry, we demonstrate that HpPex11p is also phosphorylated on a Serine residue present at a similar position to that of ScPex11p and PpPex11p. Furthermore, through the use of mutants designed to mimic both phosphorylated and unphosphorylated forms of HpPex11p, we have investigated the role of this post-translational modification. Our data demonstrate that mutations to the phosphorylation site do not disturb the function of Pex11p in peroxisomal fission, nor do they alter the localization of Pex11p. Also, no effect on peroxisome inheritance was observed. Taken together, these data lead us to conclude that peroxisomal fission in H. polymorpha is not modulated by phosphorylation of Pex11p.
- Published
- 2015
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27. Saline nasal irrigation for acute upper respiratory tract infections.
- Author
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King D, Mitchell B, Williams CP, and Spurling GK
- Subjects
- Acute Disease, Adult, Child, Common Cold therapy, Humans, Laryngitis therapy, Nasal Lavage adverse effects, Pharyngitis therapy, Randomized Controlled Trials as Topic, Rhinitis therapy, Sinusitis therapy, Sodium Chloride adverse effects, Nasal Lavage methods, Respiratory Tract Infections therapy, Sodium Chloride therapeutic use
- Abstract
Background: Acute upper respiratory tract infections (URTIs), including the common cold and rhinosinusitis, are common afflictions that cause discomfort and debilitation and contribute significantly to workplace absenteeism. Treatment is generally by antipyretic and decongestant drugs and sometimes antibiotics, even though most infections are viral. Nasal irrigation with saline is often employed as an adjunct treatment for URTI symptoms despite a relative lack of evidence for benefit in this clinical setting. This review is an update of the Cochrane review by Kassel et al, which found that saline was probably effective in reducing the severity of some symptoms associated with acute URTIs., Objectives: To assess the effects of saline nasal irrigation for treating the symptoms of acute URTIs., Search Methods: We searched CENTRAL (2014, Issue 7), MEDLINE (1966 to July week 5, 2014), EMBASE (1974 to August 2014), CINAHL (1982 to August 2014), AMED (1985 to August 2014) and LILACS (1982 to August 2014)., Selection Criteria: Randomised controlled trials (RCTs) comparing topical nasal saline treatment to other interventions in adults and children with clinically diagnosed acute URTIs., Data Collection and Analysis: Two review authors (DK, BM) independently assessed trial quality with the Cochrane 'Risk of bias' tool and extracted data. We analysed all data using the Cochrane Review Manager software. Due to the large variability of outcome measures only a small number of outcomes could be pooled for statistical analysis., Main Results: We identified five RCTs that randomised 544 children (three studies) and 205 adults (exclusively from two studies). They all compared saline irrigation to routine care or other nose sprays, rather than placebo. We included two new trials in this update, which did not contribute data of sufficient size or quality to materially change the original findings. Most trials were small and we judged them to be of low quality, contributing to an unclear risk of bias. Most outcome measures differed greatly between included studies and therefore could not be pooled. Most results showed no difference between nasal saline treatment and control. However, one larger trial, conducted with children, did show a significant reduction in nasal secretion score (mean difference (MD) -0.31, 95% confidence interval (CI) -0.48 to -0.14) and nasal breathing (obstruction) score (MD -0.33, 95% CI -0.47 to -0.19) in the saline group. However, a MD of -0.33 on a four-point symptom scale may have minimal clinical significance. The trial also showed a significant reduction in the use of decongestant medication by the saline group. Minor nasal discomfort and/or irritation was the only side effect reported by a minority of participants., Authors' Conclusions: Nasal saline irrigation possibly has benefits for relieving the symptoms of acute URTIs. However, the included trials were generally too small and had a high risk of bias, reducing confidence in the evidence supporting this. Future trials should involve larger numbers of participants and report standardised and clinically meaningful outcome measures.
- Published
- 2015
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28. Intravitreal bevacizumab injection in unrecognised early pregnancy.
- Author
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Sullivan L, Kelly SP, Glenn A, Williams CP, and McKibbin M
- Subjects
- Adult, Bevacizumab, Female, Humans, Intravitreal Injections, Pregnancy, Pregnancy Trimester, First, Young Adult, Angiogenesis Inhibitors administration & dosage, Antibodies, Monoclonal, Humanized administration & dosage, Choroidal Neovascularization drug therapy, Pregnancy Complications, Pregnancy Outcome, Retinal Diseases drug therapy
- Abstract
Purpose: The use of intravitreal vascular endothelial growth factor (VEGF) inhibitor medications has widened considerably to include indications affecting females of reproductive age., Patients and Methods: We present our experiences following intravitreal injection of bevacizumab during the first trimester of unrecognised pregnancies in four women., Results: All our patients were inadvertently exposed to bevacizumab within the first trimester when placental growth and fetal organogenesis take place. There were three cases of pregnancy without complication and one case of complicated pregnancy in which there was a significant past obstetric history., Conclusion: This case series provides further insights into intravitreal injection of bevacizumab in early pregnancy. There is insufficient information to suggest that such use is safe, nor is there definitive evidence to suggest that it causes harm. We advise that ophthalmologists discuss pregnancy with women of childbearing age undergoing intraocular anti-VEGF injections. Should a woman become pregnant, counselling is needed to explain the potential risks and benefits, and the limited available data relating to the use of these agents in early pregnancy.
- Published
- 2014
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29. The short to medium-term risks of intracameral phenylephrine.
- Author
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Williams GS, Radwan M, Kadare S, and Williams CP
- Subjects
- Aged, Aged, 80 and over, Anterior Chamber, Female, Follow-Up Studies, Humans, Incidence, Injections, Intraoperative Period, Male, Middle Aged, Mydriatics administration & dosage, Postoperative Complications epidemiology, Retrospective Studies, Risk Factors, Wales epidemiology, Phacoemulsification, Phenylephrine administration & dosage, Postoperative Complications prevention & control
- Abstract
Purpose: To compare outcomes and complications of patients undergoing phacoemulsification with and without the administration of intracameral phenylephrine., Materials and Methods: In this retrospective study, a chart review was performed. Two groups with an equal number of patients who did or did not receive intracameral phenylephrine during phacoemulsification were compared for differences in outcomes, risk factors and complications. The Chi-square test was used for comparison between groups. P<0.05 was statistically significant., Results: The two groups were well matched with regard to preoperative ophthalmic and systemic risk factors for complications and had very similar phacoemulsification power and time profiles. No differences in outcome were detected (P>0.05, all comparisons)., Conclusion: This retrospective study suggests that intracameral phenylephrine normalizes the intraoperative risk of small pupil cataract surgery and is not associated with an increased risk of systemic or postoperative ophthalmic complications.
- Published
- 2012
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30. The Peroxisomal Targeting Signal 1 in sterol carrier protein 2 is autonomous and essential for receptor recognition.
- Author
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Williams CP, Schueller N, Thompson CA, van den Berg M, Van Haren SD, Erdmann R, Bond CS, Distel B, Schliebs W, Wilmanns M, and Stanley WA
- Subjects
- Amino Acid Sequence, Binding Sites, Carrier Proteins genetics, Humans, Kinetics, Models, Molecular, Molecular Sequence Data, Peroxisome-Targeting Signal 1 Receptor, Peroxisomes chemistry, Peroxisomes genetics, Protein Binding, Protein Transport, Receptors, Cytoplasmic and Nuclear chemistry, Receptors, Cytoplasmic and Nuclear genetics, Sequence Alignment, Two-Hybrid System Techniques, Carrier Proteins chemistry, Carrier Proteins metabolism, Peroxisomes metabolism, Protein Sorting Signals, Receptors, Cytoplasmic and Nuclear metabolism
- Abstract
Background: The majority of peroxisomal matrix proteins destined for translocation into the peroxisomal lumen are recognised via a C-terminal Peroxisomal Target Signal type 1 by the cycling receptor Pex5p. The only structure to date of Pex5p in complex with a cargo protein is that of the C-terminal cargo-binding domain of the receptor with sterol carrier protein 2, a small, model peroxisomal protein. In this study, we have tested the contribution of a second, ancillary receptor-cargo binding site, which was found in addition to the characterised Peroxisomal Target Signal type 1., Results: To investigate the function of this secondary interface we have mutated two key residues from the ancillary binding site and analyzed the level of binding first by a yeast-two-hybrid assay, followed by quantitative measurement of the binding affinity and kinetics of purified protein components and finally, by in vivo measurements, to determine translocation capability. While a moderate but significant reduction of the interaction was found in binding assays, we were not able to measure any significant defects in vivo., Conclusions: Our data therefore suggest that at least in the case of sterol carrier protein 2 the contribution of the second binding site is not essential for peroxisomal import. At this stage, however, we cannot rule out that other cargo proteins may require this ancillary binding site., (© 2011 Williams et al; licensee BioMed Central Ltd.)
- Published
- 2011
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31. Effect of biomaterial design criteria on the performance of surgical meshes for abdominal hernia repair: a pre-clinical evaluation in a chronic rat model.
- Author
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Voskerician G, Jin J, White MF, Williams CP, and Rosen MJ
- Subjects
- Abdomen, Animals, Biocompatible Materials therapeutic use, Collagen, Female, Hernia, Polypropylenes therapeutic use, Prostheses and Implants, Rats, Rats, Sprague-Dawley, Tissue Adhesions physiopathology, Tissue Adhesions prevention & control, Hernia, Abdominal surgery, Surgical Mesh
- Abstract
Despite the recognized advantage of surgical meshes in abdominal hernia repair, reports of long term complications after implantation are increasing. 25 chronic hernia rats underwent incisional repair (n = 5/mesh group) with compressed poly(tetra-fluoro-ethylene) (cPTFE), expanded poly(tetra-fluoro-ethylene) (ePTFE), polypropylene (PP), poly(ethylene-terephtalate) + collagen (PET + C), and porcine intestinal submucosa (SIS). At 30 days, the extent and strength of intra-abdominal adhesions was evaluated, along with tissue-mesh integration, material shrinkage, and inflammatory response. The extent and tenacity of adhesions were reduced in PET + C and SIS, while tissue contraction was largely reduced in the presence of cPTFE. The tissue integration was not affected by composition or material construction. The host tissue response was elevated and arrested in a chronic imflammatory phase in the presence of PET + C and SIS, and resolved in the case of cPTFE. The different composition and material construction did not affect significantly the overall performance of the evaluated surgical meshes, apart from PP.
- Published
- 2010
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32. Outcome of intravitreal triamcinolone acetonide in postoperative cystoid macular oedema.
- Author
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Konstantopoulos A, Williams CP, and Luff AJ
- Subjects
- Aged, Aged, 80 and over, Anti-Inflammatory Agents adverse effects, Drug Evaluation, Female, Follow-Up Studies, Glucocorticoids administration & dosage, Glucocorticoids therapeutic use, Humans, Injections methods, Macular Edema etiology, Macular Edema physiopathology, Male, Middle Aged, Phacoemulsification adverse effects, Retrospective Studies, Treatment Outcome, Triamcinolone Acetonide administration & dosage, Visual Acuity drug effects, Vitrectomy adverse effects, Vitreous Body, Anti-Inflammatory Agents therapeutic use, Macular Edema drug therapy, Triamcinolone Acetonide therapeutic use
- Abstract
Aims: To assess the efficacy and safety of intravitreal triamcinolone in the treatment of postoperative cystoid macular oedema (CMO)., Methods: A retrospective case series review of 21 eyes (20 patients) that had an intravitreal injection of triamcinolone 4 mg for postoperative CMO. Diagnosis was confirmed by fundus fluorescein angiography and/or optical coherence tomography in all eyes., Results: Mean age of patients was 71.1 years. CMO had developed following routine phacoemulsification cataract extraction (13 eyes), phacoemulsification cataract extraction complicated by posterior capsule tear and vitreous loss (two eyes), vitrectomy (three eyes), or planned combined phacoemulsification and vitrectomy (three eyes). Mean duration of CMO before triamcinolone injection was 4.9 months. Mean duration of follow-up was 7.4 months. Two eyes required a repeat injection. Mean logarithm of minimum angle of resolution (LogMAR) visual acuity (VA) before treatment was 0.53; at 1 month post injection, this increased significantly to 0.33 (P<0.001). Improvement in VA was maintained throughout follow-up; at 6 months or later, mean LogMAR VA was significantly better than baseline (0.33 vs 0.53, P=0.02). At the latest review, 43% of eyes had improved Snellen VA by two or more lines and 86% by one or more lines compared to baseline. The remaining 14% had reduced Snellen VA compared to baseline. In the post-injection period, 33% of eyes developed an intraocular pressure of 22 mm Hg or higher and all responded well to short-term topical agents. There were no other post-injection complications., Conclusion: Intravitreal triamcinolone results in a rapid improvement in VA that may be sustained for more than 6 months.
- Published
- 2008
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33. Intravitreal bevacizumab (Avastin) for the treatment of choroidal neovascularization in age-related macular degeneration: results from 118 cases.
- Author
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Madhusudhana KC, Hannan SR, Williams CP, Goverdhan SV, Rennie C, Lotery AJ, Luff AJ, and Newsom RS
- Subjects
- Aged, Aged, 80 and over, Angiogenesis Inhibitors therapeutic use, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized, Bevacizumab, Choroidal Neovascularization physiopathology, Female, Follow-Up Studies, Humans, Injections, Macula Lutea, Macular Degeneration diagnosis, Male, Middle Aged, Retrospective Studies, Tomography, Optical Coherence, Visual Acuity, Vitreous Body, Angiogenesis Inhibitors administration & dosage, Antibodies, Monoclonal administration & dosage, Choroidal Neovascularization complications, Choroidal Neovascularization drug therapy, Macular Degeneration complications
- Published
- 2007
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34. An unusual maculopathy after routine cataract surgery.
- Author
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Costen MT, Williams CP, Asteriades S, and Luff AJ
- Subjects
- Acute Disease, Aged, Female, Humans, Male, Middle Aged, Remission, Spontaneous, Retinal Diseases pathology, Retinal Diseases physiopathology, Tomography, Optical Coherence, Visual Acuity, Cataract Extraction adverse effects, Macula Lutea pathology, Retinal Diseases etiology
- Abstract
Aims: To report the presentation of apparent acute and transient vitreomacular traction causing reduction in visual acuity following routine cataract surgery., Methods: A case series describing three patients that developed acute and transient vitreomacular traction following routine cataract surgery by experienced surgeons. No patients had any significant past medical or ophthalmic history. The patients presented shortly after surgery with reduction in visual acuity and dramatic optical coherence tomography (OCT) images suggesting vitreomacular traction., Results: All three patients experienced spontaneous resolution of symptoms and clinical signs within the first few weeks after surgery. Two patients experienced continued mild metamorphopsia., Conclusion: To our knowledge, this is the first documented report of such cases with associated confirmation by OCT imaging.
- Published
- 2007
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35. Ocular morbidity associated with intravitreal triamcinolone acetonide.
- Author
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Konstantopoulos A, Williams CP, Newsom RS, and Luff AJ
- Subjects
- Adult, Aged, Aged, 80 and over, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents adverse effects, Diabetic Retinopathy complications, Diabetic Retinopathy drug therapy, Diabetic Retinopathy physiopathology, Endophthalmitis chemically induced, Exfoliation Syndrome complications, Exfoliation Syndrome physiopathology, Eye Diseases physiopathology, Female, Glaucoma complications, Glaucoma physiopathology, Glucocorticoids administration & dosage, Humans, Injections methods, Intraocular Pressure drug effects, Macular Edema complications, Macular Edema drug therapy, Macular Edema physiopathology, Male, Middle Aged, Retinal Detachment chemically induced, Retinal Diseases complications, Retinal Diseases physiopathology, Retrospective Studies, Triamcinolone Acetonide administration & dosage, Vitreous Body, Eye Diseases chemically induced, Glucocorticoids adverse effects, Retinal Diseases drug therapy, Triamcinolone Acetonide adverse effects
- Abstract
Aim: To report on the complications associated with the use of intravitreal triamcinolone acetonide (IVTA) in a tertiary referral hospital setting., Materials and Methods: A retrospective case series review of all IVTA injections carried out over a period of 30 months., Results: One hundred and thirty IVTA injections were performed; nine with limited local follow-up were excluded. Thus, 121 injections (108 patients, 114 eyes) were included in the study. Triamcinolone (4 mg) was used in all cases. Indications were diabetic macular oedema (n=41 eyes), retinal vein occlusions (n=27), postoperative cystoid macular oedema (n=24), exudative age-related macular degeneration (n=16), and others (n=6). No intraoperative complications were recorded. Postoperative intraocular pressure (IOP) readings of 22, 28, 35, and 40 mmHg or higher were recorded in 46.5, 29.8, 12.3, and 7.9% of eyes, respectively. IOP elevation was treated with antiglaucoma medication in all but one eye (0.9%) that required trabeculectomy and one (0.9%) that required vitrectomy with cataract extraction for suspected phacoanaphylactic glaucoma. Two eyes (1.8%) developed retinal detachment; both had previously been treated for retinal breaks. One eye (0.9%) developed culture-positive endophthalmitis., Conclusions: Significant morbidity is associated with IVTA injection; clinicians should be aware when considering treatment options.
- Published
- 2007
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36. Globe rupture as a complication of intravitreal injection of triamcinolone.
- Author
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Ung T, Williams CP, and Canning CR
- Subjects
- Aged, 80 and over, Humans, Injections, Macular Edema drug therapy, Male, Rupture etiology, Vitreous Body, Glucocorticoids adverse effects, Sclera injuries, Triamcinolone adverse effects
- Published
- 2007
- Full Text
- View/download PDF
37. Birth defects and anti-heat shock protein 70 antibodies in early pregnancy.
- Author
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Child DF, Hudson PR, Hunter-Lavin C, Mukhergee S, China S, Williams CP, and Williams JH
- Subjects
- Autoantibodies blood, Case-Control Studies, Female, HSP70 Heat-Shock Proteins analysis, Humans, Infant, Newborn, Pregnancy, Retrospective Studies, Time Factors, Autoantibodies immunology, Congenital Abnormalities, Gestational Age, HSP70 Heat-Shock Proteins immunology
- Abstract
Abstract It has been suggested that induction of the heat shock response in the mammalian embryo during the critical period of organogenesis can result in anatomical malformation. We measured serum heat shock protein 70 (Hsp70), anti-Hsp70, and anti-Hsp60 in samples taken from expectant mothers at 16 weeks gestation. Samples from women whose babies were born with a birth defect (n = 30) were compared with controls who gave birth to healthy babies (n = 46). Anti-Hsp70 levels were significantly elevated in patients who later gave birth to babies with cleft lip or palate or neurological abnormalities (n = 10): 260 (223-406) microg/mL compared to 150 (88-207) microg/mL in controls (P < 0.001). No significant differences were found in serum Hsp70 and anti-Hsp60 levels between cases and controls. This finding of increased maternal anti-Hsp70 in patients who later gave birth to babies with these abnormalities suggests a previous stressful event may have contributed to the pathogenesis. Further work is required to determine whether Hsp70 has a direct or indirect role in this pathogenesis or whether anti-Hsp70 is simply a marker of a prior increase in Hsp70 due to a physiological stress that itself resulted in the damage. This work is consistent with previous studies showing a buffering role for Hsps in evolution.
- Published
- 2006
- Full Text
- View/download PDF
38. Expulsion of a lacrimal dacryolith by sneezing: a rare event.
- Author
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Salam A, Williams CP, and Manners RM
- Subjects
- Calculi complications, Humans, Lacrimal Apparatus Diseases etiology, Male, Middle Aged, Nasolacrimal Duct pathology, Calculi therapy, Lacrimal Apparatus Diseases therapy, Sneezing
- Abstract
Purpose: To describe the case of a man presenting with intermittent epiphora of the right eye and a low grade dacryocystitis due to a dacryolith., Methods/results: He was treated conservatively and was offered a Dacryocystorhinostomy. A few weeks before surgery, he developed swelling and pain over the right medial canthus followed by violent sneezing with spontaneous extrusion of the dacryolith., Discussion: The authors propose that the dacryolith fragmented spontaneously and once it reached the nasal cavity, was expelled by violent sneezing to the nostril, a mechanism not previously reported., Conclusions: Reformation of dacryolith is a likely possibility, and recurrence of symptoms in such cases may ultimately require a Dacryocystorhinostomy.
- Published
- 2006
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- View/download PDF
39. A randomised, double-blind trial of topical ketorolac vs artificial tears for the treatment of episcleritis.
- Author
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Williams CP, Browning AC, Sleep TJ, Webber SK, and McGill JI
- Subjects
- Adult, Aged, Aged, 80 and over, Cyclooxygenase Inhibitors therapeutic use, Double-Blind Method, Female, Humans, Male, Middle Aged, Ophthalmic Solutions, Pain Measurement, Prospective Studies, Severity of Illness Index, Treatment Outcome, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Ketorolac therapeutic use, Polyvinyl Alcohol therapeutic use, Scleritis drug therapy
- Abstract
Purpose: To determine whether topical ketorolac (Acular) is more effective than artificial tears in treating the signs and symptoms of idiopathic episcleritis., Methods: In this prospective, randomised, double-blind study, 38 eyes of 37 patients presenting with idiopathic episcleritis were allocated to receive either topical ketorolac (0.5%) or artificial tears three times a day for 3 weeks. The severity of patients' signs (episcleral injection and the number of clock hours affected) were recorded at weekly intervals. Patients' symptoms (perceived redness and pain scores) were recorded using a daily diary., Results: There was no significant difference in the ophthalmic signs between the two groups at each assessment, including intensity of episcleral injection and the number of clock hours affected. No significant difference was found in the time to halve the baseline redness intensity scores (4.4 vs 6.1 days, P=0.2) or pain scores (3.6 vs 4.3 days, P=0.55). Significantly more patients on ketorolac reported stinging at the first follow-up visit (P<0.001)., Conclusion: Topical ketorolac is not significantly better than artificial tears in treating the signs or symptoms of idiopathic episcleritis.
- Published
- 2005
- Full Text
- View/download PDF
40. Folate supplementation reduces serum hsp70 levels in patients with type 2 diabetes.
- Author
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Hunter-Lavin C, Hudson PR, Mukherjee S, Davies GK, Williams CP, Harvey JN, Child DF, and Williams JH
- Subjects
- Chaperonin 60 immunology, Erythrocytes metabolism, HSP70 Heat-Shock Proteins immunology, Humans, Diabetes Mellitus, Type 2 metabolism, Dietary Supplements, Folic Acid metabolism, HSP70 Heat-Shock Proteins metabolism
- Abstract
Type 2 diabetes patients are subject to oxidative stress as a result of hyperglycemia. The aim of this study was to determine whether administration of the antioxidant folic acid, previously shown to reduce homocysteine levels, would reduce circulating levels of Hsp70 while improving the condition of type 2 diabetes patients with microalbuminuria. Plasma homocysteine fell from pretreatment values of 12.9 to 10.3 microM (P < 0.0001). The urine albumin-creatinine ratio fell from 12.4 to 10.4 mg/mM (P = 0.38). Pretreatment Hsp70 levels were higher in patients not taking insulin (5.32 ng/mL) compared with those on insulin (2.44 ng/mL) (P = 0.012). Folic acid supplementation resulted in a significant fall in Hsp70 (5.32 to 2.05 ng/mL) (P = 0.004). There was no change in Hsp70 in those receiving insulin. Folic acid supplementation in non-insulin-treated type 2 diabetes patients, therefore, resulted in a fall in Hsp70, reflecting an improvement in oxidative stress. The data shows that improvement in homocysteine status can lead to a reduction in Hsp70, indicating the possibility of its use as a marker for severity of disease.
- Published
- 2004
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41. Troponin I, laboratory issues, and clinical outcomes in a district general hospital: crossover study with "traditional" markers of myocardial infarction in a total of 1990 patients.
- Author
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Jishi F, Hudson PR, Williams CP, Jones RP, Davies GK, Yousef ZR, Trent RJ, and Cowell RP
- Subjects
- Aged, Aged, 80 and over, Biomarkers blood, Cross-Over Studies, Diagnosis, Differential, Female, Hospitals, District, Hospitals, General, Humans, Length of Stay, Male, Middle Aged, Myocardial Infarction blood, Myocardial Infarction mortality, Patient Readmission, Sensitivity and Specificity, Myocardial Infarction diagnosis, Troponin I blood
- Abstract
Aims: Review of the clinical outcomes and practical issues of replacing traditional cardiac enzymes with troponin I (cTnI) in a district general hospital., Methods: Crossover study of three sequential three month stages during which serial cardiac enzymes were replaced with a single cTnI measurement available at three set times within 24 hours for the duration of the second three month stage. The study was carried out in a 630 bed district general hospital with 1990 admissions of suspected cardiac ischaemia over the study period as a whole. Account was taken of seasonal factors., Results: The introduction of troponin was associated with 8.5% more patients with non-ischaemic heart disease (IHD) being discharged on the day after admission, saving approximately 107 bed days each year. Approximately 50% more patients were diagnosed with myocardial infarction during the cTnI stage. There was no increase in readmission within one month or early death with cTnI. Approximately 3% false positive and 1.5% false negative cTnI results were recorded. All false positive cTnI results were coding errors or attributable to known assay interference effects. All false negatives were potentially explained by sample timing factors. The lack of standardisation in troponin assay services impacts clinically., Conclusion: Younger patients without IHD were discharged earlier during the cTnI stage in apparent safety. Blood sample timing needs to be verified when cTnI is used as an adjunct to early discharge. There were no unexplained false positives or negatives. Standardisation related issues arose.
- Published
- 2004
- Full Text
- View/download PDF
42. 360 degree giant retinal tear as a result of presumed non-accidental injury.
- Author
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Lash SC, Williams CP, Luff AJ, and Hodgkins PR
- Subjects
- Child of Impaired Parents, Eye Injuries complications, Female, Humans, Infant, Shaken Baby Syndrome complications, Shaken Baby Syndrome diagnosis, Child Abuse diagnosis, Retinal Perforations etiology
- Published
- 2004
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- View/download PDF
43. Phosphorylation and putative ER retention signals are required for protein kinase A-mediated potentiation of cardiac sodium current.
- Author
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Zhou J, Shin HG, Yi J, Shen W, Williams CP, and Murray KT
- Subjects
- Amino Acid Sequence, Animals, Binding Sites genetics, Enzyme Activation, Female, Humans, Membrane Potentials physiology, Molecular Sequence Data, Mutation, Myocardium metabolism, Oocytes, Phosphorylation, Rats, Sequence Homology, Amino Acid, Serine genetics, Signal Transduction, Sodium Channels genetics, Xenopus laevis, Cyclic AMP-Dependent Protein Kinases metabolism, Endoplasmic Reticulum metabolism, Sodium Channels physiology
- Abstract
Activation of protein kinase A (PKA) increases Na+ current derived from the human cardiac Na+ channel, hH1, in a slow, nonsaturable manner. This effect is prevented by compounds that disrupt plasma membrane recycling, implying enhanced trafficking of channels to the cell membrane as the mechanism responsible for Na+ current potentiation. To investigate the molecular basis of this effect, preferred consensus sites (serines 483, 571, and 593) and alternative sites phosphorylated by PKA in the rat heart isoform (serines 525 and 528) were removed in the I-II interdomain linker, a region in the channel previously implicated in the PKA response. Our results demonstrate that the presence of either serine 525 or 528 is required for Na+ current potentiation. The role of amino acid sequences that can mediate channel-protein interactions was also examined. Removal of a PDZ domain-binding motif at the carboxy terminus of hH1 did not alter the PKA response. The I-II interdomain linker of the channel contains 3 sites (479RKR481, 533RRR535, and 659RQR661) with the sequence RXR, a motif known to mediate retention of proteins in the endoplasmic reticulum (ER). The PKA-mediated increase in Na+ current was abolished when all 3 sites were eliminated, with RRR at position 533 to 535 primarily responsible for this effect. These results demonstrate that both alpha-subunit phosphorylation and the presence of putative ER retention signals are required for the PKA-mediated increase in cardiac Na+ current, an effect that likely involves interaction of the I-II interdomain linker with other proteins or regions of the channel.
- Published
- 2002
- Full Text
- View/download PDF
44. Why oral calcium supplements may reduce renal stone disease: report of a clinical pilot study.
- Author
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Williams CP, Child DF, Hudson PR, Davies GK, Davies MG, John R, Anandaram PS, and De Bolla AR
- Subjects
- Administration, Oral, Adult, Analysis of Variance, Calcium urine, Calcium Oxalate urine, Cross-Over Studies, Down-Regulation, Follow-Up Studies, Humans, Kidney Calculi blood, Kidney Calculi urine, Male, Middle Aged, Parathyroid Hormone blood, Phosphates urine, Pilot Projects, Seasons, Calcium therapeutic use, Dietary Supplements, Kidney Calculi prevention & control
- Abstract
Aims: To investigate whether increasing the daily baseline of gut calcium can cause a gradual downregulation of the active intestinal transport of calcium via reduced parathyroid hormone (PTH) mediated activation of vitamin D, and to discuss why such a mechanism might prevent calcium oxalate rich stones. To demonstrate the importance of seasonal effects upon the evaluation of such data., Methods: Within an intensive 24 hour urine collection regimen, daily calcium supplementation (500 mg) was given to five stone formers for a 10 week period during a six month crossover study. In a further population of patients on follow up for previous renal stone disease, observations were made on 1066 24 hour urine samples collected over five years in respect of seasonal effects relevant to the interpretation of the study., Results: In the group of patients on calcium supplements the following results were found. During calcium supplementation, the proportion of urine calcium to oxalate was higher (increased calcium to oxalate molar ratio), the 24 hour urine product of calcium and oxalate did not rise, and urine oxalate was lower during the first six weeks of supplementation. Twenty four hour urine calcium was 10.2% higher than baseline in the final four weeks of the 10 weeks of supplementation. Twenty four hour urine phosphate was 11.4% lower during the first six weeks of supplementation, but then rose while the patients were still on supplementation; renal tubular reabsorption of phosphate (TmP/GFR) mirrored the urine phosphate changes inversely. PTH was higher after stopping supplementation, but 1,25-(OH)2-cholecalciferol changes were not detected. In the 1066 urine samples collected over five years the following results were found. Calcium and oxalate excretion correlated positively and not inversely. Urine calcium and phosphate excretion were 5.5% and 2.5% higher, respectively, in "light" months of the year compared with "dark" months. A post summer decline in both urine calcium and urine phosphate was relevant to the interpretation of the study., Conclusions: Regular calcium supplementation does not raise the product of calcium and oxalate in urine and the proportion of oxalate to calcium is reduced. The underlying mechanisms of the changes seen in phosphate, calcium, and PTH and the observations on 1,25-(OH)2-cholecalciferol are not clear. Observed changes in phosphate could possibly be part of a calcium regulating feedback loop operating over a period of weeks. In evaluating these mechanisms background seasonal effects are important. It is possible that "programming" of the gut mucosa in terms of calcium transport is a major determinant of the relation between calcium and oxalate concentrations in urine and their relative abundance. Increased oral calcium, in association with a reduction of the relative proportion absorbed, may be pertinent to the prevention of calcium oxalate rich stones.
- Published
- 2001
- Full Text
- View/download PDF
45. Toxic bile acids in gastro-oesophageal reflux disease: influence of gastric acidity.
- Author
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Nehra D, Howell P, Williams CP, Pye JK, and Beynon J
- Subjects
- Adult, Aged, Barrett Esophagus etiology, Barrett Esophagus metabolism, Chromatography, High Pressure Liquid, Esophagitis, Peptic metabolism, Esophagus metabolism, Female, Gastric Acidity Determination, Gastroesophageal Reflux complications, Humans, Hydrogen-Ion Concentration, Male, Middle Aged, Bile Acids and Salts metabolism, Gastroesophageal Reflux metabolism
- Abstract
Background: Bile acid toxicity has been shown in the gastric, colonic, and hepatic tissues; the effect on oesophageal mucosa is less well known., Aims: To determine the spectrum of bile acids refluxing in patients with gastro-oesophageal reflux disease and its relation to oesophageal pH using a new technique of combined oesophageal aspiration and pH monitoring., Methods: Ten asymptomatic subjects and 30 patients with symptoms of gastro-oesophageal reflux disease (minimal mucosal injury, erosive oesophagitis (grade 2 or 3 Savary-Miller), Barrett's oesophagus/stricture; n=10 in each group) underwent 15 hour continuous oesophageal aspiration with simultaneous pH monitoring. Bile acid assay of the oesophageal samples was performed using modified high performance liquid chromatography., Results: The peak bile acid concentration and DeMeester acid scores were significantly higher in the patients with oesophagitis (median bile acid concentration 124 micromol/l; acid score 20.2) and Barrett's oesophagus/stricture (181 micromol/l; 43. 3) than patients with minimal injury (14 micromol/l; 12.5) or controls (0 micromol/l; 11.1). The predominant bile acids detected were cholic, taurocholic, and glycocholic acids but there was a significantly greater proportion of secondary bile acids, deoxycholic and taurodeoxycholic acids, in patients with erosive oesophagitis and Barrett's oesophagus/stricture. Although bile acid reflux episodes occurred at variable pH, a temporal relation existed between reflux of taurine conjugates and oesophageal acid exposure (r=0.58, p=0.009)., Conclusion: Toxic secondary bile acid fractions have been detected in patients with extensive mucosal damage. Mixed reflux is more harmful than acid reflux alone with possible toxic synergism existing between the taurine conjugates and acid.
- Published
- 1999
- Full Text
- View/download PDF
46. Inappropriate phosphate excretion in idiopathic hypercalciuria: the key to a common cause and future treatment?
- Author
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Williams CP, Child DF, Hudson PR, Soysa LD, Davies GK, Davies MG, and De Bolla AR
- Subjects
- Adult, Aged, Calcium blood, Calcium metabolism, Calcium urine, Ergocalciferols blood, Female, Glomerular Filtration Rate, Humans, Kidney Tubules physiopathology, Male, Middle Aged, Parathyroid Hormone blood, Phosphates blood, Phosphates urine, Regression Analysis, Serum Albumin analysis, Kidney Calculi physiopathology, Phosphates metabolism
- Abstract
Aims: To present experimental evidence in support of a proposed common cause for absorptive hypercalciuria, renal hypercalciuria, renal phosphate leak and enhancement of 1,25-(OH)2-vitamin D concentrations in patients presenting with renal stone disease; and to suggest further investigation with a view to new management., Methods: An oral calcium loading test was administered to 15 patients with renal stones and 10 normal controls in the fasting state: urine and blood were collected hourly. After the second urine sample, 400 mg calcium dissolved in water was administered orally. Serum calcium, albumin, parathyroid hormone (PTH), and phosphate were measured together with urine calcium clearance and urinary phosphate from which the TmPO4/glomerular filtration rate (GFR) ratio was calculated. Serum 1,25-(OH)2-vitamin D was measured in the first serum sample. In addition, 24 hour urine calcium results were collected retrospectively from the patients' case notes over the previous 18 months., Results: In the basal state, renal stone patients had an overall greater phosphaturia (lower TmPO4/GFR: median 1.72 compared with 2.10 in controls) and increased calcium clearance. Serum corrected calcium and PTH concentrations did not differ between the groups. After calcium loading, serum calcium and urine calcium clearance rose in both groups, with patients with renal stones experiencing a greater percentage fall in phosphaturia. In both groups TmPO4/GFR fell (greater phosphaturia) with increased serum corrected calcium, with the patients showing notably greater phosphaturia for any given calcium concentration. Patients also had notably greater phosphaturia compared with the serum calcium concentration for any given PTH value. Serum 1,25-(OH)2-vitamin D was higher in patients than controls and for any 1,25-(OH)2-vitamin D concentration phosphaturia measured against serum calcium was greater in patients than controls. 1,25-(OH)2-vitamin D did not correlate with phosphaturia relative to serum calcium concentrations within the patient and control groups., Conclusions: It is proposed that patients with idiopathic hypercalciuria have an "inappropriately' high phosphate excretion for any given serum calcium concentration. Loss of phosphate may induce increased activation of 1,25-(OH)2-vitamin D. Some of the commonly described causes of stone formation may be manifestations of a single mechanism.
- Published
- 1996
- Full Text
- View/download PDF
47. Hyperthyroidism and radio-iodine therapy in a district general hospital.
- Author
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Child DF, Mughni MA, Hudson P, Williams CP, and Harvey JN
- Subjects
- Adult, Age Distribution, Aged, Aged, 80 and over, Body Weight, Carbimazole therapeutic use, Combined Modality Therapy, Female, Follow-Up Studies, Hospitals, District, Hospitals, General, Humans, Hyperthyroidism blood, Hyperthyroidism drug therapy, Male, Middle Aged, Retrospective Studies, Thyrotropin blood, Triiodothyronine blood, Hyperthyroidism radiotherapy, Iodine Radioisotopes therapeutic use
- Abstract
A retrospective analysis was performed of 48 patients with hyperthyroidism (41 women aged 35-80, mean 56.6 years; 7 men aged 31-77, mean 52.1 years) treated with a fixed dose of 550 MBq 131I during a 12 month period May 1991-April 1992. Weight loss was common at presentation but 28.57% of women aged 35-49 years weighed over 80 kg compared to 9.98% in a standard UK population P < 0.05. Patients treated with carbimazole (73%) prior to 131I had higher FT3 levels at presentation (14.0 +/- 4.4 pmol/l) compared to those (27%) who were considered not to require such treatment (8.9 +/- 1.4 pmol/l, P < 0.001). Four months following radio-iodine, 67% were hypothyroid, 25% were euthyroid and 8% remained thyrotoxic and were retreated. Another patient became hypothyroid during 1 year of follow-up. Pre-treatment with carbimazole did not protect against the development of hypothyroidism (carbimazole treated 69% hypothyroid at 4 months, untreated 62% hypothyroid at 4 months). Patients with continuing thyrotoxicosis had very high FT3 levels at presentation (18.6, 21.1, 20 and in one patient reported only as > 10 pmol/l). A rationalized programme of follow-up assessments at 2, 3, 4, 8 and 12 months is suggested for patients treated with this dose of radio-iodine.
- Published
- 1994
- Full Text
- View/download PDF
48. Heat shock protein and the double insult theory for the development of insulin dependent diabetes.
- Author
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Child DF, Smith CJ, and Williams CP
- Subjects
- Animals, Antigens immunology, Bacterial Infections immunology, Glutamate Decarboxylase immunology, Heat-Shock Proteins physiology, Humans, Mice, Autoimmune Diseases etiology, Diabetes Mellitus, Type 1 etiology, Heat-Shock Proteins immunology
- Abstract
Heat shock proteins (HSP) are the most widely conserved group of proteins in phylogeny and play an important role in infection and autoimmunity. HSP65 has been suggested as the primary antigen in insulin dependent diabetes while an alternative antigen glutamic acid decarboxylase (GAD), has similar amino acid sequences. A 'double insult theory' for the development of insulin dependent diabetes is suggested whereby a bacterial infection leads to the production of HSP antibody. If during a 'window of opportunity' this is followed by a viral infection of the islet cells this could, in certain histocompatibility locus antigen (HLA) groups only, lead to the production of HSPs on the cell surface and a destructive autoimmune reaction.
- Published
- 1993
- Full Text
- View/download PDF
49. Decreased myofilament responsiveness in myocardial stunning follows transient calcium overload during ischemia and reperfusion.
- Author
-
Carrozza JP Jr, Bentivegna LA, Williams CP, Kuntz RE, Grossman W, and Morgan JP
- Subjects
- Aequorin, Animals, Ferrets, Heart physiopathology, In Vitro Techniques, Male, Reperfusion Injury physiopathology, Actin Cytoskeleton metabolism, Calcium metabolism, Myocardium metabolism, Reperfusion Injury metabolism
- Abstract
The purpose of this study was to test the hypothesis that abnormal intracellular calcium handling characterizes myocardial stunning. Isolated, isovolumic, buffer-perfused ferret hearts were loaded with the bioluminescent calcium indicator aequorin for simultaneous measurement of individual calcium transients and left ventricular pressure. After 15 minutes of global ischemia and 20 minutes of reperfusion, left ventricular developed pressure was significantly reduced (75 +/- 7 versus 93 +/- 6 mm Hg, p < 0.05). During ischemia, [Ca2+]i levels were significantly elevated compared with preischemic levels, both during systole (1.38 +/- 0.31 versus 0.88 +/- 0.2 microM, p < 0.05) and end diastole (0.85 +/- 0.16 versus 0.38 +/- 0.13 microM, p < 0.05). Early during reperfusion, [Ca2+]i was also significantly elevated during systole (1.63 +/- 0.44 versus 0.88 +/- 0.20 microM, p < 0.05) and end diastole (0.75 +/- 0.15 versus 0.38 +/- 0.13 microM, p < 0.05). After 20 minutes of reperfusion, myocardial stunning occurred, but [Ca2+]i was not significantly different from preischemic levels. Thus, myocardial stunning does not result from decreased levels of activator calcium. The force-pCa relation generated by the stunned hearts was shifted downward compared with that generated by the control hearts, consistent with a decrease in maximum calcium-activated force (Fmax). At steady state during tetanus, the decrease in Fmax was confirmed, but there was no significant difference in the slope of the force-pCa relation of the stunned hearts versus controls. Thus, we conclude that stunned myocardium is characterized by decreased Fmax without desensitization of the myofilaments to [Ca2+]i.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1992
- Full Text
- View/download PDF
50. Persistent hypersecretion of ACTH in treated Addison's disease.
- Author
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Child DF, Lewis F, and Williams CP
- Subjects
- Addison Disease blood, Addison Disease drug therapy, Adrenocorticotropic Hormone blood, Aged, Cortisone analogs & derivatives, Cortisone therapeutic use, Feedback, Female, Fludrocortisone therapeutic use, Humans, Addison Disease physiopathology, Adrenocorticotropic Hormone metabolism, Skin Pigmentation physiology
- Published
- 1990
- Full Text
- View/download PDF
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