The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.
Objective To evaluate the effectiveness of remote proactive management of toxicities during chemotherapy for early stage breast cancer. Design Pragmatic, cluster randomised trial. Setting 20 cancer centres in Ontario, Canada, allocated by covariate constrained randomisation to remote management of toxicities or routine care. Participants All patients starting adjuvant or neoadjuvant chemotherapy for early stage breast cancer at each centre. 25 patients from each centre completed patient reported outcome questionnaires. Interventions Proactive, standardised, nurse led telephone management of common toxicities at two time points after each chemotherapy cycle. Main outcome measures The primary outcome, cluster level mean number of visits to the emergency department or admissions to hospital per patient during the whole course of chemotherapy treatment, was evaluated with routinely available administrative healthcare data. Secondary patient reported outcomes included toxicity, self-efficacy, and quality of life. Results Baseline characteristics of participants were similar in the intervention (n=944) and control arms (n=1214); 22% were older than 65 years. Penetration (that is, the percentage of patients who received the intervention at each centre) was 50-86%. Mean number of visits to the emergency department or admissions to hospital per patient was 0.91 (standard deviation 0.28) in the intervention arm and 0.94 (0.40) in the control arm (P=0.94); 47% (1014 of 2158 patients) had at least one visit to the emergency department or a hospital admission during chemotherapy. Among 580 participants who completed the patient reported outcome questionnaires, at least one grade 3 toxicity was reported by 48% (134 of 278 patients) in the intervention arm and by 58% (163 of 283) in the control arm. No differences in self-efficacy, anxiety, or depression were found. Compared with baseline, the functional assessment of cancer therapy trial outcome index decreased by 6.1 and 9.0 points in the intervention and control participants, respectively. Conclusions Proactive, telephone based management of toxicities during chemotherapy did not result in fewer visits to the emergency department or hospital admissions. With the rapid rise in remote care because of the covid-19 pandemic, identifying scalable strategies for remote management of patients during cancer treatment is particularly relevant. Trial registration ClinicalTrials.gov NCT02485678 .
Clin Invest Med 2009; 32 (3): E239-E249. AbstractPurpose. The demand for cancer care has increased among aging North American populations as cancer treatment innovations have proliferated. Gaps between supply and demand may be growing. This study examined whether socioeconomic status has a differential effect on waits for surgical and adjuvant radiation treatment (RT) of breast cancer in Canada and the US. Methods. Ontario and California cancer registries provided 929 and 984 breast cancer cases diagnosed between 1998 and 2000 in diverse urban and rural places. Residencebased socioeconomic data were taken from censuses. Cancer care variables were reliably abstracted from health records: stage, receipt of surgery and RT, and waits from diagnosis to initial and initial to adjuvant treatment. Median waits were compared within-and between-country with the non-parametric Mann-Whitney U-test. Categorically long, age-adjusted wait comparisons used the Mantel-Haenszel chi-square test.Results. There were significant associations between lower socioeconomic status and longer surgical waits, lower access to adjuvant RT and to longer RT waits across diverse places in California. None were observed in Ontario. The two cohorts did not practically differ on access to surgery or on surgical waits. Compared with their counterparts in California, low-income Ontarians, particularly those in small urban places, gained greater access to RT, while high-income Americans had shorter waits for RT. Conclusions. This historical study contextualized Canada's "waiting-list problems" with evidence on breast cancer care, where lower income Americans seemed to have waited as long as similar Canadians. Many more lowincome Americans seemed to experience the longest wait of all for adjuvant care. They simply did not receive it. In contrast to stark American socioeconomic inequity, this study evidenced remarkable equity in Canadian breast cancer care.Clinical and common wisdom converged in the 1990s to ignite scientific and political interest in Canada's "waiting-list problem. that the gap between supply and demand may have been getting larger in Canada than in America. 4,5 However, the only previous study to test that hypothesis found no significant treatment delay differences among women diagnosed with breast cancer in 1988 in Washington state and the province of British Columbia. 6 No study has since compared evidence on cancer care delays in Canada and the United States (US). Breast cancer care has been most studied in this field. For a number of reasons it seems a sentinel indicator of health care performance. The most common type of cancer among Canadian and American women, its prognosis is excellent with early diagnosis and timely access to the best treatments. 7,8 Moreover, surgical innovations and new adjuvant radiation therapies (RT) after both breast conserving surgery and mastectomy were advanced over the past 20 years, 4,9 so their timely access seems of legitimate clinical and policy concern. The possibility of socioeconomic status (...
Objectives-We examined the differential effects of socioeconomic status on colon cancer care and survival in Toronto, Ontario, Canada, and San Francisco, California.Methods-We analyzed registry data for colon cancer patients from Ontario (n=930) and California (n=1014), diagnosed between 1996 and 2000 and followed until 2006, on stage, surgery, adjuvant chemotherapy, and survival. We obtained socioeconomic data for individuals' residences from population censuses.Correspondence should be sent to Kevin Gorey, School of Social Work, University of Windsor, 401 Sunset Ave, Windsor, Ontario, N9B 3P4 gorey@uwindsor.ca. Reprints can be ordered at http://www.ajph.org by clicking the "Reprints/Eprints" link. ContributorsK. M. Gorey conceptualized and supervised the study and led the writing. K. Y. Fung led the analysis. All authors assisted with study design, data analysis, and interpretation and writing. Human Participant Protection CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptResults-Income was directly associated with lymph node evaluation, chemotherapy, and survival in San Francisco but not in Toronto. High-income persons had better survival rates in San Francisco than in Toronto. After adjustment for stage, survival was better for low-income residents of Toronto than for those of San Francisco. Middle-to low-income patients were more likely to receive indicated chemotherapy in Toronto than in San Francisco.Conclusions-Socioeconomic factors appear to mediate colon cancer care in urban areas of the United States but not in Canada. Improvements are needed in screening, diagnostic investigations, and treatment access among low-income Americans.A study of cancer survival in low-income areas of Toronto, Ontario, and Detroit, Michigan, during the 1980s found advantages among Canadians for common cancers. 1 The Toronto survival advantage was replicated for breast cancer across diverse low-income Canadian and US contexts through the 1990s. 2 Studies of that era, however, were not able to account for differences in stage of disease at diagnosis. More recent studies that accounted for breast cancer stage again found Canadian advantages. [3][4][5][6] In the United States, women with breast cancer who lived in low-income areas waited longer for surgery and adjuvant radiation therapy and were less likely to receive radiation therapy or to survive. Similar disparities between high-and low-income women with breast cancer did not exist in Canada; thus lowincome Canadians fared better across most breast cancer care indices than their US counterparts. More inclusive health insurance in Canada was advanced as the most plausible explanation.Colon cancer care may be an even more important health care performance indicator. The second most frequent cause of cancer death in North America, its prognosis can be excellent with early diagnosis and treatment. 7,8 For several reasons, colon cancer seems particularly instructive for Canada-US cancer care comparisons. First, research on income and colon cancer survi...
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