Selecting, implementing and evaluating patient-reported outcome measures for routine clinical use in cancer: the Cancer Care Ontario approach.

BACKGROUND: The use of Patient-Reported Outcome Measures (PROMs) in routine clinical care can help ensure symptoms are identified, acknowledged and addressed. In 2007, the provincial cancer agency, Cancer Care Ontario, began to implement routine symptom screening with the Edmonton Symptom Assessment System (ESAS) for ambulatory cancer patients. Having had a decade of experience with ESAS, the program developed a strategic interest in implementing new and/or additional measures. This article describes the development of a streamlined PROM selection and implementation evaluation process with core considerations. METHODS: Development of the PROM selection and implementation evaluation process involved analysis of quantitative and qualitative data as well as consensus building through a multi-stakeholder workshop. Core PROM selection considerations were developed through a literature scan, review and refinement by a panel of methodological experts and patient advisors, and testing via a test case. Core PROM implementation evaluation considerations were developed through analysis of PROM evaluation frameworks, and review and refinement by a committee of provincial implementation leads. RESULTS: Core PROM selection considerations were identified under three overarching themes: symptom coverage, usability and psychometric properties. The symptom coverage category assesses each PROM to determine how well the PROM items address the most prevalent and burdensome symptoms in the target patient population. The usability category aims to assess each measure on characteristics key to successful implementation in the clinical setting. The psychometric properties category assesses each PROM to ensure the data collected is credible, meaningful and interpretable. A scoring system was developed to rate PROM performance by assigning a grade of "weak", "average" or "good" for each category. The process results in a summary matrix which illustrates the overall assessment of each PROM. Implementation evaluation considerations were identified under three overarching concepts: acceptability, outcomes, and sustainability. A consensus building exercise resulted in the further identification of patient, provider, and clinic specific indicators for each consideration. CONCLUSION: To address the need for a systematic, evidence-based approach to selection, implementation and evaluation of PROMs in the clinical setting, Cancer Care Ontario defined a process with embedded core considerations to facilitate decision-making and encourage standardization.

The role of biomarkers in diagnosis of COVID-19 - A systematic review.

AIMS: As of the 28th April 2020, the COVID-19 pandemic has infiltrated over 200 countries and affected over three million confirmed people. We review different biomarkers to evaluate if they are able to predict clinical outcomes and correlate with the severity of COVID-19 disease. METHODS: A systematic review of the literature was carried out to identify relevant articles using six different databases. Keywords to refine the search included 'COVID-19', 'SARS-CoV2', 'Biomarkers', among others. Only studies which reported data on pre-defined outcomes were included. KEY FINDINGS: Thirty-four relevant articles were identified which reviewed the following biomarkers: C-reactive protein, serum amyloid A, interleukin-6, lactate dehydrogenase, neutrophil-to-lymphocyte ratio, D-dimer, cardiac troponin, renal biomarkers, lymphocytes and platelet count. Of these, all but two, showed significantly higher levels in patients with severe complications of COVID-19 infection compared to their non-severe counterparts. Lymphocytes and platelet count showed significantly lower levels in severe patients compared to non-severe patients. SIGNIFICANCE: Although research is still in its early stages, the discovery of how different biomarkers behave during the course of the disease could help clinicians in identifying severe disease earlier and subsequently improve prognosis. Nevertheless, we urge for more research across the globe to corroborate these findings.

Are population-based patient-reported outcomes associated with overall survival in patients with advanced pancreatic cancer?

BACKGROUND: Advanced pancreatic cancer (APC) patients often have substantial symptom burden. In Ontario, patients routinely complete the Edmonton Symptom Assessment Scale (ESAS), which screens for nine symptoms (scale: 0-10), in cancer clinics. We explored the association between baseline patient-reported outcomes, via ESAS, and overall survival (OS). METHODS: Advanced pancreatic cancer patients with ESAS records prior to receiving publicly funded drugs from November 2008 to March 2016 were retrospectively identified from Cancer Care Ontario's administrative databases. We examined three composite ESAS scores: total symptom distress score (TSDS: 9 symptoms), physical symptom score (PHS: 6/9 symptoms), and psychological symptom score (PSS: 2/9 symptoms); Composite scores greater than defined thresholds (TSDS ≥36, PHS ≥24, PSS ≥8) were considered as high symptom burden. Crude OS was assessed using Kaplan-Meier method. Hazard ratios (HRs) were assessed using multivariable Cox models. Analysis was repeated in a sub-cohort with Eastern Cooperative Oncology Group (ECOG) status and metastasis. RESULTS: We identified 2199 APC patients (mean age 64 years, 55% male) with ESAS records prior to receiving chemotherapy. Crude median survival was 4.5 and 7.3 months for high and low TSDS, respectively. High TSDS was associated with lower OS (HR = 1.47, 95% CI: 1.33, 1.63). In the sub-cohort (n = 393) with ECOG status and metastasis, high TSDS was also associated with lower OS (HR = 1.34, 95% CI: 1.04, 1.73). Similar trends were observed for PHS and PSS. CONCLUSIONS: Higher burden of patient-reported outcome was associated with reduced OS among APC patients. The effect was prominent after adjusting for ECOG status.

Effect of cardio-metabolic risk factors on all-cause mortality among HIV patients on antiretroviral therapy in Malawi: A prospective cohort study.

BACKGROUND: Cardiovascular disease (CVD) risk among people living with HIV is elevated due to persistent inflammation, hypertension and diabetes comorbidity, lifestyle factors and exposure to antiretroviral therapy (ART). Data from Africa on how CVD risk affects morbidity and mortality among ART patients are lacking. We explored the effect of CVD risk factors and the Framingham Risk Score (FRS) on medium-term ART outcomes. METHODS: A prospective cohort study of standardized ART outcomes (Dead, Alive on ART, stopped ART, Defaulted and Transferred out) was conducted from July 2014-December 2016 among patients on ART at a rural and an urban HIV clinic in Zomba district, Malawi. The primary outcome was Dead. Active defaulter tracing was not done and patients who transferred out and defaulted were excluded from the analysis. At enrolment, hypertension, diabetes and dyslipidemia were diagnosed, lifestyle data collected and the FRS was determined. Cox-regression analysis was used to determine independent risk factors for the outcome Dead. RESULTS: Of 933 patients enrolled, median age was 42 years (IQR: 35-50), 72% were female, 24% had hypertension, 4% had diabetes and 15.8% had elevated total cholesterol. The median follow up time was 2.4 years. Twenty (2.1%) patients died, 50 (5.4%) defaulted, 63 (6.8%) transferred out and 800 (85.7%) were alive on ART care (81.7% urban vs. 89.9% rural). In multivariable survival analysis, male gender (aHR = 3.28; 95%CI: 1.33-8.07, p = 0.01) and total/HDL cholesterol ratio (aHR = 5.77, 95%CI: 1.21-27.32; p = 0.03) were significantly associated with mortality. There was no significant association between mortality and hypertension, body mass index, central obesity, diabetes, FRS, physical inactivity, smoking at enrolment, ART regimen and WHO disease stage. CONCLUSIONS: Medium-term all-cause mortality among ART patients was associated with male gender and elevated total/HDL cholesterol ratio.

Dyslipidemia among rural and urban HIV patients in south-east Malawi.

BACKGROUND: While dyslipidemia importantly contributes to increased cardiovascular disease risk among patients on antiretroviral therapy (ART), data on lipid patterns among African adults on ART are limited. We describe the prevalence of lipid abnormalities and associated factors in two HIV clinics in Malawi. METHODS: We conducted a cross-sectional study in 2014 and enrolled adult patients at a rural and an urban HIV clinic in Zomba district, Malawi. We recorded patient characteristics, CVD risk factors and anthropometric measurements, using the WHO STEPS validated instrument. Non-fasting samples were taken for determination of total cholesterol (TC), triglyceride (TG) and HDL-cholesterol (HDL-c) levels. Logistic regression analysis was used to determine factors associated with elevated TC and elevated TC/HDL-c ratio. RESULTS: 554 patients were enrolled, 50% at the rural HIV clinic, 72.7% were female, the median (IQR) age was 42 years (36-50); 97.3% were on ART, 84.4% on tenofovir/lamivudine/efavirenz, 17.5% were overweight/obese and 27.8%% had elevated waist/hip ratio. 15.5% had elevated TC, 15.9% reduced HDL-c, 28.7% had elevated TG and 3.8% had elevated TC/HDL-c ratio. Lipid abnormalities were similar in rural and urban patients. Women had significantly higher burden of elevated TC and TG whereas men had higher prevalence of reduced HDL-c. Waist-to-hip ratio was independently associated with elevated TC (aOR = 1.90; 95% CI: 1.17-3.10, p = 0.01) and elevated TC/HDL-c ratio (aOR = 3.50; 95% CI: 1.38-8.85, p = 0.008). Increasing age was independently associated with elevated TC level (aOR = 1.54, 95% CI 0.51-4.59 for age 31-45; aOR = 3.69, 95% CI 1.24-10.95 for age >45 years vs. ≤30 years; p-trend <0.01). CONCLUSIONS: We found a moderate burden of dyslipidemia among Malawian adults on ART, which was similar in rural and urban patients but differed significantly between men and women. High waist-hip ratio predicted elevated TC and elevated TC/HDL-c ratio and may be a practical tool for CVD risk indication in resource limited settings.

COST-EFFECTIVENESS IMPACTS CANCER CARE FUNDING DECISIONS IN BRITISH COLUMBIA, CANADA, EVIDENCE FROM 1998 TO 2008.

OBJECTIVES: The Priorities and Evaluation Committee (PEC) funding recommendations for new cancer drugs in British Columbia, Canada have been based on both clinical and economic evidence. The British Columbia Ministry of Health makes funding decisions. We assessed the association between cost-effectiveness of cancer drugs considered from 1998 to 2008 and the subsequent funding decisions. METHODS: All proposals submitted to the PEC between 1998 and 2008 were reviewed, and the association between cost-effectiveness and funding decisions was examined by (i) using logistic regression to test the hypothesis that interventions with higher incremental cost-effectiveness ratios (ICERs) have a lower probability of receiving a positive funding decision and (ii) using parametric and nonparametric tests to determine if a statistically significant difference exists between the mean cost-effectiveness of funded versus not funded proposals. A sub-analysis was conducted to determine if the findings varied across different outcome measures. RESULTS: Of the 149 proposals reviewed, 78 reported cost-effectiveness using various outcome measures. In the proposals that used life-years gained as the outcome (n = 22), a statistically significant difference of nearly $115,000 was observed between the mean ICERs for funded proposals ($42,006) and for unfunded proposals ($156,967). An odds ratio indicating higher ICERs have a lower probability of being funded was also found to be statistically significant (p < .05). CONCLUSIONS: Economic evidence appears to play a role in British Columbia cancer funding decisions from 1998 to 2008; other decision-making criteria may also have an important role in recommendations and subsequent funding decisions.

Oncology Nurses' Attitudes Toward the Edmonton Symptom Assessment System: Results From a Large Cancer Care Ontario Study.

PURPOSE/OBJECTIVES: To examine oncology nurses' attitudes toward and reported use of the Edmonton Symptom Assessment System (ESAS) and to determine whether the length of work experience and presence of oncology certification are associated with their attitudes and reported usage.
. DESIGN: Exploratory, mixed-methods study employing a questionnaire approach.
. SETTING: 14 regional cancer centers (RCCs) in Ontario, Canada.
. SAMPLE: Oncology nurses who took part in a larger province-wide study that surveyed 960 interdisciplinary providers in oncology care settings at all of Ontario's 14 RCCs.
. METHODS: Oncology nurses' attitudes and use of ESAS were measured using a 21-item investigator-developed questionnaire. Descriptive statistics and Kendall's tau-b or tau-c test were used for data analyses. Qualitative responses were analyzed using content analysis.
. MAIN RESEARCH VARIABLES: Attitudes toward and self-reported use of standardized symptom screening and ESAS.
. FINDINGS: More than half of the participants agreed that ESAS improves symptom screening, most said they would encourage their patients to complete ESAS, and most felt that managing symptoms is within their scope of practice and clinical responsibilities. Qualitative comments provided additional information elucidating the quantitative responses. Statistical analyses revealed that oncology nurses who have 10 years or less of work experience were more likely to agree that the use of standardized, valid instruments to screen for and assess symptoms should be considered best practice, ESAS improves symptom screening, and ESAS enables them to better manage patients' symptoms. No statistically significant difference was found between oncology-certified RNs and noncertified RNs on attitudes or reported use of ESAS.
. CONCLUSIONS: Implementing a population-based symptom screening approach is a major undertaking. The current study found that oncology nurses recognize the value of standardized screening, as demonstrated by their attitudes toward ESAS.
. IMPLICATIONS FOR NURSING: Oncology nurses are integral to providing high-quality person-centered care. Using standardized approaches that enable patients to self-report symptoms and understanding barriers and enablers to optimal use of patient-reported outcome tools can improve the quality of patient care.

The burden of hypertension, diabetes mellitus, and cardiovascular risk factors among adult Malawians in HIV care: consequences for integrated services.

BACKGROUND: Hypertension and diabetes prevalence is high in Africans. Data from HIV infected populations are limited, especially from Malawi. Integrating care for chronic non-communicable co-morbidities in well-established HIV services may provide benefit for patients by preventing multiple hospital visits but will increase the burden of care for busy HIV clinics. METHODS: Cross-sectional study of adults (≥18 years) at an urban and a rural HIV clinic in Zomba district, Malawi, during 2014. Hypertension and diabetes were diagnosed according to stringent criteria. Proteinuria, non-fasting lipids and cardio/cerebro-vascular disease (CVD) risk scores (Framingham and World Health Organization/International Society for Hypertension) were determined. The association of patient characteristics with diagnoses of hypertension and diabetes was studied using multivariable analyses. We explored the additional burden of care for integrated drug treatment of hypertension and diabetes in HIV clinics. We defined that burden as patients with diabetes and/or stage II and III hypertension, but not with stage I hypertension unless they had proteinuria, previous stroke or high Framingham CVD risk. RESULTS: Nine hundred fifty-two patients were enrolled, 71.7% female, median age 43.0 years, 95.9% on antiretroviral therapy (ART), median duration 47.7 months. Rural and urban patients' characteristics differed substantially. Hypertension prevalence was 23.7% (95%-confidence interval 21.1-26.6; rural 21.0% vs. urban 26.5%; p = 0.047), of whom 59.9% had stage I (mild) hypertension. Diabetes prevalence was 4.1% (95%-confidence interval 3.0-5.6) without significant difference between rural and urban settings. Prevalence of proteinuria, elevated total/high-density lipoprotein-cholesterol ratio and high CVD risk score was low. Hypertension diagnosis was associated with increasing age, higher body mass index, presence of proteinuria, being on regimen zidovudine/lamivudine/nevirapine and inversely with World Health Organization clinical stage at ART initiation. Diabetes diagnosis was associated with higher age and being on non-standard first-line or second-line ART regimens. CONCLUSION: Among patients in HIV care 26.6% had hypertension and/or diabetes. Close to two-thirds of hypertension diagnoses was stage I and of those few had an indication for antihypertensive pharmacotherapy. According to our criteria, 13.0% of HIV patients in care required drug treatment for hypertension and/or diabetes.

Cost-effectiveness of annual versus biennial screening mammography for women with high mammographic breast density.

OBJECTIVES: The sensitivity of screening mammography is much lower among women who have dense breast tissue, compared with women who have largely fatty breasts, and they are also at much higher risk of developing the disease. Increasing mammography screening frequency from biennially to annually has been suggested as a policy option to address the elevated risk in this population. The purpose of this study was to assess the cost-effectiveness of annual versus biennial screening mammography among women aged 50-79 with dense breast tissue. METHODS: A Markov model was constructed based on screening, diagnostic, and treatment pathways for the population-based screening and cancer care programme in British Columbia, Canada. Model probabilities and screening costs were calculated from screening programme data. Costs for breast cancer treatment were calculated from treatment data, and utility values were obtained from the literature. Incremental cost-effectiveness was expressed as cost per quality adjusted life year (QALY), and probabilistic sensitivity analysis was conducted. RESULTS: Compared with biennial screening, annual screening generated an additional 0.0014 QALYs (95% CI: -0.0480-0.0359) at a cost of $819 ($ = Canadian dollars) per patient (95% CI: 506-1185), resulting in an incremental cost effectiveness ratio of $565,912/QALY. Annual screening had a 37.5% probability of being cost-effective at a willingness-to-pay threshold of $100,000/QALY. CONCLUSION: There is considerable uncertainty about the incremental cost-effectiveness of annual mammography. Further research on the comparative effectiveness of screening strategies for women with high mammographic breast density is warranted, particularly as digital mammography and density measurement become more widespread, before cost-effectiveness can be reevaluated.