S. Yousuf Zafar

Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial.

IMPORTANCE For patients with limited prognosis, some medication risks may outweigh the benefits, particularly when benefits take years to accrue; statins are one example. Data are lacking regarding the risks and benefits of discontinuing statin therapy for patients with limited life expectancy. OBJECTIVE To evaluate the safety, clinical, and cost impact of discontinuing statin medications for patients in the palliative care setting. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter, parallel-group, unblinded, pragmatic clinical trial. Eligibility included adults with an estimated life expectancy of between 1 month and 1 year, statin therapy for 3 months or more for primary or secondary prevention of cardiovascular disease, recent deterioration in functional status, and no recent active cardiovascular disease. Participants were randomized to either discontinue or continue statin therapy and were monitored monthly for up to 1 year. The study was conducted from June 3, 2011, to May 2, 2013. All analyses were performed using an intent-to-treat approach. INTERVENTIONS Statin therapy was withdrawn from eligible patients who were randomized to the discontinuation group. Patients in the continuation group continued to receive statins. MAIN OUTCOMES AND MEASURES Outcomes included death within 60 days (primary outcome), survival, cardiovascular events, performance status, quality of life (QOL), symptoms, number of nonstatin medications, and cost savings. RESULTS A total of 381 patients were enrolled; 189 of these were randomized to discontinue statins, and 192 were randomized to continue therapy. Mean (SD) age was 74.1 (11.6) years, 22.0% of the participants were cognitively impaired, and 48.8% had cancer. The proportion of participants in the discontinuation vs continuation groups who died within 60 days was not significantly different (23.8% vs 20.3%; 90% CI, -3.5% to 10.5%; P=.36) and did not meet the noninferiority end point. Total QOL was better for the group discontinuing statin therapy (mean McGill QOL score, 7.11 vs 6.85; P=.04). Few participants experienced cardiovascular events (13 in the discontinuation group vs 11 in the continuation group). Mean cost savings were

Electronic patient-reported data capture as a foundation of rapid learning cancer care.

3.37 per day and

Adverse Events Among the Elderly Receiving Chemotherapy for Advanced Non–Small-Cell Lung Cancer

716 per patient. CONCLUSIONS AND RELEVANCE This pragmatic trial suggests that stopping statin medication therapy is safe and may be associated with benefits including improved QOL, use of fewer nonstatin medications, and a corresponding reduction in medication costs. Thoughtful patient-provider discussions regarding the uncertain benefit and potential decrement in QOL associated with statin continuation in this setting are warranted. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01415934.

Malignancy After Solid Organ Transplantation: An Overview

Background:“Rapid learning healthcare” presents a new infrastructure to support comparative effectiveness research. By leveraging heterogeneous datasets (eg, clinical, administrative, genomic, registry, and research), health information technology, and sophisticated iterative analyses, rapid learning healthcare provides a real-time framework in which clinical studies can evaluate the relative impact of therapeutic approaches on a diverse array of measures. Purpose:This article describes an effort, at 1 academic medical center, to demonstrate what rapid learning healthcare might look like in operation. The article describes the process of developing and testing the components of this new model of integrated clinical/research function, with the pilot site being an academic oncology clinic and with electronic patient-reported outcomes (ePROs) being the foundational dataset. Research Design:Steps included: feasibility study of the ePRO system; validation study of ePRO collection across 3 cancers; linking ePRO and other datasets; implementation; stakeholder alignment and buy in, and; demonstration through use cases. Subjects:Two use cases are presented; participants were metastatic breast cancer (n = 65) and gastrointestinal cancer (n = 113) patients at 2 academic medical centers. Results:(1) Patient-reported symptom data were collected with tablet computers; patients with breast and gastrointestinal cancer indicated high levels of sexual distress, which prompted multidisciplinary response, design of an intervention, and successful application for funding to study the interventions impact. (2) The system evaluated the longitudinal impact of a psychosocial care program provided to patients with breast cancer. Participants used tablet computers to complete PRO surveys; data indicated significant impact on psychosocial outcomes, notably distress and despair, despite advanced disease. Results return to the clinic, allowing iterative update and evaluation. Conclusions:An ePRO-based rapid learning cancer clinic is feasible, providing real-time research-quality data to support comparative effectiveness research.

A strategy to advance the evidence base in palliative medicine: formation of a palliative care research cooperative group.

PURPOSE To describe chemotherapy use and adverse events (AEs) for advanced-stage, non-small-cell lung cancer (NSCLC) in community practice, including descriptions according to variation by age. METHODS We interviewed patients with newly diagnosed, stages IIIB and IV NSCLC in the population-based cohort studied by the Cancer Care Outcomes Research and Surveillance Consortium, and we abstracted the patient medical records. AEs were medical events occurring during chemotherapy. Using logistic regression, we assessed the association between age and chemotherapy; with Poisson regression, we estimated event rate ratios and adjusted the analysis for age, sex, ethnicity, radiation therapy, stage, histology, and presence and grade of 27 comorbidities. RESULTS Of 1,371 patients, 58% (95% CI, 55% to 61%) received chemotherapy and 35% (95% CI, 32% to 38%) had AEs. After adjustment, 72% (95% CI, 65% to 79%) of those younger than 55 years and 47% (95% CI, 42% to 52%) of those age 75 years and older received chemotherapy. Platinum-based therapies were less common in the older-age groups. Pretreatment medical event rates were 18.6% for patients younger than 55 years and were only 9.2% for those age 75 years and older (adjusted rate ratio, 0.49; 95% CI, 0.26 to 0.91). In contrast, older adults were more likely to have AEs during chemotherapy. The adjusted rate ratios compared with age younger than 55 years were 1.70 for 65- to 74-year-olds (95% CI, 1.19 to 2.43) and 1.34 for those age 75 years and older (95% CI, 0.90 to 2.00). CONCLUSION Older patients who received chemotherapy had fewer pretherapy events than younger patients and were less likely to receive platinum-based regimens. Nevertheless, older patients had more adverse events during chemotherapy, independent of comorbidity. Potential implicit trade-offs between symptom management and treatment toxicity should be made explicit and additionally studied.

Patient-Oncologist Cost Communication, Financial Distress, and Medication Adherence

With improving survival following solid organ transplantation, clinicians must be aware of post-transplant complications. One increasingly frequent complication is the development of malignancy after transplantation. The most common malignancies encountered in the post-solid organ transplant setting are nonmelanoma skin cancers, post-transplant lymphoproliferative disorders, and Kaposis sarcoma (KS). The pathogenesis of these tumors is likely related to the immunosuppressive drugs used post-transplantation and subsequent viral infection. Treatment involves modification of the immunosuppressive drug regimen, resection of localized disease, and chemotherapy. We present the second reported case of a patient with lung transplantation who developed KS in the lung graft.

Decision making and quality of life in the treatment of cancer: a review

BACKGROUND Palliative medicine has made rapid progress in establishing its scientific and clinical legitimacy, yet the evidence base to support clinical practice remains deficient in both the quantity and quality of published studies. Historically, the conduct of research in palliative care populations has been impeded by multiple barriers including health care system fragmentation, small number and size of potential sites for recruitment, vulnerability of the population, perceptions of inappropriateness, ethical concerns, and gate-keeping. METHODS A group of experienced investigators with backgrounds in palliative care research convened to consider developing a research cooperative group as a mechanism for generating high-quality evidence on prioritized, clinically relevant topics in palliative care. RESULTS The resulting Palliative Care Research Cooperative (PCRC) agreed on a set of core principles: active, interdisciplinary membership; commitment to shared research purposes; heterogeneity of participating sites; development of research capacity in participating sites; standardization of methodologies, such as consenting and data collection/management; agile response to research requests from government, industry, and investigators; focus on translation; education and training of future palliative care researchers; actionable results that can inform clinical practice and policy. Consensus was achieved on a first collaborative study, a randomized clinical trial of statin discontinuation versus continuation in patients with a prognosis of less than 6 months who are taking statins for primary or secondary prevention. This article describes the formation of the PCRC, highlighting processes and decisions taken to optimize the cooperative groups success.

Stigma, perceived blame, self‐blame, and depressive symptoms in men with colorectal cancer

BACKGROUND Little is known about the association between patient-oncologist discussion of cancer treatment out-of-pocket (OOP) cost and medication adherence, a critical component of quality cancer care. METHODS We surveyed insured adults receiving anticancer therapy. Patients were asked if they had discussed OOP cost with their oncologist. Medication nonadherence was defined as skipping doses or taking less medication than prescribed to make prescriptions last longer, or not filling prescriptions because of cost. Multivariable analysis assessed the association between nonadherence and cost discussions. RESULTS Among 300 respondents (86% response), 16% (n = 49) reported high or overwhelming financial distress. Nineteen percent (n = 56) reported talking to their oncologist about cost. Twenty-seven percent (n = 77) reported medication nonadherence. To make a prescription last longer, 14% (n = 42) skipped medication doses, and 11% (n = 33) took less medication than prescribed; 22% (n = 66) did not fill a prescription because of cost. Five percent (n = 14) reported chemotherapy nonadherence. To make a prescription last longer, 1% (n = 3) skipped chemotherapy doses, and 2% (n = 5) took less chemotherapy; 3% (n = 10) did not fill a chemotherapy prescription because of cost. In adjusted analyses, cost discussion (odds ratio [OR] = 2.58; 95% CI, 1.14 to 5.85; P = .02), financial distress (OR = 1.64, 95% CI, 1.38 to 1.96; P < .001) and higher financial burden than expected (OR = 2.89; 95% CI, 1.41 to 5.89; P < .01) were associated with increased odds of nonadherence. CONCLUSION Patient-oncologist cost communication and financial distress were associated with medication nonadherence, suggesting that cost discussions are important for patients forced to make cost-related behavior alterations. Future research should examine the timing, content, and quality of cost-discussions.

Consensus-based standards for best supportive care in clinical trials in advanced cancer

IntroductionComplexity in decision making for cancer treatment arises from many factors. When considering how to treat patients, physicians prioritize factors such as stage of disease, patient age, and comorbid illnesses. However, physicians must balance these priorities with the patient’s preferences, quality of life, social responsibilities, and fear of uncertainty. Although these factors are important, physicians are often unable to effectively judge their patients’ preferences. Patients are often unable to fully understand their prognoses and the treatment intent.DiscussionThese differences influence how patients and physicians make treatment-related decisions. Partially due to these differences, patients are initially more likely than their physicians to accept greater risk for lesser benefit from treatment. As time progresses and as they experience treatment, a patient’s preference changes, yet little is known about this process since few studies have examined it in a prospective longitudinal manner. We present an overview of the literature related to patient and physician decision making and quality of life in patients with advanced cancer, and we propose approaches to future decision-making models in cancer treatment.

Association of Financial Strain With Symptom Burden and Quality of Life for Patients With Lung or Colorectal Cancer

We measured the prevalence of stigma, self‐blame, and perceived blame from others for their illness among men with colorectal cancer (CRC) and examined whether these factors were associated with depressive symptoms, independent of clinical and sociodemographic factors.