Diane L. Fairclough

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

IMPORTANCEnFor 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.nnnOBJECTIVEnTo evaluate the safety, clinical, and cost impact of discontinuing statin medications for patients in the palliative care setting.nnnDESIGN, SETTING, AND PARTICIPANTSnThis 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 All analyses were performed using an intent-to-treat approach.nnnINTERVENTIONSnStatin therapy was withdrawn from eligible patients who were randomized to the discontinuation group. Patients in the continuation group continued to receive statins.nnnMAIN OUTCOMES AND MEASURESnOutcomes included death within 60 days (primary outcome), survival, cardiovascular events, performance status, quality of life (QOL), symptoms, number of nonstatin medications, and cost savings.nnnRESULTSnA 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

Practical and statistical issues in missing data for longitudinal patient-reported outcomes.

3.37 per day and

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

716 per patient.nnnCONCLUSIONS AND RELEVANCEnThis 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.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT01415934.

Randomized efficacy trial of two psychotherapies for depression in youth with inflammatory bowel disease.

Patient-reported outcomes are increasingly used in health research, including randomized controlled trials and observational studies. However, the validity of results in longitudinal studies can crucially hinge on the handling of missing data. This paper considers the issues of missing data at each stage of research. Practical strategies for minimizing missingness through careful study design and conduct are given. Statistical approaches that are commonly used, but should be avoided, are discussed, including how these methods can yield biased and misleading results. Methods that are valid for data which are missing at random are outlined, including maximum likelihood methods, multiple imputation and extensions to generalized estimating equations: weighted generalized estimating equations, generalized estimating equations with multiple imputation, and doubly robust generalized estimating equations. Finally, we discuss the importance of sensitivity analyses, including the role of missing not at random models, such as pattern mixture, selection, and shared parameter models. We demonstrate many of these concepts with data from a randomized controlled clinical trial on renal cancer patients, and show that the results are dependent on missingness assumptions and the statistical approach.

Comparing longitudinal assessments of quality of life by patient and parent in newly diagnosed children with cancer: the value of both raters’ perspectives

BACKGROUNDnPalliative 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.nnnMETHODSnA 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.nnnRESULTSnThe 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.

Longitudinal Results of Cognitive Behavioral Treatment for Youths with Inflammatory Bowel Disease and Depressive Symptoms

OBJECTIVEnPediatric inflammatory bowel disease (IBD) is associated with high rates of depression. This study compared the efficacy of cognitive behavioral therapy (CBT) to supportive nondirective therapy (SNDT) in treating youth with comorbid IBD and depression.nnnMETHODnYouth (51% female and 49% male; age 9-17 years, mean age 14.3 years) with depression and Crohns disease (n = 161) or ulcerative colitis (n = 56) were randomly assigned to a 3-month course of CBT or SNDT. The primary outcome was comparative reduction in depressive symptom severity; secondary outcomes were depression remission, increase in depression response, and improved health-related adjustment and IBD activity.nnnRESULTSnA total of 178 participants (82%) completed the 3-month intervention. Both psychotherapies resulted in significant reductions in total Childrens Depression Rating Scale Revised score (37.3% for CBT and 31.9% for SNDT), but the difference between the 2 treatments was not significant (p = .16). There were large pre-post effect sizes for each treatment (d = 1.31 for CBT and d = 1.30 for SNDT). More than 65% of youth had a complete remission of depression at 3 months, with no difference between CBT and SNDT (67.8% and 63.2%, respectively). Compared to SNDT, CBT was associated with a greater reduction in IBD activity (p = .04) but no greater improvement on the Clinical Global Assessment Scale (p = .06) and health-related quality of life (IMPACT-III scale) (p = .07).nnnCONCLUSIONnThis is the first randomized controlled study to suggest improvements in depression severity, global functioning, quality of life, and disease activity in a physically ill pediatric cohort treated with psychotherapy. Clinical trial registration information-Reducing Depressive Symptoms in Physically Ill Youth; http://clinical trials.gov; NCT00534911.

Burdensome Physical and Depressive Symptoms Predict Heart Failure–Specific Health Status Over One Year

PurposeHealth-related quality of life (HRQoL) information from children facing rare and/or life-threatening disease serves important clinical functions. Longitudinal HRQoL ratings from 222 child–parent dyads collected at four time points during the first 16xa0weeks of cancer treatment are presented. Patient and parent HRQoL reports at the domain level, based on the Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales, were compared over time, and variation in child/parent agreement by age, treatment intensity, and time on treatment was explored.Patients and methodsAnalyses included consideration of missingness, differences between child and parent group mean domain scores averaged over assessments, agreement between individual child and parent, compared to group averages, and within-subject changes between assessments.ResultsChildren consistently reported higher functioning than their parents with differences varying by child age and HRQoL domain and diminishing over time. No differences were found by intensity of treatment. The between-subject correlation ranged from 0.61 (social functioning) to 0.86 (physical functioning) across time. Agreement within groups, defined by age, treatment intensity, and time were generally similar.ConclusionsResults indicate moderate-to-good child/parent agreement with variability by domain of HRQoL. Findings underscore the complexity of self- and proxy-based report and support the use of information from both raters.

Distress among caregivers of phase I trial participants: a cross-sectional study

Youths with chronic physical illnesses face increased rates of psychological problems and the burden of coping with physical illness-related challenges. The following data describes treatment outcome maintenance results from a randomized clinical trial investigating the impact of a cognitive behavioral intervention Primary and Secondary Control Enhancement Therapy-Physical Illness (PASCET-PI) as compared to treatment as usual (TAU) on youths with inflammatory bowel disease (IBD). Forty-one participants aged 11–17 with IBD and concurrent depressive symptomatology were randomized to PASCET-PI (nxa0=xa022) or TAU (nxa0=xa019). Self-reported depressive features, global functioning, and DSM-IV depressive symptomatology were assessed immediately post-treatment (T2), followed by assessments at 6-months (T3) and 12-months (T4) post-treatment initiation. Repeated measure models revealed significantly improved global psychosocial functioning in youths randomized to PASCET-PI compared to youths randomized to TAU. Improvements in self-reported depressive features and DSM-IV depressive symptoms were found at the trend level for youths randomized to PASCET-PI relative to those receiving TAU. Effect size estimates for all outcome variables suggested large to medium treatment effects.

Rationale and study design of a patient-centered intervention to improve health status in chronic heart failure: The Collaborative Care to Alleviate Symptoms and Adjust to Illness (CASA) randomized trial

CONTEXTnHeart failure (HF)-specific health status (symptom burden, functional status, and health-related quality of life) is an important patient-reported outcome that is associated with palliative care needs, hospitalizations, and death.nnnOBJECTIVESnTo identify potentially modifiable patient-reported factors that predict HF-specific health status over one year.nnnMETHODSnThis was a prospective cohort study using data from the Patient-Centered Disease Management trial. Participants were identified using population-based sampling of all patients with an HF diagnosis at four VA Medical Centers. Patients were enrolled with reduced HF-specific health status (i.e., significant HF symptoms, limited functional status, and poor quality of life, defined by a Kansas City Cardiomyopathy Questionnaire [KCCQ] score <60). Patient-reported factors at baseline were chest pain, other noncardiac pain, dry mouth, numbness/tingling, constipation, nausea, cough, dizziness, depressive symptoms (Patient Health Questionnaire-9), and spiritual well-being (validated, single-item measure). Patients reported HF-specific health status (KCCQ) at 3, 6, and 12xa0months.nnnRESULTSnOf 384 U.S. veterans, 42% screened positive for depression and 76% described burdensome physical symptoms at baseline. In bivariate analyses, all patient-reported factors were correlated with KCCQ score over one year. Multivariable mixed-effect modeling showed that baseline chest pain, numbness/tingling, depressive symptoms, and higher comorbidity count predicted HF-specific health status over the following year.nnnCONCLUSIONnBurdensome physical and depressive symptoms independently predicted subsequent HF-specific health status in patients with symptomatic HF. Whether addressing these aspects of the patient experience can improve health status and well-being in symptomatic HF should be studied further.

Handling missing items in the Hospital Anxiety and Depression Scale (HADS): a simulation study

PurposeThe number of patients with cancer enrolling in phase I trials is expected to increase as these trials incorporate patient selection and exhibit greater efficacy in the era of targeted therapies. Despite the fact that people with advanced cancer often require a caregiver, little is known about the experience of caregivers of people enrolling in oncology phase I clinical trials. We conducted a cross-sectional study assessing the distress and emotion regulation of caregivers of phase I trial participants to inform the design of future interventions targeting the unique needs of this population.MethodsCaregivers of oncology patients were approached at the patient’s phase I clinical trial screening visit. Caregiver participants completed a one-time survey incorporating validated instruments to comprehensively assess distress and emotion regulation. Basic demographic information about both the caregiver and patient was collected.ResultsCaregivers exhibited greater distress than population norms. Emotion regulation was also moderately impaired. Respondents identified positive aspects of caregiving despite exhibiting moderate distress.ConclusionEnrollment of a patient in a phase I clinical trial is a time of stress for their caregivers. This pilot study demonstrates the feasibility of engaging caregivers of phase I trial participants and the need to better support them through this component of their caregiving experience.