On clinical trial fragility due to patients lost to follow up

Wells ′ research was partially supported by NIH grant U19 AI111143, PCORI IHS-2017C3-8923, and Cornell’s Center for the Social Sciences project on Algorithms, Big Data, and Inequality.Background Clinical trials routinely have patients lost to follow up. We propose a methodology to understand their possible effect on the results of statistical tests by altering the concept of the fragility index to treat the outcomes of observed patients as fixed but incorporate the potential outcomes of patients lost to follow up as random and subject to modification. Methods We reanalyse the statistical results of three clinical trials on coronary artery bypass grafting (CABG) to study the possible effect of patients lost to follow up on the treatment effect statistical significance. To do so, we introduce the LTFU-aware fragility indices as a measure of the robustness of a clinical trial’s statistical results with respect to patients lost to follow up. Results The analyses illustrate that clinical trials can either be completely robust to the outcomes of patients lost to follow up, extremely sensitive to the outcomes of patients lost to follow up, or in an intermediate state. When a clinical trial is in an intermediate state, the LTFU-aware fragility indices provide an interpretable measure to quantify the degree of fragility or robustness. Conclusions The LTFU-aware fragility indices allow researchers to rigorously explore the outcomes of patients who are lost to follow up, when their data is the appropriate kind. The LTFU-aware fragility indices are sensitivity measures in a way that the original fragility index is not.Peer reviewe

Contemplative self healing in women breast cancer survivors: a pilot study in underserved minority women shows improvement in quality of life and reduced stress

Background: Among underserved, largely minority women who were breast cancer survivors, this pilot project was designed to evaluate the quality of life outcomes of a 20 week Contemplative Self-Healing Program. Methods: Women previously treated for stage I-III breast cancer were assessed before and after the 20 week program with the FACT-G, FACT-B, FACIT-Spirituality, ECOG, and the Impact of Events Scale. They participated in a 20-week intervention involving guided meditation and cognitive-affective-behavioral learning. Results: With an average age of 63, 62% of the participants were African-American or Latino. With an average of 5.4 years since the diagnosis of breast cancer, 72% had an ECOG performance status of 1. 57% were currently working. Their baseline FACT-G was 80.5 ± 15.1, and their baseline Impact of Events Scale was 26.3 ± 18.9. The within-patient improvement on the FACT-G was 4.6 ± 10.9 (p = .01); in parallel the FACT-B improved by 2.8 ± 12.8 points (p = .03). The Impact of Events Scale improved by 6.6 ± 15.5 points (p = .01). There was significant within-patient improvement on both the avoidance scale (3.8 ± 9.2) and on the intrusion scale (2.9 ± 7.9). Patients who attended more sessions and conducted more home practice had greater improvements in quality of life. Conclusion: Persons receiving a 20-session contemplative self healing intervention showed improved quality of life, with a clinically and statistically significant increase in the FACT-G. In addition, this population showed a significant reduction in post-traumatic stress symptoms assessed by the Impact of Events Scale. Trial registration: Clinical Trials Gov NCT00278837

Can Disease Management Target Patients Most Likely to Generate High Costs? The Impact of Comorbidity

CONTEXT: Disease management programs are increasingly used to manage costs of patients with chronic disease. OBJECTIVE: We sought to examine the clinical characteristics and measure the health care expenditures of patients most likely to be targeted by disease management programs. DESIGN: Retrospective analysis of prospectively obtained data. SETTING: A general medicine practice with both faculty and residents at an urban academic medical center. PARTICIPANTS: Five thousand eight hundred sixty-one patients enrolled in the practice for at least 1 year. MAIN OUTCOMES: Annual cost of diseases targeted by disease management. MEASUREMENTS: Patients’ clinical and demographic information were collected from a computer system used to manage patients. Data included diagnostic information, medications, and resource usage over 1 year. We looked at 10 common diseases targeted by disease management programs. RESULTS: Unadjusted annual median costs for chronic diseases ranged between $1,100 and$1,500. Congestive heart failure ($1,500), stroke ($1,500), diabetes ($1,500), and cancer ($1,400) were the most expensive. As comorbidity increased, annual adjusted costs increased exponentially. Those with comorbidity scores of 2 or more accounted for 26% of the population but 50% of the overall costs. CONCLUSIONS: Costs for individual chronic conditions vary within a relatively narrow range. However, the costs for patients with multiple coexisting medical conditions increase rapidly. Reducing health care costs will require focusing on patients with multiple comorbid diseases, not just single diseases. The overwhelming impact of comorbidity on costs raises significant concerns about the potential ability of disease management programs to limit the costs of care

Long-Term Associations between Cholinesterase Inhibitors and Memantine Use and Health Outcomes among Patients with Alzheimer's Disease

OBJECTIVES: To examine in an observational study (1) relationships between cholinesterase inhibitors (ChEI) and memantine use, and functional and cognitive end points and mortality in patients with Alzheimer's disease (AD); (2) relationships between other patient characteristics and these clinical end points; and (3) whether effects of the predictors change across time. METHODS: The authors conducted a multicenter, natural history study that included three university-based AD centers in the United States. A total of 201 patients diagnosed with probable AD with modified Mini-Mental State Examination (MMSE) scores >/= 30 at study entry were monitored annually for 6 years. Discrete-time hazard analyses were used to examine relationships between ChEI and memantine use during the previous 6 months reported at each assessment, and time to cognitive (MMSE score /= 10) end points and mortality. Analyses controlled for clinical characteristics, including baseline cognition, function, and comorbid conditions, and presence of extrapyramidal signs and psychiatric symptoms at each assessment interval. Demographic characteristics included baseline age, sex, education, and living arrangement at each assessment interval. RESULTS: ChEI use was associated with delayed time in reaching the functional end point and death. Memantine use was associated with delayed time to death. Different patient characteristics were associated with different clinical end points. CONCLUSIONS: Results suggest long-term beneficial effects of ChEI and memantine use on patient outcomes. As for all observational cohort studies, observed relationships should not be interpreted as causal effects

A comparison between the APACHE II and Charlson Index Score for predicting hospital mortality in critically ill patients

<p>Abstract</p> <p>Background</p> <p>Risk adjustment and mortality prediction in studies of critical care are usually performed using acuity of illness scores, such as Acute Physiology and Chronic Health Evaluation II (APACHE II), which emphasize physiological derangement. Common risk adjustment systems used in administrative datasets, like the Charlson index, are entirely based on the presence of co-morbid illnesses. The purpose of this study was to compare the discriminative ability of the Charlson index to the APACHE II in predicting hospital mortality in adult multisystem ICU patients.</p> <p>Methods</p> <p>This was a population-based cohort design. The study sample consisted of adult (>17 years of age) residents of the Calgary Health Region admitted to a multisystem ICU between April 2002 and March 2004. Clinical data were collected prospectively and linked to hospital outcome data. Multiple regression analyses were used to compare the performance of APACHE II and the Charlson index.</p> <p>Results</p> <p>The Charlson index was a poor predictor of mortality (C = 0.626). There was minimal difference between a baseline model containing age, sex and acute physiology score (C = 0.74) and models containing either chronic health points (C = 0.76) or Charlson index variations (C = 0.75, 0.76, 0.77). No important improvement in prediction occurred when the Charlson index was added to the full APACHE II model (C = 0.808 to C = 0.813).</p> <p>Conclusion</p> <p>The Charlson index does not perform as well as the APACHE II in predicting hospital mortality in ICU patients. However, when acuity of illness scores are unavailable or are not recorded in a standard way, the Charlson index might be considered as an alternative method of risk adjustment and therefore facilitate comparisons between intensive care units.</p

Health-Care Use and Cost in Dementia Caregivers: Longitudinal Results from the Predictors Caregiver Study

OBJECTIVE: To examine the effects of caregiver and patient characteristics on caregivers' medical care use and cost. METHODS: One hundred forty-seven caregiver/patient dyads were followed annually for 6 years in three academic Alzheimer's disease centers in the United States. Logistic, negative binomial, and generalized linear mixed models were used to examine overall effects of caregiver/patient characteristics on caregivers' hospitalizations, doctor visits, outpatient tests and procedures, and prescription and over-the-counter medications. RESULTS: Patients' comorbid conditions and dependence were associated with increased health-care use and costs of caregivers. Increases in caregiver depressive symptoms are associated with increases in multiple domains of caregivers' health-care use and costs. DISCUSSION: Findings suggest expanding our focus on dementia patients to include family caregivers to obtain a fuller picture of effects of caregiving. Primary care providers should integrate caregivers' needs in health-care planning and delivery. Clinical interventions that treat patients and caregivers as a whole will likely achieve the greatest beneficial effects

The association of cardioprotective medications with pneumonia-related outcomes

Introduction: Little research has examined whether cardiovascular medications, other than statins, are associated with improved outcomes after pneumonia. Our aim was to examine the association between the use of beta-blockers, statins, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) with pneumonia-related outcomes. Materials and Methods: We conducted a retrospective population-based study on male patients ≥65 years of age hospitalized with pneumonia and who did not have pre-existing cardiac disease. Our primary analyses were multilevel regression models that examined the association between cardiovascular medication classes and either mortality or cardiovascular events. Results: Our cohort included 21,985 patients: 22% died within 90 days of admission, and 22% had a cardiac event within 90 days. The cardiovascular medications studied that were associated with decreased 90-day mortality included: statins (OR 0.70, 95% CI 0.63-0.77), ACE inhibitors (OR 0.82, 95% CI 0.74-0.91), and ARBs (OR 0.58, 95% CI 0.44-0.77). However, none of the medications were significantly associated with decreased cardiovascular events. Discussion: While statins, ACE inhibitors, and ARBs, were associated with decreased mortality, there was no significant association with decreased CV events. These results indicate that this decreased mortality is unlikely due to their potential cardioprotective effects

A descriptive study of older adults with persistent pain: Use and perceived effectiveness of pain management strategies [ISRCTN11899548]

BACKGROUND: Persistent pain is a common, often debilitating, problem in older adults; however, few studies have focused on the experiences of older adults in managing their pain. The objective of this study was to describe the use and perceived effectiveness of pain management strategies in a sample of older adults and to explore the associations of these variables with demographic and psychosocial characteristics. METHODS: Adults ≥ 65 years old and living in retirement facilities who reported persistent pain (N = 235, mean age = 82 years, 84% female, 94% white) completed measures of demographics, pain, depression, self-efficacy for managing pain, and a Pain Management Strategies Survey. Participants identified current and previous-year use of 42 pain management strategies and rated helpfulness of each on a 5-point scale. RESULTS: Acetaminophen, regular exercise, prayer, and heat and cold were the most frequently used pain management strategies (61%, 58%, 53%, and 48%, respectively). Strategies used by >25% of the sample that were rated moderately or more helpful (i.e., >2 on a 0 to 4 scale) were prayer [mean (SD) = 2.9 (0.9)], opioids [2.6 (0.8)], regular exercise [2.5 (1.0)], heat/cold [2.5 (1.0)], nonsteroidal anti-inflammatory drugs [2.4 (1.0)], and acetaminophen [2.3 (1.0)]. Young-old (65–74 years) study participants reported use of more strategies than did old-old (85+ years) participants (p = .03). Perceived helpfulness of strategy use was significantly associated with pain intensity (r = -.14, p < .0001), self-efficacy (r = .28, p < .0001), and depression (r = -.20, p = .003). CONCLUSION: On average, older adults view the strategies they use for persistent pain as only moderately helpful. The associations between perceived helpfulness and self-efficacy and depression suggest avenues of pain management that are focused less on specific treatments and more on how persons with persistent pain think about their pain

The effect on survival of continuing chemotherapy to near death

<p>Abstract</p> <p>Background</p> <p>Overuse of anti-cancer therapy is an important quality-of-care issue. An aggressive approach to treatment can have negative effects on quality of life and cost, but its effect on survival is not well-defined.</p> <p>Methods</p> <p>Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified 7,879 Medicare-enrolled patients aged 65 or older who died after having survived at least 3 months after diagnosis of advanced non-small cell lung cancer (NSCLC) between 1991 and 1999. We used Cox proportional hazards regression analysis, propensity scores, and instrumental variable analysis (IVA) to compare survival among patients who never received chemotherapy (n = 4,345), those who received standard chemotherapy but not within two weeks prior to death (n = 3,235), and those who were still receiving chemotherapy within 14 days of death (n = 299). Geographic variation in the application of chemotherapy was used as the instrument for IVA.</p> <p>Results</p> <p>Receipt of chemotherapy was associated with a 2-month improvement in overall survival. However, based on three different statistical approaches, no additional survival benefit was evident from continuing chemotherapy within 14 days of death. Moreover, patients receiving chemotherapy near the end of life were much less likely to enter hospice (81% versus 51% with no chemotherapy and 52% with standard chemotherapy, P < 0.001), or were more likely to be admitted within only 3 days of death.</p> <p>Conclusions</p> <p>Continuing chemotherapy for advanced NSCLC until very near death is associated with a decreased likelihood of receiving hospice care but not prolonged survival. Oncologists should strive to discontinue chemotherapy as death approaches and encourage patients to enroll in hospice for better end-of-life palliative care.</p