Fragility indices for only sufficiently likely modifications.

The fragility index is a clinically meaningful metric based on modifying patient outcomes that is increasingly used to interpret the robustness of clinical trial results. The fragility index relies on a concept that explores alternative realizations of the same clinical trial by modifying patient measurements. In this article, we propose to generalize the fragility index to a family of fragility indices called the incidence fragility indices that permit only outcome modifications that are sufficiently likely and provide an exact algorithm to calculate the incidence fragility indices. Additionally, we introduce a far-reaching generalization of the fragility index to any data type and explain how to permit only sufficiently likely modifications for nondichotomous outcomes. All of the proposed methodologies follow the fragility index concept.

Charlson Comorbidity Index: A Critical Review of Clinimetric Properties.

The present critical review was conducted to evaluate the clinimetric properties of the Charlson Comorbidity Index (CCI), an assessment tool designed specifically to predict long-term mortality, with regard to its reliability, concurrent validity, sensitivity, incremental and predictive validity. The original version of the CCI has been adapted for use with different sources of data, ICD-9 and ICD-10 codes. The inter-rater reliability of the CCI was found to be excellent, with extremely high agreement between self-report and medical charts. The CCI has also been shown either to have concurrent validity with a number of other prognostic scales or to result in concordant predictions. Importantly, the clinimetric sensitivity of the CCI has been demonstrated in a variety of medical conditions, with stepwise increases in the CCI associated with stepwise increases in mortality. The CCI is also characterized by the clinimetric property of incremental validity, whereby adding the CCI to other measures increases the overall predictive accuracy. It has been shown to predict long-term mortality in different clinical populations, including medical, surgical, intensive care unit (ICU), trauma, and cancer patients. It may also predict in-hospital mortality, although in some instances, such as ICU or trauma patients, the CCI did not perform as well as other instruments designed specifically for that purpose. The CCI thus appears to be clinically useful not only to provide a valid assessment of the patient's unique clinical situation, but also to demarcate major diagnostic and prognostic differences among subgroups of patients sharing the same medical diagnosis.

Clinimetric Criteria for Patient-Reported Outcome Measures.

Patient-reported outcome measures (PROMs) are self-rated scales and indices developed to improve the detection of the patients' subjective experience. Given that a considerable number of PROMs are available, it is important to evaluate their validity and usefulness in a specific research or clinical setting. Published guidelines, based on psychometric criteria, do not fit in with the complexity of clinical challenges, because of their quest for homogeneity of components and inadequate attention to sensitivity. Psychometric theory has stifled the field and led to the routine use of scales widely accepted yet with a history of poor performance. Clinimetrics, the science of clinical measurements, may provide a more suitable conceptual and methodological framework. The aims of this paper are to outline the major limitations of the psychometric model and to provide criteria for clinimetric patient-reported outcome measures (CLIPROMs). The characteristics related to reliability, sensitivity, validity, and clinical utility of instruments are critically reviewed, with particular reference to the differences between clinimetric and psychometric approaches. Of note is the fact that PROMs, rating scales, and indices developed according to psychometric criteria may display relevant clinimetric properties. The present paper underpins the importance of the clini-metric methodology in choosing the appropriate PROMs. CLIPROM criteria may also guide the development of new indices and the validation of existing PROMs to be employed in clinical settings.

On clinical trial fragility due to patients lost to follow up.

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.

Medicine based evidence and personalized care of patients.

BACKGROUND: For the past 70- years patient care has been dominated by Evidence Based Medicine (EBM) with its emphasis on Randomized Controlled Trials (RCTs) and clinical guidelines to standardize medical decision-making. METHODS: Critical assessment of the literature and analyses of the arguments that favor patient care based primarily on individual variability in disease risk or treatment response versus emphasis on group standardization. RESULTS: Medicine Based Evidence (MBE) is used to guide decision making for an individual patient at hand by profiling the clinical features (biology) and life experience (biography) of the patient and then finding approximate matches to the patient in a clinical library of patients assembled from diverse sources (RCTs, cohorts, registries, electronic health records and more). CONCLUSION: Medicine is transitioning from population based model of clinical care that relies on average results from RCTs to an individual-based model of "personalized" medicine. For individualized care of the patient at hand, MBE is the preferred scientific strategy to generate evidence for patient care.

Sources of distress among patients undergoing surgery for colorectal cancer: a qualitative study.

BACKGROUND: Distress is common among cancer and surgical patients and can lead to worse outcomes if untreated. The objective of this study was to explore sources of distress among colorectal cancer patients undergoing surgery. MATERIALS AND METHODS: This was a qualitative study using in-depth, semistructured, one-on-one interviews in an academic setting. Patients were recruited if they had a pathologically confirmed diagnosis of colon or rectal cancer. Purposive sampling was used to recruit patients who were about to undergo (preoperative), or had recently undergone (postoperative), curative resection for colorectal cancer. RESULTS: All participants (n = 24) reported experiencing distress during treatment. Participants identified sources of distress preoperatively (negative emotional reaction to diagnosis, distress from preconception of cancer diagnosis, and distress interacting with healthcare system). Sources of distress during in-hospital recovery included negative emotional reaction to having a surgery and negative emotions experienced in the hospital. Postoperative sources of distress included mismatch of expectations and experience of recovery, dealing with distressing physical symptoms and complications after surgery, and distress worrying about recurrence. Participants identified other sources of distress that were not time-specific (distress related to social support network, from disruption of life, and worrying about death). CONCLUSIONS: Our results highlight a potential role for a comprehensive screening program to identify which patients require assistance with addressing sources of distress during the surgical experience. Understanding how sources of distress may vary by time will help us tailor interventions at different time points of the surgical experience.

Readmission After Ileostomy Creation: Retrospective Review of a Common and Significant Event.

OBJECTIVE: To evaluate causes and predictors of readmission after new ileostomy creation. BACKGROUND: New ileostomates have been reported to have higher readmission rates compared with other surgical patients, but data on predictors are limited. METHODS: A total of 1114 records at 2 associated hospitals were reviewed to identify adults undergoing their first ileostomy. Primary outcome was readmission within 60 days of surgery. Multiple logistic regression was used to identify independent predictors; area under the receiver-operator characteristic curves (AUC) were used to evaluate age-stratified models in secondary analysis. RESULTS: In all, 407 patients underwent new ileostomy; 58% had cancer, 31% IBD; 49% underwent LAR, 27% colectomy, and 14% proctocolectomy. Median length of stay was 8 days. Among the patients, 39% returned to hospital, and 28% were readmitted (n = 113) at a median of 12 days postdischarge. The most common causes of readmission were dehydration (42%), intraperitoneal infections (33%), and extraperitoneal infections (29%). Dehydration was associated with later, longer, and repeated readmission. Independent significant predictors of readmission were Clavien-Dindo complication grade 3 to 4 [odds ratio (OR) 6.7], Charlson comorbidity index (OR 1.4 per point), and loop stoma (OR 2.2); longer length of stay (OR 0.5) and age 65 years or older (OR 0.4) were protective. Cohort stratification above or below age 65 revealed that older patient readmissions were more predictable (AUC 0.84) with more preventable causes, whereas younger patient readmissions were difficult to predict or prevent (AUC 0.65). CONCLUSIONS: Readmissions are most commonly caused by dehydration, and are predicted by serious complications, comorbidity burden, loop stoma, shorter length of stay, and age. Readmissions in older patients are easier to predict, representing an important target for improvement.

Environmental influences on small eating behavior change to promote weight loss among Black and Hispanic populations.

Small eating behavior changes are proposed as more feasible to achieve and maintain than larger changes used in traditional behavioral weight loss studies. However, it is unclear whether overweight Black and Hispanic adults in a low-income urban setting experience small changes as feasible and what might influence feasibility. Participants' experiences in a 12-week pilot weight loss intervention were explored qualitatively to determine the feasibility of making small eating behavior changes in this population. After the intervention (69% retention), semi-structured interviews with 46 men and women (mean age 51, 50% Non-Hispanic Black, 43% Hispanic) revealed that making small eating changes was a process shaped by participants' intrapersonal and interpersonal eating environments. Participants responded to intrapersonal and interpersonal eating environmental challenges by adapting small change strategies, navigating eating environments, and negotiating household eating practices. Findings highlight how even small eating behavior changes called for adaptation, navigation, and negotiation of complex eating environments in daily life. These findings were used to improve the trial that followed and underline the importance of feasibility studies to inform community trials. Findings also add to understanding of contextual challenges and the skills needed to implement small changes in a low income, ethnic minority population.

Results from the Trial Using Motivational Interviewing, Positive Affect, and Self-Affirmation in African Americans with Hypertension (TRIUMPH).

OBJECTIVE: Our objective was to determine the effectiveness of combining positive affect and self-affirmation strategies with motivational interviewing in achieving blood pressure control among hypertensive African Americans (AA) compared with AA hypertensives in an education-only control group. DESIGN: Randomized trial. SETTING: Ambulatory practices in the South Bronx and Harlem, New York City. PARTICIPANTS: African American adults with uncontrolled hypertension. INTERVENTIONS: Participants were randomized to a positive affect and self-affirmation intervention or an education control group. The positive affect and self-affirmation intervention involved having participants think about things that made them happy and that reminded them of their core values on a daily basis. These strategies were reinforced every two months through motivational interviewing. The control arm received a workbook of strategies on blood pressure control. All participants were called every two months for one year. MAIN OUTCOMES: Blood pressure control rate. RESULTS: A total of 238 participants were randomized. The average age was 56 ± 11 years, approximately 70% were female, 80% were not married, and up to 70% had completed high school. There was no difference in control rates between the intervention and the control group. However, at one year, female participants were more likely to be controlled. Participants with high depressive symptoms or high perceived stress at baseline were less likely to be controlled. CONCLUSIONS: While this study did not demonstrate an intervention effect, it does provide important insight into the psychosocial factors that may underlie blood pressure control in African Americans. Implications for future behavioral intervention trials are discussed.

Predictive value of the Age-Adjusted Charlson Comorbidity Index on perioperative complications and survival in patients undergoing primary debulking surgery for advanced epithelial ovarian cancer.

OBJECTIVE: To assess the ability of the Age-Adjusted Charlson Comorbidity Index (ACCI) to predict perioperative complications and survival in patients undergoing primary debulking for advanced epithelial ovarian cancer (EOC). METHODS: Data were analyzed for all patients with stage IIIB-IV EOC who underwent primary cytoreduction from 1/2001-1/2010 at our institution. Patients were divided into 3 groups based on an ACCI of 0-1, 2-3, and ≥4. Clinical and survival outcomes were assessed and compared. RESULTS: We identified 567 patients; 199 (35%) had an ACCI of 0-1, 271 (48%) had an ACCI of 2-3, and 97 (17%) had an ACCI of ≥4. The ACCI was significantly associated with the rate of complete gross resection (0-1=44%, 2-3=32%, and ≥4=32%; p=0.02), but was not associated with the rate of minor (47% vs 47% vs 43%, p=0.84) or major (18% vs 19% vs 16%, p=0.8) complications. The ACCI was also significantly associated with progression-free (PFS) and overall survival (OS). Median PFS for patients with an ACCI of 0-1, 2-3, and ≥4 was 20.3, 16, and 15.4 months, respectively (p=0.02). Median OS for patients with an ACCI of 0-1, 2-3, and ≥4 was 65.3, 49.9, and 42.3 months, respectively (p<0.001). On multivariate analysis, the ACCI remained a significant prognostic factor for both PFS (p=0.02) and OS (p<0.001). CONCLUSIONS: The ACCI was not associated with perioperative complications in patients undergoing primary cytoreduction for advanced EOC, but was a significant predictor of PFS and OS. Prospective clinical trials in ovarian cancer should consider stratifying for an age-comorbidity covariate.

Nocturnal systemic hypotension increases the risk of glaucoma progression.

OBJECTIVE: The objective of this prospective, longitudinal study of patients with normal-tension glaucoma (NTG) was to determine whether patients with nocturnal hypotension are at greater risk for visual field (VF) loss over 12 months than those without nocturnal hypotension. DESIGN: Prospective, longitudinal study. PARTICIPANTS: Consecutive patients with NTG with at least 5 prior VF tests were screened for eligibility. METHODS: The baseline evaluation assessed demographic and clinical characteristics, covering systemic comorbid conditions, including systemic hypertension. All oral and ophthalmologic medications were recorded. A complete ophthalmological examination was performed at baseline and follow-up. Patients had their blood pressure (BP) monitored every 30 minutes for 48 hours with an ambulatory recording device at baseline and 6 and 12 months. MAIN OUTCOME MEASURES: The primary outcome was based on the global rates of VF progression by linear regression of the mean VF threshold sensitivity over time (decibels/year). RESULTS: Eighty-five patients with NTG (166 eyes; mean age, 65 years; 67% were women) were included. Of the 85 patients, 29% had progressed in the 5 VFs collected before study enrollment. The nocturnal mean arterial pressure (MAP) was compared with the daytime MAP. Multivariate analysis showed that the total time that sleep MAP was 10 mmHg below the daytime MAP was a significant predictor of subsequent VF progression (P<0.02). CONCLUSIONS: Cumulative nocturnal hypotension predicted VF loss in this cohort. Our data suggest that the duration and magnitude of decrease in nocturnal blood pressure below the daytime MAP, especially pressures that are 10 mmHg lower than daytime MAP, predict progression of NTG. Low nocturnal blood pressure, whether occurring spontaneously or as a result of medications, may lead to worsening of VF defects.

Medicaid managed care: how to target efforts to reduce costs.

BACKGROUND: To be successful, cost control efforts must target Medicaid Managed Care (MMC) beneficiaries likely to incur high costs. The critical question is how to identify potential high cost beneficiaries with simple, reproducible, transparent, auditable criteria. Our objective in this analysis was to evaluate whether the total burden of comorbidity, assessed by the Charlson comorbidity index, could identify MMC beneficiaries who incurred high health care costs. METHODS: The MetroPlus MMC claims database was use to analyze six months of claims data from 07/07-12/07; the analysis focused on the total amount paid. Age, gender, Charlson comorbidity score, serious mental illness and pregnancy were analyzed as predictors of total costs. RESULTS: We evaluated the cost profile of 4,614 beneficiaries enrolled at MetroPlus, an MMC plan. As hypothesized, the comorbidity index was a key correlate of total costs (p < .01). Yearly costs were more related to the total burden of comorbidity than any specific comorbid disease. For adults, in addition to comorbidity (p < .01) both serious mental illness (p < .01) and pregnancy (p < .01) were also related to total costs, while age, drug addiction and gender were not. The model with age, gender, comorbidity, serious mental illness, pregnancy and addiction explained 20% of the variance in total costs. In children, comorbidity (p < .01), serious mental illness (p < .01), addiction (p < .03) and pregnancy (p < .01) were associated with log cost; the model with those variables explained 6% of the variance in costs. CONCLUSIONS: Comorbidity can be used to identify MMC beneficiaries most likely to have high costs.

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.

Interval life events are an important determinant of heterogeneity in outcomes in a randomised trial: a novel, simple method of assessment.

OBJECTIVE: Although life events are clearly important to health, most of the scientific focus has been on baseline life events that occur prior to a study. Life events that occur after enrolment, that is, interval life events, have had almost no attention. The aim of this analysis of data was to develop a method for measuring interval life events that could be used in clinical trials and other longitudinal studies. DESIGN: Small Changes and Lasting Effects (SCALE) was a 12-month weight-loss randomised controlled trial (RCT). This was an analysis of the SCALE follow-up data. SETTING: Healthcare networks, outpatient clinics and community churches in the South Bronx and Harlem areas of New York City. PARTICIPANTS: Overweight black and Latino adults. This analysis focuses on the 330 of the 405 patients who had >4 weeks of follow-up with at least one perceived stress score (PSS). INTERVENTION: The SCALE RCT was published elsewhere and involved positive affect and self-affirmation to increase behaviour change. OUTCOME: 5% weight loss. FOLLOW-UP: Over 12 months, up to 27 follow-ups were conducted that evaluated interval life events, eating and physical activity behaviour, weight and perceived stress. During these follow-ups, participants were asked two open-ended questions to capture interval life events. The interval life events were qualitatively coded into categories. The interval life events categories were compared with interval monthly measures of perceived stress using the 4-item PSS scale. RESULTS: During the interval follow-ups for the RCT, 70.6% of the 330 patients reported at least one interval life event, which occurred during a median of 15 follow-ups (95% CI: 5 to 24). The median number of interval events was 2 (95% CI: 0 to 8): 30.6% reported their own illness; 22%, death or bereavement; 21.8%, illness in the family and 13.1%, family conflicts. The mean perceived stress score (PSS-4) assessed over the year of follow-up was 3.2±2.7. Mean perceived stress (PSS-4) increased, especially for interval financial events, major conflict with a partner and unemployment, but by less for deaths, family illness and family conflict. Participants with the most interval life events had the greatest increase in interval perceived stress (p<0.0001). Of note, neither high baseline perceived stress (PSS-10 >20) nor baseline depression (Patient Health Questionnaire-9 >10) were associated with higher interval life events (p>0.05); but those with lower social support had more events. However, those with either depression or stress had higher interval stress responses. Most participants had neither baseline nor interval events, and the percentage with both was small so that baseline events did not predict subsequent perceived stress. CONCLUSIONS: This method provides a straightforward method of assessing interval life events, by asking two open-ended questions, that can be coded in a simple categorical framework. Such events can affect outcomes in longitudinal studies and trials in part by increasing perceived stress. This framework moves beyond the events identified as important in the 1950s and recognises that specific life events may have significantly different life impacts in different individuals. TRIAL REGISTERATION NUMBER: NCT01198990; Post-results.

Identifying important predictors for anastomotic leak after colon and rectal resection: prospective study on 616 patients.

OBJECTIVE: The purpose of this study was to identify patient, clinical, and surgical factors that may predispose patients to anastomotic leak (AL) after large bowel surgery. BACKGROUND: Anastomotic leak is still one of the most devastating complications following colorectal surgery. Knowledge about factors predisposing patients to AL is vital to its early detection, decision making for surgical time, managing preoperative risk factors, and postoperative complications. METHODS: This was a prospective observational, quality improvement study in a cohort of 616 patients undergoing colorectal resection in a single institution with the main outcome being AL within 30 days postoperatively. Some of the predictor variables were age, sex, Charlson Comorbidity Index (CCI), radiation and chemotherapy, immunomodulator medications, albumin, preoperative diagnoses, surgical procedure(s), surgical technique (laparoscopic vs open), anastomotic technique (staple vs handsewn), number of major arteries ligated at surgery, surgeon's experience, presence of infectious condition at surgery, intraoperative adverse events, and functional status using 36-Item Short Form General Health Survey. RESULTS: Of the 616 patients, 53.4% were female. The median age of the patients was 63 years and the mean body mass index was 25.9 kg/m. Of them, 80.3% patients had laparoscopic surgery and 19.5% had open surgery. AL occurred in 5.7% (35) patients. In multivariate analysis, significant independent predictors for leak were anastomoses less than 10 cm from the anal verge, CCI of 3 or more, high inferior mesenteric artery ligation (above left colic artery), intraoperative complications, and being of the male sex. CONCLUSIONS: Multiple risk factors exist that predispose patients to ALs. These risk factors should be considered before and during the surgical care of colorectal patients.

Improvement in asthma quality of life in patients enrolled in a prospective study to increase lifestyle physical activity.

OBJECTIVE: Asthma patients know the benefits of exercise but often avoid physical activity because they are concerned that it will exacerbate asthma. The objective of this analysis was to assess longitudinal asthma status in 256 primary care patients in New York City enrolled in a trial to increase lifestyle physical activity. METHODS: Patients were randomized to two protocols to increase physical activity during a period of 12 months. At enrollment, patients completed the Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) and received asthma self-management instruction through an evaluative test and workbook. Exercise and self-management were reinforced every 2 months. The AQLQ was repeated every 4 months and the ACQ was repeated at 12 months. RESULTS: The mean age was 43 years and 75% were women. At 12 months there were clinically important increases in physical activity with no differences between groups; thus, data were pooled for asthma analyses. The enrollment AQLQ score was 5.0 ± 1.3 and increased to 5.9 ± 1.1 corresponding to a clinically important difference. Correlations between AQLQ and physical activity were approximately 0.35 (p < .0001) at each time point. In a mixed effects model, the variables associated with improvement in AQLQ scores over time were male sex, less severe asthma, not taking asthma maintenance medications, fewer depressive symptoms, and increased physical activity (all variables, p < .03). According to the ACQ, asthma was well controlled in 38% at enrollment and in 60% at 12 months (p < .0001). CONCLUSION: With attention to self-management, increased physical activity did not compromise asthma control and was associated with improved asthma.

Recruitment and retention techniques for developing faith-based research partnerships, New York city, 2009-2012.

BACKGROUND: Faith-based organizations are recognized as an influential venue for behavioral health interventions. However, less is known about efficient approaches for identifying and recruiting these organizations and about the processes that enable successful partnership. COMMUNITY CONTEXT: In 2007, 66% of Latinos and 70% of blacks in New York City reported being overweight or obese. Project SCALE (Small Changes and Lasting Effects) is a 5-year randomized behavioral weight loss intervention trial aimed to help black and Latino adults lose weight by making small changes in eating behaviors and daily leisure physical activity. The study partnered with faith-based organizations. METHODS: Faith-based organizations were identified primarily through direct referrals. Recruitment consisted of screening faith-based organizations, establishing a memorandum of understanding, and intervention modification. Partnership maintenance occurred primarily via progress meetings. OUTCOMES: We identified processes that supported and impeded study recruitment and retention. Obtaining leadership support and using group orientation sessions were successful recruitment and retention processes. A balance must be found between leadership, advocacy, and causing members to feel pressured to participate in the study. INTERPRETATION: Behavioral health interventions implemented in faith-based organizations can reduce health disparities. However, researchers must determine whether faith-based organizations have the capacity to partner in intensive interventions. Focusing on the establishment of strong partnerships at the onset will help ensure that mutual objectives are achieved and sustained long-term.