The confounder matrix: A tool to assess confounding bias in systematic reviews of observational studies of etiology.

Systematic reviews and meta-analyses are essential for drawing conclusions regarding etiologic associations between exposures or interventions and health outcomes. Observational studies comprise a substantive source of the evidence base. One major threat to their validity is residual confounding, which may occur when component studies adjust for different sets of confounders, fail to control for important confounders, or have classification errors resulting in only partial control of measured confounders. We present the confounder matrix-an approach for defining and summarizing adequate confounding control in systematic reviews of observational studies and incorporating this assessment into meta-analyses. First, an expert group reaches consensus regarding the core confounders that should be controlled and the best available method for their measurement. Second, a matrix graphically depicts how each component study accounted for each confounder. Third, the assessment of control adequacy informs quantitative synthesis. We illustrate the approach with studies of the association between short interpregnancy intervals and preterm birth. Our findings suggest that uncontrolled confounding, notably by reproductive history and sociodemographics, resulted in exaggerated estimates. Moreover, no studies adequately controlled for all core confounders, so we suspect residual confounding is present, even among studies with better control. The confounder matrix serves as an extension of previously published methodological guidance for observational research synthesis, enabling transparent reporting of confounding control and directly informing meta-analysis so that conclusions are drawn from the best available evidence. Widespread application could raise awareness about gaps across a body of work and allow for more valid inference with respect to confounder control.

Addressing the burden of illness in adults with cystic fibrosis with screening and triage: An early intervention model of palliative care.

BACKGROUND: Novel models that improve generalist-level palliative care for cystic fibrosis (CF) are needed to address the burden of this illness. A screening-and-triage model has the potential to identify clinical problems requiring immediate follow-up by CF professionals. This study describes such a model and its immediate impact on care delivery for CF patients during a two-year period. METHODS: Eligible adults completed monthly online screening for sources of distress. If results revealed one or more "indicators of concern" on two consecutive screenings, this triggered an attempted triage by a social worker. Completed triages led to prompt follow-up by CF professionals for clinical problems, if indicated. Process data were summarized and generalized linear mixed models were used to evaluate baseline patient characteristics (symptom distress, quality of life, and sociodemographics) associated with the need for prompt follow-up. RESULTS: A total of 1,015 monthly surveys were completed by 74 patients; 634 (66 patients) had >1 indicators of concern; and 164 surveys (46 patients) had >1 indicators for two consecutive surveys (e.g., global distress, pain, dyspnea, and psychological symptoms). The 164 attempted triages yielded 84 completed triages (51.2%), of which 39 (46.4%) required prompt follow-up. In multivariable analyses, older patients and those with higher symptom distress at baseline were more likely to require prompt follow-up (p < .05). CONCLUSIONS: Web-based screening that assesses varied domains of distress or burden can identify a subset of CF patients whose clinical problems may benefit from immediate medical or psychological attention. Additional investigations should improve screening efficiency.

Partition: a surjective mapping approach for dimensionality reduction.

MOTIVATION: Large amounts of information generated by genomic technologies are accompanied by statistical and computational challenges due to redundancy, badly behaved data and noise. Dimensionality reduction (DR) methods have been developed to mitigate these challenges. However, many approaches are not scalable to large dimensions or result in excessive information loss. RESULTS: The proposed approach partitions data into subsets of related features and summarizes each into one and only one new feature, thus defining a surjective mapping. A constraint on information loss determines the size of the reduced dataset. Simulation studies demonstrate that when multiple related features are associated with a response, this approach can substantially increase the number of true associations detected as compared to principal components analysis, non-negative matrix factorization or no DR. This increase in true discoveries is explained both by a reduced multiple-testing challenge and a reduction in extraneous noise. In an application to real data collected from metastatic colorectal cancer tumors, more associations between gene expression features and progression free survival and response to treatment were detected in the reduced than in the full untransformed dataset. AVAILABILITY AND IMPLEMENTATION: Freely available R package from CRAN, https://cran.r-project.org/package=partition. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Symptom Distress Among Diverse Patients Referred for Community-Based Palliative Care: Sociodemographic and Medical Correlates.

CONTEXT: Community-based palliative care programs are appearing in the U.S. Many of these programs, particularly those in large cities, serve highly diverse populations. Information about the sources of variation in the conditions that drive illness burden, like symptom distress, may be useful in program planning. OBJECTIVES: To characterize variation in symptom distress among highly diverse patients referred for palliative care in an urban setting. METHODS: This is a retrospective cross-sectional survey of data obtained from patients at the time of enrollment in a community-based palliative care program. Symptom distress was measured using the Condensed Memorial Symptom Assessment Scale. Severe distress was defined as reporting either "quite a bit"/"very much" or "frequently"/"almost constantly" for one or more symptoms. Multivariate analysis evaluated the associations between symptom distress and sources of patient variability. RESULTS: Patients (n = 1532) were aged 72.2 years on average; 60.0% were women, 56.4% were African-American or Hispanic, and 30.8% were non-English speaking. Most had cancer or congestive heart failure (68.6%); 90.2% had a Karnofsky Performance Status score of 40-70. The most prevalent symptoms were fatigue (71.8%), pain (47.3%), and sadness (41.6%); the most distressing symptoms were fatigue (58.5%), worrying (54.8%), and weight loss (52.1%). In multivariate analyses, Caucasian race, non-Asian language, low Karnofsky Performance Status scores, and cancer diagnosis predicted severe symptom distress. CONCLUSION: In a diverse urban population receiving community-based palliative care, symptoms were highly prevalent and distressing, and both sociodemographic and medical factors predicted severe distress. Program planning should consider the needs of subpopulations at risk for high symptom burden.

Race and Ethnicity Do Not Clinically Associate with Quality of Life Among Patients with Chronic Severe Pain in a Federally Qualified Health Center.

Objective: Previous research suggests that race/ethnicity predicts health-related quality of life (HRQL) in chronic pain populations but has not examined this in community settings. This study evaluated this association in 522 community-dwelling patients with chronic pain treated at a Federally Qualified Health Center (FQHC). Design: Cross-sectional secondary analysis. Setting: Six practice sites of an FQHC in New York. Subjects: One hundred forty-two non-Hispanic blacks, 121 non-Hispanic whites, 219 Hispanics, and 40 classified as "other" with severe chronic pain. Methods: Patients with chronic severe pain (three or more months with worst pain ≥ 4/10 or T-score > 60.5 on the Patient-Reported Outcomes Measurement Information System pain interference tool) were interviewed as part of a clinical trial. Race/ethnicity and other potential predictors of HRQL were assessed. Results: Mean age was 53.0 years, and 70.1% were women; 62.8% earned less than $10,000 per year, and 22.8% were Spanish-speaking with low acculturation. Mean worst pain during the past week was 8.6/10, and 39.6% used opioids. In multivariate analyses, race/ethnicity was not significantly associated with mental HRQL. Hispanics had significantly lower physical HRQL than non-Hispanic whites or blacks, but this difference was not clinically meaningful (mean T-scores = 33.9 [Hispanics], 35.8 [non-Hispanic whites], and 35.6 [non-Hispanic blacks]). Mental HRQL was predicted by depression, anxiety, pain disability, income, and physical HRQL; physical HRQL was predicted by race/ethnicity, anxiety, pain disability, age, care satisfaction, and mental HRQL. Conclusions: Race/ethnicity does not explain important variation in HRQL reported by diverse patients with chronic pain. Psychological distress, pain disability, age, and socioeconomic status predicted this health outcome. Future studies may clarify modifiers of these associations to guide treatment in FQHC populations.

Trajectories of caregiver burden in families of adult cystic fibrosis patients.

ABSTRACTObjectives:Little is known about the experience of family caregivers of adults with cystic fibrosis (CF). This information is important for the identification of caregivers at risk for burden. METHODS: This was a longitudinal analysis of survey data obtained from caregivers of adult CF patients participating in an early intervention palliative care trial. Caregivers completed the validated Brief Assessment Scale for Caregivers (BASC) repeatedly over a 28-month period. Mixed-effects modeling evaluated multivariate associations with positive and negative caregiver perceptions over time. RESULTS: Of the 54 caregivers, 47.9% were spouses. The mean age was 50.9 years (SD = 13.2); 72.2% were women; 75.9% were married; and 63.0% were employed. At baseline, the BASC revealed large variations in positive and negative perceptions of caregiving. Although average scores over time were unchanging, variation was greater across caregivers than within caregivers (0.49 vs. 0.27, respectively). At baseline, the positive impact of caregiving in the sample was higher than the negative impact. Multivariate analysis revealed that patients' baseline pulmonary function and their full-time employment status predicted caregiver burden over time. SIGNIFICANCE OF RESULTS: Caregivers of CF patients varied in their positive and negative caregiving experiences, although burden levels in individual caregivers were stable over time. When the disease was advanced, caregivers of CF patients experienced more overall burden but also more positive impact. This suggests that the role of caregivers may become more meaningful as disease severity worsens. In addition, full-time patient employment was associated with lower caregiver burden regardless of disease severity. This suggests that burden in CF caregivers may be predicted by financial strain or benefits conferred by patient employment. These associations require further investigation to determine whether highly burdened caregivers can be identified and assisted using tailored interventions.

Intrauterine Device Use and Cervical Cancer Risk: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate the association between use of an intrauterine device (IUD) and risk of cervical cancer by subjecting existing data to critical review, quantitative synthesis, and interpretation. DATA SOURCES: We searched PubMed, Web of Science, ClinicalTrials.gov, and catalogs of scientific meetings and abstracts, theses, and dissertations queried from inception through July 2016. METHODS OF STUDY SELECTION: Examination of abstracts from 225 reports identified 34 studies with individual-level measures of use of an IUD and incident cervical cancer. By critically assessing the full text of these reports, independent reviewers identified 17 studies conducted without recognized sources of systematic error, of which 16 could be harmonized for meta-analysis. TABULATION, INTEGRATION, AND RESULTS: Point and interval estimates of the association between use of an IUD and incident cervical cancer were extracted from original reports into a structured database along with key features of study design and implementation. A random-effects meta-analysis was implemented to quantitatively synthesize extracted estimates and assess likely influence of publication bias, residual confounding, heterogeneity of true effect size, and human papillomavirus prevalence and cervical cancer incidence in source populations. Women who used an IUD experienced less cervical cancer (summary odds ratio 0.64, 95% CI 0.53-0.77). Neither confounding by recognized risk factors nor publication bias seems a plausible explanation for the apparent protective effect, which may be stronger in populations with higher cervical cancer incidence. CONCLUSION: Invasive cervical cancer may be approximately one third less frequent in women who have used an IUD. This possible noncontraceptive benefit could be most beneficial in populations with severely limited access to screening and concomitantly high cervical cancer incidence.

Quality of Life in Community-Dwelling Chinese American Patients with Cancer Pain.

Although pain can be a powerful influence on health-related quality of life (HRQL) in cancer populations, culturally-based beliefs and behaviors may directly impact HQRL or modify the association between pain and HQRL. Studies of well-defined ethnic groups may clarify these relationships and inform culturally competent clinical practices intended to reduce illness burden. We evaluated HRQL in 121 non-English-speaking Chinese immigrants with cancer pain using the Functional Assessment of Cancer Therapy-General (FACT-G) scale. Overall, 91.2 % were born in China and 86.0 % were Cantonese-speaking; 50.8 % had no formal education (mean age = 63.2 years; 68.6 % women). Although the mean FACT-G score did not differ from U.S. population norms, most subscale scores for Chinese immigrants were lower and the score for social/family well-being was higher (all p < 0.05). Higher educational level, caregiver presence, lower psychological distress, lower pain intensity and interference, and lower symptom distress were associated with better HRQL (all p < 0.05). These findings confirm the importance of diverse influences on HQRL in ethnic Chinese cancer patients with chronic pain and suggest that this group may be distinguished from the majority population by the extent to which social/family well-being is preserved. Future studies in the growing population of Chinese Americans with cancer are needed to evaluate various aspects of social/family well-being and determine whether they modify the association between pain and HRQL.