Missing data is a key methodological consideration in longitudinal studies of aging. We described missing data challenges and potential methodological solutions using a case example describing ...five-year frailty state transitions in a cohort of older adults.
We used longitudinal data from the National Health and Aging Trends Study, a nationally-representative cohort of Medicare beneficiaries. We assessed the five components of the Fried frailty phenotype and classified frailty based on their number of components (robust: 0, prefrail: 1-2, frail: 3-5). One-, two-, and five-year frailty state transitions were defined as movements between frailty states or death. Missing frailty components were imputed using hot deck imputation. Inverse probability weights were used to account for potentially informative loss-to-follow-up. We conducted scenario analyses to test a range of assumptions related to missing data.
Missing data were common for frailty components measured using physical assessments (walking speed, grip strength). At five years, 36% of individuals were lost-to-follow-up, differentially with respect to baseline frailty status. Assumptions for missing data mechanisms impacted inference regarding individuals improving or worsening in frailty.
Missing data and loss-to-follow-up are common in longitudinal studies of aging. Robust epidemiologic methods can improve the rigor and interpretability of aging-related research.
Asymmetrically differentiating cells are formed with the aid of RNA-binding proteins (RBPs), which can bind, stabilize, regulate, and transport target mRNAs. The loss of RBPs in neurons may lead to ...severe neurodevelopmental diseases such as the Fragile X Syndrome with the absence of the Fragile X Mental Retardation Protein (FMRP). Because the latter is ubiquitous and shares many similarities with other RBPs involved in the development of peripheral cells, we suggest that FMRP would have a role in the differentiation of all tissues where it is expressed. A MEG-01 differentiation model was, therefore, established to study the global developmental functions of FMRP. PMA induction of MEG-01 cells causes important morphological changes driven by cytoskeletal dynamics. Cytoskeleton change and colocalization analyses were performed by confocal microscopy and sucrose gradient fractionation. Total cellular protein content and de novo synthesis were also analyzed. Microtubular transport mediates the displacement of FMRP and other RBP-containing mRNP complexes towards regions of the cell in development. De novo protein synthesis decreases significantly upon differentiation and total protein content composition is altered. Because those results are comparable with those obtained in neurons, the absence of FMRP would have significant consequences in cells everywhere in the body. The latter should be further investigated to give a better understanding of the systemic implications of imbalances of FMRP and other functionally similar RBPs.
Women with small HER2+ breast cancers may have excellent prognosis with adjuvant single-agent chemotherapy and HER2-targeted therapy. The role of de-escalated therapy in the neoadjuvant setting, ...however, remains uncertain. We conducted a cohort study of adult women with T1-2/cN0 HER2+ breast cancer diagnosed 2013-2016 in the National Cancer Database treated with neoadjuvant chemotherapy (NAC) and HER2-targeted therapy. Factors associated with pathologic complete response (pCR) and overall survival were examined. In total, 6994 patients were included, 32% cT1 and 68% cT2. Multi-agent NAC was given to 90% of women while single-agent NAC was given to 10% of women. pCR was achieved in 46% of cT2 patients and 43% of cT1, and in 46% of patients treated with multi-agent versus 38% single agent. Patients receiving multi-agent chemotherapy were younger, had fewer comorbidities, and had higher cT stage and grade. In all patients, pCR was associated with improved survival (p < 0.01). Multi-agent chemotherapy (OR 1.3, p = 0.003), hormone receptor negative (OR 2.6, p < 0.001), higher grade (OR 2.2, p < 0.001), younger age (OR 1.4, p = 0.011), and later year of diagnosis (OR 1.3, p = 0.005) were associated with achieving pCR. Multi-agent chemotherapy was associated with higher likelihood of pCR, but this effect was modest compared to other factors. Single-agent NAC with HER2-directed therapy in selected patients may provide excellent outcome with reduced toxicity, while allowing escalated therapy in the adjuvant setting for patients with residual disease. Prospective studies are needed to determine effects of de-escalation in the neoadjuvant setting on survival and optimal selection strategies.
Frailty is a dynamic syndrome characterized by reduced physiological reserve to maintain homeostasis. Prospective studies have reported frailty worsening in women with breast cancer during ...chemotherapy, with improvements following treatment. We evaluated whether the Faurot frailty index, a validated claims-based frailty measure, could identify changes in frailty during chemotherapy treatment and identified predictors of trajectory patterns.
We included women (65+ years) with stage I-III breast cancer undergoing adjuvant chemotherapy in the SEER-Medicare database (2003-2019). We estimated the Faurot frailty index (range: 0-1; higher scores indicate greater frailty) at chemotherapy initiation, 4 months postinitiation, and 10 months postinitiation. Changes in frailty were compared to a matched noncancer comparator cohort. We identified patterns of frailty trajectories during the year following chemotherapy initiation using K-means clustering.
Twenty-one thousand five hundred and ninety-nine women initiated adjuvant chemotherapy. Mean claims-based frailty increased from 0.037 at initiation to 0.055 4 months postchemotherapy initiation and fell to 0.049 10 months postinitiation. Noncancer comparators experienced a small increase in claims-based frailty over time (0.055-0.062). We identified 6 trajectory patterns: a robust group (78%), 2 resilient groups (16%), and 3 nonresilient groups (6%). Black women and women with claims for home hospital beds, wheelchairs, and Parkinson's disease were more likely to experience nonresilient trajectories.
We observed changes in a claims-based frailty index during chemotherapy that are consistent with prior studies using clinical measures of frailty and identified predictors of nonresilient frailty trajectories. Our study demonstrates the feasibility of using claims-based frailty indices to assess changes in frailty during cancer treatment.
Studies evaluating the effects of cancer treatments are prone to immortal time bias that, if unaddressed, can lead to treatments appearing more beneficial than they are.
To demonstrate the impact of ...immortal time bias, we compared results across several analytic approaches (dichotomous exposure, dichotomous exposure excluding immortal time, time-varying exposure, landmark analysis, clone-censor-weight method), using surgical resection among women with metastatic breast cancer as an example. All adult women diagnosed with incident metastatic breast cancer from 2013-2016 in the National Cancer Database were included. To quantify immortal time bias, we also conducted a simulation study where the "true" relationship between surgical resection and mortality was known.
24,329 women (median age 61, IQR 51-71) were included, and 24% underwent surgical resection. The largest association between resection and mortality was observed when using a dichotomized exposure HR, 0.54; 95% confidence interval (CI), 0.51-0.57, followed by dichotomous with exclusion of immortal time (HR, 0.62; 95% CI, 0.59-0.65). Results from the time-varying exposure, landmark, and clone-censor-weight method analyses were closer to the null (HR, 0.67-0.84). Results from the plasmode simulation found that the time-varying exposure, landmark, and clone-censor-weight method models all produced unbiased HRs (bias -0.003 to 0.016). Both standard dichotomous exposure (HR, 0.84; bias, -0.177) and dichotomous with exclusion of immortal time (HR, 0.93; bias, -0.074) produced meaningfully biased estimates.
Researchers should use time-varying exposures with a treatment assessment window or the clone-censor-weight method when immortal time is present.
Using methods that appropriately account for immortal time will improve evidence and decision-making from research using real-world data.
Frailty is an aging-related syndrome of reduced physiological reserve to maintain homeostasis. The Faurot frailty index has been validated as a Medicare claims-based proxy for predicting frailty ...using billing information from a user-specified ascertainment window.
We assessed the validity of the Faurot frailty index as a predictor of the frailty phenotype and 1-year mortality using varying frailty ascertainment windows.
We identified older adults (66+ y) in Round 5 (2015) of the National Health and Aging Trends Study with Medicare claims linkage. Gold standard frailty was assessed using the frailty phenotype. We calculated the Faurot frailty index using 3, 6, 8, and 12 months of claims prior to the survey or all-available lookback. Model performance for each window in predicting the frailty phenotype was assessed by quantifying calibration and discrimination. Predictive performance for 1-year mortality was assessed by estimating risk differences across claims-based frailty strata.
Among 4253 older adults, the 6 and 8-month windows had the best frailty phenotype calibration (calibration slopes: 0.88 and 0.87). All-available lookback had the best discrimination (C-statistic=0.780), but poor calibration. Mortality associations were strongest using a 3-month window and monotonically decreased with longer windows. Subgroup analyses revealed worse performance in Black and Hispanic individuals than counterparts.
The optimal ascertainment window for the Faurot frailty index may depend on the clinical context, and researchers should consider tradeoffs between discrimination, calibration, and mortality. Sensitivity analyses using different durations can enhance the robustness of inferences. Research is needed to improve prediction across racial and ethnic groups.
Feedback is an essential component in complex work environments. Different generations have been shown to have different sets of values, derived from societal and cultural changes. We hypothesize ...that generational differences may be associated with preferred feedback patterns among medical trainees and faculty in a large academic institution.
A survey was distributed to all students, residents/fellows, and faculty at a large academic medical institution from April 2020 through June 2020. Survey questions evaluated feedback methods for six domains: preparedness, performance, attitude, technical procedures, inpatient, and outpatient care. Participants selected a preferred feedback method for each category. Patient demographics and survey responses were described using frequency statistics. We compared differences in feedback preferences based on generation and field of practice.
A total of 871 participants completed the survey. Preferred feedback patterns in the medical field do not seem to align with sociologic theories of generational gaps. Most participants preferred to receive direct feedback after an activity away from their team, irrespective of their age or medical specialty. Individuals preferred direct feedback during an activity in front of their team only for technical procedures. Compared to nonsurgeons, surgeons were more likely to prefer direct feedback in front of team members for preparedness, performance, and attitude.
Generational membership is not significantly associated with preferred feedback patterns in this complex medical academic environment. Variations in feedback preferences are associated with field of practice that may be due to specialty-specific differences in culture and personality traits present within certain medical specialties, particularly surgery.
Background
Sleep disorders are common among older adults, leading to high prevalence of over‐the‐counter and prescription sleep medication use. Socioeconomically disadvantaged individuals have higher ...prevalence of sleep disorders. Frequent use of sleep medications can increase the risk of falls. Little is known about the association between wealth and sleep medication use in older adults.
Methods
We conducted a cross‐sectional analysis using a nationwide sample of 7603 Medicare beneficiaries (65+ years) from Round 1 (2011) of the National Health and Aging Trends Study. We measured self‐reported wealth as the sum of assets (retirement savings, stocks/bonds, checking/savings accounts, business assets, and home value) minus liabilities (mortgage, credit card, and medical debt). Self‐reported sleep medication use in the past month was categorized as frequent (5–7 nights/week), sometimes (1–4 nights/week), or never (0 night/week). We estimated differences in the prevalence of sleep medication use by quintiles of wealth using crude and adjusted binomial regression models. Individuals missing sleep medication information were excluded.
Results
Median wealth was $152 582 (IQR: $24 023–412 992). Sixteen percent reported frequent sleep medication use, 15% reported some use, and 70% reported no use. Frequent sleep medication use was more common in lower wealth quintiles (lowest: 20%, highest: 12%). Alternatively, some use was more common in higher wealth quintiles (lowest: 11%, highest: 18%). Results were similar after adjustment for demographic factors, anxiety, depression, and sleep disorders.
Conclusions
In this study, less wealthy older adults had higher prevalence of frequent sleep medication use. This may lead to dependency or increased fall risk in this vulnerable population.
Background
It is unknown if opioid naïve patients who undergo minimally invasive, benign foregut operations are at risk for progressing to persistent postoperative opioid use. The purpose of our ...study was to determine if opioid naïve patients who undergo minimally invasive, benign foregut operations progress to persistent postoperative opioid use and to identify any patient- and surgery-specific factors associated with persistent postoperative opioid use.
Methods
Opioid-naïve, adult patients who underwent laparoscopic fundoplication, hiatal hernia repair, or Heller myotomy from 2010 to 2018 were identified within the IBM® MarketScan® Commercial Claims and Encounters Database. Daily drug logs of the preoperative and postoperative period were evaluated to assess for changes in drug use patters. The primary outcome of interest was persistent postoperative opioid use, defined as at least 33% of the proportion of days covered by opioid prescriptions at 365-day follow-up. Patient demographic information and clinical risk factors for persistent postoperative opioid use at 365 days postoperatively were estimated using log-binomial regression.
Results
A total of 17,530 patients met inclusion criteria; 6895 underwent fundoplication, 9235 underwent hiatal hernia repair, and 1400 underwent Heller myotomy. 9652 patients had at least one opioid prescription filled in the perioperative period. Sixty-five patients (0.4%) were found to have persistent postoperative opioid use at 365 days postoperatively. Lower Charlson comorbidity index scores and a history of mental illness or substance use disorder had a statistically but not clinically significant protective effect on the risk of persistent postoperative opioid use at 365 days postoperatively.
Conclusions
Only half of opioid naïve patients undergoing minimally invasive, benign foregut operations filled an opioid prescription postoperatively. The risk of progression to persistent postoperative opioid use was less than 1%. These findings support the current guidelines that limit the number of opioid pills prescribed following general surgery operations.
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