Coaches Activating, Reaching, and Engaging Patients to Engage in Advance Care Planning: A Randomized Clinical Trial.

Importance: Advance care planning (ACP) remains low among patients with advanced cancer. Multilevel interventions compared with clinician-level interventions may be more effective in improving ACP. Objective: To evaluate whether a multilevel intervention could improve clinician-documented ACP compared with a clinician-level intervention alone. Design, Setting, and Participants: This randomized clinical trial, performed from September 12, 2019, through May 12, 2021, included adults with advanced genitourinary cancers at an academic, tertiary hospital. Data analysis was performed by intention to treat from May 1 to August 10, 2023. Intervention: Participants were randomized 1:1 to a 6-month patient-level lay health worker structured ACP education along with a clinician-level intervention composed of 3-hour ACP training and integration of a structured electronic health record documentation template (intervention group) or to the clinician-level intervention alone (control group). Main Outcome and Measures: The primary outcome was ACP documentation in the electronic health record by the oncology clinician within 12 months after randomization. Secondary, exploratory outcomes included shared decision-making, palliative care use, hospice use, emergency department visits, and hospitalizations within 12 months after randomization. Results: Among 402 participants enrolled in the study, median age was 71 years (range, 21-102 years); 361 (89.8%) identified as male. More intervention group participants had oncology clinician-documented ACP than control group participants (82 [37.8%] vs 40 [21.6%]; odds ratio [OR], 2.29; 95% CI, 1.44-3.64). At 12-month follow-up, more intervention than control group participants had palliative care (72 [33.2%] vs 25 [13.5%]; OR, 3.18; 95% CI, 1.91-5.28) and hospice use (49 [22.6%] vs 19 [10.3%]; OR, 2.54; 95% CI, 1.44-4.51). There were no differences in the proportion of participants between groups with an emergency department visit (65 [30.0%] vs 61 [33.0%]; OR, 0.87; 95% CI, 0.57-1.33) or hospitalization (89 [41.0%] vs 85 [46.0%]; OR, 0.82; 95% CI, 0.55-1.22). Intervention group participants had fewer hospitalizations than control group participants (mean [SD] number of hospitalizations per year, 0.87 [1.60] vs 1.04 [1.77]) and a lower risk of hospitalization (incidence rate ratio, 0.80; 95% CI, 0.65-0.98). Conclusions and Relevance: In this randomized clinical trial, a multilevel intervention improved oncology clinician-documented ACP compared with a clinician-level intervention alone for patients with genitourinary cancer. The intervention is one approach to effectively increase ACP among patients with cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03856463.

Randomized Trial of a Volunteer-Led Symptom Assessment Intervention on Documentation, Patient-Reported Outcomes, and Health Care Use Among Veterans With Lung Cancer.

PURPOSE: Identification and documentation of Veterans' symptoms are crucial for optimal lung cancer care delivery. The objective of this study was to determine whether a volunteer-led proactive telephone symptom assessment intervention could improve comprehensive symptom documentation. METHODS: Veterans with lung cancer were randomly assigned to usual care (control group) or usual care with proactive symptom assessment in which a peer volunteer made weekly phone calls to assess patient symptoms under nurse practitioner supervision. The primary outcome was oncologist documentation of symptoms in the electronic health record at all clinical visits within 6 months after enrollment. Secondary outcomes included patient satisfaction with decision, patient activation, health-related quality of life (HRQOL), and symptom burden, measured at baseline, and 3, 6, and 9 months after enrollment, and acute care use within 9 months after enrollment. RESULTS: Among 60 Veterans randomly assigned, median (range) age was 70.2 (50-86) years; 57 (95.0%) were male. More intervention participants had oncologist documentation of symptoms than control group participants (24 [77.4%] v seven [24.1%], respectively; odds ratio, 16.46 [95% CI, 4.58 to 59.16]). Intervention group participants had greater improvements over time in HRQOL (expected mean difference, 25.3 [95% CI, 15.00 to 35.70]) and patient activation (expected mean difference, 13.6 [95% CI, 3.79 to 23.39]), lower symptom burden (expected mean difference, -6.39 [95% CI, -15.21 to -2.46]), lower rates of emergency room visits (incidence rate ratio, 0.48 [95% CI, 0.30 to 0.75]), and hospitalizations (incidence rate ratio, 0.47 [95% CI, 0.28 to 0.77]) than control group participants. CONCLUSION: This symptom assessment intervention is an effective strategy for Veterans with lung cancer.

Effect of a Community Health Worker-Led Intervention Among Low-Income and Minoritized Patients With Cancer: A Randomized Clinical Trial.

PURPOSE: To determine whether a community health worker (CHW)-led intervention could improve health-related quality of life (HRQoL; primary outcome) more than usual care among low-income and racial and ethnic minoritized populations newly diagnosed with cancer. METHODS: This randomized clinical trial was conducted from November 1, 2018, until August 31, 2021, in outpatient cancer clinics in Atlantic City, NJ, and Chicago, IL. Hourly low-wage worker members of an employer union health fund age 18 years or older with newly diagnosed solid tumor and hematologic malignancies were randomly assigned 1:1 to usual care (control group) or usual care augmented with a trained CHW for 12 months (intervention group). The CHW assisted participants with advance care planning (ACP), proactively screened symptoms, and referred participants to community-based resources for identified health-related social needs. Usual care comprised nurse case management and benefits redesign (waived copayments and free transportation for any cancer care received at preferred oncology clinics in each city). The primary outcome was HRQoL. Secondary outcomes included patient activation, satisfaction with decision, ACP documentation, health care use, total health care costs, and overall survival. RESULTS: A total of 160 participants were enrolled. Intervention group participants had a greater increase in mean HRQoL scores at 4-month and 12-month follow-up as compared with baseline than control group participants (expected mean difference, 11.25 [95% CI, 7.28 to 15.22]; 11.29 [95% CI, 6.96 to 15.62], respectively). CONCLUSION: In this randomized trial, a CHW-led intervention significantly improved HRQoL for low-income and racial and ethnic minoritized patients with cancer more than usual care alone.

An Overview of Current Methods for Real-world Applications to Generalize or Transport Clinical Trial Findings to Target Populations of Interest.

It has been well established that randomized clinical trials have poor external validity, resulting in findings that may not apply to relevant-or target-populations. When the trial is sampled from the target population, generalizability methods have been proposed to address the applicability of trial findings to target populations. When the trial sample and target populations are distinct, transportability methods may be applied for this purpose. However, generalizability and transportability studies present challenges, particularly around the strength of their conclusions. We review and summarize state-of-the-art methods for translating trial findings to target populations. We additionally provide a novel step-by-step guide to address these challenges, illustrating principles through a published case study. When conducted with rigor, generalizability and transportability studies can play an integral role in regulatory decisions by providing key real-world evidence.

Transporting observational study results to a target population of interest using inverse odds of participation weighting.

Inverse odds of participation weighting (IOPW) has been proposed to transport clinical trial findings to target populations of interest when the distribution of treatment effect modifiers differs between trial and target populations. We set out to apply IOPW to transport results from an observational study to a target population of interest. We demonstrated the feasibility of this idea with a real-world example using a nationwide electronic health record derived de-identified database from Flatiron Health. First, we conducted an observational study that carefully adjusted for confounding to estimate the treatment effect of fulvestrant plus palbociclib relative to letrozole plus palbociclib as a second-line therapy among estrogen receptor (ER)-positive, human epidermal growth factor receptor (HER2)-negative metastatic breast cancer patients. Second, we transported these findings to the broader cohort of patients who were eligible for a first-line therapy. The interpretation of the findings and validity of such studies, however, rely on the extent that causal inference assumptions are met.

Characterizing real world safety profile of oral Janus kinase inhibitors among adult atopic dermatitis patients: evidence transporting from the rheumatoid arthritis population.

OBJECTIVE: To address potential safety concerns of Janus Kinase Inhibitors (JAK-Is), we characterized their safety profile in the atopic dermatitis (AD) patient population. METHODS: In this retrospective observational study, we used propensity score-based methods and a Poisson modeling framework to estimate the incidence of health outcomes of interest (HOI) for the AD patient. To that end, two mutually exclusive cohorts were created using a real world data resource: a rheumatoid arthritis (RA) cohort, where we directly quantify the safety risk of JAK-Is on HOIs, and an AD cohort, that comprises the target population of interest and to whom we transport the results obtained from the RA cohort. The RA cohort included all adults who filled at least one prescription for a JAK-I (tofacitinib, baricitinib, or upadacitinib) between 1 January 2017 and 31 January 2020. The AD cohort consisted of all adults diagnosed with AD during the same period. We first estimated the incidence rate of each HOI in the RA cohort, and then transported the results to the AD population. RESULTS: The RA and AD cohorts included 5,296 and 261,855 patients, respectively. On average, patients in the AD cohort were younger, more often male, more likely to be Asian, and had higher household income. They also had a lower prevalence of several comorbid conditions including hypertension, chronic kidney disease, obesity, and depression. Overall, the transported incidence rates of the HOIs to the AD cohort were lower than those obtained in the RA cohort by 13-50%. CONCLUSION: We applied transportability methods to characterize the risk of the HOIs in the AD population and found absolute risks higher than that of the general population. Future work is needed to validate these conclusions in comparable populations.

Examination of fetal growth trajectories following infertility treatment.

PURPOSE: The objective of this retrospective cohort study was to compare fetal growth during the second and third trimesters for ovulation induction with intrauterine insemination (IUI), fresh embryo transfer (ET), frozen embryo transfer (FET), and spontaneous conception following infertility. METHODS: Three hundred ninety-five women with viable pregnancies confirmed at a single academic fertility center participated. All women achieved pregnancy either by treatment or spontaneously after a diagnosis of infertility. Inclusion criteria included autologous singleton pregnancies. Exclusion criteria included pregnancies from donor oocytes, twins, unavailable ultrasound data, and treatment methods with small number of participants. Primary outcomes of interest were head circumference (HC), abdominal circumference (AC), HC/AC ratio, and estimated fetal weight (EFW). Conditional growth curve models were created, and growth curves were selected for each outcome of interest. RESULTS: For ovulation induction with IUI, fresh ET, FET, and spontaneous conception, the slope analysis of growth curves for per-week growth rate of HC, AC, HC/AC ratio, and EFW demonstrated no difference. A subgroup analysis of fresh ET and FET groups, for same outcomes, also showed no difference. CONCLUSION: These findings contribute to the very limited literature on fetal growth trajectories following infertility treatment and suggest no significant differences in fetal growth for ovulation induction with IUI, fresh ET, FET, and spontaneous conception following infertility. It is possible there were no differences in growth trajectories between these conception methods because the majority of children born following infertility are of normal birth weight. While results are reassuring, further research with larger populations is warranted.

Alcohol Use and Breast Cancer Survival among Participants in the Women's Health Initiative.

BACKGROUND: Alcohol increases the risk of breast cancer even at moderate levels of intake. However, the relationship between alcohol consumption and mortality among breast cancer patients is less clear. METHODS: This study included women from the Women's Health Initiative observational study and randomized trial diagnosed with breast cancer (n = 7,835). Cox proportional hazards regression was used to estimate adjusted HRs and 95% confidence intervals (CI) for overall and breast cancer-specific (BCS) mortality associated with drinking alcohol before or after a breast cancer diagnosis. We also assessed whether changes in drinking habits after diagnosis are related to mortality. RESULTS: Women who were consuming alcohol prior to their breast cancer diagnosis had a nonstatistically significant 24% (95% CI, 0.56-1.04) reduced risk of BCS mortality and a 26% (95% CI, 0.61-0.89) reduced risk of all-cause mortality. Some variation was observed by estrogen receptor (ER) status as alcohol consumption was associated with a 49% (95% CI, 0.31-0.83) reduced risk of BCS mortality among ER(-) patients with no change in risk observed among ER(+) patients (HR = 0.97; 95% CI, 0.31-1.54), though the difference between these risks was not statistically significant (P for interaction = 0.39). Postdiagnosis alcohol consumption, and change in consumption patterns after diagnosis, did not appear to be associated with all-cause or BCS mortality. CONCLUSION: In this large study, consumption of alcohol before or after breast cancer diagnosis did not increase risks of overall or cause-specific mortality. IMPACT: Coupled with existing evidence, alcohol consumption is unlikely to have a substantial impact on mortality among breast cancer patients. Cancer Epidemiol Biomarkers Prev; 25(8); 1268-73. ©2016 AACR.

Weight loss on low-fat vs. low-carbohydrate diets by insulin resistance status among overweight adults and adults with obesity: A randomized pilot trial.

OBJECTIVE: To test for differential weight loss response to low-fat (LF) vs. low-carbohydrate (LC) diets by insulin resistance status with emphasis on overall quality of both diets. METHODS: Sixty-one adults, BMI 28-40 kg/m(2) , were randomized in a 2 × 2 design to LF or LC by insulin resistance status in this pilot study. Primary outcome was 6-month weight change. Participants were characterized as more insulin resistant (IR) or more insulin sensitive (IS) by median split of baseline insulin-area-under-the-curve from an oral glucose tolerance test. Intervention consisted of 14 one-hour class-based educational sessions. RESULTS: Baseline % carbohydrate:% fat:% protein was 44:38:18. At 6 months, the LF group reported 57:21:22 and the LC group reported 22:53:25 (IR and IS combined). Six-month weight loss (kg) was 7.4 ± 6.0 (LF-IR), 10.4 ± 7.8 (LF-IS), 9.6 ± 6.6 (LC-IR), and 8.6 ± 5.6 (LC-IS). No significant main effects were detected for weight loss by diet group or IR status; there was no significant diet × IR interaction. Significant differences in several secondary outcomes were observed. CONCLUSIONS: Substantial weight loss was achieved overall, but a significant diet × IR status interaction was not observed. Opportunity to detect differential response may have been limited by the focus on high diet quality for both diet groups and sample size.